FitSugar

Foods to Sleep On

FitSugar — Wed, 31 Jan 2007 17:30:00 -0800

Come 10 pm, when the rest of the world is starting to wind down, you're winding up. Maybe it's something more, but it could be what you're eating (or not eating). Yahoo Health has created this list of the top 10 foods to help you get a good night's sleep.

Bananas. They're practically a sleeping pill in a peel. In addition to a bit of soothing melatonin and serotonin, bananas contain magnesium, a muscle relaxant.

Chamomile tea. The reason chamomile is such a staple of bedtime tea blends is its mild sedating effect - it's the perfect natural antidote for restless minds/bodies.

Warm milk. It's not a myth. Milk has some tryptophan - an amino acid that has a sedative - like effect - and calcium, which helps the brain use tryptophan. Plus there's the psychological throw-back to infancy, when a warm bottle meant "relax, everything's fine."

Honey. Drizzle a little in your warm milk or herb tea. Lots of sugar is stimulating, but a little glucose tells your brain to turn off orexin, a recently discovered neurotransmitter that's linked to alertness.

Potatoes. A small baked spud won't overwhelm your GI tract, and it clears away acids that can interfere with yawn-inducing tryptophan. To up the soothing effects, mash it with warm milk.

There's more so read more

Oatmeal. Oats are a rich source of sleep - inviting melatonin, and a small bowl of warm cereal with a splash of maple syrup is cozy - plus if you've got the munchies, it's filling too.

Almonds. A handful of these heart-healthy nuts can be snooze-inducing, as they contain both tryptophan and a nice dose of muscle-relaxing magnesium.

Flaxseeds. When life goes awry and feeling down is keeping you up, try sprinkling 2 tablespoons of these healthy little seeds on your bedtime oatmeal. They're rich in omega-3 fatty acids, a natural mood lifter.

Whole-wheat bread. A slice of toast with your tea and honey will release insulin, which helps tryptophan get to your brain, where it's converted to serotonin and quietly murmurs "time to sleep."

Turkey. It's the most famous source of tryptophan, credited with all those Thanksgiving naps. But that's actually modern folklore. Tryptophan works when your stomach's basically empty, not overstuffed, and when there are some carbs around, not tons of protein. But put a lean slice or two on some whole-wheat bread mid-evening, and you've got one of the best sleep inducers in your kitchen.

To read the full article, check out Yahoo health.

Fit's Tip: It's all about the serotonin and melatonin.

Weight control and diet

FitSugar — Wed, 08 Oct 2008 17:34:58 -0700

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

Cancer and Weight Control:

Cancer prevention guidelines from the American Cancer Society stress the importance of maintaining a healthy weight throughout life. A healthy weight is even more important than eating specific healthy foods, when it comes to cancer prevention.

Drug Warning:

The US Food and Drug Administration (FDA) is warning consumers not to buy a product known as the "Brazilian diet pill." This product is labeled as a dietary supplement, but contains several chemicals found in powerful prescription drugs. The products are also known as Emagrece Sim and Herbathin dietary supplements.

New Over-the-Counter Medication:

In February 2007, the FDA approved the first over-the-counter (OTC) weight-loss drug. Orlistat, previously available only by prescription as Xenical, will be available OTC at half its prescription strength. It will be sold under the name alli. Those eager to use the new pill should consider its cost and modest benefits compared with its side effects, most commonly oily diarrhea. This pill, which prevents fat absorption from food, also increases the risk of not absorbing important nutrients from food while using it. The FDA recommends taking a daily multivitamin supplement when using alli.

Research News:

A small study in Norway found that a diet low in fat and high in carbohydrates ("carbs") increases symptoms of psychological distress, such as depression and anger. The study compared three different diets with varying amounts of fat and carbohydrates.
A study released in March 2007 found that obesity in young girls results in early puberty -- as early as age 9.

Effects of Obesity on the Body:

Obesity is associated with certain problems related to infertility, such as uterine fibroids or menstrual irregularities. In men, obesity can contribute to reduced testosterone levels.
People who are obese are at higher risk for carpal tunnel syndrome and other problems involving nerves in their wrists and hands.
The Pickwickian syndrome, named for an overweight character in a Dickens novel, occurs in severe obesity when lack of oxygen produces intense and chronic sleepiness and, eventually, heart failure.

Introduction

A stable weight depends on a good balance between the energy you get from food and the energy you use. You use energy during the day in three ways:

As energy expended during rest (basal metabolism)
As energy used to break down food (thermogenesis)
As energy used during physical activity

Basal metabolism accounts for about two-thirds of spent energy. Your body generally uses this energy to keep your body temperature steady and keep the muscles of your heart and intestine working. Thermogenesis accounts for about 10% of spent energy.

When a person consumes more calories than the energy they use, the body stores the extra calories in fat cells. Fat cells function as energy reservoirs. They enlarge or shrink depending on how people use energy. If people do not balance energy input and output by eating right and exercising, fat can build up. This can lead to weight gain.

When energy input is equal to energy output, there is no expansion of fat cells (lipocytes) to accommodate excess. It is only when more calories are taken in than used that the extra fat is stored in the lipocytes and the person begins to accumulate fat.

Obesity is determined by measuring body fat, not just body weight. People might be over the weight limit for normal standards, but if they are very muscular with low body fat, they are not obese. Others might be normal or underweight, but still have excessive body fat. The following measurements and factors are used to determine whether or not a person is overweight to a degree that threatens their health:

Body mass index (BMI) (a measure of body fat)
Waist circumference (size around the waist)
Waist-hip ratio
Skin fold measurement (anthropometry)
The presence or absence of other disease risk factors (e.g., smoking, high blood pressure, unhealthy cholesterol levels, diabetes, relatives with heart disease)

A person's disease risk factors plus BMI may be the most important components in determining health risks with weight.

The Body Mass Index (BMI). The current standard measurement for obesity is the body mass index (BMI). In general, a BMI of 25 - 29.9 means you are overweight. Obesity is a BMI of 30 and above. Obesity is then classified into three categories:

Class 1: BMI of 30 - 34.9
Class II: BMI 35 - 39.9
Class III: BMI of 40 and greater

These guidelines are very important for people at risk for diabetes, heart disease, or certain cancers. It is also used to determine treatment approaches such as when surgery may be appropriate. The higher the BMI, the greater the risk for significant health problems.

Calculating Body Mass Index (BMI). One's body mass index (BMI) is calculated by multiplying a person's weight in pounds by 703, dividing by the height in inches, and then dividing that number by the height in inches. The steps are as follows:

Multiply one's weight in pounds by 703
Divide that answer by height in inches
Divide that answer again by height in inches

For example, a woman who weighs 150 pounds and is five feet eight inches (or 68 inches) tall has a BMI of 22.8.

Waist Circumference and Waist-Hip Ratio. The extent of abdominal fat can also be used in assessing risk of disease. Some studies suggest that:

Women whose waistlines are over 31.5 inches and men whose waists measure over 37 inches should watch their weight.
A waist size greater than 35 inches in women and 40 inches in men is associated with a higher risk for heart disease, diabetes, and impaired functioning.

Evidence strongly suggests that more body fat around the abdomen and hips (the apple-shape) is a more consistent predictor of heart problems and health risks than BMI.

The distribution of fat can be evaluated by dividing waist size by hip size. For example, a woman with a 30-inch waist and 40-inch hip circumference would have a ratio of 0.75; one with a 41-inch waist and 39-inch hips would have a ratio of 1.05. The lower the ratio the better. The risk of heart disease rises sharply for women with ratios above 0.8 and for men with ratios above 1.0.

Click the icon to see a depiction of the waist-to-hip ratio.

Anthropometry. Anthropometry is the measurement of skin fold thickness in different areas, particularly around the triceps, shoulder blades, and hips. This measurement is useful in determining how much weight is due to muscle or fat.

Biological and Medical Causes

Obesity results when a person consumes more calories than they need for the energy they use. Several different factors may influence weight gain.

About 90% of people who lose weight through dieting gain every pound back regardless of their weight-loss method.

Some evidence suggests that every person has an inherited weight. This range varies by only about 10% either up or down from some set point. For instance, a man whose "genetically-determined" weight is 200 pounds would tend to swing from 180 - 220 pounds. He would be unlikely to lose or gain more than this.

Genetic factors may play some part in 70 - 80% of obesity cases.

Appetite is determined by processes that occur both in the brain and gastrointestinal tract. Eating patterns are controlled by areas in the hypothalamus and pituitary glands (in the brain). The body produces a number of molecules that increases or decreases appetite. In some cases, the following factors may produce imbalances in this process:

Insulin. Insulin is a hormone that helps change blood sugar (glucose) into energy. During digestion, carbohydrates from our diet break down into different types of sugar molecules (including glucose). Proteins from our diet break down into smaller molecules called amino acids. Immediately after eating, blood glucose levels rise. This triggers the release of insulin, which pours into the bloodstream. Insulin pushes the glucose and amino acids into cells and muscles. Insulin and other hormones determine which nutrients will be burned for energy or stored for future use. The inability to use insulin efficiently (insulin resistance) has been associated with both obesity and diabetes.
Leptin. Leptin is a hormone that is released by fat cells. A number of scientists think this hormone may also be released by cells in the stomach. Leptin appears to play an important role in insulin resistance and fat storage in the body, but its role in obesity is unclear. The most likely scenario is that leptin levels rise as the cells store more fat. This increase in leptin levels decreases appetite. Falling levels of leptin make you feel hungry. In people who have genetically lower levels of leptin, however, the brain may be tricked into thinking that it is always starving because there is no leptin to decrease appetite. This can lead to weight gain.
Resistin. Resistin is a hormone produced by fat cells. It makes the body resistant to insulin activity. Some experts believe it may help explain the role of obesity in diabetes type 2.
Intestinal Chemicals. Ghrelin is a chemical produced in the stomach. It appears to be important in triggering the desire to eat. Peptide YY3–36 (PYY) is a substance secreted in the intestines after a meal. The level of PYY is proportionate to the number of calories a person eats. PYY tells the brain that you feel full. Deficiencies in ghrelin and PYY may contribute to some cases of obesity. Researchers are hoping that blocking ghrelin or infusing PYY may be possible treatments for obesity.
Other Chemicals. Many brain chemicals are being studied for their role in appetite stimulation and weight gain. Among them are neuropeptide Y, melanocortins, agouti-related protein, and melanocyte stimulating hormone. Pain-relieving chemicals called endorphins may be critical in reducing appetite and regulating energy use. Cholecystokinin, a hormone released in the upper intestine that stimulates digestive juices, may work to control meal size.

Insulin is a hormone produced by the pancreas that is necessary for cells to be able to use blood sugar.

Genetics may directly contribute to severe obesity in people with family histories of the problem. Genetic factors such as slow metabolisms may also make people more likely to be overweight. At least seven genetic mutations have been associated with specific and uncommon cases of severe obesity. Some are outlined below.

HOB1 (human obesity 1) is a gene that is linked to a high BMI in women.
Leptin gene variants have been linked to leptin deficiencies and obesity.
Melanocortin-4 receptor is a gene that helps turn off the urge to eat. It may not work properly in those with a family history of obesity.
Researchers have also identified a mutation in a gene for a protein called proopiomelanocortin, which results in a syndrome of obesity, red hair, and deficiencies in stress hormones.
A protein called agouti-related protein increases hunger. About 5% of severely obese people have mutations that over-respond to agouti-related protein.

Genetics also determine the number of fat cells a person has. Some people are simply born with more. It should be noted that even when genetic factors are present, a person can still control their diet.

The Thrifty Gene. Some experts think the existence of a so-called "thrifty" gene regulates changes in hormone levels, to accommodate seasonal changes. Theoretically, it works in the following manner:

In certain populations, hormones are released during seasons when food supplies have traditionally been low. This leads to insulin resistance and increased fat storage.
The process is reversed in seasons when food is readily available.
Because modern industrialization has made high carbohydrate and fatty foods available all year long, the gene no longer serves a useful function. Fat, originally stored for famine situations, is not used.

This theory could explain why the previously nomadic Native American tribes who now have Western dietary habits have such high rates of Type 2 diabetes and obesity. In the past, the traditional low-fat, high-fiber foods tribe members ate may have protected them from obesity and type 2 diabetes. Today, these tribes' diet consists of more Western foods, which are higher in fat. Furthermore, these foods are readily available year-round, and many members of the tribe are sedentary. The result is a very high incidence of Type 2 diabetes and obesity. Although genetic abnormalities may make it harder or easier to lose weight, the occurrence of obesity has dramatically increased over the past two decades, and genes cannot have changed within that short amount of time. Our ability to use the food that we eat evolved so that our body could conserve energy and store fat during times of famine. Most cases of obesity now occur in people with normal body function who live in industrialized nations, where there is more than enough food.

A number of medical conditions may contribute to being overweight, but rarely are they a primary cause of obesity.

Hypothyroidism is sometimes associated with weight gain. But, patients with an underactive thyroid generally show only a moderate weight increase of five to 10 pounds.
Very rare genetic disorders, including Froehlich's syndrome in boys, Laurence-Moon-Biedl, and the Prader-Willi syndromes, cause obesity.
Abnormalities or injury to the hypothalamus gland can cause hypothalamic obesity.
Cushing's disease is a rare condition caused by high levels of steroid hormones. It results in obesity, a moon-shaped face, and muscle wasting.
Obesity is also linked to polycystic ovarian syndrome, a hormonal disorder in women.

Click the icon to see an image of polycystic ovaries.

Some prescription medications contribute to weight gain, usually by increasing appetite. Such drugs include the following:

Corticosteroids
Female hormone treatments, including some oral birth control pills (effect is usually temporary), and certain progestins (such as Megestrol) used to treat cancer
Antidepressants and anti-psychotic drugs, including lithium and valproate
Insulin and insulin-stimulating drugs used to treat diabetes often lead to weight gain, a particularly unfortunate conflict of interest for obese individuals with type 2 diabetes

You should not stop taking any medications without your doctor's knowledge.

Cultural and Emotional Causes

Enough food is produced in the US to supply 3,800 calories every day to each man, woman, and child in the country, far more than the average person needs to sustain life. In a 2002 study, participants carefully recorded everything they ate and drank, and all activities and psychological factors surrounding the eating events. The people who gained weight ate more and their portions were larger than those who did not. This may be an obvious conclusion, but the public press often plays up biologic factors involved with obesity and overlooks the simple notion that Americans eat too much and exercise too little.

Obesity is dramatically increasing not only in American children and adults, but also in every country that has adopted similar cultural habits. The World Health Organization now considers obesity to be a global epidemic and a public health problem as more nations become "Westernized." In spite of the proven health risks of obesity, the government, insurance companies, and the medical profession do not spend nearly enough money to balance the commercial and cultural pressures that are producing millions of overweight people.

In 2007, the Robert Wood Johnson Foundation sounded a positive note with the announcement of a $500 million initiative, aimed at “reversing the childhood obesity epidemic by 2015.” The money will be used for research, education, and activities that promote healthy eating among America’s children.

Perhaps the primary reason for the dramatic rise in obesity is the sedentary (inactive) lives led by most Americans, including children and young people. In a 2003 study comparing modern life to the past, researchers found that labor saving devices had reduced a person's energy use by 111 calories a day -- adding up to an extra 11 pounds a year. Half the difference in energy use was due to less walking. At the same time, according to the U.S. Centers for Disease Control and Prevention, between 1970 and 2000 the typical American man increased his caloric intake by 168 calories a day (good for 17 pounds a year) while the average woman added 335 calories a day.

Regular television watching has been singled as the most hazardous pastime. According to a major 2003 study, for every 2 hours a person spends in front of the TV each day, the risk for obesity increases by 23% and for type 2 diabetes by 14%. In the study, TV watching produced the lowest metabolic rates compared to sewing, playing board games, reading, writing, and driving a car. Just the act of watching TV encourages unhealthy snacks and eating patterns. In addition, the advertising on the television complicates the problem by promoting fast foods, cereal, and snack products that are high in salt, fats, and carbohydrates. Even worse, much of these advertisements are directed at children -- the most vulnerable group.

People are not only eating more food than they did 20 years ago, they are also replacing home cooking with packaged foods, fast food, and dining out. This behavior, according to studies, places people at higher risk for obesity. Fast foods may be more harmful than restaurant cooking. These foods tend to be served in larger portions. They generally contain more calories and unhealthy fats, and less nutritious ingredients, than homemade or restaurant meals. Snack foods and sweet beverages, including juice and soft drinks, are specific problems that add to the increasing rates of obesity. Frequent small, healthy meals (instead of two or three large daily meals) have been associated with lower weights.

People react differently to stress. Some overeat and gain weight and others stop eating and lose weight. People who gain weight in response to stress often overeat foods high in sugar, fats, and salt. A 2003 study on rats suggested that stress hormones increase the pleasure of eating such so-called "comfort foods." Furthermore, the study supported previous research showing that stress-related eating was connected to the unhealthy accumulation of abdominal fat.

Risk Factors

Where you live plays a role in your risk for obesity. Simply living in the United States makes a person more susceptible to obesity. The prevalence of obesity in America has risen dramatically over the past few years and continues to increase.

According to the latest figures available, 32.2% of American adults (aged 20 and older) are obese (BMI over 30) -- up from about 23% in the early 1990s.
The number of Americans aged 20 - 74 who were overweight also increased -- from about 44.8% in 1960 to 65.2% in 2002.
The rate of extreme obesity (BMI > 40) increased from 0.8% in 1960 to 4.9% in 2002.
Obesity has increased in every state, in both men and women, across all age groups, and in every ethnic group, although some groups may face slightly higher risks than others.

Fat tends to settle in certain regions, depending on gender. Women gain fat predominantly in the stomach, hips and thighs, while men tend to gain fat in the belly and waist.

Risk by Age. People of any age are at risk for obesity. More children and adolescents are overweight in America than ever before. Gaining some weight is inevitable with age and adding about 10 pounds to a normal base weight over time is not harmful. The current weight gain in American adults over 50, however, is significant. By age 55, the average American has added nearly 40 pounds of fat during the course of adulthood. This condition is made worse by the fact that muscle and bone mass decrease with age.

Risk by Gender. In men, BMI tends to increase until age 50 and then it levels off. In women, weight tends to increase until age 70 before it plateaus. A 2000 study found that there are three high-risk periods for weight gain in women.

The first is at the onset of menstruation, particularly if it is early. In fact, a study released in March 2007 found that obesity in young girls results in early puberty -- as early as age 9. This, in turn, increases the risk for more weight gain as girls enter puberty.
The second is after pregnancy, with higher risk for women who are already overweight.
Finally, many women gain weight after menopause.

These findings are significant because they may allow women to target high-risk times, and consequently prevent unnecessary weight gain.

Risk by Economic Group. Obesity is more prevalent in lower economic groups. One 2002 study reported that women who reported that they did not have enough food were more likely to be overweight than those who said they had sufficient food. Researchers discovered that the low-income women tended to have fewer fruits and vegetables but were actually taking in more calories a day than higher-income women. However, obesity is increasing in young adults with college education as well as in other groups.

Ethnic Groups. Among ethnic groups in general, African-American women are more overweight than Caucasian women but African-American men are less obese than Caucasian men. (Currently, 80% of African-American women are overweight.) Hispanic men and women tend to weigh more than Caucasians.

US Regions. Regionally, the prevalence of obesity is lowest in the Western states and highest in the South.

A number of dietary habits put people at risk for becoming overweight:

Night-Eating Syndrome. Night-eating syndrome is defined as having no appetite in the morning, insomnia, and consuming more than half of daily food intake after 6:00 PM. It is associated with obesity and is difficult to treat. Stress reduction and relaxation techniques may be helpful.
Binge Eating and Eating Disorders. About 30% of people who are obese are binge eaters who typically consume 5,000 - 15,000 calories in one sitting. To be diagnosed as a binge eater, a person has to binge at least twice a week for 6 months. Many experts believe that binge-eating carbohydrates causes an increase in a natural opiate leading to dependence on carbohydrates. Therefore, this condition should be treated as an addiction. Other eating disorders are bulimia and anorexia. Bulimia is binge eating followed by purging in order to lose weight. Anorexia nervosa is a mental illness in which the person refuses to maintain weight at the normal level. The patient with anorexia has a terrible fear of getting fat, and an abnormal perception of what his or her body looks like. Both conditions pose risks for serious medical problems, and anorexia nervosa can be life-threatening. A combined approach using behavioral therapy and antidepressants may help these individuals. [See In-Depth Report #49: Eating disorders.]
Restrained Eating. Some people, mostly middle-aged women who have normal weight, have a pattern referred to as restrained eating. This pattern requires a high level of conscious control and usually maintains a lower weight. However, such restraint places these individuals at higher risk for loss of control and subsequent overeating.
Infrequent Eating. There is some evidence to suggest that eating small frequent meals uses more calories than infrequent large meals. It should be strongly noted, however, that packaged snack foods add calories and some do not produce a feeling of being full, so that people simply eat more than they should.

Anyone with Sedentary Lifestyles. Office workers, drivers, and anyone whose lifestyle involves sitting for long periods are at higher risk for obesity.

Ex-Smokers. The trend toward weight increase has followed the trend for quitting smoking. Nicotine increases the metabolic rate, and quitting, even without eating more, can cause weight gain, which may be considerable. It is important to note that weight control is not a valid reason to smoke. People in previous centuries did not smoke cigarettes, nor were they usually obese.

Shift-Workers. A recent study found that individuals who work late shifts (between 4 p.m. and 8 a.m.) tend to eat more and take longer naps than day workers and are more likely to gain excess weight.

People with Disabilities. Obesity rates are higher than average in people with physical or mental disabilities. Those with disabilities in the lower part of the body, such as the legs, are at highest risk.

Overweight in children and adolescents is rising at an alarming rate. In 2004, 19% of young children aged 6 - 11 were overweight, an increase of 8% from 1994. Among children aged 25, 13.9% were overweight in 2004, up from 7.2% 10 years earlier.

Definition of Overweight in Children

Children and adolescents are considered to be overweight if their BMI is above 95% of the children in their age and sex categories. Ethnic variations, timing of growth spurts, and higher normal fat levels around puberty can affect these measurements.

Causes and Risk Factors for Overweight in Children

Lifestyle Factors. Without educational or parental guidance, children are extremely vulnerable to the intense cultural pressures that are largely responsible for the obesity epidemic. The following are some specific problems created by the culture:

Excessive television watching plays a critical role in obesity in children. Not only is it a sedentary activity, but television also offers innumerable temptations with its advertisements for fast foods, sugar cereals, and unhealthy snacks. In one study obesity rates were lowest in children who watched television 1 hour or less a day and highest in those who watched 4 or more hours.
Sugar, particularly from soda, other sweetened beverages, and fruit juice, may be the major contributor to childhood obesity. One study reported that drinking soda regularly increases a child's risk for obesity by 60%. The average American adolescent consumes 15 - 20 extra teaspoons of sugar a day just from soda and sugary drinks. (Juice, while better than soda, is still filled with sugar.)
Less physical exercise and greater sedentary activities play another significant role in obesity in children. A high level of physical activity -- not just using up energy -- is important for weight control in young people. Unfortunately, according to one study, the annual distance walked by children has fallen by nearly 30% since 1972, partially because more parents are driving their children to school out of fear of abduction, molestation, and traffic accidents. Schools are also offering fewer opportunities for daily physical activities than in the past.

Neither the media nor the educational system has strong well-financed programs that encourage healthy alternatives, including exercise and healthy foods.

Family History. Parental obesity more than doubles the risk that a young child, whether thin or overweight, will become obese as an adult. In older children and teenagers, obesity in parents starts to count less as a predictor for body weight than their own weight. The risk for obesity may be due to environmental or genetic factors, or both.

Ethnic and Socioeconomic Factors. As in adult populations, children from lower socioeconomic groups and minority populations are at higher risk for obesity. For example, among young Mexican Americans and African-Americans, there has been an increase in overweight prevalence of about 13% to over 23%.

Factors Surrounding Birth. The following factors surrounding birth are associated with a child's weight:

Low birth weight is a risk factor for later obesity and diabetes. One theory is that humans have a "thrifty gene" that produces metabolic changes in infants with low birth weight. Such changes affect insulin and fat accumulation, in order to produce a "catch-up" weight in these young children as quickly as possible. This rapid weight gain in infancy increases the risk for obesity in children and young adults.
In a study of African-American children, having an overweight pregnant mother increased the risk for later weight gain, but low birth weight did not.

Although some small studies have reported protection against obesity from breastfeeding, evidence is weak. In a 2003 study, for example, children who were breast fed for 3 - 5 months had a lower risk for obesity, but prolonged breastfeeding had no effect. Nevertheless, given the healthful effects of breast feeding and the possibility that it may have even a slight impact on childhood obesity, it is highly recommended.

Biological Effect of Childhood Overweight on Adult Weight

Achieving a healthy weight becomes more difficult as children get older. The odds of obesity persisting into adulthood ranges from 20% in 4 year olds to 80% in teenagers. One reason for the persistence is biological. The fat cells change in number or mass depending on a person's age:

Fat cells themselves multiply during two growth periods: early childhood and adolescence. Overeating during those times increases the number of fat cells. Some people are also just born with more fat cells.
After adolescence, fat cells tend to increase in mass rather than quantity, so that adults who overeat and gain weight tend to have larger fat cells, not more of them. This growth in mass may be responsible for the greater risk of persistent obesity among teenagers compared to small children who are overweight. Losing weight after adolescence reduces the size of the fat cells but not their number, so weight loss becomes much more difficult.

Health Consequences of Childhood Overweight

Children and adolescents who are overweight have poorer health than other children. Studies are reporting unhealthy cholesterol levels and high blood pressure in overweight children and adolescents. Of great concern is the dramatic increase in type 2 diabetes in young people, which is largely due to the increase in overweight children. Overweight in children is also linked to asthma, gallbladder problems, sleep apnea, and liver abnormalities. Overweight girls are more likely to enter puberty early, according to a new study, and subsequently be at higher risk for breast cancer.

It is not clear yet how many of these childhood problems persist in people who achieve normal weight as adults. Staying overweight into adulthood certainly carries health risks.

Managing Overweight Children

Childhood obesity is best treated by a non-drug, multidisciplinary approach including diet, behavior modification, and exercise. Evidence suggests that reducing calories by only 200 - 260 per day would prevent weight gain in most overweight children. Here some tips for children who are overweight:

Limit (or avoid, if possible) take out, fast foods, high-sugar snacks, commercial packaged snacks, soda, and sugar-sweetened beverages (including too much juice).
Let children snack but make sure the snacks are healthy. Eating small frequent healthy meals (instead of two or three large ones) has been associated with being thinner and having a better cholesterol profile.
Let children choose their own food portions. One study indicated that children naturally ate 25% less when they chose their own portion size. When they were given larger portions their bite sizes were larger and they ate more.
Do not criticize a child for being overweight. It does not help and such attitudes could put children at risk for eating disorders, which are equal or even greater dangers to their health.
Limit television, video games, and computer use to a few hours a week. This can contribute significantly to weight control, regardless of diet and physical activity.
For young children, try the traffic-light diet. Food is designated with stoplight colors depending on their high caloric content: Green for go (low calories); yellow for "eat with caution" (medium calories); red for "stop" (high calories).
Try a low glycemic index diet. This may be as beneficial, and possibly more, than a standard reduced-fat diet in overweight children. Such a diet focuses on certain carbohydrates (for example, dried beans and soy), which raise blood sugar more slowly than other types of carbohydrates. This diet is sometimes used in diabetes, and as a dietary approach in overweight adults. [See In-Depth Report #42: Diabetes diet.]

Click the icon to see an image about TV watching.

Click the icon to see an image of childhood overweight.

Complications

General Adverse Effects of Obesity. Obesity, defined as a BMI of 30 or over, accounts for nearly 300,000 deaths in the U.S. each year. It is associated with more chronic health problems than smoking, heavy drinking, or poverty. Furthermore, given the current increase in obesity, it will surpass smoking as the most important preventable cause of death in America.

Some studies indicate the following health risks by body mass:

The lowest risks for heart disease, diabetes, and some cancers are in people with BMI values of 21 - 25.
The risks increase slightly when BMI values are between 25 - 27.
The risks are significant in BMIs between 27 - 30.
The same risks are dramatic at BMIs over 30.

Anyone with chronic health problems such as heart or lung disease, stroke, or arthritis, should be concerned about extra weight. This same concern also applies to people with known risk factors for such conditions.

Metabolic Changes. As fat stores increase, the fat cells themselves enlarge and produce chemicals that increase the risk for several diseases. Such diseases may include diabetes, high blood pressure, gallbladder disease, and some cancers.
Increased Mass. The increased body weight itself causes problems that result in injury and diseases, including osteoarthritis and sleep apnea.
Harmful Fat Cell Types. Weight concentrated around the abdomen and in the upper part of the body (the apple shape) poses a higher health risk than fat that settles around the hips and flank (the pear shape). Fat cells in the upper part of the body appear to have different qualities from those found in the lower parts. In fact, studies suggest a higher risk for diabetes in people with the "apple shape" and lower risk in those who are "pear shaped."

Weight gain in the area of and above the waist (apple type) is more dangerous than weight gained around the hips and flank area (pear type). Fat cells in the upper body have different qualities than those found in hips and thighs.

General Adverse Effects of Being Overweight (Not Obese). It is still not clear if being overweight (a BMI of 25 - 29.9) hurts healthy people with no risk factors for serious illnesses.

According to one 2001 study, just being overweight increased the risk for developing diabetes, gallstones, hypertension, heart disease, stroke, and colon cancer. The risk rose according to how much the individuals were overweight. In any case, adults who are overweight in middle age face a poor quality of life as they age, with the quality declining the greater the weight. One study suggested, however, that being over 65 and overweight (but not obese) is not associated with higher mortality rates.

Some experts argue, in fact, that in anyone who is not severely obese, it is the unhealthy diet and sedentary lifestyle that causes harm -- not weight per se. In support of this argument, a British study found that overweight fit individuals had half the death rate of unfit trim individuals.

Being somewhat overweight may also have some benefits under specific circumstances:

In older women, some excess fat may produce extra estrogen that helps slow down bone loss, and insulates bones from fall-related injuries. It should be strongly noted, however, that when older overweight women lose weight they report less pain, improved vitality, and improved physical function. The same positive effect of overweight does not appear to hold in older men.
Conditioned athletes may have high BMIs because of very dense muscle tissue. Being fit in general may protect many overweight people.
Some evidence suggests that Caucasians have the lowest mortality with BMIs of 24.3 - 24.7 while African-Americans are better off in the range of 26.8 - 27.1.
Children may have higher normal fat levels during growth spurts and around puberty.

Individuals with a BMI of at least 30 have a 10 - 50% increased rate of death from all causes, compared with individuals with a BMI of 20 - 25. Mortality rates from many causes are higher in obese people, but heart disease is the primary cause of death. People who are obese have almost three times the risk for heart disease as people with normal weights. Being physically unfit adds to the risk.

Weight concentrated around the abdomen and in the upper part of the body (apple shape) is particularly associated with insulin resistance and diabetes, heart disease, high blood pressure, stroke, and unhealthy cholesterol levels. Fat that settles in a pear shape around the hips and lower body appears to have a lower association with these conditions.

Obesity poses many dangers to the heart and circulatory system.

Damage in the Blood Vessels. As people age, changes in body fat (particularly increasing abdominal fat) seem to cause stiffness in the aorta, the major blood vessel leading from the heart. Studies are finding higher levels of a factor called C-reactive protein (CRP) in people with obesity and abdominal fat. CRP is now considered to be a marker for inflammation and damage in the arteries. (Losing weight reduces CRP levels.)

High Blood Pressure. High blood pressure is the health problem most commonly associated with obesity, and the greater the weight, the greater the risk. High blood pressure carries serious risks of stroke, heart attack, and heart failure. The link between obesity and high blood pressure is complex, and may be a combination of genetic, population, and biological factors. Many studies have reported that modest weight loss is beneficial for reducing existing high blood pressure. [See In-Depth Report #14: High blood pressure.]

Heart Failure. An important 2002 study reported that obesity might account for 11% of heart failure cases in men and 14% in women. This link existed independently of other risk factors, such as high blood pressure, sleep apnea, and diabetes, which are also associated with obesity. The biologic mechanisms involved in obesity that lead specifically to heart failure are not clear. [See In-Depth Report #13: Heart failure.]

Unhealthy Cholesterol Levels and Lipid Levels. The effect of obesity on cholesterol levels is complex. Although obesity does not appear to be strongly associated with overall cholesterol levels, among obese individuals triglyceride levels (the major form of fat storage in the body) are usually high, while HDL levels (the "good" cholesterol) tend to be low. Both conditions are risk factors for heart disease. [See In-Depth Report #23: Cholesterol.]

Click the icon to see an image of coronary artery disease.

Stroke. Obesity is also associated with a higher risk for stroke. [See In-Depth Report #45: Stroke.]

Type 2 Diabetes and Insulin Resistance. Most people with type 2 diabetes are obese and, in fact, studies strongly suggest that weight loss may be the key in controlling the current epidemic of type 2 diabetes. The common factor appears to be insulin resistance. Insulin is a critical hormone in the use of sugar. In type 2 diabetes, different factors cause the body to become insulin resistant -- that is, the body can no longer respond properly to insulin. This has the effect of increasing sugar levels in the blood, the hallmark of diabetes. Both obesity and insulin resistance, at different phases, are marked by high levels of certain chemicals. It is not known yet if the higher levels are simply a product of obesity, or play some role in causing diabetes.

Insulin resistance is also associated with high blood pressure and abnormalities in blood clotting. Some research indicates that obesity, in fact, is the one common element linking insulin resistance, diabetes type 2, and high blood pressure. [See In-Depth Report #60: Diabetes - type 2.]

Metabolic Syndrome. Metabolic syndrome (also called syndrome X) is a pre-diabetic condition that is significantly associated with heart disease and higher mortality rates from all causes. The syndrome consists of obesity marked by abdominal fat, unhealthy cholesterol levels, high blood pressure, and insulin resistance. A 2002 study estimated that nearly a quarter of the U.S. population now has this condition. Even worse, according to a 2003 study, nearly a million American teenagers have this syndrome. A combination of weight loss and exercise is an effective treatment for this syndrome.

The American Cancer Society released new cancer prevention guidelines in September 2006. The guidelines stress the importance of keeping a healthy weight throughout life. The Society indicates that healthy weight is even more important than eating specific healthy foods, when it comes to cancer prevention.

Obesity has been associated with a higher risk for cancer in general and specific cancers in particular. Studies have also suggested that restricting calories reduces the risk for cancer. Some experts believe that effective weight control for children and adults could reduce cancer rates by 30 - 40%. One way obesity may increase the risk for cancer is its association with high levels of hormones called growth factors, which can trigger rapid cell production leading to cancer.

Uterine Cancers. The risk of uterine cancer in obese women appears to be two or three times higher than in thinner women.

Prostate Cancer. New studies from 2005 and 2006 report that obesity is associated with an increase in prostate cancer mortality, although not with the risk for less aggressive forms of prostate cancer.

Click the icon to see an image of prostate cancer.

Breast Cancer. Studies are mixed on the association between obesity and breast cancer. A number of studies have linked obesity to breast cancer in postmenopausal women, particularly in women who begin to gain weight after age 18.

Click the icon to see an illustrated series detailing a breast cancer surgery (mastectomy).

Gallbladder Cancer. Obese women are at higher risk for gallbladder cancer.

Gastrointestinal Cancers. A number of cancers in the gastrointestinal tract have been associated with obesity:

Cancer of the esophagus may be due to a higher incidence of gastroesophageal reflux disorder (heartburn) in people who are overweight.
Colon cancer has been linked to increased body mass in both men and women.
Pancreatic cancer and obesity have been weakly linked, with one study reporting a lower risk in overweight people who are physically active.

Click the icon to see an illustrated series detailing a colon cancer surgery.

Muscles and Bones

Obesity places stress on bones and muscles. Studies report that the incidence of osteoarthritis is significantly increased in people who are overweight. People who are obese are also at higher risk for carpal tunnel syndrome and other problems involving nerves in their wrists and hands. It should be noted that some weight may be protective against osteoporosis (loss of bone thickness).

Obesity increases the risk for the following mouth and eye disorders:

Gum disease
Cataracts
Maculopathy, an eye disease related to aging

Infertility. Abnormal amounts of body fat, either 10 - 15% too high or too low, can contribute to infertility in women. Obesity is specially related to certain infertility problems, such as uterine fibroids or menstrual irregularities. In men, obesity can contribute to reduced testosterone levels.

Effect on Pregnancy. Obesity has many dangerous effects on pregnancy. These include high blood pressure, gestational diabetes (diabetes, usually temporary, that occurs during pregnancy), urinary tract infections, blood clots, prolonged labor, and higher fetal death rate in late stages of pregnancy. Obesity is also associated with increased rates of cesarean delivery. Infants of women who are obese are also at higher risk for neural tube birth defects, which affect the brain or spine. Folic acid supplements, ordinarily effective in preventing these conditions, may not be as protective in overweight women.

Obesity is thought to be a risk factor for symptoms of adult-onset asthma. Though there is evidence that obesity causes wheezing and shortness of breath, it does not appear to be strongly associated with the disease mechanisms in the lungs that cause true asthma.

Obesity also puts people at risk for hypoxia, a condition in which there is not enough oxygen to meet the body's needs. Obese people need to work harder to breathe. They tend to have breathing muscles and lungs that do not work as well as those in thinner people.

The Pickwickian syndrome, named for an overweight character in a Dickens novel, occurs in severe obesity when lack of oxygen produces intense and chronic sleepiness and, eventually, heart failure.

Nonalcoholic Fatty Liver Disease. People with obesity, particularly if they also have type 2 diabetes, are at higher risk for a condition called nonalcoholic fatty liver disease, also called nonalcoholic steatohepatitis (NASH). This condition causes liver damage that is similar to liver injury seen in alcoholism. In some cases, it can be very serious and require liver transplantation. It occurs in about half of people with diabetes, and 20 - 50% of obese people, depending on how severe their obesity is. NASH can also occur in overweight children.

Gallstones. The incidence of gallstones is significantly higher in obese women and men. The risk for stone formation is also high if a person loses weight too quickly. In people on ultra-low calorie diets, gallstones may be prevented by taking ursodeoxycholic acid (Actigall).

Click the icon to see an image of gallstones.

People who are obese and nap tend to fall asleep faster and sleep longer during the day. At night, however, it takes them longer to fall asleep, and they sleep less than people with normal weights. In an apparent vicious circle, studies have suggested that obesity not only interferes with sleep but that sleep problems may actually contribute to obesity.

Sleep Apnea. Obesity, particularly the apple shape, is strongly associated with sleep apnea, which occurs when the upper throat relaxes and collapses from time to time during sleep. This collapse temporarily blocks the passage of air. Sleep apnea is increasingly being viewed as a potentially serious health problem, which may lead to complications such as heart disease and stroke. Some studies suggest that among overweight people, those who have sleep apnea have a greater risk of heart disease than those without it. In one study, the more obese a person with sleep apnea was, the higher the pressure on the airway, and therefore the greater the obstruction of the airway. Obstructive sleep apnea may also add to obesity, however, as sleepy people tend to be sedentary. Some studies indicate that treating sleep apnea may help people lose abdominal fat.

Narcolepsy. A small European study found a link between narcolepsy (a sleep disorder characterized by excessive daytime sleepiness with frequent daily sleep attacks) and high BMI.

Depression. A number of studies have reported an association between depression and obesity, particularly in obese women. There may be a number of factors to explain the link. In some cases of atypical depression, people overeat and may gain weight. Overweight people may also become depressed because of social problems and a poor self-image. In these cases, depression usually disappears when people lose weight.

There is evidence, however, that obesity itself may impair levels of tryptophan -- a chemical needed to make serotonin, a brain chemical associated with mental well-being. In one study, even after people lost weight, tryptophan levels were lower than normal.

There does not appear to be any association between depression and obesity in men.

Social Problems. One long-term study reported that overweight young women completed fewer years of school, were 20% less likely to be married, and had 10% higher rates of household poverty than their thinner peer. Obese young men were also less likely to be married, and their incomes were lower than their thinner peers. Nevertheless, studies consistently show that overweight males (both boys and men) are not as severely emotionally affected as females of any age. Women and girls tend to blame themselves for being heavy, while males tend to blame being overweight on outside factors.

Weight Loss and Maintenance

Even modest weight loss can reduce the risk factors for heart disease and diabetes. The simplest (but still difficult) approach to weight loss is reducing calories and exercising at least 150 minutes a week. Behavioral and mental changes in eating habits, physical activity, and attitudes about food and weight are also essential to weight management. For people who are very overweight and cannot lose weight through lifestyle changes, a number of effective weight-loss medications are available. For those with severe obesity, surgical procedures are proving to be very beneficial.

Some Tips for Losing Weight. The following are some general suggestions for dieters:

Start with realistic goals. Diet failure is extremely common, and the odds of significant weight loss are low, particularly in people with the highest weights. People who are able to restrict calories, engage in an exercise program, and get help in making behavioral changes can expect to lose between 5 - 10% of their current body weight. That is generally all that is needed to achieve meaningful health changes. Certainly, the distorted image of a super-thin female shape should not be anyone's goal.
Maintain a regular exercise program, assuming you have no health problems that will stop you. Choose a program that you enjoy. Check with your doctor about any health considerations. [See In-Depth Report #29: Exercise.]
Do not use hunger pangs as cues to eat. A stomach that has been stretched by large meals will continue to signal hunger for large amounts of food until its size reduces over time with smaller meals.
Be honest about how much you eat and start by recording all calories in writing. Studies suggest that when many people report their own calories intake they significantly underestimate their consumption of high-calorie and over-estimate the low-calorie foods. People who do not carefully note everything they eat tend to take in too many calories when they believe they are dieting.
Observe weekend eating. People tend to eat more on the weekends. If it is difficult to monitor all meals during the week, it be may be useful to at least track eating habits during the weekends.
Once the pounds are lost, do your best to keep the healthier weight. Make daily, even hourly, conscious decisions about eating and exercising activities. Such thinking, in many cases, can become automatic and not painful.
Don't give up, even after repeated weight loss failures. Most studies indicate that yo-yo dieting or weight cycling have no bad psychological or physical effects. Repeated dieting also does not harm the body's ability to burn calories efficiently.
Weight loss, in any case, should not be the only or even the primary goal for people concerned about their health. The success of weight loss efforts should be evaluated according to improvements in disease risk factors or symptoms, and by the adoption of healthy lifestyle habits, not just by the number of pounds lost.


Lifestyle	Reduce rate of eating. Keep food records. Eliminate environmental triggers to eating. Identify high-risk situations for overeating. Separate eating from other activities.
Exercise	Face up to emotional barriers to exercise. Understand the link between exercise and weight control. Establish reasonable exercise goals. Develop a plan for regular activity. Add increased activity into daily lifestyle.
Attitudes	Develop reasonable weight-loss goals. Avoid "all or none" thinking. Focus attention away from the scale and toward behavior. Uncouple weight from self-esteem. If you "fall off the wagon," take steps to ensure the situation does not repeat (recover from lapses with constructive action).
Relationships	Understand the key role of social support to health. Identify supportive others. Match personal style to support-seeking activities. Be specific in making support requests. Be assertive but reinforcing in drawing help from others.
Nutrition	Resist the temptation of popular fad diets. Eat with your health in mind; do not concentrate on what should be "off-limits." Eat with moderation in mind. Maximize fiber. Develop a tailored plan.
From Brownell KD. The LEARN Program for Weight Control. 7th ed. Dallas, Tex: American Health Publishing Company; 1998.

Weight Management

There are many approaches to dieting and many claims for great success with various fad diets. To date, although many diets achieve effective immediate weight loss, none has emerged as an effective tool for maintaining healthy weight. The only definite recommendation that can be made about any diet plan is to be sure it includes an exercise program, assuming there are no health problems to forbid it.

The original food pyramid, with four food groups, has been replaced with an updated food guide called "My Pyramid." This illustrates the relative proportions of different foods that make up a nutritious, well-balanced diet and includes exercise.

Calorie restriction has been the cornerstone of obesity treatment. The standard dietary recommendations for losing weight are the following:

As a rough rule of thumb, one pound of fat equals about 3,500 calories. A person could lose a pound a week by reducing daily caloric intake by about 500 calories a day. Naturally, the more severe the daily calorie restriction, the faster the weight loss. Very-low calorie diets have also been associated with better success, but extreme diets can have some serious health consequences.
To determine your daily calories requirements, multiply the number of pounds of ideal weight by 12 - 15 calories. The number of calories per pound depends on gender, age, and activity levels. For instance, a 50-year old woman who wants to maintain a weight of 135 pounds and is mildly active might require only 12 calories per pound (1,620 calories a day). A 25-year old female athlete who wants to maintain the same weight might require 25 calories per pound 2,025 (calories a day).
Fat intake should be no more than 30% of total calories. Most fats should be in the form of monounsaturated fats (such as olive oil). Saturated fats (found in animal products) should be avoided.

Extreme diets of less than 1,100 calories carry health risks. They are also often followed by bingeing or overeating, and a return to the obese state. Such diets often do not have enough vitamins and minerals, which must then be taken as supplements. Most of the initial weight loss is in fluids. Later, fat is lost, but so is muscle, which can account for more than 30% of the weight loss. No one should be on severe diets for longer than 16 weeks, or fast for more than 2 or 3 days. Severe dieting has unpleasant side effects including fatigue, intolerance to cold, hair loss, gallstone formation, and menstrual irregularities. There have been rare reports of death from heart arrhythmias when liquid formulas did not have sufficient nutrients. Pregnant women who excessively diet during the first trimester put their unborn children at risk for birth defects. Of note, those whose diets include a high intake of fluids and much reduced protein and sodium are at risk for hyponatremia, which can cause fatigue, confusion, dizziness, and in extreme cases, coma and death.

This dietary approach requires counting only grams of fat with the goal of achieving 30% or fewer calories from fat. One gram of fat contains nine calories, while one gram of carbohydrates or protein has only four calories. Fat in your diet converts more readily to fat in the body, compared with carbohydrates or proteins. Simply switching to low-fat or skimmed dairy products may be enough for some people.

There are possible drawbacks to this approach:

Some people who reduce their fat intake may not get enough basic nutrients, including vitamins A and E, folic acid, calcium, iron, and zinc. People on low-fat diets should eat a wide variety of foods and take a multivitamin supplement, if appropriate. Calcium deficiencies may be particularly harmful in women at risk for osteoporosis.
Many people start eating foods with too many carbohydrates, believing that they are not adding calories. No one should use a low-fat diet as an excuse for eating too many carbohydrates, particularly starchy foods and sugar. A high-calorie diet from any source will add pounds.
A small study in Norway found that a diet low in fat and high in carbohydrates ("carbs") increases symptoms of psychological distress, such as depression and anger. The study compared three different diets that had varying amounts of fat and carbohydrates in each. The diets contained the same amount of calories, but differed in the percentage and type of fat. People on the low-fat, high-carbohydrate diet reported more anger and depression compared with the other two diets.
Replacing fatty foods, such as cakes, cookies, and chips, with their commercial "low-fat" counterparts does not constitute a low-fat diet. These foods generally contain more sugar and hence calories, not to mention other ingredients, which have virtually no nutritional value. In fact, a 2002 study suggested that increasing sugar may, over time, reduce levels of HDL ("good") cholesterol.
Very low-fat diets may increase the risk for stroke from hemorrhage in the brain.

Some fat in a diet is essential. It should come from plant oils and fish, however, and not from animal products or hardened oils, such as margarine. Trans-fatty acids, found in hardened oils, are actually more of a risk factor for obesity than saturated fats from animal products, although both should be avoided.

Fiber and Complex Carbohydrates. In all cases, complex carbohydrates found in whole grains and vegetables are preferred over those found in starch-heavy foods, such as pastas, white-flour products, and potatoes. Fiber is an important component of many complex carbohydrates. Fiber is almost always found only in plants, particularly vegetables, fruits, whole grains, nuts, and legumes (beans and peas). One exception is chitosan, a dietary fiber made from shellfish skeletons. Fiber cannot be digested but passes through the intestines, drawing water with it, and is eliminated as part of feces content. The following are specific advantages from high-fiber diets (up to 55 grams a day):

Insoluble fiber (found in wheat bran, whole grains, seeds, nuts, and fruit and vegetable peels) has been associated with weight loss. Studies also suggest that diets rich in fiber from whole grains reduce the risk for type 2 diabetes.
Soluble fiber (found in dried beans, oat bran, barley, apples, citrus fruits, and potatoes) has important benefits for the heart, particularly for achieving healthy cholesterol levels and possibly benefiting blood pressure as well. Simply adding breakfast cereal to a diet appears to reduce cholesterol levels. People who increase their levels of soluble fiber should also increase water and fluid intake.

High-protein, low carbohydrate diets, such as the Atkins and South Beach diets, have been touted as effective ways to produce short-term weight loss. Because of their emphasis on fats and proteins, many experts are concerned about long-term health problems. A report in the March 2006 Lancet linked the Atkins diet to life-threatening complications that caused the death of one woman. The 40-year-old woman had a deadly buildup of acids called ketones in her blood, a condition called ketoacidosis. Ketoacidosis can cause coma and death. Ketones are a known by-product of high protein, low carbohydrate diets. At low levels they can cause nausea, lightheadedness, and bad breath.

The long-term effects of these diets are still unknown. For example, the Atkins diet restricts some vegetables and most fruits, which are known to protect against serious diseases such as heart problems and cancer. The diet may also cause too much calcium to build up in the urine. This can increase the risk for kidney stones and osteoporosis. In addition, high-protein intake, particularly from meat, can be harmful in people with kidney problems. Individuals at risk for kidney stones, or those who have other kidney problems, should not go on high-protein diets without talking to their doctor first. Unfortunately, many people with diabetes are at risk of kidney problems, which could reverse any possible benefits a high-protein diet may bring them. Eating a lot of meat has also been associated with certain common cancers, notably prostate and colon cancers. A 2002 study suggested that such diets during pregnancy may increase the risk for high blood pressure in the child.

Still, significant studies say that such diets improve cholesterol and blood sugar levels. Studies in 2002 and 2003 have indicated that these diets lower blood glucose levels, which can be important in people who are diabetic. The diets also reduce triglyceride levels (unhealthy fat molecules) and increases HDL (" good") cholesterol levels. High triglyceride and low HDL levels are important risk factors for heart disease, and are common in people with type 2 diabetes. Studies are mixed on whether this type of diet reduces overall cholesterol or LDL ("bad") cholesterol levels.

Experts that promote the low carbohydrate approach argue that heart problems from obesity are due to insulin disturbances from sugar imbalances. Therefore, they believe that restricting carbohydrates is the best approach for obesity -- especially for overweight people with diabetes. More research is needed, however, to determine the long-term impact of such diets on health.

High-protein, low-carbohydrate diets include Atkins, Protein Power, Sugar Busters, and Dr. Stillman. The Atkins diet is one of the most popular and has a four-phase program:

Induction. For the first 2 weeks, individuals consume no more than 20 grams of carbohydrates a day. The diet consists of pure protein and fats. There is no fruit, bread, grains, starchy vegetables, or dairy products other than cheese, cream, or butter. This phase is not suitable for children, pregnant women, or anyone with kidney disease.
On-going Weight Loss. After the first phase, individuals continue to lose weight while they increase carbohydrate levels by five grams each day.
Premaintenance. When individuals get close to their weight goal, they add another 10 grams of carbohydrates per day as long as they do not begin to gain weight. Weight loss is very slow at this time, but the individual is now getting used to maintenance.
Maintenance. Lifetime maintenance is usually between 40 and 100 grams of carbohydrates a day, depending on steady weight level.

Anyone who chooses this diet should prefer fish or soy products to meat as protein sources. Fish may reduce leptin, a hormone associated with fat storage and heart diseases, and would be the best protein source. People on this diet should also choose monounsaturated fats (as in olive oil) over saturated fats or trans-fatty acids fat. Patients often need supplements, at least a multivitamin and possibly calcium, chromium, omega-3 fatty acids (found in fish oil), and other supplements.

The South Beach and Zone diets encourage healthy fats. They also allow certain carbohydrates. For example the Zone uses healthy carbohydrates (vegetables and dried beans) and unsaturated fats. The South Beach diet uses carbohydrates that have a lower impact on blood sugar levels. This is called a low-glycemic index. Low-glycemic foods include barley, dried bean and peas, milk, strawberries, and apples. High-glycemic foods include refined grains, white bread, white potatoes, and bananas and other tropical fruits. The glycemic index was developed for use in diabetes -- not for weight loss. Nevertheless, there is some evidence that foods with low glycemic indexes may produce a feeling of fullness and so discourage further eating. As with any high-protein diets, people at risk for kidney stones, or those who have other kidney problems, should avoid these plans.

Replacing fats and sugars with substitutes may help many people who have trouble maintaining weight. In fact, in one 2003 study, people with type 2 diabetes used the artificial sweetener sucralose and a beta-glucan fat substitute (derived from oats) as part of a low-calorie diet. At the end of the 4 weeks, they achieved better weight, glucose control, and HDL levels than those on a standard diabetic diet.

Fat Substitutes. Fat substitutes added to commercial foods or used in baking deliver some of the desirable qualities of fat, but do not add as many calories. It should be stressed that eliminating all fats from a diet can be harmful to general health.

Fat substitutes include the following:

Stanols. Stanols are plant compounds used in margarines (Benecol, Take Control). Benecol is derived from pine bark and Take Control from soybeans. Two servings a day of either brand, as part of a low-fat, diet can lower LDL and total cholesterol by impairing its absorption in the intestinal tract. Some studies have reported that the use of stanols can allow lower doses of statins (cholesterol lowering medications). Stanols do not appear to block absorption of fat-soluble nutrients or vitamins, as olestra does.
Olestra (Olean) passes through the body without leaving behind any calories from fat. Studies suggest that it improves cholesterol levels and helps people lose weight when it is used to replace a third of normal dietary fats. (Note that simply adding snacks containing olestra does not appear to have any effect on cholesterol or weight loss.) Early reports of cramps and diarrhea after eating food containing olestra have not proven to be significant. Of greater concern is the fact that even small amounts of olestra deplete the body of certain vitamins and nutrients that may help protect against serious diseases, including cancer. The FDA requires that the missing vitamins be added back to olestra products, but not other nutrients. The side health effects, if any, are unknown.
Beta-glucan is a soluble fiber found in oats and barley. Products using this substance (e.g., Nu-Trim) may reduce cholesterol and have additional health benefits.

A number of other fat-substitutes are also available. Although studies to date are not showing any significant side effects, these products' effect on weight control is uncertain, since many of the products containing them may be high in sugar.

Artificial Sweeteners. Many artificial or low-calories sweeteners are available. A 2002 study confirmed that people who consumed artificial sweeteners and reduced their sugar intake weighed less over time than those who took in similar types and amounts of drinks and food containing sugar. It should be noted that using these artificial sweeteners should not give dieters a license to increase their fat intake. Studies indicate that consuming some sugar is not a significant contributor to weight gain, as long as the total amount of calories in the diet is under control. There is some public concern about chemicals used to produce many of these sweeteners, and the side effects seen in studies using rats. Natural low-calories sweeteners are available that may be more acceptable to many people.

Saccharin (Sugar Twin, Sweet n' Low, Sucaryl, and Featherweight). Saccharin has been used for years. Some studies found that large amounts of saccharin cause bladder cancer in rats. However, the rats were fed huge amounts that do not apply to human diets. Currently there is no evidence that saccharin causes cancer in humans.
Aspartame (Nutra-Sweet, Equal, NutraTase). Aspartame has come under scrutiny because of rare reports of nervous system disorders, including headaches or dizziness, associated with its use. People with phenylketonuria (PKU), a genetic condition, should not use it. Studies have not reported any serious health dangers, but some people may be sensitive to it.
Sucralose (Splenda). Sucralose has no bitter aftertaste and works well in baking, unlike other artificial sweeteners. It is made from real sugar by replacing part of the sugar with chlorine. Some people are concerned because chlorinated molecules used in major industrial chemicals have been associated with cancer and birth defects. Over 100 studies have been conducted on sucralose over a 20-year period, with no reports of such risks.
Acesulfame-potassium (Sweet One, SwissSweet, Sunette). It has been used in the U.S. since 1988 with no reported side effects.
Neotame (Neotame). Neotame is a synthetic variation of aspartame, but was developed to avoid its side effects. The association with aspartame has raised some concerns. Studies to date have reported no effects that would cause alarm, and it appears to be safe for general consumption.
D-tagatose (Tagatose). This reduced-calorie sweetener is made from lactose, which is the sugar found in dairy products and other foods. It may be especially beneficial for people with type 2 diabetes. It may also have additional benefits that help the intestinal tract.
Alitame (Aclame) is formed from amino acids, the building blocks of proteins. It has the potential to be used in all products that contain sugar, including baked goods.
Stevioside (Stevia). This is a natural sweetener derived from a South American plant. It is available in health food stores. People with diabetes should avoid alcohol-based forms. It has not been carefully tested.

Other sugar substitutes being investigated include glycyrrhizin (derived from licorice) and dihycrochalcone (derived from citrus fruits).

Some studies have reported good success with meal replacement beverages (Slim-Fast, Sweet Success). They contain major nutrients needed for daily requirements. Each serving typically contains between 200 - 250 calories and replaces one meal. (Note: Using them for all meals reduces calories to a severe extent and can be harmful.)

One study reported that most subjects who had undergone a 12-week weight loss program and then used Ultra Slim Fast supplements as directed for maintenance kept off more than half their weight loss after more than 3 years. A quarter of the subjects were still losing weight.

Medical evidence suggests that a diet rich in magnesium could reduce a person's risk of metabolic syndrome, a cluster of problems including obesity, high blood pressure, and high cholesterol. Metabolic syndrome can lead to diabetes and heart disease. A long-term study of thousands of Americans found that the risk for metabolic syndrome decreased in those who consumed the most magnesium from meals. The findings were published in the journal Circulation.

Commercial and Non-Profit Support Programs for Weight Loss. There are many different types of weight-loss program. (This report cannot address all of the many commercial and nonprofit weight-loss programs currently available, nor can it assess their claims.)

Taking off Pounds Sensibly (TOPS), a nonprofit support organization with many local chapters, is one of the least expensive programs, costing $20 a year.

Most of the commercial programs such as Weight Watchers, Jenny Craig, and NutriSystem offer individual or group support, lifestyle changes and packaged meals. These programs tend to be expensive. There are few well-conducted studies on these programs. One 2003 study reported modest weight loss over 2 years with Weight Watchers compared to a self-help program. There were no differences in heart risk factors.

Cognitive Behavioral Approaches. Most support programs use some form of cognitive-behavioral methods to change the daily patterns associated with eating. They are very useful for preventing relapse after initial weight loss. The following is a typical approach:

The patient first records in a diary all activity related to eating patterns, including the times of day, length of meal, emotional states, companions, and, of course, the kind and amounts of food eaten. Most people -- even professional dieticians, according to one study -- tend to underreport their daily calorie intake. However, writing it down is still a good method for increasing a person's awareness of eating patterns. (One patient said that recording circumstances surrounding relapses was a particularly valuable guide for understanding the stresses leading to her own eating behaviors.)
The patient reviews the diary with a therapist or group to set realistic goals and identify patterns that the patient can change. For instance, if food is normally eaten while watching television, then the patient may be advised to eat in another room instead.
Good eating habits are reinforced by rewards. These rewards are other pleasures that substitute the high calorie consumption and sedentary activities.

Behavioral modification has been shown to be helpful particularly for people who have an overly strong response to the taste, smell, and appearance of food. It also may be useful for binge eaters.

Stress-Reduction Techniques. Stress reduction and relaxation techniques may be helpful for some people with obesity, such as those whose weight is related to night-eating syndrome. [See In-Depth Report #31: Stress.]

Changing Sedentary Habits. Making even small changes in physical activity can expend energy. For example, simply getting up to turn the TV on and off instead of using the remote, and standing (instead of sitting) while talking on the phone may help a person lose up to five pounds a year. Other suggestions include cooking one's own food (instead of eating take-out or fast food), walking to as many places as possible, using stairs instead of escalators or elevators, and gardening. Even fidgeting may be helpful in keeping pounds off, and, in one study, chewing gum increased energy expenditure.

No one should rely on such mild activities, however, for serious weight loss. Only high levels of physical activity -- not just using up energy -- help prevent obesity.

Approach to Exercise. Exercise, which replaces fat with muscle, is the critical companion for any weight control program. In a one-year study, women who regularly averaged 3.5 days (176 minutes) of exercise each week lost significantly more weight than women who did not exercise regularly. Women who exercised more than 195 minutes a week lost nearly 7% of their abdominal fat.

People who exercise are more apt to stay on a diet plan. Exercise improves psychological well-being and replaces sedentary habits that usually lead to snacking. Exercise may even act as a mild appetite suppressant. Moreover, exercise improves overall health even with modest weight loss. In support of this, a British study found that overweight fit individuals had half the death rate of unfit trim individuals.

Be aware, however, that the pounds won't melt off magically. Losing significant weight requires both intensive exercise and calorie restriction. In addition, if a person exercises but doesn't diet, any actual pounds lost may be minimal, because denser and heavier muscle mass replaces fat. Nonetheless, regardless of weight loss, a fit body will look more toned and be healthier. In addition, exercise benefits the heart even with modest weight loss.

The following are some suggestions and observations on exercise and weight loss:

The more strenuous the exercise, the better the chances for short-term and long-term success. With intense exercise, the metabolism continues to burn calories before returning to its resting level. This state of elevated metabolism can last for as little as a few minutes after light exercise to as long as several hours after prolonged or heavy exercise.
Of the standard aerobic machines, the treadmill burns the most calories. It may be particularly effective when used in short multiple bouts during the day. In fact, frequent exercise sessions as short as 10 minutes in duration (about four times a day) may be the most successful exercise program for obese people.
Resistance, or strength, training is excellent for replacing fat with muscles. It should be performed two or three times a week.
As people slim down, their initial level of physical activity becomes easier and they burn fewer calories per mile of walking or jogging. The rate of weight loss slows down, sometimes discouragingly so, after an initial dramatic head start using diet and exercise combinations. People should be aware of this phenomenon and keep adding to their daily exercise program.
As people age, they also need to exercise more to keep off the same amount of weight.
Changes in fat and muscle distribution may differ between men and women as they exercise. Men tend to lose abdominal fat (which lowers their risk for heart disease faster than reducing general body fat). Exercise, however, does not appear to have the same effect on weight distribution in women. In one interesting study, women in aerobic and strength training programs lost fat in their arms and trunk, but did not gain muscle tissue in these regions.

Warning Note. Because obesity is one of the risk factors for heart disease and diabetes, anyone who is overweight must discuss their exercise program with a doctor before starting. Sudden demanding exercise, in such cases, can be very dangerous. [See In-Depth Report #29: Exercise.]

Medications

There are several different drugs used for weight loss. Unless specifically instructed by a doctor, people should use non-drug methods for losing weight. Except under rare circumstances, pregnant or nursing women should never take diet medications of any sort, including herbal and over-the-counter remedies.

A 2001 study reported that 7% of American adults use nonprescription weight-loss products. People must be cautious when using any weight-loss medications, including over-the counter diet pills and herbal or so-called natural remedies. Buying unverified products over the Internet can be particularly dangerous.

Green tea. Perhaps the best alternative advice for people who are overweight is to drink tea. Studies have indicated that regular tea drinking is associated with lower weight, particularly in people who drink it for years. Green tea specifically has been associated with increased energy expenditure. One study reported that people who took a green tea extract (Exolise) lost weight and reduced their waist size. Better evidence is needed to confirm the results on this supplement.

Thermogenic Approach to Weight Loss. An approach to weight loss called thermogenic (also hepatothermic) therapy is based on the idea that certain natural compounds have properties that enable the liver to increase energy in the cells and stimulate the metabolism. Theoretically, the result would be fat loss. Among the natural substances used in such products are EPA-rich fish oil, sesamin, hydroxycitrate, pantethine, L-carnitine, pyruvate, aloe vera, aspartate, chromium, coenzyme Q10, green tea polyphenols, aloe vera, DHEA derivatives, cilostazol, diazoxide, and fibrate drugs.

Nearly all the current over-the-counter dietary aids contain some combination of these ingredients. There is no evidence that any of these ingredients can produce weight loss, and some may even have harmful effects.

Chromium is a common ingredient in many diet supplements (e.g., Xenadrine, Dexatrim, Acutrim Natural, Twinlab Diet Fuel). It is claimed to specifically promote fat loss, rather than lean muscle loss. Some evidence suggests that niacin-bound chromium may improve insulin sensitivity. On the negative side, animal studies have suggested that chromium may have damaging effects on genetic materials in cells. This could cause sterility.

Ephedra, Ephedrine, and Ma Huang. The FDA does not allow the sale of drugs that contain ephedrine. In May 2004, the FDA banned the sale of dietary supplements that contain ephedra (also called Ma Huang). Ephedra has been linked to serious side effects, including strokes and heart attacks.

Brazilian Diet Pill. The US Food and Drug Administration (FDA) is warning consumers not to buy a product known as the "Brazilian diet pill." This product is labeled as a dietary supplement, but contains several chemicals found in powerful prescription drugs. The products are also known as Emagrece Sim and Herbathin dietary supplements.

Conjugated Linoleic Acid (CLA). Conjugated linoleic acid is found in many dietary products (e.g., Biosculpt Liquid, Body Success, GNC Optibolic Body Answers Dietary Formula). There is no evidence that it produces weight loss. Furthermore, there is some concern that CLA might increase insulin resistance and a dangerous inflammatory response in people with obesity.

Tiratricol. Over-the-counter products containing tiratricol, a thyroid hormone, have been sold for weight loss. Such products may increase the risk for thyroid disorders, heart attack, and stroke.

Laxative Actions in Natural Substances. Many dietary herbal teas contain laxatives, which can cause gastrointestinal distress, and, if overused, may lead to chronic pain, constipation, and dependency. In rare cases, dehydration and death have occurred. Some laxative substances found in teas include senna, aloe, buckthorn, rhubarb root, cascara, and castor oil.

Guar Gum. Some fiber supplements containing guar gum have also caused obstruction of the gastrointestinal tract.

Chitosan. Chitosan, a dietary fiber from shellfish, prevents a small amount of fat from being absorbed in the intestine. Well-conducted studies, however, have not found it to be effective. Products containing it include Cheat & Lean Fat Blocker, Natrol, Chroma Slim, and Enforma. People who are allergic to shellfish should not take these supplements.

Plantain. Dietary remedies that list the ingredient plantain may contain digitalis, a powerful chemical that affects the heart. NOTE: This substance should not be confused with the harmless banana-like plant also called plantain.

Orlistat (Xenical) can help about one-third of obese patients with modest weight loss, and can assist in long-term maintenance of weight loss. It works by slowing the absorption of fat (by about 30%) in the intestine. Studies indicate that between 50 - 80% of patients can achieve weight loss of 5% or greater, depending on other lifestyle changes. However, many people regain a significant portion of this weight back within 2 years. It does not work for all patients, however. In one survey of patients who took it, 10% gained weight or did not lose any, and 43% lost less than 5%. Nevertheless, orlistat may delay or even prevent the onset or progression of diabetes and improve cholesterol levels, regardless of weight loss.

The drug can cause gastrointestinal problems and may interfere with absorption of the fat-soluble vitamins A, D, and E and other important nutrients. The most unpleasant side effect is oily leakage of feces from the anus. Restricting fats can reduce this effect. People with bowel disease should probably avoid it. In spite of these side effects, most patients are able to tolerate this agent.

In February 2007, the FDA approved an over-the-counter (OTC) version of orlistat. It will be sold under the name alli, and will be available at half the prescription strength of Xenical. Those eager to use the new pill should consider its cost and modest benefits compared with its side effects, most commonly oily diarrhea. This pill, which prevents fat absorption from food, also increases the risk of not absorbing important nutrients from food while using it. The FDA recommends taking a daily multivitamin supplement when using alli.

Sibutramine (Meridia) helps balance the brain chemicals serotonin and norepinephrine. This helps increase metabolism, causes a feeling of fullness, and increases energy levels. It may be particularly useful for binge-eaters. Studies indicate that sibutramine is effective in achieving weight loss, although the weight loss slows considerably after the first 3 months. The drug also appears to improve cholesterol and lipid (fat) levels, and may have other effects that benefit the heart.

Side effects of sibutramine are common. They include dry mouth, constipation, and insomnia. In one study, almost half the patients dropped out as a result of these side effects. There have been reports of increases in heart rate and blood pressure while taking this medication, although a 2001 study indicates that blood pressure stabilizes over time.

At this time, people who have a history of high blood pressure, stroke, heart disease, or arrhythmias should not take this drug. People taking decongestants, bronchodilators (such as for asthma), monoamine oxidase inhibitors, or serotonin reuptake inhibitors should also avoid sibutramine.

Phentermine and Other Sympathomimetics. Sympathomimetics are drugs that act like the stress hormone (and chemical messenger) norepinephrine. These medications act as stimulants in the brain. Some are approved for treating obesity, but only for short-term use. They include:

Phentermine (Ionamin, Adipex-P, Fastin)
Benzphetamine (Didrex)
Phendimetrazine (Adipost, Bontril, Melfiat, Plegine, Prelu-2, Statobex)

Phentermine is the most commonly prescribed appetite suppressant, and is less expensive than orlistat or sibutramine. Its effects are not long lasting, however. It can also raise blood pressure. In addition, phentermine is associated with depression, which is already a problem in many cases of obesity. A combination (Phen-Pro) containing phentermine and the antidepressant fluoxetine (Prozac) is being investigated to help reduce this problem. Note: Neither phentermine nor such combinations are associated with the heart problems linked to the previous phentermine combination known as Fen-Phen (phentermine and fenfluramine).

Amphetamines. The amphetamines dextroamphetamine (Dexedrine), methamphetamine (Desoxyn), and phenmetrazine (Pleudin) are powerful stimulants. They were used most often in the past but are no longer prescribed for weight loss. These drugs improve mood and produce some modest weight loss over the short term, but carry serious risks of addiction, agitation, and insomnia.

Rimonabant. Rimonabant (Accompli) belongs to a new class of drugs called selective CB1 blockers. The drug is designed to block receptors in the brain associated with the regulation of eating. Rimonabant also targets receptors in fat tissue. The Rimonabant in Obesity-Lipids (RIO-Lipids) study looked at how rimonabant affected metabolic risk factors in high-risk overweight or obese patients with blood fat disorders. The study involved more than 1,000 participants. The findings, published in the November 2005 New England Journal of Medicine, said that people who took the drug significantly reduced their body weight and size of their waist.

Earlier studies involving the drug reported that obese patients treated with 20 mg of rimonabant lost significantly more weight and inches from their waist than patients who received placebo. The drug also appeared to have beneficial effects on raising HDL ("good") cholesterol levels.

Note: Fake rimonabant has been found for sale on several web sites. Patients should be aware that this drug is still experimental, and rimonabant is not available for sale. Buying and taking counterfeit drugs can have serious health consequences. In addition, an FDA advisory panel in April 2007 rejected the drug, citing fears it may cause psychiatric problems and seizures in some patients.

Axokine. Axokine is a type of drug called a ciliary neurotrophic factor. It signals the brain to suppress one's appetite. It is proving to be effective in achieving weight loss, and also improves cholesterol, lipid, and glucose levels regardless of food intake. It could be particularly helpful for people with type 2 diabetes. Early study results found that severely obese patient who took the drug lost more weight than those who took a dummy pill (placebo). Nearly half (46%) of patients who took the drug lost at least 10 pounds, compared to 5% of those who received the placebo. Study participants tolerated the drug well. There were no reports of serious side effects.

Zonisamide. Zonisamide (Zonegran) is an anti-seizure medication that is also being investigated for weight loss. In one study, patients who took it lost more weight than those on placebo. Zonisamide increases the risk for kidney stones, which can be reduced with increased fluid intake and citrate. It has also been associated with reduced sweating and a sudden rise in body temperature, especially in hot weather. Other side effects include dizziness, forgetfulness, headache, and nausea.

Topiramate. Topiramate (Topamax) is another anti-seizure medication being investigated for weight reduction. Three clinical trials have reported that patients given topiramate lost more weight than those receiving placebo. Weight loss was sustained for up to 1 year. The drug is also being studied for binge-eating disorders associated with obesity.

Other Treatments

Surgical procedures for obesity may be appropriate for some dangerously obese people, and may reduce heart problems and many of the risks associated with obesity. These risks include high blood pressure, sleep apnea, and diabetes. In fact, some evidence suggests that surgery may provide much greater control of weight and diabetes than nonsurgical weight-loss methods. Studies are reporting significant reductions in diabetes, and the need for diabetic medications, after surgery. Other medical conditions that often improve after surgery include heartburn, arthritis, and other joint and circulation problems.

Bariatric surgeries produce weight loss through one of two approaches:

Restrictive Banding Procedures. These procedures restrict the amount of food by closing off parts of the stomach with bands.
Malabsorptive Bypass Procedures. This approach restricts the amount of food and also reduces absorption by using a bypass of parts of the intestine.

The malabsorptive procedures are more successful in achieving weight loss than the banding approach, but they carry a greater risk for nutritional deficiencies.

Most people who have bariatric surgery lose about two-thirds of excess weight within 2 years. In addition, diseases associated with obesity (such as diabetes, high blood pressure, sleep apnea, joint pain, and incontinence) often improve.

Researchers at the Mayo Clinic looked at records from patients who had the surgery between 1990 and 2003. They found that those who had bariatric surgery reduced their risk of cardiovascular events such as a heart attack much more than those who lost weight without surgery. The findings were published in the September 2005 Mayo Clinic Proceedings.

Other studies have shown that even though most patients maintain significant weight loss, the majority regain about to 10% of their weight. Patients must still develop a healthy life style and be calorie conscious after the operation. Follow-up must be life-long.

Any surgical candidate must have failed consistently in losing weight through less invasive methods. Experts recommend bariatric surgery only for the following:

Those whose BMI is above 40 (about 100 pounds overweight)
Those with BMIs of over 35 who have type 2 diabetes or serious obesity-related medical problems
Those with severe obesity that interfered with employment, normal physical activity (e.g., walking), and important relationship

About a third of people who undergo these procedures achieve normal weight, and 80% experience some weigh loss. They are less successful than the bypass procedures, but carry a lower risk of nutritional deficiencies.

Vertical Banded Gastroplasty. Vertical banded gastroplasty (VBG) was the most common restrictive procedure. It involves creating a hole through both stomach walls and sealing the edges with a staple. This narrows the stomach, similar to a funnel, and allows only small amounts of food to pass through.

Laparoscopic Gastric Banding. Laparoscopic gastric banding (the Lap-Band) usually does not require a major incision and avoids some of the major complications of gastric bypass:

It employs an adjustable silicone band that is placed around the upper part of the stomach.
A small balloon-like reservoir attached to the band under the abdominal skin contains saline, which can be added or removed to tighten or loosen the band.
The procedure restricts the amount of food a person can eat and gives the feeling of fullness.

The band is removable, if necessary. Studies to date indicate that the intestinal tract returns to normal afterward. Studies, including those done in the elderly, have reported significant weight loss and improved quality of life with the procedure.

Malabsorptive procedures produce greater weight loss than restrictive procedures. Patients generally achieve about two-thirds of their weight loss within 2 years. Furthermore, in a 2003 study, after standard bypass surgery, 83% of patients with type 2 diabetes experienced normal blood glucose levels and the rest had significant reductions.

Roux-en-Y Gastric Bypass Procedure. This is the most common and successful malabsorptive surgery in the United States. It involves creating a small stomach pouch that serves as a reservoir and restricts food intake. The pouch eventually holds up to 3 ounces of food and has a small outlet that delays emptying and causes a feeling of fullness. Then the surgeon creates a Y-shaped section in the small intestine that attaches to the pouch. This section allows food to bypass the lower stomach and upper part of the intestine. One 2003 study reported that this procedure was associated with significant weight loss, and 80% of patients with type 2 diabetes were able to reduce their medications. A more recent study, published in the March 14, 2006, issue of Archives of Surgery, found that gastric bypass surgery also helps lower the blood pressure of very obese patients.

The procedure produces greater and more sustained weight loss than banding procedures, but it is also more complicated, and carries a higher risk of nutritional deficiencies. Laparoscopy techniques, which are less invasive, are now preferred over open surgery. They achieve equally good results with fewer complications.

Biliopancreatic Diversion. This procedure is more complicated and removes portions of the stomach. The pouch that is created attaches directly to the lower part of the small intestine. It poses a higher risk for nutritional deficiencies than other procedures and is not used as often.

Click the icon to see an image of gastric bypass surgery.

General Side Effects and Complications. Side effects and complications of bariatric procedures are common, and up to 25% of patients require corrective or repeat procedures. After any of these procedures people must chew all their food carefully, and they cannot eat large amounts of food at one time. If patients do not follow these guidelines, they will experience nausea, abdominal distress, or both.

Complications from any bariatric procedure includes the following:

Vomiting: This is the most common complication, and it is most common with banding procedures.
Nutritional deficiencies: There is a strong risk of nutritional deficiencies, particularly with malabsorptive operations. This complication can lead to anemia and increase the risk of bone loss and osteoporosis. Taking enough mineral and vitamin supplements is important after bariatric surgery.
Deep-vein thrombosis: There is a significant risk for deep-vein thrombosis (blood clots in the veins).
Abdominal hernia: This is another common complication. Newer, laparoscopic techniques do not carry this risk, but not all individuals are candidates for this less-invasive approach.
Rapid weight loss after surgery: This complication puts people at high risk for gallstones.
Women who wish to be pregnant should wait until their weight has stabilized. Rapid weight loss and nutritional deficiencies can harm the fetus.

People at highest risk for complications are those with heart or lung problems, severe obesity, and a history of abdominal surgeries. The mortality rate from bariatric surgeries is 0.2%, which is lower than the morality rates from severe obesity itself. Other surgical variations and less invasive techniques using laparoscopy have been developed.

Specific Complications of Restrictive Banding Procedures. Nausea, vomiting, or both occurs in half the patients, and severe heartburn occurs in a third. Device-related complications include band slippage, pouch dilation (widening), or both in nearly a quarter of patients, and obstruction in 12% of patients. Very serious complications are rare, but include blood clots, bleeding, infection, pneumonia, and perforation (tearing) of the stomach.

Specific Complications of Malabsorptive Bypass Procedures. Vomiting often occurs. Nutritional deficiencies occur more often in these procedures. The so-called dumping syndrome is a common unpleasant side effect, which occurs when food waste moves too quickly through the intestine. Symptoms include nausea, weakness, sweating, and faintness (particularly after eating sweets).

Spot Exercising. Anyone seeking to lose weight must expect that the results may not be as cosmetically satisfying as one would wish. Spot exercising (training particular areas of the body) is ineffective in reducing fat in specific locations because exercise draws on fat stores throughout the body. Gimmicky devices such as bust developers, vacuum pants, and exercise belts do absolutely nothing to reduce fat or add bulk in specific locations. Electrical pads wrapped around the waist, arms, or thighs were reported to cause burns and fires.

Cellulite-Removal Creams. Many women try to reduce fat in their thighs (cellulite) with creams that contain aminophylline (Skinny Dip, Thermojetics Body Toning Cream, Smooth Contours). Studies provide no evidence that these creams are effective. Their apparent effect on fat may simply be from narrowing blood vessels and forcing water from the skin, which could be dangerous for people with blood flow problems.

Endermologie. Endermologie uses motorized rollers and regulated suction to smooth out cellulite. In one study, about 28.6% of patients reported improved appearance after using it.

Liposuction. Liposuction eliminates fat in specific areas, such as the abdomen, thighs, buttocks, or knees. Special instruments are inserted through the skin into the pockets and suction is used to move the fat, break it up, and remove it. Small tubes may be used to drain blood and fluid during the first few days. The pain after the operation can be severe and often the skin does not contract, resulting in a flabby look. Complications can include burns from the vibrators, bruising, blood clots, and bleeding. Weight gain generally tends to develop in other locations after the operation. Some doctors are using this procedure in overweight people with diabetes to remove abdominal fat. Although there is no proof that it has an effect on diabetes, some experts believe the procedure deserves attention.

Liposuction is not recommended for major weight loss.

Resources

www.healthierus.gov/dietaryguidelines -- Dietary Guidelines for Americans 2005
www.naaso.org -- North American Association for the Study of Obesity
www.eatright.org -- American Dietetic Association
www.nutrition.gov. -- Nutrition.gov
www.asbs.org -- American Society for Bariatric Surgery
www.cnpp.usda.gov -- Center for Nutrition Policy and Promotion
http://fnic.nal.usda.gov -- Food and Nutrition Information Center
www.americanheart.org -- American Heart Association
www.nationaleatingdisorders.org -- National Eating Disorders Organization
www.aabt.org -- Association for Advancement of Behavior Therapy
www.fda.gov -- Food and Drug Administration
http://win.niddk.nih.gov -- Weight-Control Information Network

References

US Food and Drug Administration FDA Approves Orlistat for Over-the-Counter Use. Rockville, MD: National Press Office; February 7, 2007.

Ogden CL, Carroll MD, Curtin LR, McDowell MA, Tabak CJ, Flegal KM. Prevalence of overweight and obesity in the United States, 1999-2004. Journal of the American Medical Association. 2006; 295:1549-1555.

National Center for Health Statistics. Chartbook on Trends in the Health of Americans. Health, United States, 2005. Hyattsville, MD: Public Health Service. 2005

National Institute of Diabetes and Digestive and Kidney Diseases - Weight-control Information Network. Statistics Related to Overweight and Obesity. Available online.

National Center for Health Statistics. Prevalence of Overweight Among Children and Adolescents: United States, 2003-2004.

Morino M, Toppino M, Bonnet G, Rosa R, et al. Laparoscopic vertical banded gastroplasty for morbid obesity. Assessment of efficacy. Surg Endosc. 2002 Nov;16(11):1566-72.

Brethauer SA, Schauer PR, Chand B. Risks and benefits of bariatric surgery: Current evidence. Cleveland Clinic Journal Of Medicine. 2006 Nov; 73(11): 993-1007.

Rosenthal RJ, Szomstein S, Kennedy CI, et al. Laparoscopic surgery for morbid obesity: 1,001 consecutive bariatric operations performed at The Bariatric Institute, Cleveland Clinic Florida. Obes Surg. 2006 Feb;16(2):119-24.

He K, Liu K, Daviglus ML, et al. Magnesium Intake and Incidence of Metabolic Syndrome Among Young Adults. Circulation. 2006: Published online before print. March 27, 2006.

Chen TY, Smith W, Rosenstock JL, Lessnau KD. A life-threatening complication of Atkins diet. Lancet. 2006 Mar 18;367(9514):958.

Lopez-Jimenez F, Bhatia S, Collazo-Clavell ML, Sarr MG, Somers VK. Safety and efficacy of bariatric surgery in patients with coronary artery disease. Mayo Clin Proc. 2005 Sep;80(9):1157-62.

Sidhaye A, Cheskin LJ. Pharmacologic treatment of obesity. Adv Psychosom Med. 2006;27:42-52.

Fernstrom JD, Courcoulas AP, Houck PR, Fernstrom MH. Long-term changes in blood pressure in extremely obese patients who have undergone bariatric surgery. Arch Surg. 2006 Mar;141(3):276-83.

Despres JP, Golay A, Sjostrom L; Rimonabant in Obesity-Lipids Study Group. Effects of rimonabant on metabolic risk factors in overweight patients with dyslipidemia. N Engl J Med. 2005 Nov 17;353(20):2121-34.

Lanningham-Foster L, Nysse LJ, Levine JA. Labor saved, calories lost: the energetic impact of domestic labor-saving devices. Obes Res. 2003 Oct;11(10):1178-81.

Review Date:
6/14/2007
Reviewed By:
A.D.A.M. Editorial Team: Greg Juhn, M.T.P.W., David R. Eltz, Kelli A. Stacy. Previously reviewed by Harvey Simon, MD, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital (4/30/2007).

A.D.A.M., Inc. is accredited by URAC, also known as the American Accreditation HealthCare Commission (www.urac.org). URAC's accreditation program is an independent audit to verify that A.D.A.M. follows rigorous standards of quality and accountability. A.D.A.M. is among the first to achieve this important distinction for online health information and services. Learn more about A.D.A.M.'s editorial policy, editorial process and privacy policy. A.D.A.M. is also a founding member of Hi-Ethics and subscribes to the principles of the Health on the Net Foundation (www.hon.ch).

A.D.A.M. Copyright

The information provided herein should not be used during any medical emergency or for the diagnosis or treatment of any medical condition. A licensed medical professional should be consulted for diagnosis and treatment of any and all medical conditions. Call 911 for all medical emergencies. Links to other sites are provided for information only -- they do not constitute endorsements of those other sites. © 1997-2009 A.D.A.M., Inc. Any duplication or distribution of the information contained herein is strictly prohibited.

adam.com

Insomnia

FitSugar — Wed, 08 Oct 2008 17:35:00 -0700

In This Report

Highlights
Introduction
Causes of Short-Term or Tra...
Causes of Chronic Insomnia...
Risk Factors
Prognosis
Diagnosis
Treatment
Medications
Resources
References

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

Sedative Hypnotic Drug Warnings

In March 2007, the FDA ordered stronger warning labels on sedative hypnotic drugs. These medications include benzodiazepine and non-benzodiazepine drugs, such as zolpidem (Ambien), eszopiclone (Lunesta), ramelteon (Rozerem), and triazolam (Halcion). The FDA warned that these drugs may be associated with:

Severe allergic reactions (anaphylaxis) and severe facial swelling (angioedema), which can occur even the first time a drug is taken
Complex sleep-related behaviors, such as sleep driving, making phone calls, and preparing and eating food while asleep

Patients who take sleeping pills should be sure to follow the directions. These include not combining sleeping pills with alcohol or other drugs and not taking more than the prescribed dose. All patients prescribed sedative hypnotic drugs should receive a patient medication guide that describes the potential risks, and precautions to reduce these risks.

Behavioral and Psychological Therapies

Behavioral and psychological treatments, such as cognitive behavioral therapy and relaxation techniques, are effective approaches for insomnia and can produce long-lasting benefits, according to a 2006 study in Sleep.
Behavioral interventions help over 80% of children who try them, indicates another 2006 Sleep study.

Complementary and Alternative Medicine

More than 1.6 million adults use complementary and alternative medicine to treat their insomnia, according to results of a national survey published in the Archives of Internal Medicine. About half of patients who tried herbal medicine or relaxation techniques found that these approaches helped improve their sleep.
In 2006, the American Academy of Sleep Medicine issued a position statement advising that there is only limited scientific evidence that herbal remedies are effective sleep aids.

Insomnia and Mood Disorders

Chronic insomnia can increase the risk of developing depression and anxiety, according to a 2007 study in Sleep. Research also indicates that insomnia and daytime sleepiness can cause and worsen depression and anxiety in children as well as adults.

Introduction

Insomnia comes from the Latin words for “no sleep.” Insomnia is characterized by:

Difficulty falling asleep
Difficulty staying asleep
Waking up too early in the morning

Some experts believe that poor quality (“non-restorative”) sleep is also related to insomnia. Insomnia can cause daytime fatigue, irritability, and impaired performance. About 60 million Americans each year suffer from insomnia.

Insomnia may be primary or secondary:

Primary insomnia means that the inability to sleep is not caused by other health problems.
Secondary insomnia is due to other health conditions that interfere with sleep. Some experts prefer the term “co-morbid insomnia.”

Insomnia, usually temporary, is often categorized by how long it lasts:

Transient insomnia lasts for a few days.
Short-term insomnia lasts for no more than 3 weeks.
Chronic insomnia occurs at least 3 nights per week for 1 month or longer.

Insomnia may also be defined in terms of inability to sleep at conventional times. The following examples are referred to as circadian rhythm disorders:

Delayed Sleep-Phase Syndrome. Delayed sleep-phase syndrome is the term for a circadian clock that runs late but reliably. People who have this condition (usually adolescents) fall asleep very late at night or in early morning hours, but then sleep normally.
Advanced Sleep-Phase Syndrome. This syndrome tends to develop in older people. It produces excessive sleepiness in the morning and undesired awakening early (3 - 5 a.m.) in the morning.

In sleep studies, subjects spend about one-third of their time asleep, suggesting that most people need about 8 hours of sleep each day. Individual adults differ in the amount of sleep they need to feel well rested, however. (Infants may sleep as many as 16 hours a day.)

The daily cycle of life, which includes sleeping and waking, is called a circadian (meaning "about a day") rhythm, commonly referred to as the biologic clock. Hundreds of bodily functions follow biologic clocks, but sleeping and waking comprise the most prominent circadian rhythm. The sleeping and waking cycle is approximately 24 hours. (If confined to windowless apartments, with no clocks or other time cues, sleeping and waking as their bodies dictate, humans typically live on slightly longer than 24-hour cycles.) It usually takes the following daily patterns:

Humans are designed for daytime activity and nighttime rest.
Additionally, there is a natural peak in sleepiness at mid-day, the traditional siesta time.

In addition, daily rhythms intermesh with other factors that may interfere or change individual patterns:

The fraction-of-a-second-firing of nerve cells in the brain may be faster or slower in different individuals.
The monthly menstrual cycle in women can shift the pattern.
Light signals coming through the eyes reset the circadian cycles each day, so changes in season or various exposures to light and dark can unsettle the pattern. The importance of sunlight as a cue for circadian rhythms is dramatized by the problems experienced by people who are totally blind. They commonly suffer trouble sleeping and other rhythm disruptions.

The response to light signals in the brain is an important key factor in sleep:

Light signals travel to a tiny cluster of nerves in the hypothalamus in the center of the brain, the body's master clock, which is called the supra chiasmatic nucleus (SCN).
This nerve cluster takes its name from its location, which is just above (supra) the optic chiasm, which is a major junction for nerves transmitting information about light from the eyes.
The approach of dusk each day prompts the SCN to signal the nearby pineal gland (named so because it resembles a pine-cone) to produce the hormone melatonin.
Melatonin is thought to act as the body's time-setting hormone. The longer a person is in darkness the longer the duration of melatonin secretion. Secretion can be diminished by staying in bright light. Melatonin also appears to trigger the need to sleep.

Sleep consists of two distinct states that alternate in cycles and reflect differing levels of brain nerve cell activity:

Non-Rapid Eye Movement Sleep (NonREM). NonREM sleep is also termed quiet sleep. NonREM is further subdivided into three stages of progression:

Stage 1 (light sleep)
Stage 2 (so-called true sleep)
Stage 3 to 4 (deep "slow-wave" or delta sleep)

With each descending stage, awakening becomes more difficult. It is not known what governs NonREM sleep in the brain. A balance between certain hormones, particularly growth and stress hormones, may be important for deep sleep.

Rapid Eye-Movement Sleep (REM). REM sleep is termed active sleep. Most vivid dreams occur in REM sleep. REM-sleep brain activity is comparable to that in waking, but the muscles are virtually paralyzed, possibly preventing people from acting out their dreams. In fact, except for vital organs like lungs and heart, the only muscles not paralyzed during REM are the eye muscles. REM sleep may be critical for learning and for day-to-day mood regulation. When people are sleep-deprived, their brains must work harder than when they are well rested.

The REM/NREM Cycle. The cycle between quiet (nonREM) and active (REM) sleep generally follows this pattern:

After about 90 minutes of nonREM sleep, eyes move rapidly behind closed lids, giving rise to REM sleep.
As sleep progresses the nonREM/REM cycle repeats.
With each cycle, nonREM sleep becomes progressively lighter, and REM sleep becomes progressively longer, lasting from a few minutes early in sleep to perhaps an hour at the end of the sleep episode.

Causes of Short-Term or Transient Insomnia

A reaction to change or stress is one of the most common causes of short-term and transient insomnia. This condition is sometimes referred to as adjustment sleep disorder.

The trigger could be a major or traumatic event such as:

An acute illness
Injury or surgery
The loss of a loved one
Job loss

Temporary insomnia could also develop after a relatively minor event, including:

Extremes in weather
An exam
Traveling
Trouble at work

In most cases, normal sleep almost always returns when the condition resolves, the individual recovers from the event, or the person becomes used to the new situation. Treatment is needed if sleepiness interferes with functioning or if it continues for more than a few weeks. Individual responses to stress vary and some people may not experience insomnia at all, even during very stressful situations while others may suffer from insomnia in response to very mild stressors.

Fluctuations in female hormones play a major role in insomnia in women over their lifetimes. This insomnia is usually temporary.

During Menstruation. Progesterone promotes sleep, and levels of this hormone plunge during menstruation, causing insomnia. (When they rise during ovulation, women may become sleepier than usual.)
During Pregnancy. The effects of changes in progesterone levels in the first and last trimester can disrupt normal sleep patterns.
Menopause. Insomnia can be a major problem in the first phases of menopause, when hormones are fluctuating intensely. Insomnia during this period may be due to different factors that occur. In some women, hot flashes, sweating, and a sense of anxiety can awaken women suddenly and frequently at night. Insomnia may also be caused by psychologic distress provoked by this life passage. In many cases, insomnia is temporary. However, a 2006 study found that hot flashes in perimenopausal and postmenopausal women are strongly associated with chronic insomnia (sleep problems lasting more than 1 month). Treating hot flashes may help resolve chronic insomnia.

Air travel across time zones often causes insomnia. After long plane trips, 1 day of adjustment is usually needed for each time zone crossed. Traveling west to earlier times seems to be less traumatic than going east to a later time because it is easier to lengthen a circadian phase than to shorten it.

In one study, 20% of adults reported that light, noise, and uncomfortable temperatures caused their sleeplessness. Depending on the time of day, too much or too little light can disrupt sleep.

Excessive Light at Night. A person's biologic circadian clock is triggered by sunlight, and very bright artificial light maintains wakefulness. One study indicated that even dim artificial light might disrupt sleep.
Insufficient Light During the Day. Insufficient exposure to light during the day, as occurs in some disabled elderly patients who rarely venture outside, may also be linked with sleep disturbances. One study suggested that when a person is exposed to bright daylight, melatonin levels increase in response to darkness at night, which aids sleep.

Caffeine. Caffeine is a stimulant, which can interfere with falling asleep.

Nicotine. Nicotine is also a stimulant, but quitting smoking itself can lead to transient insomnia. In fact, it has been suggested that if sleeping could be improved during withdrawal from smoking, perhaps it would be easier to quit smoking.

Partner's Sleep Habits. In one survey, 17% of women and 5% of men reported that their partner's sleep habits impaired their own sleep. Snoring can certainly be a factor in a partner's insomnia.

Medications. Insomnia is a side effect of many common medications, including over-the-counter preparations that contain caffeine. People who suspect their medications are causing them to lose sleep should check with their doctors or pharmacists.

Causes of Chronic Insomnia

Sleep problems seem to run in families. About 35% of people with insomnia have a family history of insomnia, with the mother being the most commonly affected family member. Still, because so many factors are involved in insomnia, a genetic component is difficult to define.

Abnormal levels of certain brain chemicals have been observed in some people with chronic insomnia.

Melatonin. Low levels of melatonin, the hormone secreted by the pineal gland, have sometimes been observed in chronic insomnia.
Stress Hormones. Some studies have reported persistently high levels of stress hormones, particularly cortisol, in people with chronic insomnia, particularly insomnia related to aging and psychiatric disorders. High levels of cortisol reduce REM sleep. However, a 2003 study of people with chronic insomnia reported that cortisol levels were high only when their sleep was of poor quality. When they slept well, levels were lower. This study and other research suggests that high levels of stress hormones are caused by poor sleep, rather than being the cause.
Growth Hormone. Normal aging is associated with a blunting of regular, cyclical surges of growth hormone, which may affect sleep as one gets older. This hormone, which is normally secreted in the late night, is associated not only with growth but with deep, slow-wave sleep. (Older people generally have less slow-wave sleep.)

Chronic insomnia occurs in people who have persistently high levels of stress hormones and a shift in the levels of certain immune factors. Studies indicate that people with chronic insomnia have higher levels of interleukin-6 and tumor necrosis factor during the day, but lower levels at night. These immune factors, called cytokines, cause symptoms of fatigue. Levels are usually higher at night in people with healthy sleep. The implications of these immune changes in people with insomnia are not known.

Many cases of chronic insomnia cases have a psychologic or psychiatric basis. The disorders that most often cause insomnia are:

Anxiety.
Depression. Sleep abnormalities are an integral part of depressive disorders, with more than 90% of depressed patients experiencing insomnia.
Bipolar disorder.

Insomnia may also cause emotional problems. It is often unclear which condition has triggered the other, or if the two conditions, in fact, have a common source.

In many cases, it is unclear if chronic insomnia is a symptom of some physical or psychological condition or if it is a primary disorder of its own. In most instances, a mix of psychological and physical conditions causes the insomnia.

Psychophysiologic insomnia occurs when:

An episode of transient insomnia disrupts the person's circadian rhythm.
The patient begins to associate the bed not with rest and relaxation but with a struggle to sleep. A pattern of sleep failure emerges.
Over time, this event repeats, and bedtime becomes a source of anxiety. Once in bed, the patient broods over the inability to sleep, the consequences of sleep loss, and the lack of mental control. All attempts to sleep fail.
Eventually excessive worry about sleep loss becomes persistent and provides an automatic nightly trigger for anxiety and arousal. Unsuccessful attempts to control thoughts, images, and emotions only worsen the situation. After such a cycle is established, insomnia becomes a self-fulfilling prophecy that can persist indefinitely.

Sometimes anxiety and the inability to sleep dates back to childhood when parents used various threats to force their children into sleep for which they may not have been ready.

In one survey, 22% of adults reported that health conditions, pain, or discomfort impaired their sleep. These conditions can include:

Nightly Leg Problems. Leg disorders that occur at night, such as restless legs syndrome or leg cramps, are of special note. They are very common and an important cause of insomnia, particularly in older people.

Medical Problems. Among the many medical problems that can cause chronic insomnia are allergies, arthritis, cancer, fibromyalgia, heart disease, gastroesophageal reflux disease (GERD), hypertension, asthma, emphysema, rheumatologic conditions, Alzheimer's disease, Parkinson's disease, hyperthyroidism, and attention deficit hyperactivity disorder.

Medications. Among the many medications that can cause insomnia are antidepressants (fluoxetine, bupropion), theophylline, lamotrigine, felbamate, beta-blockers, and beta-agonists.

An estimated 10 -15% of chronic insomnia cases result from substance abuse, especially alcohol, cocaine, and sedatives. One or two alcoholic drinks at dinner, for most people, pose little danger of alcoholism and may help reduce stress and initiate sleep. Excess alcohol or alcohol used to promote sleep, however, tends to fragment sleep and cause wakefulness a few hours later. It also increases the risk for other sleep disorders, including sleep apnea and restless legs. Alcoholics often suffer insomnia during withdrawal and, in some cases, for several years during recovery.

Shift work throws off the body's circadian rhythm and may lead to chronic insomnia.

Risk Factors

Studies estimate that between 25 - 33% of adults experience some insomnia each year. In spite of this widespread problem, however, studies suggest that only about 30% of American adults who visit their doctor ever discuss sleep problems. And, doctors seem rarely to ask patients about their sleep habits or problems.

A 2003 study suggested that there were seven significant factors that predicted high risk for insomnia:

Being older
Having conflicts with relatives
Being overworked on the job
Being overworked at home
Having a sick relative
Having low social status
Having a psychiatric or psychologic problem

Stressful events do not cause insomnia in everyone. However, negative thoughts and attitudes toward events can be significant factors in insomnia. In one study, for example, the number of stressful events did not differ between good and poor sleepers. Those with insomnia, however, tended to experience these stressful events more intensively than the healthy sleepers.

In another study, patients with insomnia and good sleepers were asked to record their pre-sleep images using a handheld counter. People with insomnia not only reported fewer images, but their images also tended to be more unpleasant than those of good sleepers. More of the images in people with insomnia were related to intimate relationships and to sleep itself. The images of sleepers were more likely to be random and disconnected.

Studies report that the strongest risk factors for insomnia are psychiatric problems (particularly depression) and physical complaints (such as headaches and chronic pain) that have no identifiable cause (called somatic symptoms). About 90% of people with depression have insomnia. A study presented at the 2005 Associated Professional Sleep Societies meeting indicated that insomnia may contribute to, and prolong, depression. Researchers analyzed data from over 1,800 adults age 65 years and older. Compared with depressed patients who did not have sleep problems, depressed patients with insomnia were 11 times more likely to remain depressed after 6 months and 17 times more likely to still be depressed after a year. The researchers suggested that treating insomnia may help patients recover from depression more quickly.

Overall, insomnia is more common in women than men, although men are not immune from insomnia. Sleep efficiency deteriorates equally in men and women as they get older.

Men. One major study suggested that as men age from 16 - 50, they lose about 80% of their deep sleep. During that period, light sleep increases and REM sleep remains unchanged. (The study did not use women as subjects, and there is some evidence to suggest they are not as affected.) After age 44, REM and total sleep diminish and awakenings increase.

Women. It is not clear why women suffer more from insomnia than men. Some theories include:

In women, a number of hormonal events can disturb sleep, including premenstrual syndrome, menstruation, pregnancy, and menopause. All these conditions are short-term, however, and in most cases the wakefulness associated with them is temporary and can be eliminated with sleep hygiene and time.
After childbirth, most women develop a high sensitivity to the sounds of their children, which causes them to wake easily. Women who have had children sleep less efficiently than women who have not had children. It is possible that many women never unlearn this sensitivity and continue to wake easily long after the children have grown.
Women are at higher risk than men are for depression and anxiety, which are known risk factors for insomnia. In fact, some researchers believe that this is a main reason for the gender differences in insomnia.

After menopause, women are susceptible to the same environmental and biologic causes of insomnia as men. In fact, older women who are not bothered by sleeplessness tend to have longer and better sleep than noninsomniac men their own age.

As people grow older, sleep patterns change. In a major 2003 survey, a third of older adults reported that they woke up frequently during the night. About a quarter of participants reported waking up too early and being unable to go back to sleep. In the same study, 33% of adults age 55 - 64 reported waking up feeling unrefreshed.

Although age itself does not appear to be a risk factor for insomnia, a number of factors may interfere with sleep as one gets older:

Elderly people are more likely to be sedentary than younger adults.
Medical conditions that cause pain or nighttime distress are common in the elderly and pose a high risk for insomnia. They include arthritis, gastrointestinal distress, frequent urination, lung disease, and heart conditions.
Neurologic diseases in the elderly, such as restless legs syndrome, Parkinson's, Alzheimer's, and other forms of dementia can cause nighttime disorientation, confused wandering, and delirium.
Older people often take a number of prescription drugs whose side effects include insomnia.
The elderly are prone to grief, depression, and anxiety, emotional factors that can cause sleeplessness. One study of healthy older adults found that psychologic factors, such as anxiety and depression, were more likely to cause insomnia than illness, medications, or living conditions.
Melatonin levels are generally lower in older people. Some research suggests, however, that elderly people have lower levels simply because they stay mostly indoors and do not receive adequate sunlight.

Lack of sleep at night can lead to excessive sleepiness during the day. A 2006 study reported the following risk factors for excessive daytime sleepiness among the elderly:

Male gender
Sleep apnea or other sleep breathing disorders
Nighttime chest wheezing
Poor sleep quality
Longer time spent in REM sleep
More than 3 episodes of nighttime pain within a week
Medications that cause sleepiness

Sleep loss among the elderly is not inevitable. While older people are more susceptible to many conditions that can cause insomnia, treatments and a healthy lifestyle, particularly regular exercises, are as useful in providing relief to the elderly as to the young. And, a number of studies have found no significant increase in insomnia in older healthy adults.

Shift workers are at considerable risk for insomnia. In a major survey, 65% of shift workers reported one or more symptoms of insomnia at least a few nights a week. Workers over age 50 and those whose shifts are always changing are particularly susceptible to insomnia, although night-shift workers also have a high rate of sleeplessness. One study found that 53% of night-shift workers fall asleep on the job at least once a week, implying that their internal clocks do not adjust to unusual work times. (They are also at much higher risk than other workers for automobile accidents due to their drowsiness and may also have a higher risk for health problems in general.) A Japanese study reporting on different aspects of insomnia found that excessive computer work was associated with all forms of insomnia. People who were over-involved with their work tended to have trouble falling asleep, and they tended to awaken earlier than average.

Among the many conditions that pose a high risk for insomnia are:

Frequent travel, particularly crossing time lines
Post-traumatic stress syndrome
Brain injuries
Many chronic medical conditions ranging from seemingly minor ones, such as tinnitus (ringing in the ears) to major conditions, such as respiratory problems, heart disease, or being on dialysis

Prognosis

A 2002 study of sleeping habits in over 1 million people reported that people who slept 7 hours a night lived the longest. People who slept more than 8 hours or less than 6 hours, or who took sleeping pills, had lower survival rates.

Insomnia is not life-threatening, except in very rare cases, such as in those who have the genetic disorder called fatal familial insomnia. This rare degenerative brain disease develops in late adulthood.

Sleepiness causes as many as 200,000 automobile accidents in the U.S. and 1,500 deaths from such accidents. Studies indicate that drowsy driving is as risky as drunk driving. In a major 2003 survey, 60% of young adults reported driving while drowsy, and 20% dosed off while driving. In the study, 1% of adults who dozed off reported having an accident because of it. (One study strongly suggested that it is habitual sleepiness, however, and not just being sleepy at the time of an accident that places people at higher risk.)

Surveys show that people with severe insomnia have a quality of life that is almost as poor as those who have chronic conditions, such as heart failure. In addition to more daytime sleepiness, people with insomnia complain of more attention and memory problems compared to good sleepers.

Insomnia can also lead to irritability, mistakes at work, and poorer relationships.

Effect on Thinking and Performance. Studies suggest that insomnia makes it harder to concentrate and perform tasks.

Reduced concentration. Deep sleep deprivation impairs the brain's ability to process information.
Impaired task performance. One study reported that missing only 2 - 3 hours of sleep every night for a week significantly impaired performance and mood. An Australian study reported that 17 hours of sleep deprivation causes impaired performance levels comparable to those found in people who have blood alcohol levels indicating intoxication.
Memory problems. Whether insomnia significantly impairs learning is unclear. Some studies have reported problems in memorization, although others have found no differences in test scores between people with temporary sleep loss and those with full sleep.

Insomnia and Depression. Although stress and depression are major causes of insomnia, insomnia may also increase the activity of the hormones and pathways in the brain that can produce emotional problems. Research indicates that chronic insomnia can increase the risk of developing depression and anxiety. Some investigators are exploring the possibility of preventing psychiatric disorders by early recognition and treatment of insomnia.

Even modest alterations in waking and sleeping patterns can have significant effects on a person's mood. In both children and adults, the combination of insomnia and daytime sleepiness can produce more severe depression than either condition alone.

Effects on the Heart. Although there has been some concern that insomnia may increase the risk for heart problems, little evidence has supported any significant dangers. One study reported signs of heart and nervous system activity in people with chronic insomnia that might place such individuals at risk for coronary heart disease. If it exists, however, this increased danger is very modest compared with other risk factors for heart disease. Yet another report suggested that sleep complaints in elderly people without coronary artery disease predicted a first heart attack. Sleep disorders in such cases may have been a marker for depression, however, which is a risk factor for heart attacks in elderly people.

Effects on Weight. Lack of sleep can cause weight gain and obesity. In a 16-year study of over 68,000 women, those who slept no more than 5 hours a night were 32% more likely to gain at least 33 pounds, and those who slept 6 hours had a 12% increased risk of weight gain compared to women who slept at least 7 hours a night.

Effects on the Immune System. A 2003 study reported significant differences in immune factors among sleepers, with higher levels of certain infection-fighters observed in good sleepers than in people with chronic insomnia. The significance of these findings is still unknown, however.

Diagnosis

Diagnosing sleep disturbance and its cause is the most important step in restoring healthy sleep. However, there is little agreement, even among experts, on the best methods for effectively assessing a patient's insomnia.

A major difficulty in diagnosing this problem is its subjective nature. One study showed that there was no difference in sleep behaviors between people who said they were insomniacs and people who said they weren't. People who believe they have insomnia may have actually had frequent brief awakenings during sleep that they perceive as being continuously awake.

A number of questionnaires are available for determining whether a patient has insomnia or other sleep disorders. For example, the doctor may ask:

How would you describe your sleep problem?
How long have you had the sleep problem?
How long does it take to fall asleep?
How many times a week does it occur?
How restful is sleep?
Do you have trouble falling asleep or do you wake up too early?
What is the sleep environment like (Noisy? Not dark enough?)?
How does insomnia affect daytime functioning?
What medications do you take? (Include herbs, alcohol, and over-the-counter or prescription drugs.)
Are you taking or withdrawing from stimulants, such as coffee or tobacco?
How much alcohol is consumed per day?
What stresses or emotional factors may be present?
Have you experienced any significant life changes?
Do you snore or gasp during sleep (an indication of sleep apnea)?
Do you have leg problems (cramps, twitching, crawling feelings)?
If there is a bed partner? Is this person's behavior distressing or disturbing?
Are you a shift worker?

Sleep Diary. If the patient cannot answer these questions, keeping a sleep diary is a helpful diagnostic tool. Every day for 2 weeks, the patient should record all sleep-related information, including responses to questions listed above described on a daily basis. A bed partner can help by adding their observations of the patient's sleep behavior.

The Epworth Sleepiness Scale. The Epworth Sleepiness Scale (ESS) uses a simple questionnaire to measure excessive sleepiness during eight situations.


Situation	Chance of Dozing 0 = no chance of dozing 1 = slight chance of dozing 2 = moderate chance of dozing 3 = high chance of dozing
Sitting and reading.	(Indicate a score of 0 to 3)
Watching TV.	(Indicate a score of 0 to 3)
Sitting inactive in a public place (e.g., a theater or a meeting).	(Indicate a score of 0 to 3)
As a passenger in a car for an hour without a break.	(Indicate a score of 0 to 3)
Lying down to rest in the afternoon when circumstances permit.	(Indicate a score of 0 to 3)
Sitting and talking to someone.	(Indicate a score of 0 to 3)
Sitting quietly after a lunch without alcohol.	(Indicate a score of 0 to 3)
In a car, while stopped for a few minutes in traffic.	(Indicate a score of 0 to 3)
Score Results	1-6: Getting enough sleep 4-8: Tends to be sleepy but is average. 9-15: Very sleepy and should seek medical advice. Over 16: Dangerously sleepy

Multiple Sleep Latency Test. The multiple sleep latency test (MSLT) uses a machine to measure the time it takes to fall asleep while lying in a quiet room during the day:

The patient takes four or five scheduled naps 2 hours apart.
People with healthy sleep habits fall asleep in about 10 - 20 minutes.
The test can detect changes in sleepiness associated with sleep deprivation in patients with insomnia.

It has limitations, however, and does not take into consideration any situations that may affect the patients' mental state and the actual home situation. The test is used mainly after other sleep disorders have been ruled out and the doctor is uncertain whether or not insomnia is a correct diagnosis.

If unexplained insomnia persists after treatment or there is evidence of a primary sleep disorder, such as sleep apnea or narcolepsy, the doctor may recommend a sleep specialist or a sleep disorders center. Centers are accredited by the American Academy of Sleep Medicine. Patients should investigate centers carefully, to be sure that they offer full sleep studies.

Among the signs that may indicate a need for a sleep disorders center are:

Insomnia due to psychologic disorders
Sleeping problems due to substance abuse
Snoring and sudden awakening with gasping for breath (possible sleep apnea)
Severe restless legs syndrome
Persistent daytime sleepiness
Sudden episodes of falling asleep during the day (possible narcolepsy)

At most sleep disorders centers, patients undergo an in-depth analysis, usually supervised by a multidisciplinary team of consultants who can provide both physical and psychiatric evaluations.

Treatment

The American Academy of Sleep Medicine (AASM) recommends cognitive behavioral therapy (CBT) and prescription medications as the main treatments for insomnia. According to the AASM, these treatment options can improve both quality and quantity of sleep for people with insomnia.

Experts agree that behavioral therapies should be the first-line treatment for insomnia. For children in particular, medications should rarely be used as initial treatment. A 2006 study reported that behavioral interventions can provide sustained improvement in over 80% of children with insomnia.

Prevention of sleeplessness depends upon the patient's ability to learn how to relax and sleep well. A number of behavioral methods are aimed at achieving these goals. Behavioral techniques can actually cure chronic insomnia in many cases and studies report that they help nearly all patients with primary chronic insomnia. The benefits of psychological and behavioral therapy in managing insomnia are long-lasting.

Although medications are equally effective for helping people with insomnia to sleep, they cannot cure the condition. In addition, behavioral methods act faster. Behavioral methods work in all age groups, including children and elderly patients.

Behavioral methods include:

Stimulus control
Cognitive behavioral therapy
Progressive muscle relaxation
Paradoxical intention
Biofeedback
Sleep restriction
Imagery tasks

Studies have reported that between 70 - 80% of patients who are treated with non-drug methods experience improved sleep with an average treatment duration of only 5 hours over a 4-week period. Furthermore, studies report that 75% of those who have been taking drugs are able to stop or reduce their use.

Proper sleep hygiene is the first step and should accompany any behavioral method. A number of behavioral approaches are available, but all have the same basic goals:

To reduce the time it takes to go to sleep to below 30 minutes
Reduce wake-up periods during the night

Stimulus Control. Stimulus control is now considered the standard treatment for primary chronic insomnia and may be helpful for some patients with secondary insomnia as well. The primary goal of stimulus control is to regain the idea that the bed is for sleeping. It involves the following:

Go to bed only when ready to sleep or for sex.
If unable to sleep within 15 - 20 minutes, get up and go into another room. (People who find it physically difficult to get out of bed should sit up and do something relatively arousing, like reading a book.)
Maintain a regular wake-up time no matter how few hours you actually sleep.
Avoid naps.

Cognitive-Behavioral Therapy. Cognitive behavioral therapy (CBT) is a form of therapy that emphasizes observing and changing negative thoughts about sleep such as, "I'll never fall asleep." It uses actions intended to change behavior. A 2004 study of young and middle-aged adults suggested that CBT is more effective than medication in treating chronic insomnia, and should be considered as a first-line intervention. Adding medication to CBT did not provide additional benefit. In a 2006 study of older adults, CBT worked better than zopiclone (Imovane) in managing chronic insomnia. [Zopiclone is a European sleep medication that is similar to the American drug eszopiclone (Lunesta).] Compared to zopiclone or placebo, CBT helped patients spend less time awake at night. The benefits of 6 weeks of weekly CBT sessions lasted for 6 months.

Progressive Muscle Relaxation. Progressive muscle relaxation is another technique for inducing sleep that works well for many people. It takes about 10 minutes to perform:

Focus on one specific muscle group at a time. Most people start with the muscles in one foot. Inhale and tense the foot muscles for about 8 seconds. (Do this gently. It is not intended to cause severe pain or muscle contractions.)
Relax the foot, and let it become loose and limp. Stay relaxed for 15 seconds, then repeat with the other foot.
Move up to the next muscle group and repeat the sequence, doing one side of the body at a time. Move progressively from each foot and leg up through the abdomen and chest, to each hand and arm, then to the neck, shoulders, and face.

Paradoxical Intention. Paradoxical intention is a psychological approach that is based on doing the opposite of what one wants or fears and takes it to the extreme. The first step is to make a plan to take such a paradoxical approach to insomnia.

Instead of going through activities leading to sleep, the patient prepares for staying awake and doing something energetic.
In some cases, people may take specific psychological barriers to sleep to an extreme limit. For example, if worry is a factor in insomnia, the patient intensifies the worries.

Biofeedback. Biofeedback is also effective, but requires being monitored with an electroencephalogram (EEG), a device that measures brain waves. Patients are given feedback to recognize certain states of tension or sleep stages so that they can either avoid or repeat them voluntarily.

Sleep Restriction Therapy. Sleep restriction therapy may be effective, although evidence is inconclusive. In a 2001 study, patients practiced sleep hygiene and sleep restriction. Sleep hygiene was very helpful during the first 2 months while sleep restriction led to sustained benefits and deeper sleep. The approach is a systematic method for achieving sleep and restricting the time spent in bed.

The first step is to calculate a person's sleep efficiency number:

Keep a sleep diary for 14 days. Calculate the average hours of actual sleep and hours in bed. Then divide the average hours slept by the hours spent in bed. The result, given as a percentage, is the sleep efficiency number. (For example, if a patient sleeps an average of 5 hours out of 7 hours spent in bed then the result is .714, and the sleep efficiency percentage is 71%.)
The patient's goal is to achieve sleep efficiencies of between 85 - 90%, which means only 10 - 15% of the time is spent staying awake in bed. (Sleep efficiency in older people normally falls between 75 - 85%.)

To achieve this goal, the patient takes the following actions:

Begin by going to bed 15 minutes later than usual the first week.
If 85% sleep efficiency isn't reached by the end of the week, add another 15 minutes before going to bed. Refrain from going to bed even if tired, although bedtime should not be reduced below 5 hours.
Once efficiency reaches 90% or more, begin to go to bed 15 minutes earlier each week.

Other parts of the program include stopping any sleep medications and following good sleep hygiene. People using this treatment have reported lasting improvements after just 8 weeks, and studies suggest that it is significantly more successful than relaxation techniques.

Imagery Tasks. A 2002 study enrolled people whose chronic insomnia was associated with unwanted thoughts and worries. They were given specific positive mental tasks that gave them a sense of positive control (as opposed to their real life concerns, which felt out of their control). These images distracted them and allowed them to fall asleep faster. In support of this approach, another study evaluated patients with insomnia who were given a problem before sleep. One group was asked to think of the problem in images and the other in words. The group who used imagery fell asleep more quickly and woke up with less anxiety.

Sleep Hygiene. The term sleep hygiene is used to describe simple behaviors that may help everyone improve their sleep.

Establish a regular time for going to bed and getting up in the morning. Stick to this schedule even on weekends and during vacations.
Use the bed for sleep and sexual relations only, not for reading, watching television, or working. Excessive time in bed disrupts sleep.
Avoid naps, especially in the evening.
Exercise before dinner. A low point in energy occurs a few hours after exercise; sleep will then come more easily. Exercising close to bedtime, however, may increase alertness.
Take a hot bath about 1.5 - 2 hours before bedtime. This alters the body's core temperature rhythm and helps people fall asleep more easily and more continuously. (Taking a bath shortly before bed increases alertness.)
Do something relaxing in the 30 minutes before bedtime. Reading, meditation, and a leisurely walk are all appropriate activities.
Keep the bedroom relatively cool and well ventilated.
Do not look at the clock. Obsessing over time will just make it more difficult to sleep.
Eat light meals, and schedule dinner 4 - 5 hours before bedtime. A light snack before bedtime can help sleep, but a large meal may have the opposite effect.
Spend a half hour in the sun each day. The best time is early in the day. (Take precautions against overexposure to sunlight by wearing protective clothing and sunscreen.)
Avoid fluids just before bedtime so that sleep is not disturbed by the need to urinate.
Avoid caffeine in the hours before sleep.
If one is still awake after 15 - 20 minutes, go into another room, read or do a quiet activity using dim lighting until feeling very sleepy. (Don't watch television or use bright lights.)
If distracted by a sleeping bed partner, moving to the couch or a spare bed for a couple of nights might be helpful.
If a specific worry is keeping one awake, thinking of the problem in terms of images rather than in words may allow a person to fall asleep more quickly and to wake up with less anxiety.

Exercise may be one of the best ways to promote healthy sleep. One study found that exercise is as good for inducing sleep as the use of benzodiazepines, a prescription sleep aid. Some research has found that yoga practice may have specific benefits on sleep health. Yoga uses meditation, deep breathing techniques, and movements that emphasize stretching and balance.

The circadian rhythm is more a function of darkness and light rather than actual time of day. Bright light can discourage drowsiness, and darkness can cause sleepiness, day or night. The use of a special box that gives off very bright fluorescent light (over 4,000 lux) for about 30 minutes each day may be helpful.

The following people might benefit from light therapy:

Shift workers. Light therapy should be maximized during hours they are at work and minimized when they need to sleep.
Frequent travelers. Light therapy may be useful for adjusting to new time zones and reducing jet lag.
Nursing home patients.
People with delayed sleep-phase syndrome. These people have a natural tendency to fall asleep very late at night or in early morning hours, but then sleep normally.

Patients should check with their doctors before using light therapy. The following people should avoid light therapy or use it only under a doctor's direction:

Anyone with eyes or skin that are highly sensitive to light
Anyone taking medications that increase the risk for photosensitivity
People with bipolar disorder

Timing of the therapy depends on the type of insomnia or sleep schedule of the individual. For example, in people who cannot get to sleep at night, light therapy in the morning and restricting bright light at night may be helpful. People who wake up early in the morning may benefit from light therapy performed in the evening, although a 2002 study reported that it had no effect in this group. Some light boxes have dawn/dusk simulators that help determine the correct brightness.

Medications

According to a major 2003 survey, about 20% of American older adults use some form of sleep aid, including prescription or over-the-counter drugs or alcohol. Furthermore, 15% use such aids every night.

However, while behavioral or psychologic techniques can actually cure insomnia, prolonged use of sleeping pills can only result in dependency.

In general, the following precautions are important:

Start with non-prescription medication.
Drugs used specifically for improving sleeping are called sedative hypnotics. These drugs include benzodiazepines and non-benzodiazepines. Until recently benzodiazepines were most commonly prescribed, but newer non-benzodiazepines may be better tolerated and have less risk of dependency. These medicines, however, may be associated with potentially severe allergic reactions, such as anaphylaxis and facial swelling (angioedema). These medicines may also cause hazardous behaviors, such as driving, making phone calls, or eating while asleep. If you need to take one of these prescription drugs, start with as low a dose as possible.
For adults over age 60 years, studies suggest that the risks of sedative hypnotics may far outweigh their benefits.
As a general rule, do not take either prescription nor non-prescription sleeping pills on consecutive days or for more than 2 - 4 days a week.
If insomnia is still a problem after stopping the drug and continuing with good sleep hygiene, this pattern can be repeated again, but for only up to 4 weeks.
Medication should be withdrawn gradually, and the patient should be aware of the possibility of rebound insomnia after stopping medication.
Alcohol intensifies the side effects of all sleeping medication and should be avoided.
If chronic insomnia is a companion to depression or anxiety, treating these problems first may be the best approach.

Brands with Antihistamines. Many over-the-counter sleeping medications use antihistamines, which cause drowsiness. Diphenhydramine is the most common antihistamine used non-prescription sleep aids. Some drugs contain diphenhydramine alone (Nytol, Sleep-Eez, Sominex), while others contain combinations of diphenhydramine with pain relievers (Anacin P.M., Excedrin P.M., Tylenol P.M.). Doxylamine (Unison) is another antihistamine used in sleep medications. Certain antihistamines indicated only for allergies, such as chlorpheniramine (Chlor-Trimeton), diphenhydramine (Benadryl), or hydroxyzine (Atarax or Vistaril) may also be used as mild sleep-inducers.

Unfortunately, most of these drugs leave patients feeling drowsy the next day and may not be very effective in providing restful sleep. Side effects include:

Daytime sleepiness
Dizziness
Drunken movements
Blurred vision
Dry mouth and throat

In general, these drugs should be avoided by people with angina, heart arrhythmias, glaucoma, or problems urinating. They should not be used at the same time as medications that prevent nausea or motion sickness. Some non-prescription sleeping aids, such as those containing doxylamine, should also be avoided by patients with chronic lung disease.

Common Pain Relievers. When sleeplessness is caused by minor pain, simply taking acetaminophen (Tylenol) or a non-steroidal anti-inflammatory drug (NSAID) such as ibuprofen (Advil, Motrin), can be very helpful without causing any daytime sleepiness. The extra "P.M." antihistamine found in combination products is simply an extra, needless chemical in these situations.

Benzodiazepines, also referred to as benzodiazepine receptor agonists (BzRAs), were once the most commonly prescribed sedative hypnotics. Originally developed in the 1960s to treat anxiety, these drugs nonselectively target receptor sites in the brain that modulate the effects of the neurotransmitter gamma-aminobutyric acid (GABA).

Brands. Commonly prescribed benzodiazepines:

Long-acting benzodiazepines include flurazepam (Dalmane) and clonazepam (Klonopin), quazepam (Doral).
Medium- to short-acting benzodiazepines include triazolam (Halcion), lorazepam (Ativan), alprazolam (Xanax), temazepam (Restoril), oxazepam (Serax), prazepam (Centrax), estazolam (ProSom), and flunitrazepam (Rohypnol). Short-acting benzodiazepines may be useful for air travelers who want to reduce the effects of jet lag.

Side Effects. Elderly people are more susceptible to side effects and should usually start at half the dose prescribed for younger people. They should not take long-acting forms.

Side effects may differ depending on whether the benzodiazepine is long- or shorting acting. They include:

Severe allergic reactions, including facial swelling, can occur even with the first use of a benzodiazepine drug.
Respiratory problems may occur with overuse or in people with pre-existing respiratory illness
The drugs may increase depression, a common co-condition in many people with insomnia.
Respiratory depression may occur with overuse or with people with pre-existing respiratory illness.
Long-acting drugs have a very high rate of residual daytime drowsiness compared to other types of sleeping pills. They have been associated with a significantly increased risk for automobile accidents and falls in the elderly, particularly in the first week after taking them. Shorter-acting benzodiazepines do not appear to pose as high a risk.
Memory loss (so-called traveler's amnesia), sleepwalking, sleep driving, eating while asleep and other odd mood states may occur. These effects are enhanced by alcohol.
Incontinence. In one study, 33% of patients experienced incontinence at least twice a week. The risk is highest in the elderly and with older, long-acting drugs.
Because these drugs cross the placenta and enter breast milk, pregnant women or nursing mothers should not use them. Benzodiazepine use in the first trimester of pregnancy may be associated with the development of cleft lip in newborns.
In rare cases, overdoses have been fatal.

Interactions. Benzodiazepines are potentially dangerous when combined with alcohol. Some medications, like the ulcer medication cimetidine, can slow the metabolism of the benzodiazepine.

Withdrawal Symptoms. Withdrawal symptoms usually occur after prolonged use and indicate dependence. They can last 1 - 3 weeks after stopping the drug and may include:

Gastrointestinal distress
Sweating
Disturbed heart rhythm
In severe cases, patients might hallucinate or experience seizures, even a week or more after the drug has been stopped.

Rebound Insomnia. Rebound insomnia, which often occurs after withdrawal, typically includes 1 - 2 nights of sleep disturbance, daytime sleepiness, and anxiety. In some cases, patients may experience the return of the original severe insomnia. The chances for rebound are higher with the short-acting benzodiazepines than with the longer-acting ones.

Newer short-acting non-benzodiazepines can induce sleep with fewer side effects than the benzodiazepines. Both benzodiazepine and non-benzodiazepine sedative hypnotics act on GABA-A receptor sites in the brain, but non-benzodiazepines are more specific in the subunits they target. Developed in the late 1980s, these drugs are increasingly prescribed and are becoming the hypnotics of choice for many doctors.

Brands and Benefits. Non-benzodiazepine hypnotics currently approved in the United States are zolpidem (Ambien, Ambien CR), zaleplon (Sonata), eszopiclone (Lunesta), and ramelteon (Rozerem).

Zolpidem (Ambien, generic) is one of the most commonly prescribed drugs for insomnia. It lasts longer than zaleplon. Patients should not take it unless they plan on getting at least 7 - 8 hours of sleep. The recommended dose is 10 mg/day for adults, although elderly patients may be prescribed half that dose. A 2002 study suggested that the drug might be used on an as-needed basis, with up to 5 tablets taken a week. After 3 weeks, two-thirds of the patients taking zolpidem this way were able to reduce their tablet intake by more than 25% without losing improvements in sleep. Ambien CR, an extended-release form, received approval from the Food and Drug Administration (FDA) in late 2005. It is the first extended-release prescription medicine for insomnia. The medicine is delivered in two steps. The first layer dissolves quickly, allowing the patient to fall asleep. The second layer helps the patient stay asleep.
Zaleplon (Sonata) is the shortest-acting hypnotic available. Because it is rapidly eliminated from the body it may be best for people who have difficulty falling asleep, not those who wake up often throughout the night. The drug takes effect within 30 minutes and may be taken at bedtime or later as long as the patient can sleep for at least 4 hours. The recommended dose is 5 - 10 mg/day. The drug is usually taken for 7 - 10 days.
Eszopiclone (Lunesta) is a newer, non-benzodiazepine hypnotic approved by the FDA in 2004. It may help improve both sleep maintenance and daytime alertness. Eszopiclone is related to zopiclone (Imovane), which has been used for many years in Europe. Unlike other sleep medications, eszopiclone can be taken on a long-term basis. In clinical trials, patients used eszopiclone for up to 6 months. Recommended doses are 2 - 3 mg/day for adults and 2 mg/day for elderly patients. Patients whose main problem is falling asleep may need only 1 mg/day.
Ramelteon (Rozerem) was approved by the FDA in 2005. Ramelteon is a novel non-benzodiazepine hypnotic. Unlike most sleep drugs, which target the gamma-aminobutyric acid (GABA) receptors, ramelteon targets the MT1 and MT2 receptors. Ramelteon does not cause dependence and is the first sleep drug not designated as a controlled substance.

These drugs can be particularly helpful for preventing jet lag (but zolpidem should not be used on flights less than 7 - 8 hours). They also may be helpful for people who also have accompanying mood disorders, such as depression or post-traumatic stress disorder. Because they are short-acting, zaleplon and zolpidem may pose fewer risks for falls and memory loss in elderly patients. In general, these drugs are recommended for short-term use (7 - 10 days) and treatment should not exceed 4 weeks. No studies have yet confirmed safety for longer-term use.

Side Effects. All of these drugs have fewer morning side effects than the benzodiazepines, including morning sedation and memory loss (although they can occur to some degree). Zolpidem’s (Ambien) record of adverse effects is similar to that of triazolam (Halcion), the short-acting benzodiazepine. Zaleplon (Sonata) and Ramelteon (Rozerem) appear to have less severe morning side effects. When patients first start taking any of these drugs, they should use caution during morning activities until they are sure how the drug affects them.

General side effects are mild but may include:

Drowsiness
Dizziness
Fatigue
Headache
Unpleasant taste
Diarrhea

Rarer side effects may include sleepwalking and hallucinations. In 2006, reports emerged of zolpidem (Ambien) causing sleepwalking and, even more bizarrely, sleep-driving. Most of these cases likely were due to patients using zolpidem along with alcohol or other drugs or taking more than the recommended dose. However, in March 2007, the FDA ordered stronger warning labels for zolpidem and all other non-benzodiazepine drugs. The new labels warn that that these drugs can cause sleep-related behavior, including sleep-driving, making phone calls, and preparing and eating food while asleep. In addition, severe allergic reactions (anaphylaxis) and facial swelling (angioedema) can occur even the first time one of these drugs is taken.

Anyone who receives a prescription for these medicines will also get a patient medication guide explaining the risks of the drugs and the precautions to take. Talk to your doctor if you have any questions concerning these drugs or their potential side effects.

Patients should carefully read the information labels for all drugs and follow the directions. Some sleeping pills take 30 - 60 minutes to take effect, while others (such as zolpidem) are fast-acting. For zolpidem, patients should:

Take zolpidem immediately before going to sleep
Take zolpidem only when able to get a full night’s sleep (7 – 8 hours)
Not drink alcohol the same evening
Not take more than the prescribed dose
Use caution in the morning when getting out of bed, driving, or operating heavy machinery

Interactions. As with any hypnotics, alcohol increases the sedative effects of these drugs. These hypnotics also interact with other drugs, including rifampin, ketoconazole, erythromycin, and cimetidine. They may also interfere or be interfered by other drugs. Patients should report all medications to their doctors.

Dependency, Withdrawal Symptoms, and Rebound Insomnia. The risk for rebound insomnia, dependence, and tolerance is lower with non-benzodiazepine hypnotics than with benzodiazepine drugs. These drugs are still subject to abuse. In any case, no hypnotic should be taken for more than 7 - 10 days or at higher than the recommended dose without a doctor's approval.

Antidepressants are sometimes used to treat insomnia that may be caused by depression (secondary insomnia). In addition, some antidepressants with sedating properties are prescribed for the treatment of primary insomnia. For example, trazodone has been frequently prescribed in low doses as a hypnotic to help induce sleep. However, there are few studies that address its safety and efficacy as a drug for treating insomnia in non-depressed patients. Several studies have warned against trazodone's use in elderly patients, due to its risk for side effects (daytime sleepiness, dizziness, priapism) and drug interactions. In fact, all hypnotics can have serious side effects in the elderly, and all must be used with caution.

Chloral Hydrate. Chloral hydrate has been in use since 1832. It has significant adverse effects, however, and most experts believe it no longer has a role in the treatment of insomnia. In any case, it does not appear to be effective in the elderly. Chloral hydrate poses a risk for addiction, and it can be fatal in overdose. It also has cancer-causing properties. Side effects include irritation of the skin, mucous membranes, and stomach. People with stomach, heart, kidney, or liver disorders should not take this drug at all. If a child is given it (usually for minor surgery), that child should never be given chloral hydrate again in their lifetime.

Barbiturates. Barbiturates (Seconal, Nembutal) were the standard sleeping medications before the introduction of benzodiazepines. Overdose is dangerous and frequent; addiction and abuse are common. These drugs should rarely or never be prescribed for insomnia.

Indiplon. The FDA is reviewing indiplon, a new non-benzodiazepine hypnotic.

According to results from a national survey published in 2006 in the Archives of Internal Medicine, more than 1.6 million Americans use complementary and alternative therapies to treat insomnia. Many people choose herbal and dietary supplement remedies. Some, such as chamomile tea or lemon balm, are generally harmless for most people. Others have more serious side effects and interactions. [See Box.] According to a 2007 study, valerian and melatonin are among the most popular alternative remedies for insomnia.

Although about half of people who use herbal medicine report that these products help their sleep, experts are not sure whether these remedies really work or whether a placebo effect is the main reason for the improvement. The American Academy of Sleep Medicine (AASM) states that there is only limited scientific evidence to show that herbal and dietary supplements are effective sleep aids. The AASM recommends that these products should be taken only if approved by a doctor. Be sure to talk to your doctor if you are considering taking any herbal or dietary supplement. Some of these products can interact with prescription medications.

Melatonin is the most studied natural remedy for insomnia. A 2005 analysis of 17 melatonin studies found that melatonin significantly reduced the time to fall asleep (sleep onset) and the time spent asleep (sleep duration). However, there are no consistent standards on melatonin doses. Some research suggests that 0.3 mg may be the most effective dosage in many people with insomnia. However, higher doses may keep some people awake.

Although melatonin may not have many benefits for most people with chronic insomnia, studies suggest that it may help the following individuals:

Elderly people. It may help certain older people with insomnia, such as those with evidence of low melatonin levels and those dependent on prescription sleeping medications. It is not clear, however, how significant the benefits are.
People without sight. A 2000 study reported that melatonin can help people without sight retrain their circadian cycle so that they can sleep at regular hours. The best dosages and timing, however, need to be clarified.
Travelers suffering jet lag. Some studies have reported that melatonin may help prevent jet lag in some travelers.
Those in withdrawal from prescription sleep medication. Melatonin may help people who are dependent on sleeping medications withdraw from these drugs and maintain good quality sleep.
People with delayed sleep syndrome. It might be somewhat helpful for people who fall asleep very late at night or in early morning hours but then sleep normally.
Children. Melatonin may help some children with chronic insomnia. In one small study, or example, melatonin was specifically helpful for children with Asperger syndrome, who are at risk for sleep disturbances. More research is warranted, however. At this time, no one should give their child melatonin without a doctor's recommendation.

Melatonin is a powerful hormone that can have major effects on all parts of the body. Doses of melatonin over 0.3 mg can disrupt the circadian system in the brain. Long-term consequences are unknown. High doses have been associated with the following adverse events:

Mental impairment
Severe headaches
Nightmares

Interactions with other drugs are not completely known. Melatonin is classified as a dietary supplement and not as a drug, so its quality is not regulated in the U.S.

Generally, manufacturers of herbal remedies and dietary supplements do not need FDA approval to sell their products. Just like a drug, herbs and supplements can affect the body's chemistry, and therefore have the potential to produce side effects that may be harmful. There have been a number of reported cases of serious and even lethal side effects from herbal products. Patients should always check with their doctors before using any herbal remedies or dietary supplements.

The following are special concerns for people taking natural remedies for insomnia:

Chamomile. Many people drink chamomile tea for its sedative properties. Although it is generally safe, it may cause allergic reactions in people who have plant or pollen allergies.

Valerian root. Valerian is an herb that has sedative qualities and has been helpful in people with insomnia. One study reported that it was also useful for helping patients withdraw from benzodiazepines -- the standard prescription sleeping pills. In another study, 83% of patients rated the effects of valerian on sleep as being very good. In the same study, valerian was as effective as oxazepam, a standard prescription sleeping medication. Valerian's side effects may include vivid dreams. High doses of valerian can cause blurred vision, excitability, and changes in heart rhythm. Valerian's effects can be dangerously increased if it is used with standard sedatives.

Chinese Herbal Remedies. Studies suggest that up to 30% of herbal patent remedies imported from China are laced with potent pharmaceuticals such as phenacetin and steroids. They may also contain toxic metals. The herbal remedy Sleeping Buddha was recalled in 1998 because it contained a benzodiazepine, the major ingredient in many prescription sleeping pills, and also appeared to increase the risk for birth defects in pregnant women. Reports of a few cases of acute hepatitis have occurred from Jin Bu Huan, a Chinese herbal remedy sold as treatment for pain and insomnia.

Kava. Kava has been used to relieve anxiety and improve sleep. It is not considered safe. There have been reports of liver failure and death from this herb, with highest risk in those with liver disease. Other side effects include itchy, scaly skin, muscle weakness, and problems with coordination. It also interacts dangerously with certain medications, including alprazolam, an anti-anxiety drug. Kava also increases the strength of certain other drugs, including other sleep medications, alcohol, and antidepressants.

Tryptophan and 5-L-5-hydroxytryptophan (HTP). Tryptophan is an amino acid used in the formation of the neurotransmitter serotonin, which is known to promote well-being and has been associated with healthy sleep. L-tryptophan was marked for insomnia and other disorders but was withdrawn from the market after contaminated batches caused a rare and even fatal disorder called eosinophilia myalgia syndrome. 5-HTP, a byproduct of tryptophan, is still available as a supplement. There have been reports that some brands contain a substance called Peak X, which may be harmful. There is little evidence that 5-HTP relieves insomnia.

Resources

www.aasmnet.org -- American Academy of Sleep Medicine
www.nhlbi.nih.gov/about/ncsdr -- National Center for Sleep Disorders Research
www.sleepfoundation.org -- National Sleep Foundation
www.sleepeducation.com -- Sleep Education from the American Academy of Sleep Medicine
www.wfsrs.org -- World Federation of Sleep Research Societies
www.clinicaltrials.gov -- Find clinical trials

References

Bliwise DL, Ansari FP. Insomnia associated with valerian and melatonin usage in the 2002 National Health Interview Survey. Sleep. 2007 July 1;30(7):881-884.

Liu X, Buysse DJ, Gentzler AL, Kiss E, Mayer L, Kapornai K, et al. Insomnia and hypersomnia associated with depressive phenomenology and comorbidity in childhood depression. Sleep. 2007 Jan 1;30(1):83-90.

Mindell JA, Emslie G, Blumer J, Genel M, Glaze D, Ivanenko A, et al. Pharmacologic management of insomnia in children and adolescents: consensus statement. Pediatrics. 2006 Jun;117(6):e1223-32.

Mindell JA, Kuhn B, Lewin DS, Meltzer LJ, Sadeh A; American Academy of Sleep Medicine. Behavioral treatment of bedtime problems and night wakings in infants and young children. Sleep. 2006 Oct 1;29(10):1263-76.

Morin CM, Bootzin RR, Buysse DJ, Edinger JD, Espie CA, Lichstein KL. Psychological and behavioral treatment of insomnia: update of the recent evidence (1998-2004). Sleep. 2006 Nov 1;29(11):1398-414.

Neckelmann D, Mykletun A, Dahl AA. Chronic insomnia as a risk factor for developing anxiety and depression. Sleep. 2007 July 1;30(7):873-880.

Pearson NJ, Johnson LL, Nahin RL. Insomnia, trouble sleeping, and complementary and alternative medicine: Analysis of the 2002 National Health Interview Survey data. Arch Intern Med. 2006 Sep 18;166(16):1775-82.

Review Date:
7/18/2007
Reviewed By:
Harvey Simon, MD, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital.

A.D.A.M. Copyright

adam.com

Restless legs syndrome and related disorders

FitSugar — Wed, 08 Oct 2008 17:35:14 -0700

In This Report

Highlights
Introduction
Causes
Risk Factors
Complications
Diagnosis
Treatment
Medications
Resources
References

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

Treatment

The American Academy of Sleep Medicine recommends medications for restless legs syndrome (RLS) or periodic limb movement disorder (PLMD) only for persons who fulfill strict diagnostic criteria and experience too much daytime sleepiness as a result of these conditions. (Excessive daytime sleepiness results from nighttime sleeplessness due to RLS or PLMD symptoms).
The U.S. Food and Drug Administration (FDA) announced in March 2007 that the dopamine agonist drug pergolide (Permax) has been voluntarily withdrawn from the market. This drug can cause serious damage to the heart valves of patients who take it.
The FDA approved pramipexole (Mirapex) for use in moderate-to-severe restless legs syndrome (RLS) in November 2006.
Bupropion (Wellbutrin), a newer antidepressant, may also be helpful for RLS. Bupropion, a weak dopamine reuptake inhibitor, causes a slight increase in the availability of dopamine in the brain. It is not addictive and does not have the severe side effects of other RLS drugs, but more research is needed to determine its usefulness. It is not FDA approved for RLS.

Research

Results from a large study show that RLS is more common in children and teens than epilepsy and diabetes. The study also found that more than 70% of affected children had at least one biological parent with RLS.
Two recently-published studies found an abnormal gene on chromosome 6 makes some people susceptible to RLS and PLMD.
People with type 2 diabetes have higher rates of secondary RLS. Nerve pain (neuropathy) related to their diabetes cannot fully explain this increased rate in RLS.

Introduction

Restless legs syndrome (RLS) is an unsettling and poorly understood movement disorder affecting 3 - 15% of the general population. RLS can affect both children and adults. Although effective treatments are available, the condition often remains undiagnosed.

Symptoms of RLS. The core symptom of RLS is an irresistible urge to move the legs (medically known as akathisia). Some people describe this symptom as a sense of unease and weariness in the lower leg, which is aggravated by rest and relieved by movement. Specific characteristics of RLS include:

"Pulling, searing, drawing, tingling, bubbling, or crawling" beneath the skin, usually in the calf area, causing an irresistible urge to move the legs. These sensations can occur not only in the lower legs, but they can also affect the thighs, feet, and even the upper body. RLS-type symptoms may also occur in the arms. This may be the first symptom of RLS in some people.
About 80% of patients with RLS also experience semi-rhythmic movements called periodic limb movement disorder (PLMD).
Itching and pain, particularly aching pain, may be present.
Patients experience symptoms when they feel most relaxed and their legs are at rest. (Movement, however, brings relief.) Symptoms usually occur at night when lying down, or sometimes during the day while sitting.
Episodes of RLS usually develop between 10 p.m. and 4 a.m. Symptoms are often most severe shortly after midnight. They typically occur for 30 - 60 seconds, and they usually resolve by morning. If the condition becomes more severe, people may begin to have symptoms during the day. These symptoms are always worse at night, however.
At night, the unpleasant sensations and the resulting uncontrollable urge to move the legs can often disturb sleep. Ignoring the need to move the legs usually only builds up tension until they jerk uncontrollably. If patients experience symptoms during the day, they usually feel compelled to move their legs in order to relieve the symptoms, making it difficult to sit during air or car travel or through classes or meetings.

Late-onset and Early-onset Forms. There appear to be two forms of RLS, early-onset and late-onset. Each form may have different characteristics:

People with early-onset RLS (occurring in the teenage years or earlier) tend to have a family history of the disorder. They also usually have RLS without accompanying pain.
Those with late-onset RLS usually do not have a family history of RLS. Their condition is more likely the result of a problem with the nervous system, and symptoms may include pain in the lower legs.

The medical term for periodic limb movement disorder (PLMD) is nocturnal myoclonus. PLMD symptoms include:

Episodes that usually occur during the night, peaking near midnight, as they do in restless legs syndrome (RLS).
Leg muscles contract and jerk every 20 - 40 seconds during sleep. Such movements may last less than 1 second, or as long as 10 seconds.
Unlike RLS, contractions in PLMD usually do not wake patients. PLMD is distinct from the brief and sudden movements that occur just as people are falling asleep, jolting them awake.

Although 80% of RLS sufferers have PLMD, only about 30% of people with PLMD also have RLS. While treatments for the two conditions are similar, PLMD is a separate syndrome. PLMD is also very common in narcolepsy, a sleep disorder that causes people to fall asleep suddenly and uncontrollably.

Cramps that awaken people during sleep are very common, and they are not part of restless legs syndrome or periodic limb movement disorder. They can be very painful and may cause a person jump out of bed in the middle of the night. They typically affect a specific area of the calf or the sole of the foot.

Circadian Rhythm. In sleep studies, subjects spend about one-third of their time asleep, suggesting that most people need about 8 hours of sleep each day. However, individual adults differ in the amount of sleep they need to feel well rested. Infants may sleep as many as 16 hours a day.

The daily cycle of life, which includes sleeping and waking, is called a circadian rhythm (circadian means "about a day"), or the biological clock. Hundreds of bodily functions follow biologic clocks, but sleeping and waking comprise the most prominent circadian rhythm. The sleeping and waking cycle is about 24 hours long. If confined to windowless apartments, with no clocks or other time cues, sleeping and waking only as their bodies dictate, humans typically live on slightly longer than 24-hour cycles.

The circadian rhythm usually takes the following daily patterns:

Humans prefer daytime activity and nighttime rest.
A natural peak in sleepiness occurs at mid-day, the traditional siesta time.
Daily rhythms interact with other factors that may interfere or change individual patterns:
- The fraction-of-a-second-firing of nerve cells in the brain may be faster or slower in different individuals.
- The monthly menstrual cycle in women can shift the pattern.

Light signals coming through the eyes reset the circadian cycles each day, so changes in season, or changes in exposures to light and dark, can unsettle the pattern.

The Response in the Brain to Light Signals. The brain's response to light signals is an important key factor in sleep:

Light signals travel to a tiny cluster of nerves in the hypothalamus (in the center of the brain). This cluster is the body's master clock, which is called the supra chiasmatic nucleus (SCN). The SCN is named for its location, which is just above (supra) the optic chiasm, a major junction where nerves transmit information about light from the eyes.
The approach of dusk each day prompts the SCN to signal the nearby pineal gland (named so because it resembles a pinecone) to produce the hormone melatonin.
Researchers think that melatonin acts as the body's time-setting hormone. It also appears to trigger the need to sleep. The longer a person is in darkness, the longer the duration of melatonin secretion. Staying in bright light can decrease the secretion of melatonin.

Sleep consists of two distinct states that alternate in cycles, and reflect differing levels of brain nerve cell activity:

Non-Rapid Eye Movement Sleep. Non-rapid eye movement (NREM) sleep is also called quiet sleep. NREM is further subdivided into three stages of progression:

Stage 1: Light sleep
Stage 2: "True" sleep
Stage 3 to 4: Deep "slow-wave" or delta sleep

With each ascending stage, awakening becomes more difficult. It is not clear what governs NREM sleep in the brain. A balance between certain hormones, particularly growth and stress hormones, may be important for deep sleep.

Rapid Eye-Movement Sleep. Rapid eye-movement (REM) sleep is also called active sleep. Most vivid dreams occur in REM sleep. Brain activity in REM sleep is comparable to that in waking, but the muscles are virtually paralyzed, possibly preventing people from acting out their dreams. Except for vital organs like the lungs and heart, the only muscles not paralyzed during REM sleep are the eye muscles. REM sleep may be critical for learning and for day-to-day mood regulation. When people are sleep-deprived, their brains must work harder than when they are well rested.

The REM/NREM Cycle. The cycle between quiet and active sleep generally follows this pattern:

After about 90 minutes of NREM sleep, eyes move rapidly behind closed lids, giving rise to REM sleep.
As sleep progresses the NREM/REM cycle repeats.
With each cycle, NREM sleep becomes progressively lighter, and REM sleep becomes progressively longer, lasting from a few minutes early in sleep to perhaps an hour at the end of the sleep cycle.

The hypothalamus is a highly complex structure in the brain that regulates many important brain chemicals. Malfunction of this area of the brain may give rise to cluster headaches.

Causes

The main cause of restless legs syndrome (RLS) is unknown. Researchers are investigating neurologic (nervous system) problems that may arise either in the spinal cord or the brain. One current theory suggests that a deficiency in a brain chemical called dopamine causes restless legs syndrome.

RLS may often have a genetic basis, particularly in those who develop it before age 40. When the condition occurs in older adults, it is most likely due to a neurological problem.

The central nervous system is comprised of the brain and spinal cord. The peripheral nervous system includes all peripheral nerves.

People with restless legs syndrome (RLS) often have a family history of the disorder. Researchers have detected specific genetic locations or factors that might be responsible for this condition. Much of the research comes from studies of families with a strong history of RLS-related conditions. In 2005, researchers linked a location on chromosome 12 to RLS. They named this genetic marker RLS1. Locations on chromosomes 14 and 9 may also be associated with hereditary forms of RLS.

Dopamine and Neurologic Abnormalities in the Brain. Some research suggests that neurologic abnormalities involved with restless legs syndrome (RLS) and periodic limb movement disorder (PLMD) start in the brain. A variety of studies support the theory that an imbalance in neurotransmitters (chemical messengers in the brain), notably dopamine and serotonin, may play a part in RLS. Dopamine and serotonin cause numerous nerve impulses that affect muscle movement. The effect is similar to what happens in Parkinson's disease. Moreover, drugs that increase dopamine levels treat both disorders. However, Parkinson's disease itself does not seem to increase the risk for RLS. Nor does RLS early in life predispose to Parkinson's later on.

Neurologic Abnormalities in the Spine. Other research suggests that restless legs syndrome may be due to nerve impairment in the spinal cord. Researchers considered that such abnormalities were likely to start in nerve pathways in the lower spine. However, some patients with RLS have symptoms in the arms, indicating that the upper spine may also be involved.

Neuropathy. Some experts suggest that RLS, particularly if it occurs in older adults, may be a form of neuropathy, which is an abnormality in the nervous system outside the spine and brain. Nevertheless, there is no evidence of a causal relationship.

Iron deficiency, even at a level too mild to cause anemia, has been linked to restless legs syndrome (RLS) in some people. Studies suggest, in fact, that RLS in some people may be due to a problem with getting iron into cells that regulate dopamine in the brain. Some studies have reported RLS in 25 - 30% of people with low iron levels. The common connection between RLS and Parkinson's disease, in turn, may be not having enough iron in these patients.

The cause or causes of periodic limb movement disorder (PLMD) are not clear. Some research suggests that it may be due to abnormalities in the autonomic nervous system, which regulates the involuntary actions of the smooth muscles, heart, and glands.

Risk Factors

Restless legs syndrome (RLS) may affect 2.5 - 15% of the general population. It is more common in women than in men, and its frequency increases with age. The disorder affects an estimated 10 - 28% of adults older than age 65. In about 40% of patients, RLS begins in adolescence.

RLS may be more common than epilepsy and diabetes in children and teens. More than 70% of affected children in one study had at least one biological parent with RLS.

As many as two-thirds of people with restless legs syndrome (RLS) have a family history of the disorder. If so, RLS is more likely to occur before they turn 40. (A family history of RLS is less likely in people who develop it as older adults.) RLS is also more common in people from northern and western Europe, giving added support for a genetic basis for some cases.

Restless legs syndrome (RLS) and periodic leg movement disorder (PLMD) in children are strongly associated with inattention and hyperactivity. One study suggested that a quarter of children diagnosed with attention-deficit hyperactivity disorder (ADHD) also have RLS or PLMD, and this may actually contribute to inattentiveness and hyperactivity. The disorders have much in common, including poor sleep habits, twitching, and the need to get up suddenly and walk about frequently. Some evidence suggests that the link between the diseases may be a deficiency in the brain chemical dopamine.

About 20% of pregnant women report having restless legs syndrome (RLS). The condition usually goes away about a month after delivery. RLS in this population has been strongly associated with deficiencies in iron and the B vitamin folate.

Between 20 - 62% of people undergoing dialysis report restless legs syndrome. Symptoms often disappear after a kidney transplant.

Anxiety can cause restlessness and agitation at night. These symptoms can cause (or strongly resemble) restless legs syndrome.

The following medical conditions are also associated with restless legs syndrome (RLS), although the relationships are not clear. In some cases, these conditions may contribute to RLS, or they may have a common cause. In some cases, they may coexist due to other risk factors:

Osteoarthritis (degenerative joint disease). About 72% of patients with RLS also have osteoarthritis, a common type of arthritis affecting mostly older adults.
Varicose veins. Varicose veins occur in 14% of patients with RLS. Sclerotherapy treatments, in which doctors inject medications into affected veins, may relieve symptoms in such cases.
Obesity
Diabetes -- people with type 2 diabetes may have higher rates of secondary RLS. Nerve pain (neuropathy) related to their diabetes cannot fully explain this increased rate in RLS.
Hypertension
Hypothyroidism (a condition in which the thyroid gland does not make enough hormones)
Fibromyalgia (chronic pain of unknown cause)
Rheumatoid arthritis
Emphysema (a lung disease usually caused by smoking)
Chronic alcoholism
Sleep apnea (pauses in breathing during sleep) and snoring
Chronic headaches
Brain or spinal injuries

Many muscle and nerve disorders. Hereditary ataxia, a group of genetic diseases that affects the central nervous system and causes loss of motor control, is of particular interest. Researchers believe that hereditary ataxia may supply clues to the genetic causes of RLS.

Osteoarthritis is a chronic disease of the joint cartilage and bone, often thought to result from "wear and tear" on a joint, although there are other causes such as congenital defects, trauma, and metabolic disorders. Joints appear larger, are stiff and painful, and usually feel worse the more they are used throughout the day.

Click the icon to see an image of hypothyroidism.

Click the icon to see an image of fibromyalgia.

Click the icon to see an image of rheumatoid arthritis.

Click the icon to see an image of emphysema.

Several environmental and dietary factors can worsen or provoke restless legs syndrome (RLS):

Iron deficiencies. People who are deficient in iron are at risk for restless legs syndrome, even if they do not have anemia
Folic acid or magnesium deficiencies
Smoking
Alcohol abuse
Caffeine (coffee drinking is specifically associated with PLMD)
Stress
Fatigue
Prolonged exposure to cold

Drugs that worsen or provoke the condition include:

Antidepressants
Antipsychotic drugs
Anti-nausea drugs
Beta-blockers (a type of heart medication)
Antihistamines
Oral decongestants
Diuretics
Asthma drugs
Spinal anesthesia (anesthesia-induced restless legs syndrome typically disappears on its own within several months)

About 6% of the general population has periodic limb movement disorder (PLMD). Among the elderly, the prevalence increases to 25 - 58%. Studies suggest that PLMD may be especially common in elderly women. As with RLS, numerous conditions are associated with PLMD. They include sleep apnea, spinal cord injuries, stroke, narcolepsy, and diseases that destroy nerves or the brain over time. Certain medications, including some antidepressants and anti-seizure medications, may also contribute to PLMD.

Complications

Restless legs syndrome rarely results in any serious consequences. But in some cases, severe and persistent symptoms can cause considerable mental distress, chronic insomnia, and daytime sleepiness.

Sleep deprivation, and the daytime sleepiness that follows, is increasingly recognized as a cause of mood disruption and a contributor to industrial errors and motor vehicle crashes.

Effect on Daily Performance and Activities. Studies suggest that sleeplessness worsens many waking behaviors. These include:

Reduced concentration. Deep sleep deprivation appears to impair the brain's ability to process information.
Impaired task performance. Missing several hours of nightly sleep over the course of a week can negatively affect performance levels and mood. In fact, sleep deprivation can cause impaired performance levels comparable to those of intoxicated people.
Effect on learning. Whether sleeplessness significantly impairs learning is unclear. Some studies have reported problems in memorization, although others have found no differences in test scores between people with temporary sleep loss and those with full sleep.

In addition, since restless legs syndrome (RLS) is worse when resting, people with severe RLS may avoid daily activities that involve long periods of sitting, such as going to movies or traveling long distances.

Studies in Swedish working-aged men and women reported that those with restless legs syndrome (RLS) were more apt to be socially isolated, to have frequent daytime headaches or depression, and to complain of reduced libido or problems related to sleepiness.

RLS can contribute to insomnia. Insomnia itself can increase the activity of hormones and pathways in the brain that produce emotional problems. Even modest alterations in waking and sleeping patterns can have significant effects on a person's mood. Persistent insomnia may even predict the future development of mood disorders in some cases.

It is not clear if RLS is responsible for negative mood states or if anxiety or depression contributes to RLS. Anxiety can cause agitation and leg restlessness that resemble RLS, and depression and RLS symptoms also overlap. In addition, certain types of antidepressant drugs -- such as serotonin reuptake inhibitors -- can increase periodic limb movements during sleep.

Diagnosis

A diagnosis of restless legs syndrome or nocturnal leg cramps often relies solely on the patient's description of symptoms. In general, the recommended approach is first to take a sleep and personal history. The doctor may conduct an interview that includes the following questions:

How would you describe your sleep problem?
How long have you had this sleep problem?
How long does it take you to fall asleep?
How many times a week does the problem occur?
How restful is your sleep?
What are the leg problems like (cramps, twitching, crawling feelings)?
What is your sleep environment like? Noisy? Not dark enough?
What medications are you taking (including the use of antidepressants and self-medications -- such as herbs, alcohol, and over-the-counter or prescription drugs)?
Are you taking or withdrawing from stimulants, such as coffee or tobacco?
How much alcohol do you drink per day?
What stresses or emotional factors may be present in your life?
Have you experienced any significant life changes?
Do you snore or gasp during sleep? (This may be an indication of sleep apnea. Sleep apnea is a condition in which breathing stops for short periods many times during the night. It may worsen symptoms of restless legs syndrome or insomnia.)
If you have a bed partner, does he or she notice that you have jerking legs, interrupted breathing, or thrashing while you sleep?
Are you a shift worker?

Keeping a Record of Sleep. To help answer these questions, the patient may need to keep a sleep diary. Every day for 2 weeks, the patient should record all sleep-related information, including responses to questions listed above described on a daily basis. Recording sleep behavior using an extended-play audio or videotape can be very helpful in diagnosing sleep apnea.

A bed partner can help by adding their observations of the patient's sleep behavior.

Some high-risk patients may need to consult a sleep specialist or go to a sleep disorders center before their sleep problem can be diagnosed. At most centers, patients undergo an in-depth analysis, usually supervised by a team of consultants from various specialties, who can provide both physical and psychiatric evaluations. Centers should be accredited by the American Academy of Sleep Medicine.

Among the signs that may indicate a need for a sleep disorders center are:

Insomnia due to psychological disorders
Sleeping problems due to substance abuse
Snoring and sudden awakening with gasping for breath (possible sleep apnea)
Severe restless legs syndrome
Persistent daytime sleepiness
Sudden episodes of falling asleep during the day (possible narcolepsy)

Overnight polysomnography involves several tests to measure different functions during sleep. It is typically performed in a sleep center and may help rule out sleep apnea or confirm the effectiveness of restless legs syndrome (RLS) treatments.

The patient arrives about 2 hours before bedtime without having made any changes in daily habits. Polysomnography electronically monitors the patient as he or she passes, or fails to pass, through the various sleep stages. Polysomnography tracks the following:

Brain waves
Body movements
Breathing
Heart rate
Eye movements
Changes in breathing and blood levels of oxygen

Actigraphy uses a small wristwatch-like device (such as Actiwatch) to monitor sleep quality in people with suspected restless legs syndrome (RLS), periodic leg movement disorder (PLMD), insomnia, sleep apnea, and other sleep-related conditions. Patients can wear the device on their wrists or ankles. It measures and records muscle movements during sleep. For example, with PLMD, actigraphy can provide information on the total duration of movements, the number of occurrences, whether PLMD occurs simultaneously in both legs, and its effects on sleep.

Actigraphy is not as accurate as polygraphy because it cannot measure all the biological effects of sleep. It is more accurate than a sleep log, however, and very helpful for recording long periods of sleep.

The Epworth sleepiness scale uses a simple questionnaire to measure excessive sleepiness during eight situations.


Situation	Chance of Dosing
Sitting and reading	(Indicate a score of 0 to 3) 0 = no chance of dozing 1 = slight chance of dozing 2 = moderate chance of dozing 3 = high chance of dozing
Watching TV	(Indicate a score of 0 to 3) 0 = no chance of dozing 1 = slight chance of dozing 2 = moderate chance of dozing 3 = high chance of dozing
Sitting inactive in a public place	(Indicate a score of 0 to 3) 0 = no chance of dozing 1 = slight chance of dozing 2 = moderate chance of dozing 3 = high chance of dozing
Riding as a passenger in a car for an hour without a break	(Indicate a score of 0 to 3) 0 = no chance of dozing 1 = slight chance of dozing 2 = moderate chance of dozing 3 = high chance of dozing
Lying down to rest in the afternoon when circumstances permit	(Indicate a score of 0 to 3) 0 = no chance of dozing 1 = slight chance of dozing 2 = moderate chance of dozing 3 = high chance of dozing
Sitting and talking to someone	(Indicate a score of 0 to 3) 0 = no chance of dozing 1 = slight chance of dozing 2 = moderate chance of dozing 3 = high chance of dozing
Sitting quietly after a lunch without alcohol	(Indicate a score of 0 to 3) 0 = no chance of dozing 1 = slight chance of dozing 2 = moderate chance of dozing 3 = high chance of dozing
Sitting in a car while stopped for a few minutes in traffic	(Indicate a score of 0 to 3) 0 = no chance of dozing 1 = slight chance of dozing 2 = moderate chance of dozing 3 = high chance of dozing
Score Results 1-6: Getting enough sleep. 4-8: Tends to be sleepy but is average. 9 and over: Very sleepy and suggestive of sleep-disordered breathing. Patient should seek medical advice.

Because of the high association between restless legs syndrome and iron deficiency, a test for low iron stores should be part of the diagnostic workup in restless legs syndrome (RLS). There are two steps in making this diagnosis:

The first step is to determine if a person is actually deficient in iron.
If iron stores are low, the second step is to diagnose the cause of the iron deficiencies, which will help determine treatment.

Determining if Iron Stores are Low: The following findings are important in determining that a person is iron deficient:

Blood cells viewed under the microscope are pale (hypochromic) and abnormally small (microcytic). They are also mostly uneven in shape. These findings suggest iron deficiency, but they can also appear in anemia resulting from chronic disease and in thalassemia.
Hemoglobin and iron levels are low. These findings further suggest iron deficiency, but they can also occur in cases of anemia due to chronic disease.
Ferritin levels are low. Ferritin is a protein that binds to iron, and low levels typically mean the patient does not have enough iron in their body. However, high levels of ferritin in the blood do not always mean a patient has enough iron. For example, pregnant women may have high ferritin levels even in their third trimester, yet still be iron deficient. Ferritin levels may also be normal, or even elevated, in patients with inflammation resulting from anemia due to chronic disease, even if these patients also so not have enough iron in their body.
A test that measures a factor called serum transferrin receptor (TfR) is proving to be very sensitive in identifying iron deficiency in some patients, including the elderly with chronic diseases and possibly pregnant women.

Determining Causes of Iron Deficiency. When iron deficiency anemia is diagnosed, the next step is to determine what causes the iron deficiency itself.

Dietary iron deficiency is most common in children and infants. It is rare in adults.
Heavy menstrual or abnormal uterine bleeding is usually the cause of iron deficiencies in young women. Increased need for iron during pregnancy is also a common cause of iron deficiency in pregnant women.
If doctors suspect internal bleeding as the cause of iron deficiency, they look first to the digestive tract as the possible source. A diagnosis in such cases can often be made if the patient has noticed blood in their stools, (the stool would be black and tarry or red-streaked). Often, however, bleeding may be present but not visible. In such cases, stool tests for this hidden (occult) blood are required. The patient may need additional tests to diagnose the cause of bleeding. One common test is endoscopy, in which a fiberoptic tube is used to look into the gastrointestinal tract. Doctors recommend it particularly when the source of bleeding is unclear.

If the patient's diet suggests low iron intake and doctors cannot find other causes of iron deficiency, they may recommend a month-long trial of iron supplements. If the patient fails to respond, they will need further evaluation.

Certain laboratory tests may be helpful in determining causes of restless legs syndrome (RLS) or conditions that rule it out. They include:

Blood glucose tests for diabetes
Tests for kidney problems
In certain cases, tests for thyroid hormone, magnesium, and folate levels

In addition to other sleep-related leg disorders, a number of other medical conditions may have features that resemble restless legs syndrome (RLS). The doctor will need to consider these disorders in making a diagnosis.

Peripheral Neuropathies. Peripheral neuropathies are nerve disorders in the hands or feet. Several conditions can cause these disorders, and they can produce pain, burning, tingling, or shooting sensations in the arms and legs. Diabetes is a very common cause of painful peripheral neuropathies. Other causes include alcoholism, rheumatoid arthritis, systemic lupus erythematosus, amyloidosis, HIV infection, kidney failure, and certain vitamin deficiencies. Symptoms of peripheral neuropathies may mimic RLS. However, unlike RLS, they are not usually associated with restlessness, movement does not relieve the discomfort, and they do not worsen at bedtime.

Deep Vein Thrombosis. Deep vein thrombosis (DVT) is a blood clot in a deep vein in the body, usually in the leg. It may cause pain, swelling, and aching in the leg where the clot has developed. It can occur in people with heart disease, with varicose veins, during pregnancy, in women from hormonal treatments, from injury to the leg, or from inactivity (such as after surgery or during long flights). In women, it can also result from hormonal treatments. Left untreated, DVT can be a very serious and even life-threatening condition.

This picture shows a red and swollen thigh and leg caused by a blood clot (thrombus) in the deep veins in the groin (iliofemoral veins), which prevents normal return of blood from the leg to the heart.

Intermittent Claudication and Peripheral Artery Disease. Peripheral artery disease (PAD) occurs when atherosclerosis (commonly called hardening of the arteries) affects the feet and legs. In such cases, blocked arteries reduce the flow of oxygen-rich blood to the legs or feet. Intermittent claudication is an important symptom of PAD and occurs in between one-third and one-half of these patients. The word claudication describes the pain that occurs in PAD patients when they exercise, particularly when they walk. In intermittent claudication, blood flows only enough to meet the needs of the person at rest. The result is leg pain during exercise, which disappears during rest.

Click the icon to see an image of peripheral artery disease.

Akathisia. Akathisia is a state of restlessness or agitation, and feelings of muscle quivering. A condition called hypotensive akathisia is caused by failure in the autonomic nervous system. Unlike RLS, it occurs at any time of the day and usually only when the patient is sitting -- not lying down. Drugs used to treat schizophrenia and other psychoses can cause akathisia, as can anti-nausea drugs. The condition also occurs when drugs to treat Parkinson's disease are withdrawn.

Painful Legs and Moving Toes Syndrome. A rare disorder affecting one or both legs, painful legs and moving toes syndrome is marked by a constant, deep, throbbing ache in the limbs and involuntary toe movements. The discomfort may be mild or severe. It gets worse with activity and usually stops during sleep. Usually, the cause is unknown, though it may arise from spinal injuries or herpes zoster infection. The condition is difficult to treat, although the drug baclofen, combined with either clonazepam or carbamazepine, has shown some success. Other treatments that may help include orthotics for the shoes and transcutaneous electrical nerve stimulation (TENS).

Meralgia Paresthetica. An uncommon nerve condition, meralgia paresthetica causes numbness, pain, tingling, or burning on the front and side of the thigh. It usually occurs on one side of the body, and the cause may be compression of the thigh nerve as it passes through the pelvis. It typically occurs in people aged 30 - 60 years, but it can affect people of all ages. It often goes away on its own.

Treatment

The first step in treating a patient who complains of sleeplessness and restless legs syndrome is to try to improve sleep and eliminate possible causes of restless legs syndrome (RLS). Doctors normally try to achieve these goals without the use of drugs, initially. A non-drug approach is a particularly important first step for elderly patients.

The doctor should first try to treat any underlying medical conditions that may be causing restless legs.
If medications may be causing RLS, the doctor should try to prescribe alternatives, if possible.

If the cause cannot be determined, it is best to first try better sleep habits and relaxation methods. These approaches may help, even if the patient needs drug therapy later on.

Some people report help or relief from restless legs syndrome (RLS) with the following behaviors or devices:

Hot baths or cold compresses help some patients.
Ergonomic measures -- for example, patients might find it useful to work at a high stool, where they can dangle their legs. In meetings or during air travel, it is helpful to have an aisle seat.
Changing sleep patterns -- some patients report that symptoms do not occur if they sleep late in the morning. Therefore, if feasible, patients can try changing sleep patterns.
Avoiding caffeine, alcohol, and nicotine also improves some cases of RLS.

Some patients recommend alternative treatments for RLS, such as acupuncture and massage. To date, however, there is not enough data on the effectiveness of these treatments.

Some people have reported benefits from:

Vitamin E (800 - 1,200 IU per day)
Calcium, magnesium, or potassium supplements
Folic acid supplements for people with folate deficiencies

Folate (folic acid) is necessary for the production of red blood cells and for the synthesis of DNA (which controls heredity and is used to guide the cell in its daily activities). Folic acid also helps with tissue growth and cell function. In addition, it helps to increase appetite when needed and stimulates the formation of digestive acids.

Because restless legs syndrome (RLS) is associated with iron insufficiency, people with the condition should get enough iron from their diet. [See In-Depth Report #57: Anemia.] Iron is found in foods either in the form of heme or non-heme iron:

Foods containing heme iron are the best for increasing or maintaining healthy iron levels. Such foods include (in decreasing order of iron-richness) clams, oysters, organ meats, beef, pork, poultry, and fish.
Non-heme iron is less well absorbed. About 60% of the iron in meat is non-heme (although meat itself helps absorb non-heme iron). Eggs, dairy products, and iron-containing vegetables (including dried beans and peas) have only the non-heme form. Other sources of non-heme iron include iron-fortified cereals, bread, and pasta products, dark green leafy vegetables (chard, spinach, mustard greens, kale), dried fruits, nuts, and seeds.

The Effects of Food on Iron Absorption. The absorption of non-heme iron often depends on the food balances in meals. The following are foods that enhance absorption of non-heme iron.

Meat and fish not only contain heme iron, the best form for maintaining stores, but they also help absorb non-heme iron.
Eating more vitamin C-rich foods can enhance absorption of non-heme iron during a single meal. In any case, vitamin C-rich foods are healthy. They include broccoli, cabbage, citrus fruits, melon, tomatoes, and strawberries. One orange or 6 ounces of orange juice can double the amount of iron your body absorbs from plant foods. (Taking vitamin C supplements does not appear to have any significant effect on how much iron your body stores.)
Foods containing riboflavin (vitamin B2) may help enhance the formation of hemoglobin from iron. Sources include liver, dried fortified cereals, and yogurt.

Certain nutrients impede the body's absorption of dietary iron. They include:

Polyphenols (found in tea, coffee, red wine, berries, and apples)
Phytates (found in foods such as seeds, dried beans, soy, and bran). Such foods are typically high in fiber. It is often believed that fiber itself impedes iron absorption, but researchers report that it has little or no effect.
Calcium. Calcium impairs the absorption of heme and non-heme iron. However, calcium intake must be quite high to cause any significant problems.

The Effects of Cooking Methods on Iron. Cooking methods can enhance the amount of iron in your body. Cooking in cast iron pans and skillets is a well-known way to increase the iron content of food. According to one study, boiling, steaming, or stir-frying in utensils composed of any material significantly increased the release of non-heme iron stored in vegetables.

Iron supplements can significantly reduce symptoms in people with restless legs syndrome (RLS) who are also iron deficient. Patients should use them only when dietary measures have failed. Iron supplements do not appear to be useful for RLS patients with normal or above normal iron levels.

Supplement Forms. To replace iron, the preferred forms of iron tablets are ferrous salts, usually ferrous sulfate (Feosol, Fer-In-Sol, Mol-Iron). Other forms include ferrous fumarate (Femiron, FerroSequels, Feostat, Fumerin, Hemocyte, Ircon), ferrous gluconate (Fergon, Ferralet, Simron), polysaccharide-iron complex (Niferex, Nu-Iron), and carbonyl iron (Elemental Iron, Feosol Caplet, Ferra-Cap). Specific brands and forms may have certain advantages. The following are some examples:

Prolonged-release ferrous sulfate (Slow Fe) may enhance iron absorption with fewer side effects than standard ferrous sulfate pills.
FerroSequels contains a stool softener, which helps prevent constipation.
Polysaccharide-iron complex has fewer side effects and equal absorption rates compared to ferrous salts. It is very expensive, however.
Carbonyl iron is composed of very fine tiny uniform spheres of iron powder and may prove to be less toxic than ferrous iron.
Coated or combination pills do not appear to offer any additional advantages and may hinder absorption of the iron.

Regimen. A reasonable approach for patients with RLS is to take 65 mg of iron (or 325 mg of ferrous sulfate) along with 100 mg of vitamin C on an empty stomach, 3 times a day.

IMPORTANT: As few as 3 adult iron tablets can poison, and even kill, children. This includes any form of iron pill. No one, not even adults, should take a double dose of iron if they miss one dose.

Tips for taking iron are:

For best absorption, take iron between meals. (Iron may cause stomach and intestinal disturbances, however. Some experts believe that you can take low doses of ferrous sulfate with food and avoid the side effects.)
Always drink a full 8 ounces of fluid with an iron pill.
Keep tablets in a cool place. Bathroom medicine cabinets may be too warm and humid, which may cause the pills to disintegrate.

Side Effects. Common side effects of iron supplements include the following:

Constipation and diarrhea -- these are rarely severe, although iron tablets can aggravate existing digestive problems such as ulcers and ulcerative colitis.
Nausea and vomiting may occur with high doses, but you can control this by taking smaller amounts. Switching to ferrous gluconate may help some people with severe digestive problems.
Black stools are normal when taking iron tablets. In fact, if they do not turn black, the tablets may not be working effectively. This tends to be a more common problem with coated or long-acting iron tablets.
If the stools are tarry looking as well as black, if they have red streaks, or if cramps, sharp pains, or soreness in the stomach occurs, bleeding in the digestive tract may be causing the iron deficiency, and the patient should call the doctor immediately.
Acute iron poisoning is rare in adults, but can be fatal in children who take adult-strength tablets.

Interactions With Other Drugs. Certain medications, including antacids, can reduce iron absorption.

Iron tablets may also reduce the effectiveness of other drugs, including:

Antibiotics: tetracycline, penicillamine, and ciprofloxacin
Anti-Parkinson's disease drugs: methyldopa, levodopa, and carbidopa

At least 2 hours should elapse between doses of these drugs and doses of iron supplements.

Supplementary Treatments. The following supplements may improve iron absorption:

Adding either ascorbic acid (vitamin C) or succinic acid to ferrous sulfate treatment will improve absorption of iron stores. Ascorbic acid added to iron treatment, however, may worsen some of the side effects. Succinic acid added to ferrous sulfate does not appear to increase side effects.
Some studies have found that the addition of zinc to iron supplements increases hemoglobin levels more than iron alone. Some evidence suggests that zinc affects a hormone called insulin-like growth factor-I (IGF-I), which plays a role in the regulation of red blood cell production.

Exercise earlier in the day may be one of the best ways to achieve healthy sleep. However, vigorous exercise and stimulation (including sexual activity) within 1 - 2 hours of bed time may worsen restless legs syndrome (RLS). A study found that people who walked briskly for 30 minutes, four times a week, improved minor sleep disturbances after 4 months. Regular, moderate exercise, healthful in any case, may help prevent RLS. Patients report that either bursts of excessive energy or long sedentary periods worsen symptoms.

Benign nocturnal leg cramps, sometimes known as a charley horse, are muscle spasms in the calf that can occur one or many times during the night. Cramping may also occur in the soles of the feet. They typically last from a few seconds to a few minutes. Some people experience them regularly, others only on isolated occurrences.

Causes of Nocturnal Leg Cramps. In most cases, the cause of nocturnal leg cramps remains unknown. Among the conditions that might cause leg cramps are:

Calcium and phosphorus imbalances, particularly during pregnancy
Low potassium or sodium (salt) levels
Overexertion, standing on concrete for long periods, or prolonged sitting (especially with the legs contorted)
Having structural disorders in the legs or feet (such as flat feet)
Medical causes of muscle cramping include hypothyroidism, Addison's disease, uremia, hypoglycemia, anemia, and certain medications. Various diseases that affect nerves and muscles, such as Parkinson's, cause leg cramps. Peripheral neuropathy, a complication of diabetes, can cause cramp-like pain, numbness, or tingling in the legs. Patients with kidney disease undergoing dialysis are also prone to leg cramps.

Individuals at Higher Risk for Nocturnal Leg Cramps. Nocturnal leg cramps occur at all ages but peak at different times. They are particularly common in adolescence, during pregnancy, and in older age, affecting up to 70% of adults over age 50 at some point.

Pregnant women and those taking diuretics are also at risk for leg cramps because of low calcium levels and an imbalance in calcium and phosphorus.

Consequences of Nocturnal Leg Cramps. Nocturnal leg cramps, like restless legs syndrome, rarely have any serious consequences. However, they can be extremely painful and long lasting. In some cases, severe and persistent symptoms can cause chronic insomnia and considerable mental distress.

Managing Nocturnal Leg Cramps. Once a cramp begins, straighten the leg, flex the foot upward toward the knee, or grab the toes and pull them toward the knee.

Walking or shaking the affected leg, then elevating it, may also help.

If soreness persists, a warm bath or shower or an ice pack may bring relief.

Lifestyle Tips for Preventing Nocturnal Leg Cramps. Nighttime leg cramps are generally treated with lifestyle changes.

Everyone with leg cramps should drink plenty of water (at least 6 - 8 glasses daily) to maintain adequate fluid levels.
Pregnant women and others who get legs cramps due to low calcium levels should reduce milk intake, because drinking milk does not correct the underlying imbalances in calcium and phosphorus. Instead, they should boost calcium levels by taking nonphosphate calcium supplements.
To prevent cramps from occurring, nightly stretching exercises may be the best preventive measure. Patients should stand about 30 inches from a wall and, keeping the heels flat on the floor, lean forward and slowly move the hands up the wall to achieve a comfortable stretch. A few minutes on a stationary bicycle at bedtime may also help.
While in bed, loose covers should be used to prevent the toes and feet from pointing, which causes calf muscles to contract and cramp. Propping the feet up higher than the torso may also help.
During the week, swimming and water exercises are a good way to keep muscles stretched, and wearing supportive footwear is also important.

Quinine. Quinine had been widely used to prevent leg cramping. The U.S. Food and Drug Administration (FDA) banned its sale over the counter because it reportedly caused some serious, although rare, side effects. These side effects include bleeding problems and heart irregularities. Other, less serious side effects include headaches, vision problems, and rash.

The FDA has since banned the marketing of most quinine drugs, cautioning against the off-label (non-approved) use of the drug to treat RLS. Only one form of the drug, Qualaquin, is approved for sale, for the treatment of some types of malaria. Pregnant women and those with liver problems should avoid quinine in any form.

Supplements. Some small studies indicate that the mineral magnesium, taken as magnesium citrate or magnesium lactate, may provide some benefit to people with leg cramps, including pregnant women.

In one small study, taking vitamin B complex was helpful. Other supplements tried for leg cramps include vitamin E, calcium, and potassium or sodium chloride, but these do not appear to be very effective. Sodium chloride (salt) may be helpful, but Western diets already contain too much sodium.

Medications

The American Academy of Sleep Medicine recommends medications for restless legs syndrome (RLS) or periodic limb movement disorder (PLMD) only for persons who fit strict diagnostic criteria, and who experience excessive daytime sleepiness as a result of these conditions. (Excessive daytime sleepiness results from nighttime sleeplessness due to RLS or PLMD symptoms). Little is known about the best way to treat RLS, but some experts suggest the following:

Over-the-counter pain relievers and possibly mineral and vitamin supplements (particularly folic acid in people who might be deficient) should be the first form of treatment.
People with RLS should have a test for iron deficiency. If they are iron deficient, they should start treatment with iron supplements.
Dopaminergic drugs (drugs that increase levels of dopamine) are the standard medicines for treating severe RLS, PLMD, or both.
Other drugs may be helpful if dopaminergic drugs fail, or for patients who have frequent -- but not nightly -- symptoms. These include opiates (pain relievers), benzodiazepines (sedative hypnotic drugs), or anticonvulsants. However, benzodiazepines and opiates can become habit forming and addictive.

Before taking stronger medications, people should try over-the-counter pain relievers, such as acetaminophen (Tylenol) or non-steroidal anti-inflammatory drugs (NSAIDs), which include ibuprofen (Advil, Motrin, Rufen), naproxen (Anaprox, Naprosyn, Aleve), and ketoprofen (Orudis KT, Aktron).

Although NSAIDs work well, long-term use can cause stomach problems, such as ulcers and bleeding, and possible heart problems. In April 2005, the Food and Drug Administration asked drug manufacturers of NSAIDs to include a warning label on their product that alerts users of an increased risk for heart-related problems and digestive tract bleeding.

Dopaminergic drugs increase the availability of the chemical messenger dopamine in the brain, and are the first-line treatment for severe restless legs syndrome (RLS) and periodic leg movement disorder (PLMD). These drugs significantly reduce the number of limb movements per hour, and improve the subjective quality of sleep. Patients with either condition who take these drugs have experienced up to 100% reduction in symptoms.

Dopaminergic drugs, however, can have severe side effects (they are ordinarily used for Parkinson's disease). They do not appear to be as helpful for RLS related to dialysis as they do for RLS from other causes.

Dopaminergic drugs include dopamine precursors and dopamine receptor agonists.

Dopamine Precursors. The dopamine precursor levodopa (L-dopa) was once a popular drug for severe RLS. The standard preparations (Sinemet, Atamet) combine levodopa with carbidopa, which improves the action of levodopa and reduces some of its side effects, particularly nausea. Levodopa can also be combined with benserazide (Madopar) with similar results, but Sinemet is almost always used in America. (Levodopa combinations are well tolerated and safe.)

Patients typically start with a very low dose taken 1 hour before bedtime. The dosage is increased until the patient finds relief. Patients sometimes need to take an extended form or to take it again during the night.

Levodopa acts fast, and the treatment is usually effective within the first few days of therapy. One study reported that a combination therapy of regular-release L-dopa plus sustained release L-dopa was effective in improving sleep.

Serious common side effects of L-dopa treatment (and, to lesser extent, of dopamine receptor agonists) are augmentation and rebound. Many studies report that augmentation (worsening of symptoms that occur earlier in the day) occurs in up to 70% of patients who take L-dopa. The risk is highest for patients who take daily doses, especially doses at high levels (greater than 200 mg/day). For this reason, patients should use L-dopa only intermittently (fewer than 3 times per week). The drug should be immediately discontinued if augmentation does occur. Following withdrawal from L-dopa, patients can switch to a dopamine receptor agonist.

The rebound effect causes increased leg movements at night or in the morning as the dose wears off, or as tolerance to the drug builds up.

Dopamine Receptor Agonists. Dopamine receptor agonists (also called dopamine agonists) mimic the effects of dopamine by acting on dopamine receptors in the brain. They are now generally preferred to L-dopa. Because they have fewer side effects than L-dopa, including rebound effect and augmentation, these drugs may be used on a daily basis. (Rebound effect is the worsening of symptoms over time; augmentation means the appearance of symptoms earlier in the day. About 30% of patients who take dopamine receptor agonists have reported augmentations symptoms. As the newer drugs are taken for longer periods and at higher doses, however, their augmentation rates may become closer to those of L-dopa.)

Dopamine agonists have been shown to relieve symptoms in 70 - 90% of patients. Dopamine agonists can be ergot-derived (such as cabergoline) or non-ergot derived (such as pramipexole and ropinirole). The newer non-ergotamine derivatives may induce fewer side effects than ergot-derived drugs. Studies on these medications report the following:

Ropinirole (Requip) is a non-ergotamine dopamine agonist. Approved in 2005, ropinirole is the first drug approved specifically for treatment of moderate-to-severe RLS (more than 15 RLS episodes a month). Side effects are generally mild but may include nausea, vomiting, drowsiness, and dizziness.
The Food and Drug Administration (FDA) approved pramipexole (Mirapex) for use in moderate-to-severe RLS in November 2006. However, patients may fall asleep, without warning, while taking this drug, even while performing activities such as driving.

Cabergoline (Dostinex) is also showing promise in clinical trials. In one study, cabergoline was used for RLS after levodopa had either failed or resulted in increased symptoms. Patients in the study reported relief or freedom from symptoms after 4 weeks of use. A 2006 study indicated that a single evening dose of cabergoline improved both day and nighttime limb movements, and sleep disturbances.The FDA announced in March 2007 that the dopamine agonist pergolide (Permax) was voluntarily withdrawn from the market. Studies confirmed that this drug could cause serious damage to the heart valves of patients who take it. These problems have not been reported with ropinirole or pramipexole, which are chemically different then pergolide.

Other Dopamine Agonists. Rotigotine is a unique dopamine agonist that is being developed in patch form for RLS. In May 2007, the FDA approved this patch for treatment of early Parkinson's disease. Other dopamine agonists that have shown some promise in small studies include alpha-dihydroergocryptine, or DHEC (Almirid), and piribedil (Trivastal).

Regimens. The effects of L-dopa are apparent in 15 - 30 minutes. Dopamine receptor agonists, meanwhile, take at least 2 hours to start working. Some doctors recommend regular use of dopamine receptor agonists for patients who experience nightly symptoms, and L-dopa for those whose symptoms occur only occasionally.

Side Effects. Common side effects of dopaminergic drugs vary but may include feeling faint or dizzy (especially when standing up), headaches, abnormal muscle movements, rapid heartbeat, insomnia, bloating, chest pain, and dry mouth. Nausea may be especially common. Adding the drug domperidone may help to relieve this side effect. In rare cases, dopaminergic drugs can cause hallucinations or lung disease.

Because these drugs may cause daytime drowsiness, patients should be extremely careful while driving or performing tasks that require concentration.

Long-term use of dopaminergic drugs can lead to loss of effectiveness (tolerance). Adding a drug called entacapone (Comtan) may prolong the duration of action of carbidopa-levodopa therapy (Sinemet), but it can cause nausea.

Rebound effect, augmentation, and tolerance can reduce the value of dopaminergic drugs in the treatment of RLS. Using the lowest dose possible can minimize these effects.

Withdrawal Symptoms. Patients who withdraw from these drugs typically experience very severe RLS symptoms for the first 2 days after stopping. RLS eventually returns to pre-treatment levels after about a week. The longer a patient uses these drugs, the worse their withdrawal symptoms.

Benzodiazepines, such as clonazepam (Klonopin), are known as sedative hypnotics. Doctors prescribe them for insomnia and anxiety. They may be helpful for some patients with restless legs syndrome (RLS) that disrupts sleep. Clonazepam may be particularly helpful for children with both periodic limb movement disorder and symptoms of attention deficit hyperactivity disorder. The medicine also may be helpful for patients with RLS who are undergoing dialysis.

Side Effects. Elderly people are more susceptible to side effects. They should usually start at half the dose prescribed for younger people, and should not take long-acting forms. Side effects may differ depending on whether the benzodiazepine is long-acting or short-acting.

The drugs may increase depression, a common condition in many people with insomnia.
Breathing problems may occur with overuse or in people with pre-existing respiratory illness.
Long-acting drugs have a very high rate of residual daytime drowsiness compared to others. They have been associated with a significantly increased risk for automobile accidents and falls in the elderly, particularly in the first week after taking them. Shorter-acting benzodiazepines do not appear to pose as high a risk.
There are reports of memory loss (so-called traveler's amnesia), sleepwalking, and odd mood states after taking triazolam (Halcion) and other short-acting benzodiazepines. These effects are rare and probably enhanced by alcohol.
Because benzodiazepines cross the placenta and enter breast milk, pregnant and nursing women should not use them. There are some reports of an association between the use of benzodiazepines in the first trimester of pregnancy and the development of cleft lip in newborns. Studies are conflicting at this point, but, due to other known side effects of benzodiazepines, pregnant women should not use these drugs, if possible.
In rare cases, overdoses have been fatal.

Interactions. Benzodiazepines are potentially dangerous when used in combination with alcohol. Some drugs, such as the ulcer medication cimetidine, can slow the breakdown of benzodiazepine.

Withdrawal Symptoms. Withdrawal symptoms usually occur after prolonged use and indicate dependence. They can last 1 - 3 weeks after stopping the drug and may include:

Gastrointestinal distress
Sweating
Disturbed heart rhythm
In severe cases, patients might hallucinate or experience seizures, even a week or more after they stop taking the drug.

Rebound Insomnia. Rebound insomnia, which often occurs after withdrawal, typically includes 1 - 2 nights of sleep disturbance, daytime sleepiness, and anxiety. The chances of rebound are higher with the short-acting benzodiazepines than with the longer-acting ones.

Narcotics are pain-relieving drugs that act on the central nervous system. They are sometimes prescribed for severe cases of restless legs syndrome (RLS). They may be a good choice if pain is a prominent feature. Some evidence also suggests that narcotics reduce the frequency of periodic leg movements.

There are two types of narcotics, both of which have been used for severe RLS:

Opiates (such as morphine and codeine) come from natural opium. Some patients report relief with the use of the opiate fentanyl (Duragesic), available in skin patch form. An implanted pump that uses morphine and an anesthetic called bupivacaine is showing promise for patients with severe RLS. The pump delivers the drugs to the fluid surrounding the spinal cord (cerebrospinal fluid).
Opioids are synthetic drugs. The most common example is oxycodone (Percodan, Percocet, Roxicodone, Oxycontin). Apomorphine is a morphine derivative. In one study, when injected under the skin at night, it reduced nocturnal discomfort and leg movements in some patients.

Although the use of narcotics for severe RLS is controversial, some studies have suggested that even when the treatments are long-term, they are rarely addictive for pain sufferers except among patients with a history of substance abuse.

The use of such drugs may be beneficial when included as part of a comprehensive pain management program. Such a program involves screening prospective patients for possible drug abuse, and regularly monitoring those who are taking narcotics. Doses should be adjusted as necessary to achieve an acceptable balance between pain relief and side effects. Patients on long-term opiate therapy should also be monitored periodically for sleep apnea, a condition that causes breathing to stop for short periods many times during the night. Sleep apnea may worsen symptoms of RLS, insomnia, and other complaints.

Tramadol. Tramadol (Ultram) is a pain reliever that has been used as an alternative to opioids. In one study, tramadol was very effective for RLS and produced few or no side effects. It has opioid-like properties, but is not as addictive. (However, there are reports of dependence and abuse with this drug as well.) Withdrawal after long-term use (longer than a year) can cause intense symptoms, including diarrhea, insomnia, and even restless legs syndrome itself.

Antiseizure drugs -- such as gabapentin (Neurontin), valproic acid (valproate, divalproex, Depakote, Depakene), and carbamazepine (Tegretol) -- relax blood vessels and are being tested for restless legs syndrome (RLS). Gabapentin, a newer antiseizure drug, is showing particular promise for mild-to-moderate RLS. One study reported that it improved RLS symptoms and sleep, particularly in patients who also experienced pain. It was also effective for periodic leg movement disorder. A new gabapentin product is in phase III clinical trials for the treatment of RLS. The new drug, known as XP13512, converts to gabapentin in the intestines, and therefore may reduce some of the side effects experienced by patients taking antiseizure medications.

Side Effects. All antiseizure drugs have potentially severe side effects. Therefore, patients should try these medications only after non-drug methods have failed. Side effects of many anti-seizure drugs include nausea, vomiting, heartburn, increased appetite with weight gain, hand tremors, irritability, and temporary hair thinning and hair loss (taking zinc and selenium supplements may help reduce this last effect). Some antiseizure drugs can also cause birth defects and, in rare cases, liver toxicity. Gabapentin may have fewer of these side effects than valproic acid or carbamazepine.

Antidepressants. Bupropion (Wellbutrin), a newer antidepressant, may be helpful for restless legs syndrome (RLS). Bupropion is a weak dopamine reuptake inhibitor -- it causes a slight increase in the availability of dopamine in the brain. The drug is not addictive and does not have the severe side effects of other RLS drugs, but more research is needed to determine if it is useful.

Clonidine. Clonidine (Catapres), a drug used for high blood pressure, is helpful for some patients and may be an appropriate choice for patients who have RLS accompanied by hypertension. It also may help patients with RLS who are undergoing hemodialysis.

Baclofen. The anti-spasm drug baclofen (Lioresal) appears to reduce intensity of RLS (although not frequency of movements).

Resources

www.aasmnet.org -- American Academy of Sleep Medicine
www.sleepfoundation.org -- National Sleep Foundation
www.ninds.nih.gov -- National Institute of Neurological Disorders and Stroke
www.nhlbi.nih.gov/about/ncsdr/ -- National Center on Sleep Disorders Research
www.rls.org -- Restless Legs Syndrome Foundation
www.wemove.org -- Worldwide Education and Awareness for Movement Disorders

References

Bogan RK, Fry JM, Schmidt MH, Carson SW, Ritchie SY. Ropinirole in the treatment of patients with restless legs syndrome: a US-based randomized, double-blind, placebo-controlled clinical trial. Mayo Clin Proc. 2006 Jan;81(1):17-27.

Claman DM; Redline S; Blackwell T, Ancoli-Israel S, Surovec S, Scott N, et al. Prevalence and correlates of periodic limb movements in older women. J Clin Sleep Med. 2006 Oct;2(4):438-445.

Merlino G, Fratticci L, Valente M, et al. Association of restless legs syndrome in type 2 diabetes: a case-control study. Sleep. 2007; 30(7): 866-71.

Oertel WH, Benes H, Bodenschatz R, Peglau I, Warmuth R, Happe S, et al. Efficacy of cabergoline in restless legs syndrome: a placebo-controlled study with polysomnography (CATOR). Neurology. 2006 Sep 26;67(6):1040-6.

Partinen M, Hirvonen K, Jama L, Alakuijala A, Hublin C, Tamminen I, et al. Efficacy and safety of pramipexole in idiopathic restless legs syndrome: a polysomnographic dose-finding study--the PRELUDE study. Sleep Med. 2006 Aug;7(5):407-17.

Picchietti D, Winkelman JW. Restless legs syndrome, periodic limb movements in sleep, and depression. Sleep. 2005 Jul 1;28(7):891-8.

Picchietti D. Restless legs syndrome: prevalence and impact in children and adolescents--the Peds REST study. Pediatrics. 2007; 120(2): 253-66.

Stefansson H, Rye DB, Hicks A, et al. A Genetic Risk Factor for Periodic Limb Movements in Sleep. N Engl J Med. 2007;357:639-47.

Winkelman JW, Sethi KD, Kushida CA, Becker PM, Koester J, Cappola JJ, et al. Efficacy and safety of pramipexole in restless legs syndrome. Neurology. 2006 Sep 26;67(6):1034-9.

Winkelmann J, Schormair B, Lichtner P, et al. Genome-wide association study of restless legs syndrome identifies common variants in three genomic regions. Nat Genet (in press). [cited in: Winkelmann J. Periodic Limb Movements in Sleep - Endophenotype for Restless Legs Syndrome? N Engl J Med. 2007; 357:703-05.]

Review Date:
10/22/2007
Reviewed By:
Harvey Simon, MD, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital.

A.D.A.M. Copyright

adam.com

Epilepsy

FitSugar — Wed, 08 Oct 2008 17:35:12 -0700

In This Report

Highlights
Introduction
Causes
Outlook and Effects
Diagnosis
Treatment
Treatment After The First S...
Medications
Surgery
Lifestyle Changes
Resources
References

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

Drug Approval

In 2007, the Food and Drug Administration (FDA) approved levetiracetam (Keppra) for treatment of primary generalized tonic-clonic seizures in adults, and children ages 6 years and older, who have idiopathic generalized epilepsy. Levetiracetam was previously approved for partial-onset seizures and myoclonic seizures.

Carbamazepine and Genetic Testing

In 2007, the FDA recommended that patients of Asian ancestry get a genetic test prior to taking carbamazepine (Tegetrol, Equetro, Carbatrol). Rare, but serious, side effects of carbamazepine include life-threatening skin reactions such as Stevens-Johnson syndrome. The risk for these skin reactions is significantly higher for patients of Asian ancestry. A simple blood test can check for the presence of a genetic mutation that increases this risk. Patients who test positive for this gene should not take carbamazepine unless the benefits clearly outweigh the risks.

Epilepsy and Suicide Risk

People with epilepsy have a high risk for suicide, especially within 6 months of diagnosis, suggests a 2007 study in Lancet Neurology. The researchers found that suicide risk was especially high for people who have both epilepsy and another psychiatric condition (such as depression, anxiety, schizophrenia, or alcoholism). The researchers recommend that doctors carefully monitor newly diagnosed patients.

Ketogenic Diet

The ketogenic diet, which is characterized by high fat and low carbohydrate intake, is resurging in popularity for the treatment of children with difficult-to-control seizures, according to a 2007 review in Pediatrics. The ketogenic diet helps stop or reduce seizures in about a third of children. The diet is complex. Parents should seek supervision and guidance from a doctor or trained health professional.

Introduction

Epilepsy is characterized by unprovoked, recurring seizures that disrupt the nervous system and can cause mental and physical dysfunction. In the U.S., about 2.5 million people are affected by epilepsy and seizures. About 10% of the American population will experience at least one seizure during their lifetime.

The structures of the brain include: the brainstem, consisting of the spinal cord, the medulla oblongata, the pons and the midbrain; the cerebellum; the cerebrum (one half, or hemisphere shown); and the diencephalon.

Epilepsy affects all age groups. Males have a slightly higher risk than females. The incidence is highest in children, with another, but lesser, peak occurring after age 60. According to one estimate, 14% of epilepsy patients are under 15 years old, and about 25% are over age 64.

Every year, 25,000 - 40,000 American children have a first seizure that is unrelated to a fever. Epilepsy is decreasing in childhood but increasing in the elderly, probably because of mild strokes and cardiac arrest.

Epilepsy is not a single disorder but rather a wide spectrum of problems. What all types of epilepsy share are recurrent, unprovoked seizures caused by an uncontrolled electrical discharge from nerve cells in the cerebral cortex. This part of the brain controls higher mental functions, general movement, and the functions of the internal organs in the abdominal cavity, perception, and behavioral reactions.

Seizures are a symptom of epilepsy. Epilepsy types are generally put into two categories, which are based on the specific biologic mechanisms involved in the seizure and the anatomical location of the seizure. The two types are:

Partial (also called focal or localized) seizures. These seizures are more common than generalized seizures and occur in one or more specific locations in the brain. In some cases, partial seizures can spread to wide regions of the brain. They are likely to develop from specific injuries, but in most cases the exact origins are unknown.
Generalized seizures. These seizures typically occur in both sides of the brain. Many forms of these seizures are genetically based. There is usually normal neurologic function.

Experts are finding, however, that these categories do not actually reflect what is now known about the brain's anatomy. For example, the words "partial" and "generalized" suggest that seizures either involve only part of the brain or are widespread. However, a number of events in the brain occur with either type, muddying these distinctions. Researchers are now in the process of making clearer definitions and terms that reflect what actually is happening in the brain.

New classification systems better define specific epilepsies. Some professional groups now suggest that epilepsies be classified in the following five ways:

Type of seizure (partial or generalized)
Description of the seizure onset and evolution
Specific syndromes that are associated with one or more seizure types (however, not all seizures will be part of a syndrome)
Specific causes of the seizures, if known
Degree of impairment

These seizures are subcategorized as "simple" or "complex partial."

Simple Partial Seizures. A person with a simple partial seizure (sometimes known as Jacksonian epilepsy) does not lose consciousness, but may experience confusion, jerking movements, tingling, or odd mental and emotional events. Such events may include deja vu, mild hallucinations, or extreme responses to smell and taste. After the seizure, the patient usually has temporary weakness in certain muscles.
Complex Partial Seizures. Slightly over half of seizures in adults are complex partial type. About 80% of these seizures originate in the temporal lobe, the part of the brain located close to the ear. Disturbances there can result in loss of judgment, involuntary or uncontrolled behavior, or even loss of consciousness. They may lose consciousness briefly and appear to others as motionless with a vacant stare. Emotions can be exaggerated; some sufferers even appear to be drunk. After a few seconds, a patient may begin to perform repetitive movements, such as chewing or smacking of lips. Episodes usually last no more than 2 minutes. They may occur infrequently, or as often as every day. A throbbing headache may follow a complex partial seizure.

In some cases, simple or complex partial seizures evolve into what are known as secondarily generalized seizures. The progress may be so rapid that the partial stage is not even noticed.

While the term "partial" implies the seizures affect only small or specific brain locations, in reality, they almost always involve diffuse and even widespread areas. In the future, the term "focal seizures" will most likely replace the term "partial seizures," and its subcategories. Until new classifications are more widely in use, this report will continue to use the term "partial seizures" and its subcategories.

Generalized seizures are caused by nerve cell disturbances that occur in more widespread areas of the brain than do partial seizures. Therefore, they have a more serious effect on the patient. They are further subcategorized as tonic-clonic (or grand mal) or absence (petit mal) seizures.

Tonic-Clonic (Grand Mal) Seizures. The first stage of a grand mal seizure is called the tonic phase, in which the muscles suddenly contract, causing the patient to fall and lie stiffly for about 10 - 30 seconds. Some people experience a premonition or aura before a grand mal seizure. Most, however, lose consciousness without warning. If the throat or larynx is affected, there may be a high-pitched musical sound (stridor) when the patient inhales. Spasms occur for about 30 seconds to 1 minute. Then the seizure enters the second phase, called the clonic phase. The muscles begin to alternate between relaxation and rigidity. After this phase, the patient may lose bowel or urinary control. The seizure usually lasts a total of 2 - 3 minutes, after which the patient remains unconscious for a while and then awakens to confusion and extreme fatigue. A severe throbbing headache similar to migraine may also follow the tonic-clonic phases.
Absence (Petit Mal) Seizures. Absence or petit mal seizures are brief losses of consciousness that occur for 3 - 30 seconds. Physical movement and loss of attention may stop for only a moment. Such seizures may pass unnoticed by others. Small children may simply appear to be staring or walking distractedly. Petit mal may be confused with simple or complex partial seizures, or even with attention deficit disorder. [See In-Depth Report #30: Attention deficit hyperactivity disorder.] In petit mal, however, a person may experience attacks as often as 50 - 100 times a day. About 25% of patients with petit mal develop grand mal seizures. An electroencephalogram (EEG) test that shows a specific brain wave pattern can usually identify these patients.

Click the icon to see a depiction of a tonic-clonic seizure.

Atonic (Akinetic) Seizures. A person who has an atonic (or akinetic) seizure loses muscle tone. Sometimes it may affect only one part of the body so that, for instance, the jaw slackens and the head drops. At other times, the whole body may lose muscle tone, and the person can suddenly fall. A brief atonic episode is known as a drop attack.

Simply Tonic or Clonic Seizures. Seizures can also be simply tonic or clonic. In tonic seizures, the muscles contract and consciousness is altered for about 10 seconds, but the seizures do not progress to the clonic or jerking phase. Clonic seizures, which are very rare, occur primarily in young children, who experience spasms of the muscles but not tonic rigidity.

Myoclonic. Myoclonic seizures are a series of brief jerky contractions of specific muscle groups, such as the face or trunk.

Epilepsy is also grouped according to a set of common characteristics, including:

Patient age
Type of seizure or seizures
Whether a cause is known or not (idiopathic)

A few syndromes and inherited epilepsies are listed as follows. They do not represent all epilepsies.

West Syndrome (Infantile Spasms). West syndrome, also called infantile spasms, is a disorder that involves spasms and developmental delay in children within the first year, usually in infants ages 4 - 8 months.

Benign Familial Neonatal Convulsions. Benign familial neonatal convulsions (BFNC) are a rare, inherited form of generalized seizures that occur in infancy. BFNC appears to be caused by genetic defects that affect ion channels in nerve cells that carry potassium.

Juvenile Myoclonic Epilepsy (Impulsive Petit Mal). Juvenile myoclonic epilepsy, also called impulsive petit mal epilepsy, is characterized by generalized seizures, usually tonic-clonic marked by jerky movements (called myoclonic jerks), and sometimes absence seizures. This accounts for 7% of epilepsies, and usually occurs in individuals ages 8 - 20.

Adult Myoclonic Epilepsy. Some research suggests that adult myoclonic epilepsy may be a previously un-described and distinct syndrome. It involves the development of generalized epilepsy of unknown causes in middle-aged adults.

Lennox-Gastaut Syndrome. Lennox-Gastaut syndrome is a severe form of epilepsy in young children that causes multiple seizures and some developmental retardation. It usually involves absence, tonic, and partial seizures.

Myoclonic-Astatic Epilepsy. Myoclonic-astatic epilepsy (MAE) is a combination of myoclonic seizures and astasia (a decrease or loss of muscular coordination), often resulting in the inability to sit or stand without aid.

Progressive Myoclonic Epilepsy. Progressive myoclonic epilepsy is an inherited disorder occurring in children ages 6 - 15. It usually involves tonic-clonic seizures and marked sensitivity to light flashes. Although the disease was previously considered to be progressive throughout life, current therapies have significantly improved its outlook.

Autosomal Dominant Nocturnal Frontal Lobe Epilepsy. Autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE) is a rare, inherited syndrome that usually occurs during childhood, typically around age 11. However, onset varies widely within families. Seizures can be dystonic (twisting contractions) or tonic (muscle contractions), or involve thrashing. They are brief, frequent, and occur in clusters during the night. The seizures often subside with age. ADNFLE appears to be caused by an alteration in the brain receptor neuronal nicotinic acetylcholine,

Landau-Kleffner Syndrome. Landau-Kleffner syndrome is an epileptic condition that results in the inability to communicate either with speech or by writing (aphasia).

Contactin-Associated Protein-Like 2 (CASPR2) Epilepsy. CASPR2 is associated with a childhood epilepsy and autism disorder found in closely related relatives in Amish communities.

Status epilepticus (SE) is a serious, potentially life-threatening, condition that can lead to chronic epilepsy. It occurs in 100,000 - 150,000 people in the U.S. each year, over half of whom are children. Permanent brain damage or death can result if the seizure is not treated effectively.

The condition is defined as recurrent convulsions that last for more than 20 minutes and are interrupted by only brief periods of partial relief. Although any type of seizure can be sustained or recurrent, the most serious form of status epilepticus is the generalized convulsive or tonic-clonic type. In more than a third of cases, status epilepticus occurs with the first seizure. The trigger is often unknown, but can include the following:

Failure to take anti-epileptic medications (accounts for about a third of status epilepticus events)
Abrupt withdrawal of certain anti-epileptic drugs, particularly barbiturates and benzodiazepines
High fever
Poisoning
Electrolyte imbalances (imbalance in calcium, sodium, and potassium)
Cardiac arrest
Stroke. In one study, about 9% of stroke patients with seizures had status epilepticus, which resulted in higher disability after the stroke, particularly if these severe seizures occurred within a week of the stroke
Low blood sugar in people with diabetes
Central nervous system infection
Brain tumor
Alcohol withdrawal

Causes

The cause of a seizure is determined in about 28% of partial epilepsy patients. In the rest, however, epilepsy is deemed idiopathic, which means that the cause is unknown. The age of seizure onset can sometimes offer a clue. Idiopathic epilepsy is rare in children and young adults.

Epileptic seizures are triggered by abnormalities in the brain that cause a group of nerve cells in the cerebral cortex to become activated simultaneously, emitting sudden and excessive bursts of electrical energy. A seizure's effect depends on the location in the brain where this electrical hyperactivity occurs. Effects range from brief moments of confusion to minor spasms to loss of consciousness.

Click the icon to see an animation about the nervous system.

Ion Channels. Sodium, potassium, and calcium act as ions in the brain. They produce electric charges that must fire regularly in order for a steady current to pass from one nerve cell in the brain to another. If the ion channels that carry them are genetically damaged, a chemical imbalance occurs. This can cause nerve signals to misfire, leading to seizures. Abnormalities in the ion channels are believed to be responsible for absence and many other generalized seizures.

Neurotransmitters. Abnormalities may occur in neurotransmitters, the chemicals that act as messengers between nerve cells. Three neurotransmitters are of particular interest:

Gamma aminobutyric acid (GABA), which helps prevent nerve cells from over-firing.
Serotonin's role in epilepsy is also being studied. Serotonin is a brain chemical that is important for well-being and associated behaviors (eating, relaxation, sleep). Imbalances in serotonin are also associated with depression.
Acetylcholine is a neurotransmitter that is important for learning and memory.

Dozens of genetic syndromes representing a variety of seizure patterns may account for the different forms epilepsy.

A genetic cause has been identified for at least some cases of juvenile myoclonic epilepsy, which represents 10% of all epilepsy cases. (Such research and other studies have pointed to the GABA signaling system as an important player in many cases of epilepsy.)

Febrile seizures are caused by high fever. They usually occur in children ages 3 months to 5 years. Between 10 - 15% of children with epilepsy have a history of febrile seizures before they develop epilepsy. However, febrile seizures are quite common and occur in about 3% of all children under 5 years old. Nearly all are brief and have no long-lasting effect.

In young children, high fever from a vaccination can, in rare instances, trigger seizures. These seizures are almost always temporary and have no serious consequences.

Some controversy arose a few years ago over the possibility that the DTP (diphtheria-tetanus-pertussis) vaccine might trigger epilepsy or other neurologic diseases. Some experts suggest that children who have neurologic events following their DTP shot already have a preexisting impairment such as epilepsy, which is revealed, but not caused by, the vaccine. Children with existing epilepsy may be at risk for seizures 2 or 3 days after the vaccination. Infants with suspected neurologic problems may have their vaccinations delayed until their neurologic situation is clarified, but not beyond their first birthday. Also, a newer version of the DTP vaccine does not contain a live virus and so reduces the risk of any seizure.

Brain Tumors. Both cancerous and noncancerous brain tumors can cause seizures in all patients.

Hydrocephalus and Shunts. Hydrocephalus occurs when cerebrospinal fluid (CSF) accumulates in the brain, leading to excessive swelling of the brain ventricles. The resulting pressure can damage the brain's tissue. Hydrocephalus itself is not commonly known to cause seizures, but its treatment, which involves insertion of a shunt, may cause them. The shunt is a device that drains the excess fluid from the brain. Up to half of children who receive shunts may experience epileptic seizures, particularly if the shunt is placed before 2 years of age. More research on its relationship to epileptic seizures is needed.

Focal Cortical Dysplasia. This is an abnormality in fetal development in which the normal migration of nerve cells is altered. It can cause very severe epilepsy that is difficult to treat.

Hippocampal Sclerosis. Hardened tissue (sclerosis) in the brain's hippocampus is the most commonly identified abnormality in patients with partial epilepsy. Such abnormal brain tissue leads to structural reorganization, and both the loss and regeneration of nerve cells.

Cavernous Angiomas. Cavernous angiomas are blood vessels that grow abnormally and, like a tumor, can put pressure on nerve tissue.

Other Causes of Seizures in Children. Seizures in infants and children may be due to birth defects, difficulties during delivery, or poisoning.

Alcohol Abuse. Alcohol abuse is one of the most common causes of adolescent- and adult-onset seizures. Seizures, nearly always generalized tonic-clonic, occur in about 10% of adults during withdrawal. Multiple seizures happen in about 60% of these patients. The first seizure occurs 7 hours to 2 days after the last drink, and the time between the first and last seizure is usually 6 hours or less. [For more information, see In-Depth Report #56: Alcoholism.]

Sudden withdrawal from certain antianxiety or antidepressant drugs such as benzodiazepines, barbiturates, and tricyclic antidepressants can also contribute to seizures.

Head Injuries in Adults. Head injuries to adults can cause seizures, with the risk highest in severe head trauma. A first seizure related to the injury can occur years later, but only very rarely. People with mild head injuries, which involve loss of consciousness for fewer than 30 minutes, have only a slight risk that lasts up to 5 years after the injury.

Head Injuries in Infants and Children. Infants are at high risk for head trauma, and the severity of injury may be difficult to determine. The risk of even one seizure is generally only a concern after severe head trauma. Most children who have had a minor or not very serious head injury do not need to have medications to prevent seizures, especially when an evaluation in the emergency department was unnecessary.

Stroke. Seizure is a symptom of a major stroke. Even injury to the brain from small strokes may cause seizures. Patients who have had a severe stroke are 5 times more likely to develop epilepsy than patients who have had a mild stroke.

Seizures in adults can also be caused by:

Low blood sugar (hypoglycemia), a complication of diabetes in both children and adults.
Medications such as theophylline, meperidine, tricyclic antidepressants, phenothiazines, lidocaine, quinolones, penicillins, selective serotonin re-uptake inhibitors, isoniazid, antihistamines, cyclosporine, interferons, cocaine, lithium, amphetamines, and alcohol (withdrawal).
Occupational exposure to environmental triggers. High exposure to certain chemicals has been linked with seizures.
Alzheimer's or other degenerative brain diseases in the elderly.
Infections of the brain and central nervous system such encephalitis and meningitis.

The organs of the central nervous system (brain and spinal cord) are covered by three connective tissue layers called the meninges. They consist of the pia mater (closest to the CNS structures), the arachnoid, and the dura mater (farthest from the CNS). The meninges help support blood vessels and contain cerebrospinal fluid. The structures are involved in meningitis, an inflammation of the meninges, which, if severe, may become encephalitis, an inflammation of the brain.

Between 20 - 45% of cases of untreatable seizures have a psychologic rather than physical origin. In this form of epilepsy, known as pseudoepilepsy or psychogenic epilepsy, the patient has no conscious intent of forcing a seizure and does not show unusual emotional behavior or signs of hysteria. It is very difficult to treat and can be very disabling. Pseudoepilepsy can usually be distinguished from true epilepsy using an electroencephalogram (EEG), which measures brain waves. The cause of pseudoepilepsy is unknown.

Outlook and Effects

Most patients can control their seizures with a single drug and stop drug treatment completely after 2 years without seizures. In fact, patients who respond well to an anti-epileptic drug (AED), have a better chance for remaining seizure-free in the future. In general, patients who do not have good control with medications are more likely to have difficulty with epilepsy treatment.

Injuries from Falls. Because many people with seizures fall, injuries are common. Although such injuries are usually minor, people with epilepsy have a higher incidence of fractures than those without the disorder. Epilepsy patients who take the drug phenytoin have an even higher risk, since the drug can cause osteoporosis.

Household Accidents. According to a 2006 study, the kitchen and bathroom are two of the most dangerous places for children with epilepsy. Parents should take precautions to prevent burning accidents from stoves and other heat sources. Children with epilepsy should never be left alone when bathing.

Driving and the Risk for Accidents. Being unable to drive is an extremely distressing and severe component of epilepsy. Drivers with well-controlled epilepsy are not at a high or unacceptable risk for automobile accidents. Uncontrolled epilepsy, however, poses a high risk. Needless to say, seizures can be very dangerous if they occur while a person is driving. Studies have reported that more than a fourth of drivers with uncontrolled epilepsy had a seizure-related accident at some time. Many of these accidents resulted in injuries to the patient or others.

Certain factors can help predict who may safely drive:

A long duration between seizures. In one study, being seizure-free for 6 months reduced the risk for accidents by 85%, and being seizure-free for 1 year lowered the risk by 93%. State laws restricting driving in people with seizures vary from requiring seizure-free periods of 3 months (which is too short for protection) to 18 months.
Having few seizure-related accidents.
Having a reliable pre-seizure warning sign, such as an aura.

Accidents while Swimming. Swimming poses another danger for people with epilepsy, particularly those with tonic seizures, which can cause the diaphragm to expel air quite suddenly. People with epilepsy who swim should avoid deep and cloudy water (a clear swimming pool is best), and always swim with a knowledgeable, competent, and experienced companion or have a supervisor on site.

Epileptic patients who are cured have a normal lifespan. Their long-term survival rates are lower than average if medications or surgery fail to stop the seizures. The lower survival rate is partly due to a higher-than-average risk for death due to accidents and suicide. The specific cause of the seizure may also contribute to fatalities.

There is a very low risk for sudden death in patients with epilepsy. Although the causes of such events are not fully known, experts suspect heart arrhythmias in many cases.

Long-Term General Effects. In general, the long-term effects of seizures vary widely depending on the seizure's cause. The long-term outlook for children with idiopathic epilepsy (epilepsy of unknown causes) is very favorable. One study reported that 68 - 92% of these patients were seizure-free after 20 years. Another study reported that they had a survival rate no different from children without these seizures.

Children whose epilepsy is a result of a specific condition (for example, a head injury or neurologic disorder) have higher mortality rates than the normal population, but their lower survival rates are most often due to the underlying condition, not the epilepsy itself.

Effect on Memory and Learning. The studies on the effects of seizures on memory and learning vary widely and depend on many factors. In general, the earlier a child has seizures and the more extensive the area of the brain affected, the poorer the outcome. Children with seizures that are not well-controlled are at higher risk for intellectual decline.

Social and Behavioral Consequences. Learning and language problems, and emotional and behavioral disorders, occur in a significant number of children with several of the partial epilepsy syndromes. These children perform worse on behavioral tests than do other children. Whether these problems are caused by the seizure disorder and anti-seizure medications or are simply part of the seizure disorder remains unclear.

Effect on Mental Functioning in Adults. The effects of adult epilepsy on mental functioning are not clear. More research is needed in this area, as results have been contradictory.

Psychological Health. About 25 - 75% of adults with epilepsy show signs of depression. People with epilepsy have a high risk for suicide, particularly in the first 6 months following diagnosis. The risk for suicide is highest among people who have epilepsy and an accompanying psychiatric condition such as depression, anxiety disorder, schizophrenia, or chronic alcohol use.

Overall Health. Many patients with epilepsy describe their overall health as "fair" or "poor," compared to those who do not have epilepsy. People with epilepsy also report a higher frequency of pain, depression, anxiety, and sleep problems. In fact, their overall health state is comparable to people with other chronic diseases, including arthritis, heart problems, diabetes, and cancer. Treatments can cause considerable physical effects, such as osteoporosis and weight changes.

Effects on Sexual Function. There have been studies suggesting that up to two-thirds of patients with epilepsy experience sexual disturbances, including impotence in men. Causes of these problems may be emotional, medication induced, or a result of changes in hormone levels:

Epilepsy in childhood may cause disturbances in hormones regulating puberty.
Persistent seizures in adults may be associated with other hormonal and neurologic changes that contribute to sexual dysfunction.
Negative emotions due to epilepsy can reduce sexual drive.
Medications may be responsible for many of these cases, although newer drugs may reduce this problem.

Studies have been conflicting on the effects of fertility from epilepsy, but most suggest that fertility rates among women with epilepsy are lower than among women in the general population. A number of factors, including anti-epileptic drugs (AEDs) or social factors such as marriage at an older age, may contribute to this lower rate. Certain AEDs, particularly valproate, disrupt ovulation and menstruation by increasing male hormone levels and weight and causing polycystic ovaries.

Preparing to Become Pregnant. A woman should visit her doctor at least 3 months before becoming pregnant to talk about risks of medications and the possibility of making any changes.

A woman who has been seizure-free for 2 or more years may attempt to discontinue drugs under her doctor’s supervision.
If she has not been seizure-free, she should continue medications but try to reduce them to a single drug, if possible. (Again, under a doctor’s supervision.)
If a woman taking antiseizure medications has an unplanned pregnancy, there may be no point in switching medications right away, since the effects of the drugs last for 10 weeks. However, she should notify her doctor immediately.
Folic acid is recommended for all pregnant women, and women with epilepsy should talk with their doctor about taking a supplement of folic acid (5 mg) at least 3 months before conception as well as during the first trimester.

Effect of Pregnancy on Seizure Frequency. The frequency and intensity of seizures vary widely in women with epilepsy. About 25% of pregnant women with epilepsy face an increase in events, and the risk is highest in those who have more than one seizure per month prior to becoming pregnant. In most cases, however, there is no change at all. Some pregnant women even have a decrease in seizures. The risk is lower in women who experience less than one seizure in the 9 months prior to becoming pregnant.

The following conditions may contribute to an increase in seizures during pregnancy:

Nausea and vomiting (vitamin B6 and antihistamines may help with nausea)
Fluid retention
Higher estrogen levels
Psychological and emotional stress
Medication noncompliance from fear of side effects
Problems with sleeping
Changes in absorption of anticonvulsants

Anti-epileptic drug levels are monitored at least three times during the pregnancy, more often if seizures are occurring or levels are not normal. Dosage levels should be adjusted accordingly.

Effects of Epilepsy on the Pregnant Patient and the Fetus. Women who become pregnant have a risk for uncontrolled seizures and birth defects from antiseizure medications. In studies of women who were carefully monitored, however, 95% of pregnancies (which is close to normal) had favorable outcomes.

Isolated seizures do not appear to pose any adverse effects to the mother or the unborn child, but repeated seizures and status epilepticus can lead to great dangers. In one study, the effect of epilepsy on complications during pregnancy was the same as in non-epileptic women except for a higher rate of premature deliveries (8.2% in the women with epilepsy).

Drugs Used During Pregnancy. Some types of anti-epileptic drugs (AEDs) can increase the risks for birth defects, especially when taken during the first trimester of pregnancy. Expert guidelines advise that pregnant women use the most effective medication for their type of epilepsy at the lowest dose possible to control seizures. They should also have their doctors take blood tests during pregnancy to monitor their drug levels.

The fetus should be carefully monitored with ultrasonic evaluation and sometimes amniocentesis (visual tests and examination of the fluid in the womb for birth defects and other fetal problems).

In general, research indicates that 90% of women who take AEDs will give birth to healthy children. Still, doctors recommend that women of child-bearing age use a drug other than valproate if possible.

The risk for malformation is higher when more medications are used. For example, there is a 3% risk of birth defects with women who use one anticonvulsant. The risk increases to 20% when four drugs are used.

Birth Defects Associated with Medication. The most common birth defects related to anti-epileptic drugs are:

Cleft lip or palate (risks from lamotrigine, phenobarbital, phenytoin, valproate especially when taken during the first trimester).
Genital or urinary abnormalities (risk from most standard drugs).
Neural tube defects (NTD) in the skull or spinal column (risk of 2% with valproate and 1% with carbamazepine). These complications are most often due to lower folic acid levels caused by both pregnancy itself and antiseizure drugs. Folic acid supplements can help prevent this problem.
Mental impairment (known risk with phenytoin and valproate; inconclusive in carbamazepine and phenobarbital).
Heart defects (risk from phenobarbital, phenytoin, valproate).

Many antiseizure drugs also cause a deficiency in vitamin K clotting factors that increases the risk for hemorrhage in the newborn. Treatment with vitamin K during the last month of pregnancy and a single dose given to the newborn is recommended.

Labor and Delivery. Seizures occur during labor and after delivery in a small percentage of women with epilepsy. The following labor complications are more common among pregnant women with epilepsy: Vaginal bleeding, anemia, and preeclampsia (extremely high blood pressure in the third trimester). If seizures occur during labor, they are generally treated intravenously with benzodiazepines or phenytoin. If tonic-clonic seizures, absence seizures, or status epilepticus occur, a cesarean section may be appropriate.

Postnatal Care

Monitoring the Infant. The infant should be thoroughly examined for any birth defects. Also, if the mother was given phenobarbital or primidone while pregnant, the infant should be monitored for up to 8 months to see if withdrawal symptoms develop. Drug dosages will also need to be adjusted for the mother after delivery.

Breast-feeding. Women on most AEDs typically can nurse their babies, since usually only a small amount of the drug enters the breast milk. The lowest levels are with phenytoin and valproate. (Ethosuximide and possibly levetiracetam are exceptions and should be avoided when a woman is breast-feeding. Women taking phenobarbital are also usually advised not to nurse.) A mother should watch for signs of lethargy or extreme sleepiness in her infant, which could be caused by her medication.

Diagnosis

An epilepsy diagnosis is often made during an emergency visit for a seizure. If a person seeks medical help for a previous or suspected seizure, the doctor will ask about the patient's medical history, including seizure events.

Conditions that cause similar symptoms to epilepsy include:

Syncope. Syncope, a brief lapse of consciousness in which blood flow is reduced to the brain, can mimic epilepsy. It often misdiagnosed as epilepsy. Patients with syncope do not have the rhythmic contracting and then relaxing of the body's muscles.
Migraines. Migraine headaches, particularly migraine with auras, may sometimes be confused with epilepsy. With epileptic seizure, the preceding aura is often seen as multiple, brightly colored, circular spots, while migraine sufferers tend to see black, white, or colorless lined or zigzag flickering patterns. Typically the migraine pain expands gradually over minutes toward one side.
Panic Attacks. In some patients, partial seizures may resemble a panic disorder. Symptoms of panic disorder include palpitations, sweating, trembling, sensation of breathlessness, chest pain, feeling of choking, nausea, faintness, chills or flushes, fear of losing control, and fear of dying.
Narcolepsy. Narcolepsy, a sleep disorder that causes a sudden loss of muscle tone and excessive daytime sleepiness, can be confused with epilepsy.

Electroencephalogram (EEG). The most important diagnostic tool for epilepsy is an EEG, which measures brain waves. Ideally, it should be performed within 24 hours of a seizure. An EEG recording session may last for less than an hour, but in some cases the doctor will want a day-long recording. Long-term monitoring may be necessary in some cases when patients do not respond to medications. Portable EEG units are available in some places, which can be used to monitor patients throughout normal activities. EEGs are not foolproof. Repeated EEGs are often needed to confirm a diagnosis, particularly for certain partial seizures that often produce an initially normal EEG reading.

Video Electroencephalography (Video EEG). For this task, patients are admitted to a special part of the hospital where they are monitored both by EEG and are also watched by a video camera. Patients may need this for a variety of reasons including withdrawal or addition of medications in a patient with difficult-to treat-epilepsy, before epilepsy surgery for some patients, and also when psychogenic nonepileptic seizures are suspected.

Computerized Tomography (CT) Scans. Usually, the first brain imaging test ordered for most adults and children with first-time seizures is a CT scan. This imaging technique is sensitive enough for most purposes. In children, even if the scan is normal, the doctor will follow up to be sure other problems are not present.

A CT (computed tomography) scan is a much more sensitive imaging technique than x-ray, allowing high definition of both the bony structures and the soft tissues. Clear images of organs such as the brain, muscles, joint structures, veins and arteries, as well as anomalies like tumors and hemorrhages may be obtained with or without the injection of contrasting dye.

Magnetic Resonance Imaging (MRI). Experts strongly recommend MRIs for children with first seizures in certain cases, such as children under 1 year old and those with seizures that are associated with any unexplained significant mental or motor problems. These images may help to determine if the disorder can be treated with surgery, and may be used as a guide for surgeons.

Other Advanced Imaging Techniques. More advanced scanning techniques are emerging as important tools for epilepsy researchers. By detecting abnormalities, such as changes in brain activity, positron emission tomography (PET) may help locate damaged or scarred locations in the brain where partial seizures are triggered. These findings may help determine which patients with severe epilepsy are good candidates for surgery. Single-photon emission computer tomography (SPECT) may also be used to decide if the surgery should be performed and what part of the brain needs to be removed. Both of these imaging techniques are generally only needed when an MRI of the brain has not been helpful.

Treatment

You cannot stop a seizure, but you can help the patient prevent serious injury.

Remain calm, and do not panic, then take the following actions:

Wipe away any excess saliva to prevent obstruction of the airway. Do not put anything in the patient's mouth. It is an old wives' tale that people having seizures will swallow their tongues.
Turn the victim gently on the side. Do not try to hold the patient down to prevent shaking.
Rest the patient's head on something flat and soft to protect it from banging on the floor and to support the neck.
Move sharp objects out of the way to prevent injury.

Do not leave the seizure victim alone. Anyone nearby should call 911. Patients should be taken to an emergency room when:

A first-time seizure occurs
Any seizure lasts beyond 2 - 3 minutes
The patient has been injured
The patient is pregnant
The patient is diabetic
Parents, caregivers, or bystanders are at all uncertain

Not all patients with chronic epilepsy need to go to the hospital after a seizure. Hospitalization may not be necessary in many patients whose seizure is not severe or repetitive, and who have no risk factors for complications. All patients or caregivers, however, should contact their doctor after a seizure occurs.

Initial Management. The earlier a patient is treated, the better the results. Initial management of status epilepticus consists of:

Administer any seizure medications
Support systems to maintain or attain normal breathing, blood pressure, electrolyte balances, body temperature, and heart functions
Oxygen for patients who may need it
Attention by medical personnel trained to determine any treatable cause of status epilepticus, such as drug withdrawal, low blood sugar, infection, substance abuse (particularly cocaine), or eclampsia (elevated blood pressure induced by pregnancy)

Medications for Status Epilepticus. Doctors will try one or more of the following medications initially:

Benzodiazepine. An intravenously (IV), intramuscularly, or rectally administered benzodiazepine such as lorazepam (Ativan), diazepam (Valium), clonazepam, or midazolam (Versed) is usually used.
Phenytoin or Fosphenytoin. Many doctors use phenytoin or fosphenytoin if seizures are not controlled by a benzodiazepine.
Phenobarbital. Although effective, barbiturates, such as phenobarbital (Barbita, Luminal), are generally used only when other drugs have failed.

All of these medications carry a risk for hypotension, an abrupt and possibly dangerous drop in blood pressure, which may require treatment.

Treatment After The First Seizure

Children with febrile seizures rarely have any long-term effects and generally do not require drug treatment. In very rare cases, children experience severe fever-related seizures known as complex febrile convulsions. In such cases, there is a risk for brain injury that may lead to temporal lobe epilepsy, but this is very small. Such seizures last over 15 minutes, occur more than once within 24 hours, and may affect only one side of the body.

Treatment with anti-epileptic drugs (AEDs) is usually initiated or strongly considered for the following patients:

Children and adults who have had two or three seizures, unless there is either a long separation between seizures or the seizure is provoked by an injury or other specific causes. (In children, risk for recurrence after a single unprovoked seizure is rare. The risk even after a second seizure is low, even when the seizure is prolonged.)
Children and adults after a single seizure if tests reveal any brain injury, or if specific syndromes put a person at special risk for recurrence, for instance, in cases of myoclonic epilepsy.

There is some debate about whether to treat every adult patient with an AED after a single initial seizure. Some experts do not recommend treating adult patients after a single seizure if they have a normal neurologic examination, EEG, and imaging studies. A 2005 study of patients with single or infrequent seizures found that while early AED treatment reduced the risk of seizure for a few years, it had no effect on long-term outcomes. This study also suggested that delaying AED treatment does not increase the risk of developing lifelong epilepsy.

Some doctors believe, however, that any adult who has a first seizure should begin on-going AED treatment, since 30 - 70% of these patients are likely to experience a subsequent event. According to one study, when young adults were given a single drug (usually carbamazepine) after a first generalized seizure, only 22% had a subsequent seizure compared to about 70% of those who were not given treatment.

Most epileptic seizures can be controlled using a single-drug regimen. First-line AED drugs include phenytoin (Dilantin), carbamazepine (Tegretol, Carbatrol), and divalproex sodium (Depakote). Patients generally begin with low doses and build up until the seizures are controlled or a toxic reaction occurs. If a single drug fails to control seizures, other drugs are added on. The specific drugs and whether more than one should be used are determined by various factors, including the patient's age and the seizure's type, frequency, and cause.

Drugs fail to control epilepsy in about 30% of patients. For patients who have little or no benefit from their initial drug regimen the likelihood of good or complete control from different medications or multidrug regimens is not very high.

Reasons for Failure. An AED may fail to reduce seizures due to such factors as:

The wrong dose level.
Improper timing.
Introducing the medication too rapidly.
Not managing conditions that triggered the seizure.
Instability of the drugs. Many of the tablet forms disintegrate easily with moisture, so pills should be stored in a dry place, not in the bathroom, and kept away from heat.
Patients not taking medication as prescribed. Over 40% of patients experience toxic or bothersome effects from older AEDs, which often causes them to withdraw. Among the most distressing are sleepiness, problems in coordination, and weight gain.
Some evidence suggests that about a quarter of patients who do not respond to AEDs actually have nonepileptic seizures that in many cases are caused by psychiatric conditions (such as panic attack or personality disorders).

The doctor should first address these issues. If the patient still does not respond, the doctor will usually try a different drug. If this fails, one or even two additional drugs at a time may be used. When seizures do not respond to the first two or three drugs, the odds of a fourth or fifth working diminish greatly, despite a number of new medications on the market. In such cases, the patient should ask about surgical alternatives.

Healthy Behaviors. In young people, a positive attitude, continued support from family and health care providers, emotional well-being, and good treatment results can increase patient compliance. Unhealthful behaviors, such as smoking and alcohol use, can have a negative effect.

During the first few months of therapy, the doctor will probably order blood tests once or twice to monitor drug levels and, if necessary, adjust dosages. Monitoring is used to check for AED complications, and to be sure the patient is complying with the regimen. Many experts feel, however, that these blood tests are a less reliable indicator of problems than the patient's own self-observations of his or her responses to the drug. For instance, blood tests may suggest that the dosage levels are insufficient according to general standards, yet the individual patient may be seizure-free and leading a normal life. It is very important that women have AED levels monitored during pregnancy.

An estimated 60% of all patients treated effectively can stop taking AEDs within 5 - 10 years. Evidence suggests that medications in children should not be halted for at least 2 years after the last seizure, particularly if they have partial seizures and abnormal EEGs. It is not clear whether children who have been free of generalized seizures need to wait more than 2 years or if they can withdraw earlier.

Children who tend to relapse after withdrawal from treatment usually have the following conditions or situations:

A family history of epilepsy
Require multiple medications to control seizures
Abnormal EEG readings after treatment has started
Partial seizures

There is also no clear evidence on whether adults who are free of any seizure type can safely withdraw from their medications within 2 years of their last seizure of if they should wait.

In any case, attempts to halt drugs should be done during periods when seizures will cause the least harm. For instance, the best time to test the effects of drug withdrawal in teenagers might be about a year before they are eligible to drive.

Anti-epileptic drugs interact with many other drugs, and may cause special problems in older patients who use multiple medications for other health problems. Elderly patients should have liver and kidney function tests performed before starting antiseizure medication. Standard drugs are usually effective, while safe, newer ones (including gabapentin, lamotrigine, oxcarbazepine, and gamma-vinyl-GABA) may sometimes prove to be useful as a sole therapy. These newer drugs also increase patient compliance because they tend to have fewer side effects than the older ones.

Hormonal fluctuations affect epilepsy in about a third to a half of female patients. Estrogen appears to increase activity, and progesterone reduces it. The effect of pregnancy on women with epilepsy is complex. The following treatments may help or affect women with epilepsy:

Hormonal Drugs that Suppress Ovulation. When seizures in women are worsened by hormonal changes, such as during the menstrual cycle, suppressing ovulation may be recommended using drugs called gonadotropin-releasing hormone agonists.
Oral contraceptives. Antiseizure medications affect many oral contraceptives (OCs). Carbamazepine, phenytoin, phenobarbital, primidone, oxcarbazepine, and topiramate reduce the effects of OCs. Valproate does not, and may even increase hormonal levels. Gabapentin, lamotrigine, tiagabine, and vigabatrin may also prove to be safe with OCs, but more research is needed. Progestins may be the best contraceptive drugs for women with epilepsy at this time. Injected progestins may actually help prevent seizures in some cases.

More information on epilepsy and pregnancy can be found in this report under Outlook and Effects.

Medications

Many newer anti-epilepsy drugs (AEDs) are now available and are usually better tolerated than the older, standard AEDs. They often cause less sedation and require less monitoring. Although they are generally approved for use as add-ons to standard drugs that fail to control seizures, many doctors are now prescribing them as single drugs. Specific choices usually depend on the individual's particular condition and the specific side effects of the AED. None has emerged as being superior to either standard or newer drugs. All appear to offer some benefits, but, as with standard antiseizure drugs, they also have troublesome side effects.

Valproate (Depakene, valproic acid) and its delayed release form, divalproex sodium (Depakote), are anticonvulsants. Valproate is the most widely prescribed anti-epileptic drug worldwide.

Uses. Valproate is the first choice for patients with generalized seizures and is used to prevent nearly all other major seizures as well.

General Side Effects. These drugs have a number of side effects that vary depending on dosage and duration. Most side effects occur early in therapy and then subside. General side effects include:

Stomach and intestinal problems, which are experienced by nearly half of patients after starting the drugs and may still occur after several years of use. Divalproex sodium (Depakote) has a lower risk for these side effects than valproate (Depakene).
Increased appetite with significant weight gain often becomes a problem and can be a major reason for noncompliance, particularly in young people.
Hand tremors, irritability, and hyperactivity in children are fairly common.
Temporary hair thinning and hair loss have occurred. Taking zinc and selenium supplements may help reduce the effect.
Young girls may develop secondary male characteristics, and premenopausal women are at increased risk for menstrual irregularities and polycystic ovaries, due to elevated male hormones. The effects are reversible. (These side effects also appear in women using other anti-epileptic drugs, but the risk from valproate appears to be higher.)
Studies have reported symptoms of Parkinson's disease preceded by hearing loss in people who have taken it for more than a year, but they were reversible when the drug was withdrawn.
Valproate poses a higher risk for serious birth defects than many other AEDs. These birth defects include skull and limb deformities, and brain, heart, and lung problems. Experts recommend that women of child-bearing age use a different type of anti-epilepsy drug than valproate. If valproate is used, it should be prescribed at the lowest possible dose.
Cases of pancreatitis, a serious and even life-threatening inflammation in the pancreas, have been reported in children and adults taking valproate. (It is still very rare, however.)
Valproate and divalproex sodium are not usually recommended for young children because of an unusual, but potentially fatal, toxic effect on the liver. This very rare effect is most likely to affect children under 2 years of age who have birth defects and are taking more than one antiseizure drug. Some doctors recommend monitoring blood levels for liver function once prior to administering valproate or divalproex sodium, monthly during the first 6 months, and then periodically after that.
Children with epilepsy who take valproic acid may eventually develop some problems in the kidney, although they are generally not significant.

Symptoms of Toxic Side Effects in Liver or Pancreas.

Abdominal pain
Nausea or vomiting
Loss of appetite
Lethargy
Acute confusion
Water retention
Easy bruising
Yellowish skin coloring

Carbamazepine (Tegretol, Equetro, Carbatrol) is an effective anticonvulsant and specific analgesic when used alone or with other drugs. Carbamazepine also has the added benefit of relieving depression and improving alertness. An extended release form is available that allows twice-daily dosing rather than 3 times a day. A chewable form makes it easier for children to take.

Uses. This drug is used to prevent the following seizures or epilepsy syndromes:

Partial seizures. Patients tend to tolerate this drug better than others, although responses differ among individuals
Grand mal seizures
Combinations of grand mal and partial seizures
Autosomal dominant nocturnal frontal lobe epilepsy (an inherited disorder).

Side Effects. Different side effects may develop or resolve at different points in the treatment duration. Initial side effects may include:

Double vision, headache, sleepiness, dizziness, and stomach upset. These usually subside after a week and can be greatly reduced by starting with a small dose and building up gradually.
Some people experience visual disturbances, ringing in the ears, agitation, or odd movements when drug levels are at their peak. The extended-release form of carbamazepine (Carbatrol) may help reduce these symptoms.

Serious side effects are less common but can include:

Carbamazepine may increase the risk for birth defects, especially if it is taken during the first trimester of pregnancy.
Skin reactions, including toxic epidermal necrolysis and Stevens-Johnson syndrome, so severe the drug has to be discontinued develop in about 6% of patients. These skin reactions cause skin lesions, blisters, fever, itching, and other symptoms. People of Asian ancestry have a 10 times greater risk for skin reactions than other ethnicities. The FDA recommends that patients of Asian ancestry get a blood test prior to starting the drug to determine if they have the gene variant that increases this risk.
Water retention can be a problem in older people.
Hormonal changes, particularly higher levels of male hormones in both men and women, pose some risk for sexual dysfunction over time.
A decrease in white blood cells occurs in about 10% of those taking the drug. This is generally not serious unless infection accompanies it.
Other blood conditions can arise that are also potentially serious. Patients should be sure to inform the doctor if they have any sign of irregular heartbeats, sore throat, fever, easy bruising, or unusual bleeding.
Long-term therapy can cause bone loss (osteoporosis) in women, who should take preventive calcium and vitamin D supplements.
Children are at higher risk for behavioral problems.

Note: Citrus fruit, especially grapefruit, can increase carbamazepine's adverse effects and should be avoided by those taking this drug.

Uses. Phenytoin (Dilantin) is effective for adults who have the following seizures or conditions:

Grand mal seizures
Partial seizures
Status epilepticus
Can be effective for people with head injuries who are at high risk for seizures

This drug is not useful for the following seizures:

Petit mal seizures
Myoclonic seizures
Atonic seizures

Side Effects. Side effects are sometimes difficult to control. Some people may develop a toxic response to normal doses, while others, such as those with alcoholism, may require higher doses to achieve benefits. As with any drug, side effects generally rely on dosage and duration. Using phenytoin in combination with newer add-on drugs can allow lower doses and may reduce some of the risks. Side effects may include:

Excess body hair, eruptions and coarsening of the skin, and weight loss
Gum disease
Staggering, lethargy, nausea, depression, eye-muscle problems, anemia, and an increase in seizures can occur as a result of high doses.
Liver damage may develop in rare cases.
Bone loss from long-term therapy. Patients should take preventive calcium and vitamin D supplements and exercise regularly to improve bone mass.
Severe and even rare life-threatening skin reactions (Stevens-Johnson syndrome)
An increased risk for birth defects

Phenobarbital (Luminal), also called phenobaritone, is a barbiturate anticonvulsant and is often the initial drug prescribed for newborns and young children. It is a relatively inexpensive drug. Primidone (Mysoline) is converted in the body to phenobarbital, and has the same benefits and adverse effects. It is reported that primidone is not as well-tolerated as phenobarbital. Some experts believe that primidone has no advantage over the other drug.

Uses. Barbiturates are used to also prevent grand mal (tonic-clonic) seizures or partial seizures. They are no longer typically used as a first-line drug.

Side Effects. Phenobarbital has fewer toxic effects on other parts of the body than most anti-epileptic drugs, and drug dependence is unusual, given the low doses used for patients with epilepsy. Nevertheless, withdrawal is common because of side effects, and therefore it is less likely to be used over time than other drugs, including phenytoin, another relatively inexpensive but effective drug.

Patients sometimes describe their state as "zombie-like." The most common and troublesome side effects are:

Drowsiness
Memory problems
Problems with tasks requiring sustained performance
Problems with motor skills
Hyperactivity in some patients, particularly in children and the elderly
Depression in some adults

Some controversy has arisen over studies indicating that children taking phenobarbital score lower on intelligence tests, even for some months after going off the drug.

Uses. Ethosuximide (Zarontin) is used for petit mal (absence) in children and adults when the patient has experienced no other type of seizures. Ethosuximide succeeds in abolishing petit mal seizures in 60% of patients and controls them in up to 90%. Methsuximide (Celontin), a drug similar to ethosuximide, may be suitable as an add-on treatment for intractable epilepsy in children without causing serious or permanent side effects.

Side Effects. Use of this drug can cause stomach problems, dizziness, loss of coordination, and lethargy. In rare cases, it has caused severe and even fatal blood abnormalities. Periodic blood counts are recommended for patients taking this drug.

Uses. Clonazepam (Klonopin) is recommended for myoclonic and atonic seizures that cannot be controlled by other drugs and for Lennox-Gastaut (absence variant). It may be useful in newborns when other drugs are ineffective. Although clonazepam can prevent generalized or partial seizures, patients generally develop tolerance to the drug, and then seizures recur.

Side Effects. People who have had liver disease or acute angle glaucoma should not take clonazepam, and people with lung problems should approach the drug with caution. Clonazepam can be addictive, and abrupt withdrawal has been known to trigger status epilepticus. Side effects include the following: drowsiness, imbalance and staggering, irritability, aggression, hyperactivity in children, weight gain, eye muscle problems, slurred speech, tremors, skin problems, and stomach problems.

Uses. Lamotrigine (Lamictal) is approved as add-on (adjunctive) therapy for partial seizures, and generalized seizures associated with Lennox-Gastaut syndrome, in children aged 2 years and older and in adults. Lamotrigine is also approved as add-on therapy for treatment of primary generalized tonic-clonic (PGTC) seizures, also known as “grand mal” seizures, in children aged 2 years and older and adults. Lamotrigine can be used as a single drug treatment (monotherapy) for adults with partial seizures who have not responded to monotherapy with carbamazepine, phenytoin, phenobarbital, primidone, or valproate. Birth control pills lower blood levels of lamotrigine.

Side Effects. Common side effects include dizziness, headache, blurred or double vision, lack of coordination, sleepiness, nausea, vomiting, insomnia, and rash. Although most cases of rash are mild, in rare cases the rash can become very severe. The risk of rash increases if the drug is started at too high a dose or if the patient is also taking valproate. (Serious rash is more common in young children who take the drug than it is in adults.) Rash is most likely to develop within the first 8 weeks of treatment. Be sure to immediately notify your doctor if you develop a rash, even if it is mild.

Studies suggest that lamotrigine may cause fewer problems with sexual function in men than other antiseizure drugs. A 2006 study indicated that lamotrigine may cause fewer cognitive problems (such as confusion and difficulty concentrating) than topiramate.

Gabapentin (Neurontin) is an effective add-on drug for controlling complex partial seizures and secondarily generalized partial seizures and is approved for adults and children with these seizures. It has achieved response rates in patients with resistant partial epilepsy. It is not at all useful for generalized petit mal seizures.

Side Effects. Its toxicity is low, and side effects include sleepiness, headache, fatigue, and dizziness. Some weight gain has been reported. Gabapentin has no significant interactive effects when taken with other drugs. Children may experience hyperactivity or aggressive behavior. Long-term adverse effects are still unknown.

Pregabalin (Lyrica) is similar to gabapentin.

Uses. Approved as add-on therapy to treat partial-onset seizures in adults with epilepsy. In clinical trials, half of the patients who received pregabalin experienced a 50% reduction in seizure frequency.

Side Effects. These may include dizziness, sleepiness, dry mouth, swelling in hands and feet, blurred vision, weight gain, and trouble concentrating

Uses. Topiramate (Topamax, generic) is similar to phenytoin and carbamazepine and is effective and safe for a wide variety of seizures in adults and children. It is approved as add-on therapy for patients 2 years and older with generalized tonic-clonic seizures, partial-onset seizures, or seizures associated with Lennox-Gastaut syndrome. It is also approved as single therapy for patients 10 years and older with tonic-clonic seizures or partial-onset seizures. Studies have shown a 34 - 87% reduction in seizure frequency with some patients becoming seizure-free.

Side Effects. Most side effects are mild to moderate and can be reduced or even prevented by beginning at low doses and increasing dosage gradually. Serious side effects may include glaucoma, decreased sweating, increased body temperature, kidney stones, sleepiness, dizziness, confusion, and trouble concentrating. Patients should immediately tell their doctor if they have blurred vision or eye pain. Topiramate may have fewer interactions with oral contraceptives than other AEDs.

Oxcarbazepine (Trileptal, generic) is similar to phenytoin and carbamazepine but generally has fewer side effects.

Uses. Approved as single therapy or add-on therapy for partial seizures in adults and for children ages 4 years and older.

Side Effects. Serious side effects, while rare, include Stevens-Johnson syndrome and toxic epidermal necrolysis. These skin reactions cause a severe rash that can be life threatening. Rash and fever may also be a sign of multi-organ hypersensitivity, another serious side effect associated with this drug. Oxcarbazepine can also reduce sodium levels (hyponatremia). Your doctor may want to monitor the sodium level in your blood. This drug can also reduce the effectiveness of birth control pills. Women who take oxcarbazepine may need to use a different type of contraceptive.

Zonisamide (Zonegran) is a unique drug that blocks sodium and calcium channels and may have nerve-protecting properties.

Uses. It is approved as add-on therapy for adults with partial seizures, and studies indicate it is often effective against infantile spasms (West syndrome) and myoclonic seizures.

Side Effects. Zonisamide increases the risk for kidney stones, which can be reduced with increased fluid intake and citrate. It has also been associated with reduced sweating and a sudden rise in body temperature, especially in hot weather. Children are especially at risk for this side effect, which can be serious. (The drug has not been approved for children.) Other side effects tend to decrease over time and include dizziness, forgetfulness, headache, weight loss, and nausea.

Levetiracetam (Keppra) is known as a nootropic drug.

Uses. This drug is approved both in oral and intravenous forms as add-on therapy for:

Partial onset seizures in adults and children ages 4 years and older
Myoclonic seizures in adults and adolescents ages 12 years and older who have juvenile myoclonic epilepsy
Primary generalized tonic-clonic seizures in adults and children ages 6 years and older who have idiopathic generalized epilepsy

Some experts believe that levetiracetam represents a significant advance and will prove to be an important first-line drug. Levetiracetam appears to have fewer drug interactions than other anti-epileptic drugs and may be particularly useful for older patients.

Side Effects. These tend to occur mostly in the first month. They include sleepiness and fatigue, muscle weakness and coordination difficulties, headache, flu symptoms, dizziness, behavioral abnormalities, possible risk of a reduced white blood cell count, and a higher rate of infections. Caution is advised for patients with kidney dysfunction. There have been some reports of adverse effects on mood (irritability, depression, and anxiety), but recent studies have found fewer such effects than with other AEDs. Epilepsy, rather than the drug, is likely to be the cause of these mood changes. About 1% of patients report considerable weight loss.

Tiagabine (Gabitril) has properties similar to phenytoin and carbamazepine, and is also showing promise.

Side Effects. Evidence has reported some significant side effects with its use, including dizziness, fatigue, agitation, and tremor. At least one study suggested that it has more adverse effects than lamotrigine and is not as well tolerated. In February 2005, the FDA issued a warning advising that tiagabine may cause seizures in patients without epilepsy. Tiagabine is only approved for use with other anti-epilepsy medicines to treat partial seizures in adults and children 12 years and older.

Felbamate. Felbamate (Felbatol) is an effective antiseizure drug. However, after reports of deaths from a serious blood condition known as aplastic anemia or from liver failure, felbamate is recommended only under certain circumstances. They include severe epilepsy, such as Lennox-Gastaut syndrome or as monotherapy for partial seizures in adults when other drugs fail.

Vigabatrin. Vigabatrin (Sabril) is a chemical called gamma-vinyl GABA. It was designed to increase the brain levels of gamma aminobutyric acid (GABA), the enzyme that inhibits seizure activity. It has serious side effects, however, and is generally prescribed in the U.S. only in certain cases, such as in low doses for patients with Lennox-Gastaut syndrome. Overseas it is also used for partial seizures and as first-line therapy in children with infantile spasms (West syndrome). Between 10 - 30% of people on long-term treatment have developed irreversible visual disturbances, including reductions in acuity and color vision. Men are at higher risk for this side effect than are women. Further studies are needed to determine the extent and severity of this complication, particularly in children. There is a slight risk for depression or psychosis when vigabatrin is used as add-on therapy, and particularly if the drug is administered too quickly. These risks are far lower if the drug is used as sole therapy.

Older Drugs. Some older but less effective drugs may still play a role against epilepsy:

Acetazolamide (Diamox) is sometimes used against common types of seizures, but patients quickly develop a tolerance for it. Some experts suggest it still may be useful when drug interactions are a problem, when a rapid effect is required, or when an additional drug is needed for a short time.
Trimethadione (Tridione) is effective for petit mal seizures, but has very serious side effects, and its use is severely limited.

Infantile spasms are treated with vigabatrin, adrenocorticotropic hormone (ACTH), or valproate. Some experts recommend that vigabatrin be given first and ACTH administered 10 - 14 days later. In one small study, no infants who were given this combination relapsed after 4 months. Newer drugs may also be effective for this problem, but their effects on small children are not yet wholly known.

New AEDs. Retigabine is an investigational GABA enhancer that works in a different way from existing AEDs. It is currently in phase III trials for treatment of partial-onset seizures in patients who are receiving other AEDs. Talampanel is another new type of drug, known as an AMAP receptor antagonist, that is currently in early trials. Other drugs under investigation are related to existing AEDs. For example, brivaracetam and seletracetam are similar to levetiraceptam, fluorofelbamate is similar to felbamate, and eslicarbazepine is similar to oxcarbazepine.

Cannabinoids. Cannabinoids are compounds in marijuana (cannabis) that may have properties that protect nerve cells. Some patients claim a reduction in seizures while other active users of marijuana report no effect on seizures. No one has reported worse seizures from the drug. Animal studies further support some protection from cannabinoids against seizures. Clinical studies using humans have not been conducted.

Melatonin. Melatonin is a hormone found in the brain that is best known for its role in sleep. Some researchers believe that it might have properties that could benefit patients with epilepsy. Melatonin is a powerful hormone that can have major effects on all parts of the body. No one with epilepsy should experiment with this supplement except as part of a clinical trial. In some studies, melatonin has been found to cause seizures in children who have existing neurologic problems.

Surgery

Surgical techniques to remove injured brain tissue may be appropriate for many patients with epilepsy. The surgeon's goal is to remove only the damaged tissue in order to prevent seizures and to avoid healthy brain tissue. Surgical techniques for reaching these goals have improved significantly over the past decades due to advances in imaging and monitoring, new surgical techniques, and a better understanding of the brain and epilepsy.

A number of tests using imaging and electroencephalography (EEG) can determine if surgery is an option:

The general approach is to first use long-term EEG monitoring to locate the brain tissue that triggers the epileptic event.
Advanced imaging techniques can provide valuable additional information. They include functional magnetic resonance imaging (fMRI), positron emission tomography (PET), or single-photon emission computer tomography (SPECT) scans.

If the imaging tests indicate that more than one site is involved or their results conflict, then more invasive monitoring of the brain may be required, although the newer imaging tests are proving to be very accurate tools. If such tests pinpoint a specific area in the brain as the location for seizures, surgery is possible. MEG, for example, is now approved for imaging parts of the brain involved with motor control, sensation, and language function, and may become important in evaluating patients who are likely candidates for surgery. The doctor will also examine the test results to determine if the offending nerve cells perform vital functions and try to predict surgical outcome in certain cases.

The major areas of the brain have one or more specific functions.

The most common surgical procedure for epilepsy is temporal lobectomy, which is performed when epilepsy occurs in the temporal lobe. (Surgery is not as successful in epilepsies that occur in the frontal lobe.) It involves removing small portions from the hippocampus. The hippocampus is a part of the brain that is involved in memory processing. It is part of the limbic system, which controls emotions.

Click the icon to see an image of the limbic system of the brain.

Candidates. Candidates for this surgery usually have a history of seizures. Anti-epileptic drugs have not helped them. Young children may be more difficult candidates because they often have injured areas outside the temporal lobes. Nevertheless, surgery can be very successful in many children, even if more than one area is involved.

Success Rates. New imaging techniques are dramatically improving the success rates of temporal lobe surgery. Studies have shown that many patients remain seizure-free after temporal lobectomy. In a randomized controlled trial, around 60% of patients became free of disabling seizures after surgery versus only 8% of patients treated with medications. In general, around 60 - 80% of patients are seizure free 1 - 2 years after surgery.

Patients may still need to take medications after surgery, even if seizures are very infrequent. Cure is not always possible, and some patients may still experience some seizures. Double vision is very common after the operation, but it is typically temporary and resolves within a few months.

Studies also suggest that temporal lobe surgery improves quality of life and can help relieve depression and anxiety. Other studies indicate that surgery may even prolong survival. Some experts theorize that surgery stabilizes parts of the brain that influence heart rate and may reduce the risk of sudden death, a rare complication of epilepsy.

Effects on Mental Functioning. Although surgery on the left temporal lobe does not impair intelligence to any significant degree, some studies suggest negative effects of mental functioning and behavior. A risk of impairment of verbal memory is also present.

In general, surgical effects on mental functioning and behavior depend on the extent and location of the surgical area.

Lesionectomy is a procedure that removes abnormal tissues in certain conditions, such as:

Cavernous angiomas (abnormal clusters of blood vessels)
Low-grade brain tumors
Cortical dysplasias (these are abnormalities in fetal development in which the normal migration of nerve cells is altered for some reason)

This local surgery, which can cure the patient's epilepsy, has become possible with the advent of advanced imaging techniques such as MRI.

Other surgical procedures called hemispherectomy and corpus callosotomy offer hope for specific patients. They include infants and young children with catastrophic seizures that occur in one, or part of, a hemisphere and for patients whose seizures are due to specific structural brain abnormalities or tumors.

Hemispherectomy. Hemispherectomy is the removal of half the brain, leaving the deep structures intact. Surgery can take 12 hours and there is always some paralysis on one side of the body. There is also a small risk for hydrocephalus, coma, or even death. Quality of life is almost always improved, however, and the surgery does not reduce intelligence.

Corpus Callosotomy. Corpus callosotomy involves cutting the nerve fibers that connect one side of the brain to another. It does not remove brain tissue. It may be done in two stages. In the first, there is a partial separation. If seizures continue, the surgeon may perform a complete separation. This surgery can reduce (although not entirely stop) uncontrolled tonic clonic seizures. It has been used in patients with specific syndromes, such as Lennox-Gastaut syndrome. The procedure can have very severe complications, however.

Electrical stimulation of areas in the brain that affect epilepsy is helping many patients with refractory epilepsy. Vagus nerve stimulation (VNS), an electrical stimulation of the vagus nerve, is now an accepted therapy for severe epilepsy that does not respond to AEDs. The two vagus nerves are the longest nerves in the body. They run along each side of the neck, then down the esophagus to the gastrointestinal tract. They affect swallowing, speech, and many other functions. They also appear to connect to parts of the brain that are involved with seizures. The procedure is as follows:

Click the icon to see a depiction of epilepsy treatment.

A battery-powered device similar to a pacemaker is implanted under the skin in the upper left of the chest.
A lead is then attached to the left vagus nerve in the lower part of the neck.
The neurologist programs the device to deliver mild electrical stimulation to the vagus nerve. (Patients may also pass a magnet over the device to give it an extra dose if they sense a seizure coming on. This appears to help about 25 - 30% of patients.)
The batteries wear out after 3 - 5 years and need to be removed and replaced by a simple surgical procedure.

An investigational approach called deep brain stimulation (DBS) targets the thalamus, the part of the brain that produces most epileptic seizures. Early results have been promising. Researchers are also studying other implanted brain and nerve stimulation devices such as the responsive neurostimulator system (RNS), which detects seizures and stops them by sending electrical stimulation to the brain. A third investigational approach, trigeminal nerve stimulation (TNS), stimulates a nerve involved in inhibiting seizures.

Candidates. The American Academy of Neurology recommends VNS for:

Patients who are over 12 years old, and
Have partial seizures that do not respond to medication, and
Are not appropriate candidates for surgery

Evidence is accumulating, however, to indicate that VNS is effective and safe for many patients of all ages and for refractory epilepsy of many types.

Success Rates. Studies are reporting that the procedure reduces seizures within 4 months by up to 50% and even more in many patients. Studies report that it has been effective for longer than 7 years. In one study that followed patients for a year, the benefits of VNS appeared to increase over time.

Complications. Vagus nerve stimulation does not eliminate seizures in most patients and is still somewhat invasive. VNS can cause shortness of breath, hoarseness, sore throat, coughing, ear and throat pain, or nausea and vomiting. These side effects can be reduced or eliminated by reducing the intensity of stimulation. Some studies suggest that the treatment causes adverse changes in breathing during sleep and may cause lung function deterioration in people with existing lung disease. People who have obstructive sleep apnea also should be cautious about this procedure. Turning off the VNS (for example before an MRI or surgery) may increase the risk for status epilepticus. (However, VNS may also be helpful for treating status epilepticus in some patients.)

Stereotactic Radio Surgery. Focused beams of radiation are able to destroy lesions deep in the brain without the need for open surgery. Typically used for brain tumors, stereotactic radio surgery is also under investigation for temporal lobe epilepsy and for seizures due to cavernous malformations. It may be used for patients when an open surgical approach is not possible.

Lifestyle Changes

The best preventive measure is to comply strictly with the drug regimen as prescribed. Seizures cannot be prevented by lifestyle changes alone, but people can make behavioral changes that improve their lives and give them a sense of control.

In most cases, there is no known cause for epileptic seizures, but specific events or conditions may trigger them and should be avoided.

Inadequate or Fragmented Sleep. Inadequate or fragmented sleep can set off seizures in many people. In one study, the lowest risk for seizures was during REM sleep (when dreams occur). The highest risk was during light non-REM stages of sleep. Using sleep hygiene or other methods to improve sleep may be helpful.

Food Allergies. Food allergies may provoke seizures in children who also have migraine headaches, hyperactive behavior, and abdominal pains. Parents should consult an allergist if they suspect foods or additives might be playing a role in such cases.

Alcohol and Smoking. Alcohol and smoking should be avoided, although light alcohol consumption does not appear to increase seizure activity in people who are not alcoholics or sensitive to alcohol.

Flashing Lights. Patients should avoid exposure to flashing or strobe lights. Video games have been known to trigger seizures in people with existing epilepsy, but apparently only if they are already sensitive to flashing lights. Seizures have been reported in Japan among people who watched cartoons with rapidly fluctuating colors and quick flashes. The frequency of flashes per second is measured in hertz (Hz). Screens that emit a lower hertz (such as 50 Hz screens sold in Europe) are more likely to cause seizures in people with epilepsy than a higher-hertz screen (such as 100 Hz screens sold in the U.S.).

Relaxation methods include diaphragmatic rhythmic breathing, biofeedback, and meditation techniques. No strong evidence supports their value on reducing actual attacks (although some people have reported that they have), but they may be helpful in reducing anxiety in people who have positive experiences with them. There have been some reports that deep breathing (a common relaxation technique) triggers seizures in certain people.

Exercise is important for many aspects of epilepsy, although it can be problematic. Weight-bearing exercise helps maintain bone density, which can be reduced by many of the medications, particularly the older ones. Exercise can also help to prevent weight gain, which is a problem with some drugs. There have been some reports that exercise may trigger seizures in some patients, but this is uncommon. A number of studies have found no significant association between physical activity and a higher incidence of seizures in patients with epilepsy. Nevertheless, if patients are concerned they should discuss this issue with their doctors.

Some small studies have reported significant benefits from the practice of yoga, which employs weight bearing and balancing postures. In one study, a system of meditation called Sahaja yoga changed EEG readings of brain waves and reduced seizures. Other studies report a 50% reduction in seizures and an overall decline in the number of attacks per month. Still, well-controlled studies are needed to confirm these benefits.

All patients should maintain a healthy diet, including plenty of whole grains, fresh vegetables, and fruits. In addition, dairy foods may be important to maintain calcium levels. Fasting has been used to prevent seizures since ancient times. In the 1920s, a high-fat, no-sugar, low protein diet, known as a ketogenic diet, was used to prevent seizures. It lost popularity after the introduction of anti-epileptic drugs but is now proving to be effective with many children. Researchers are investigating whether the Atkins diet (high protein, low carbohydrate) may help people with epilepsy. Both the ketogenic diet and the Atkins diet can interfere with some anti-epileptic medications such as topiramate. Talk to your doctor before beginning any special diet or a weight loss program.

The ketogenic diet, which is very high in fat (90%), very low in carbohydrates, and low in protein, has been studied and debated for decades. It has proven to be helpful for many children with severe epilepsy that does not respond to AEDs. It is not clear why it works. The standard theory is that burning fat instead of carbohydrates causes an increase in ketones. Excess ketones (called ketosis) appears to alter certain amino acids in the brain and to increase levels of the neurotransmitter gamma aminobutyric acid (GABA), which helps prevent nerve cells from over-firing.

Benefits of the Ketogenic Diet. Studies report that about 10 - 15% of children who use the diet are seizure free after 1 year, while 30% are nearly seizure free. Some parents report that the diet helps improve their children’s alertness, even if seizures continue. Many children who try the ketogenic diet are able to stop or at least reduce their medications.

Candidates of the Ketogenic Diet. The Ketogenic Diet seems to be most helpful for children who have difficult-to-control seizures, in particular:

Generalized and partial seizures (the diet does not appear to be as helpful for children with partial-onset seizures)
Myoclonic-atastic epilepsy
Infantile spasm

Typical Ketogenic Diet. (This diet must be professionally monitored! Parents can endanger their children if they try the program on their own without consulting a doctor or trained health expert.) The child fasts for the first 1 - 2 days, then the diet is gradually introduced. The regimen uses small amounts of carbohydrates and large amounts of fats (up to 90%), with very few proteins and no sugar. Children generally consume 75% of their usual daily calorie requirements.

A typical dinner may include a chicken cutlet or piece of fish, broccoli with cheese, lettuce with mayonnaise, and a whipped cream sundae. Vegetables may include celery, cucumbers, or asparagus, cauliflower, and spinach. Breakfast might consist of an omelet, bacon, and cocoa with cream. (Artificial sweeteners are used for any desserts.)

The diet is difficult, as a slight deviation from the diet can provoke a seizure. Children cannot take medications that contain sugar (which is common in many drugs produced for children). Some sunscreens and lotions contain sorbitol, a carbohydrate that can be absorbed through skin. About 40 - 50% of patients find the diet too difficult or ineffective and stop it after 6 months.

Researchers are also investigating the Atkins diet, a popular weight-loss diet that has similar effects but is less restrictive than the ketogenic diet. Early results indicate that it might be helpful for some young people. Another alternative is a low glycemic index diet, which contains even fewer carbohydrates than the Atkins diet. Still, parents should not put their children on these diets without support from a doctor.

Side Effects and Complications. To prevent serious side effects, children need regular monitoring by a doctor, especially when the diet is first initiated.

Side effects or complications that may occur at the start of the diet include:

Acidosis, a build-up of acid in the blood and body
Low blood sugar (hypoglycemia)
Stomach upset
Dehydration
Lethargy

Side effects that may occur later on include:

Unhealthy cholesterol and lipid levels
Kidney stones, which may be a complication of acidosis, occur in about 5% of children on the diet. Patients should drink plenty of fluids. Oral potassium citrate (Polycitra K) may be protective.
Slowing of growth (tends to occur more in younger children than older children
Decreased bone density

Because most patients remain on the diet for only 2 years, the risks for potential long-term damage appear minimal.

Many patients with epilepsy and parents whose children have epilepsy can benefit from support associations. These services are usually free and available in most cities.

Tips for Helping Children. Some of the following tips may help the child with epilepsy:

Children should be treated as normally as possible by parents and siblings.
Children should be assured that they will not die from epilepsy.
Often children can be given the hope that they will outgrow the disorder.
Most children will not have seizures triggered by sports or by any other ordinary activities that are enjoyable and healthy.
As soon as they are old enough, children should be active participants in maintaining their drug regimens, which should be presented in as positive a light as possible.

Therapies for Children and Adults. Because of the risks for serious emotional consequences, psychological therapy may be beneficial and even necessary for some adults and children. In one study, cognitive behavioral therapy was helpful in lowering seizure rates in young people with juvenile myoclonic epilepsy. This approach offers a structured counseling program that helps people change behaviors that can reduce seizure risk factors such as anxiety and insomnia.

Resources

www.epilepsyfoundation.org -- Epilepsy Foundation
www.aesnet.org -- American Epilepsy Society
www.aan.com -- American Academy of Neurology
www.ninds.nih.gov -- National Institute of Neurological Disorders and Stroke

References

Christensen J, Vestergaard M, Mortensen PB, Sidenius P, Agerbo E. Epilepsy and risk of suicide: a population-based case-control study. Lancet Neurol. 2007 Aug;6(:693-8.

Foldvary-Schaefer N, Wyllie E. Epilepsy. In: Goetz C, ed. Textbook of Clinical Neurology. 3rd edition. Saunders. 2007.

Freeman JM, Kossoff EH, Hartman AL. The ketogenic diet: one decade later. Pediatrics. 2007 Mar;119(3):535-43.

Johnson MV. Seizures in childhood. In: Behrman RE, ed. Nelson Textbook of Pediatrics. 17th edition. Saunders. 2004.

Krebs PP. Psychogenic nonepileptic seizures. Am J Electroneurodiagnostic Technol. 2007 Mar;47(1):20-8.

Krumholz A, Wiebe S, Gronseth G, et al. Practice Parameter: evaluating an apparent unprovoked first seizure in adults (an evidence-based review): report of the Quality Standards Subcommittee of the American Academy of Neurology and the American Epilepsy Society. Neurology. 2007 Nov 20;69(21):1996-2007.

Kwan P, Brodie MJ. Emerging drugs for epilepsy. Expert Opin Emerg Drugs. 2007 Sep;12(3):407-22.

Leone MA, Solari A, Beghi E; FIRST Group. Treatment of the first tonic-clonic seizure does not affect long-term remission of epilepsy. Neurology. 2006 Dec 26;67(12):2227-9.

Salanova V, Worth R. Neurostimulators in epilepsy. Curr Neurol Neurosci Rep. 2007 Jul;7(4):315-9.

Spencer SS. Seizures and epilepsy. In: Goldman L, ed. Cecil Medicine. 23rd edition. Saunders. 2007.

Tomson T, Hiilesmaa V. Epilepsy in pregnancy. BMJ. 2007 Oct 13;335(7623):769-73.

Review Date:
12/31/2007
Reviewed By:
Harvey Simon, MD, Editor-in-Chief, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital. Also reviewed by David Zieve, MD, MHA, Medical Director, A.D.A.M., Inc.

A.D.A.M. Copyright

adam.com

6 Strategies For Better Sleep

FitSugar — Fri, 10 Apr 2009 13:30:00 -0700

Economic woes, daylight savings, work stress, family frenzies - there's no shortage of factors capable of interrupting our sleep time. Thankfully, there's also no shortage of strategies to help you rest easier. Here are six of my favorite surprising tactics that may help you get more shuteye.

Get outside. Being in the daylight helps regulate your body's circadian rhythms, even if it's just for 30 minutes a day.
Stop drinking water and booze a few hours before bedtime. Both will most likely make you wake up and have to pee, while alcohol can interfere with sleep and hunger patterns.
Cut out the carbs. Avoid eating carb-heavy foods at least two hours before bed or more. According to Jillian Michaels in her new book, your ghrelin (hunger hormone) needs to be high in order to slip into deep sleep, but since carbs lower your ghrelin, they may stave off slumber.

For the remaining three, read more.

Shut off exercise before shuteye. Physical activity can promote deeper sleep, but make sure to wrap it up at least five hours before bedtime.
Eat sleepy foods. Some foods may actually aid restful sleep, including milk, tuna, avocados, almonds, oats, and many more!
Set a stopping point for coffee. Caffeine in the mornings is fine and, depending on the person, early afternoon coffees are OK, too. But definitely try to steer clear of coffee within eight hours of bedtime.

Source

Migraine headache

FitSugar — Wed, 08 Oct 2008 17:34:55 -0700

Overview

Signs and Symptoms
Causes
Risk Factors
Diagnosis
Treatment Approach
Other Considerations
Supporting Research

HEALTH GUIDE REFERENCE FROM A.D.A.M

Migraines are severely painful, recurrent headaches that are sometimes accompanied by other symptoms such as visual disturbances (aura) or nausea. There are two types of migraine – migraine with aura (formerly called common migraines) and migraine without aura (formerly called classic migraines). If you have a migraine with aura, you may experience a visual disturbance (like seeing stars or zigzag lines or a temporary blind spot) about 30 minutes before the headache starts. Even if you don't experience an aura, you may have other warning signs in the period before the headaches starts (called prodrome), such as a craving for sweets, thirst, sleepiness, or depression. Although there is no cure for migraines, you can manage the condition by reducing the frequency of attacks and lessening pain once an attack starts.

Signs and Symptoms

The headache from a migraine, with or without aura, has the following characteristics:

Throbbing, pounding, or pulsating pain
Often begins on one side of your head and may spread to both or stay localized
Most intense pain is often concentrated around the temple(s) (side of the forehead)
Can last from 4 to 72 hours

These symptoms may occur at the same time or before the headache:

Nausea and vomiting
Dizziness, lightheadedness or even vertigo (feeling like the room is spinning)
Loss of appetite
Fatigue
Visual disturbances, like seeing flashing lights or zigzag lines, temporary blind spots (for example, loss of your peripheral vision), or blurred vision
Parts of your body may feel numb, weak, or tingly
Light, noise, and movement – especially bending over – make your head hurt worse; you want to lie down in a dark, quiet room
Irritability

Symptoms that may linger even after the headache is gone:

Feeling mentally dull, like your thinking is not clear or sharp
Sleepiness
Neck pain

Causes

Researchers aren't sure what causes a migraine, although they know it involves changes in the blood flow in the brain. Initially, blood vessels constrict (narrow), reducing blood flow and leading to visual disturbances, difficulty speaking, weakness, numbness, or tingling sensation in one area of the body, or other similar symptoms. Later, the blood vessels dilate (enlarge) leading to increased blood flow and a severe headache. Migraine triggers can include the following:

Alcohol, especially beer and red wine
Certain foods, such as aged cheeses, chocolate, nuts, peanut butter, some fruits (like avocado, banana, and citrus), foods with monosodium glutamate (MSG), onions, dairy products, meats containing nitrates (bacon, hot dogs, salami, cured meats) fermented or pickled foods
Skipping meals
Fluctuations in hormones (for example, during pregnancy, before and during your period, and menopause)
Certain odors, such as perfume or smoke
Bright lights
Loud noises
Stress, physical or emotional (often, the headache occurs during a period of relaxation after a particularly stressful time)
Sleeping too little or too much
Caffeine
Smoking or exposure to tobacco smoke
Some medications

Risk Factors

Gender (women are more likely to get migraines than men)
Having other family members with migraine headaches
Being under age 40; migraines tend to diminish as you age
Taking birth control pills (if your migraines are affected by fluctuations in estrogen levels)
Exposure and sensitivity to any of the potential triggers listed above

Diagnosis

Your doctor will take a detailed medical history in order to distinguish migraine headaches from other types of headaches, such as tension or sinus. He or she will ask questions about when your headaches occur, how long they last, how frequently they come on, the location of the pain, and any symptoms that accompany or precede the headaches. Sometimes it helps to keep a diary about your headaches prior to seeing the doctor, so you'll have an accurate recording of how often they happen. (See Lifestyle section for what information to include in a diary.)

Tests your doctor may order, depending on your symptoms and exam, include:

Computerized tomography (CT) scan, to look for other problems that could be causing your headache
Magnetic resonance imaging (MRI), to look for brain abnormalities, and to look closely at the blood vessels in the brain
Lumbar puncture (spinal tap), if your doctor suspects meningitis or other conditions

You should seek emergency help if you experience the following symptoms:

You have unusual neurologic symptoms you have not experienced before, such as speech problems, change in vision, loss of balance, or difficulty moving a limb.
Your headache pattern or intensity is different
You are experiencing "the worst headache of your life"
Your headache worsens when you are lying down

These may indicate a stroke, a bleed in the brain, or other serious condition.

Treatment Approach

Treatment for migraines is aimed at preventing them from occuring and lesseneing pain once an attack starts.

You can control your migraines with a combination of medications, lifestyle changes, and complementary therapies. Biofeedback (see Mind/Body Medicine) may help you control the initial contraction of blood vessels, while relaxation techniques may reduce both the frequency and intensity of attacks.

Lifestyle

Keeping a migraine diary, particularly when you first begin to experience migraines, can help identify the triggers for your headaches so you can avoid them. When a migraine occurs, write down the date and time it began. Note what you ate for the preceding 24 hours, how long you slept the night before, what you were doing just before the headache, any unusual stress in your life, how long the headache lasted, and what you did to make it stop.

Other lifestyle measures that may reduce the number of migraines include:

Avoiding cigarettes, caffeine, and alcohol
Exercising regularly
Getting enough sleep each night
Relaxing and reducing stress in your life (see Mind/Body Medicine section)

Once a headache or associated migraine symptoms begin, it helps to:

Rest in a quiet, darkened room
Drink fluids to avoid dehydration (especially if you have vomited)

Medications

Medications for migraines can be classified in two major categories: those designed to prevent attacks, and those designed to relieve pain.

Drugs for Prevention

Your doctor may prescribe preventive medications if you have two or more migraines per month, use pain relievers more than twice a week, or if your symptoms are especially debilitating. Depending on your condition and medication, your doctor may recommend taking the medication daily or when a known trigger is about to occur (such as having your period).

Beta-blockers - also used to treat heart disease; researchers aren't sure why they also work for migraines, although they may help keep blood vessels in the brain from constricting and dilating. Beta-blockers include
- Atenolol (Tenormin)
- Metoprolol (Lopressor, Toprol-XL)
- Propranolol (Inderal, Inderal LA)
Calcium-channel blockers - another type of cardiovascular drug that can help prevent migraines, including
- Verapamil (Calan, Isoptin)
- Diltiazem (Cardizem, Dilacor)
Anti-depressants - Tricyclic antidepressants are helpful in preventing all kinds of headaches, including migraines. Tricyclic antidepressants include:
- Amitriptyline (Elavil)
- Nortriptyline (Pamelor)
- Doxepin (Sinequan)
- Imipramine (Tofranil)
Anticonvulsants - Some anti-seizure drugs help prevent migraines, although researchers aren't sure why:
- Divalproex sodium (Depakote)
- Topiramate (Topamax)

Drugs for Treatment

To be effective, these medications should be taken as soon as you feel a migraine coming on.

Triptans - This class of medications tends to be the front-line treatment for severe migraines and relieve pain, nausea, and sensitivity to light and sound. They work by constricting the blood vessels in the brain. Triptans include
- Almotriptan (Axert)
- Eletriptan (Relpax)
- Frovatriptan (Frova)
- Naratriptan (Amerge)
- Rizatriptan (Maxalt)
- Sumatriptan (Imitrex)
- Zolmitriptan (Zomig)
Ergots - Ergots also work by constricting blood vessels, but tend to have more side effects than triptans. Ergots include
- Ergotamine (Ergomar, Cafergot)
- Dihydroergotamine (Migranal)
Isometheptene, dichloralphenazone, and acetaminophen (Midrin) - Midrin combines a pain reliever (acetaminophen) and sedative (dichloralphenazone) with a medication that constricts blood vessels (isometheptene) to prevent migraines.

Other medications used to treat the headache pain or associated symptoms:

Anti-nausea drugs
Acetaminophen (Tylenol) for pain
Ibuprofen (Advil, Motrin) or other nonsteroidal anti-inflammatory drugs (NSAIDs)
Narcotics, such as codeine, are sometimes used for people who can't take triptans or ergots; however, they can cause dependency and rebound headaches

Nutrition and Dietary Supplements

Diet

Certain foods may trigger migraine headaches. Some of the include:

Chocolate
Cheese
Monosodium glutamate (MSG), a flavor enhancer found often in food from Chinese restaurants
Foods containing the amino acid tyramine (found in red wine, aged cheese, smoked fish, chicken livers, figs, and some beans)
Nuts
Peanut butter
Some fruits (like avocado, banana, and citrus)
Onions
Dairy products
Meats containing nitrates (bacon, hot dogs, salami, cured meats)
Fermented or pickled foods

If you suspect that any of these foods cause your migraines, you could follow an elimination diet, eliminating all the items on this list from your diet and then reintroducing them one at a time. Pay close attention to when the number of headaches increases after eating particular foods. Then you know which trigger foods to avoid.

5-hydroxytryptophan (5-HTP, 400 to 600 mg per day) - This amino acid is made by the body from tryptophan (another amino acid you get from certain foods) and converted into serotonin, an important brain chemical. Researchers think abnormal serotonin function in blood vessels is related to migraines, and some of the drugs used to treat migraines work by affecting serotonin. Several studies indicate that 5-HTP may be about as effective as some prescription migraine medications, reducing the intensity and frequency of attacks. But not all studies have been so positive – one study found that 5-HTP was less effective than the beta-blocker Inderal. More studies are needed to be sure that 5-HTP is helpful in treating migraines. If you take an antidepressant, or supplements such as St. John's wort or SAMe, you should not take 5-HTP.
Magnesium (200 to 600 mg per day) - People with migraines often have lower levels of magnesium compared to people who do not have migraines, and several studies suggest that magnesium may reduce the frequency of migraine attacks. In one study, people who took magnesium reduce the frequency of attacks by 41.6 percent, compared to 15.8 percent in those who took placebo. Some studies also suggest that magnesium may be helpful for women whose migraines are triggered by their periods.Side effects from magnesium can include lower blood pressure and diarrhea.
Vitamin B2 (riboflavin, 400 mg per day) - A few studies indicate that riboflavin may reduce the frequency and duration of migraines. In one study, people who took riboflavin had more than a 50 percent decrease in the number of attacks. Not all studies have found riboflavin to be effective, however. More research is needed.

Preliminary research indicates that these supplements may also help prevent migraines, although much more research is needed to say for sure:

Coenzyme Q10 (100 mg three times per day)
Melatonin (5 mg per day, taken before bedtime)

Herbs

The use of herbs is a time-honored approach to strengthening the body and treating disease. Herbs, however, can trigger side effects and can interact with other herbs, supplements, or medications. For these reasons, herbs should be taken with care, under the supervision of a healthcare practitioner.

Butterbur (Petasites hybridus, 50 to 75 mg of a standardized extract two times per day) - A few studies suggest that butterbur may help reduce both the frequency and duration of migraine attacks. The studies used a standardized extract that lowered the amount of alkaloids in the herb, which might potentially be harmful to the liver. If you want to try butterbur for your migraines, ask your doctor about a safe extract and dose. Women who are pregnant or breastfeeding should not take butterbur.
Feverfew (Tanacetum parthenium, standardized leaf extract to 250 mcg parthenolide per day) - Feverfew has been used traditionally to treat headaches, and several well-designed studies have found that it may help prevent and treat migraines (not all studies agree, however). In one study of people with migraines, those who took feverfew capsules every day for 4 months saw a substantial drop in the number of attacks as well as far fewer symptoms, such as nausea and vomiting, compared to those who received placebo. Feverfew can increase the risk of bleeding, and should not be taken with anticoagulants (blood-thinners). Women who are pregnant or breastfeeding should not take feverfew.

Although there are no scientific studies showing that these herbs work, they are sometimes suggested to treat migraines and other types of headaches:

Dong quai (Angelica sinensis)
Devil's claw (Harpagophytum procumbens)
Ginger (Zingiber officinale)
Ginkgo biloba (Ginkgo biloba)
Willow bark (Salix spp.)

Acupuncture

Acupuncture has been studied as a treatment for migraine headache for more than 20 years. While not all studies have shown benefit with acupuncture, researchers do agree that acupuncture appears safe and that it may be effective for some people. Results from a study published in 2003 suggest that receiving an acupuncture treatment when migraine symptoms first begin is as effective as taking the drug Imitrex; as symptoms continue, however, the medication works better than acupuncture.

In addition to needling treatment, acupuncturists may recommend lifestyle changes, such as suggestions for specific breathing techniques, qi gong exercise, and dietary modifications.

Chiropractic

Several clinical trials indicate that spinal manipulation therapy may help in the treatment of migraine headaches. In one study of people with migraines, 22% of those who received chiropractic manipulation reported more than a 90% reduction of attacks and 49% reported a significant reduction of the intensity of each migraine.

In another study, people with migraine headaches were randomly assigned to receive spinal manipulation, a daily medication (Elavil), or a combination of both. Spinal manipulation was as effective as Elavil in reducing migraines and had fewer side effects. There was no added benefit to combining the two therapies.

In addition, researchers reviewed nine studies that tested spinal manipulative therapy for tension or migraine headaches and found that it was as effective as medications in preventing these headaches.

However, not all these studies were of good quality, and they varied in the techniques used. More research is needed to say for sure whether chiropractic is effective for preventing migraines.

Massage and Physical Therapy

Reflexology, a technique that places pressure on specific "reflex points" on the hands and feet that are believed to correspond to areas throughout the body, has been proposed as a treatment for migraines. Some early studies suggest it may relieve pain and allow people with migraines to take less pain medication. However, more research is needed. Practitioners believe reflexology helps you become more aware of you own body signals, which might help you sense the subtle signals that indicate a migraine is about to occur (before pain starts). They also believe reflexology helps improve general well-being and energy level.

Homeopathy

One of the most common reasons people seek homeopathic care is to treat chronic headaches. However, only one out of four studies included in a scientific review found that individually prescribed homeopathic remedies significantly reduced the frequency, severity, and duration of migraines. Some of these effective remedies are listed below. Professional homeopaths may also recommend various treatments based on their knowledge and clinical experience. Before prescribing a remedy, homeopaths take into account the individual's constitutional type. In homeopathic terms, a person's constitution is his or her physical, emotional, and intellectual makeup. An experienced homeopath assesses all of these factors when determining the most appropriate remedy for a particular individual.

The following are some of the remedies found to be effective:

Belladonna - for throbbing headaches that come on suddenly; these types of headaches tend to worsen with motion and light, but are partially relieved by pressure, standing, sitting, or leaning backwards
Bryonia - for headaches with a steady, sharp pain in the forehead that may radiate to the back of the head; these types of headaches worsen with movement and light touch, but improve with firm pressure; this remedy is most appropriate for individuals who are irritable and may also experience nausea, vomiting, and constipation
Gelsemium - for pain that extends around the head and feels like a tight band of constriction; pain usually originates in the back of the head and may be relieved following urination; this remedy is most appropriate for individuals who feel extremely weak and have difficulty keeping their eyes open
Ignatia - for pain that may be described as a feeling of something being driven into the skull; these types of headaches tend to be triggered by emotion, including grief or anxiety, and the treatment is appropriate for both children and adults
Iris versicolor - for periodic migraines that begin with blurred vision, especially after eating sweets; pain usually occurs on one side of the head and may be partially relieved by gentle movement and/or fresh air
Kali bichromicum - for aching and pressing pains on the forehead (particularly between and behind the eyes); may be accompanied by sinus congestion or nausea and vomiting; this remedy is most appropriate for individuals who prefer to lie down in a dark room and who experience relief from warmth and eating
Lachesis - for migraines on the left side of the head that are typically worse in the mornings and before menstruation; this type of headache is aggravated by warmth and sunlight and relieved by open air and firm pressure
Natrum muriaticum - one of the most common remedies used for migraine headaches, particularly those that are described as "hammers beating the head;" pain is relieved when the individual is lying down, alone, in a quiet dark room; these migraines may be associated with either menstruation or a grieving experience and are worse in the middle of the day; this remedy is most appropriate for children who look pale and feel nauseated, nervous, and emotional
Nux vomica - for headaches that are described as a "nail being driving into the head;" often accompanied by nausea and/or dizziness; this remedy is most appropriate for individuals who are constipated and irritable
Sanguinaria - for right-sided headaches that begin in the neck and move upwards, recur in a predictable pattern (such as every seven days), and are accompanied by nausea and vomiting; pain is aggravated by motion, light or sun exposure, odors, and noise; this remedy is appropriate for children who may have a craving for spicy or acidic foods, despite having a general aversion to eating due to the headache
Sepia - for migraines that are accompanied by nausea and are relieved when the individual is lying down; light and movement tend to worsen symptoms; this remedy is most appropriate for individuals who are moody and don't like being alone, but worry about being with others

Homeopaths may also prescribe the following remedies based on their knowledge and clinical experience:

Pulsatilla - for headaches triggered by eating rich, fatty foods, particularly ice cream; pain tends to move but may be concentrated in the forehead or on one side of the head; may be accompanied by digestive problems or occur around the time of menstruation; children for whom this remedy is appropriate often develop these symptoms while at school
Spigelia - for migraines described as a stinging, burning, or throbbing pain, often on the left side of the head; symptoms tend to worsen with exposure to cold weather and with motion, but are temporarily relieved by cold compresses and when the individual is lying on the right side with the head propped up

Mind/Body Medicine

Reducing and learning to cope with stress may help reduce the number and intensity of your headaches. Techniques that can help include:

Self-hypnosis
Biofeedback
Joining a support group
Relaxation techniques such as progressive muscle relaxation (alternately contracting and releasing muscles throughout your body), meditation, and guided imagery

Other Considerations

Pregnancy

Many of the medications, herbs, and supplements used to prevent or treat migraines should not be used if you are pregnant. Talk to your doctor before using any medication (over the counter or prescription) or any complementary therapy available prior to becoming pregnant.

Warnings and Precautions

Use medications only as directed. using some medications on a regular basis can cause rebound headaches.

Call your doctor if you experience a new headache, a change in quality of a previous headache or headache pattern, or if a medication that usually takes away the pain no longer works.

Prognosis and Complications

Migraine headaches generally don't pose a threat to your overall health, although they can be chronic, recurrent, frustrating, and interfere with your day to day life. Stroke is an extremely rare complication from severe migraines, possibly due to prolonged constriction (narrowing) of blood vessels, reducing the blood flow to parts of the brain.

Many people find that migraines into remission (meaning that they stop for a long time and happen only very infrequently) or even disappear altogether, especially as you get older. For women, this may be related to lower levels of estrogen after menopause.

Supporting Research

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Review Date:
12/18/2007
Reviewed By:
Steven D. Ehrlich, N.M.D., private practice specializing in complementary and alternative medicine, Phoenix, AZ. Review provided by VeriMed Healthcare Network.

A.D.A.M. Copyright

adam.com

Ropinirole (By mouth)

admin — Thu, 04 Sep 2008 19:56:12 -0700

Overview

Introduction
Brand Name(s)
When This Medicine Should Not Be Used
How to Use This Medicine
How to Store and Dispose of This Medicine
Drugs and Foods to Avoid
Warnings While Using This Medicine
Possible Side Effects While Using This Medicine

HEALTH GUIDE REFERENCE FROM A.D.A.M

Introduction

Ropinirole (roe-PIN-i-role)

Treats symptoms of Parkinson's disease. Also treats restless legs syndrome (RLS).

Brand Name(s)

Requip

There may be other brand names for this medicine.

When This Medicine Should Not Be Used

You should not use this medicine if you have had an allergic reaction to ropinirole.

How to Use This Medicine

Tablet

Your doctor will tell you how much of this medicine to use and how often. Your dose may need to be changed several times in order to find out what works best for you. Do not use more medicine or use it more often than your doctor tells you to.
This medicine comes with patient instructions. Read and follow these instructions carefully. Ask your doctor or pharmacist if you have any questions.
You may take this medicine with or without food.You may take this medicine with food if it upsets your stomach.
The dose of this medicine is different depending on whether you have Parkinson's disease or RLS. People who have Parkinson's usually take more medicine. Make sure you understand how much to take.

If a dose is missed:

For Parkinson's disease: If you miss a dose or forget to use your medicine, use it as soon as you can. If it is almost time for your next dose, wait until then to use the medicine and skip the missed dose. Do not use extra medicine to make up for a missed dose.
For RLS: If you miss a dose or forget to use your medicine, use it as soon as you can if it is still the same day. If it is the next day, skip the missed dose, and take your next dose at the usual time. Do not use extra medicine to make up for a missed dose.

How to Store and Dispose of This Medicine

Store the medicine in a closed container at room temperature, away from heat, moisture, and direct light.
Ask your pharmacist, doctor, or health caregiver about the best way to dispose of any leftover medicine after you have finished your treatment. You will also need to throw away old medicine after the expiration date has passed.
Keep all medicine away from children and never share your medicine with anyone.

Drugs and Foods to Avoid

Ask your doctor or pharmacist before using any other medicine, including over-the-counter medicines, vitamins, and herbal products.

Tell your doctor if you are using any medicines that make you sleepy. These include sleeping pills, cold and allergy medicine, narcotic pain relievers, and sedatives.
Make sure your doctor knows if you are also taking ciprofloxacin (Cipro®), haloperidol (Haldol®), levodopa (Sinemet®), metoclopramide (Reglan®), thiothixene (Navane®), or a phenothiazine (such as Compazine®, Phenergan®, Thorazine®).
Tell your doctor if you start or stop using estrogen. This includes birth control pills or medicine to treat menopause symptoms.
Do not drink alcohol while you are using this medicine.
Make sure your doctor knows if you smoke cigarettes.

Warnings While Using This Medicine

Make sure your doctor knows if you are pregnant or breastfeeding, or if you plan to become pregnant.
Make sure your doctor knows if you have a sleep disorder, heart disease, kidney disease, liver disease, low blood pressure, severe mental illness, history of skin cancer, or dyskinesia (trouble controlling your muscles).
This medicine could make you sleepy (more common in Parkinson's treatment). Some people have fallen asleep while doing everyday activities, such as driving. This problem could start any time during the first year of use, sometimes without warning. Be very careful, or avoid driving, using machines, or doing anything else that could be dangerous if you are not alert. Talk to your doctor if this medicine makes you too sleepy. Drinking alcohol will add to your drowsiness.
When you first start using this medicine or if your dose is increased, you might feel dizzy, lightheaded, hot, or sick to your stomach if you stand up quickly. Get up slowly to give your body some time to adjust, especially if you have been sitting or lying down for a long time.
Do not stop using this medicine suddenly without asking your doctor. You may need to slowly decrease your dose before stopping it completely.If you need to stop using this medicine, talk to your doctor before starting to use it again.
Your doctor will need to check your progress at regular visits while you are using this medicine. Your doctor may also need to check your skin regularly. Be sure to keep all appointments.
Some people who have used this medicine had hallucinations or unusual changes in their behavior, such as having problems with gambling or an increased sex drive. Talk with your doctor if this is a concern for you.
If your symptoms do not improve or if they get worse, call your doctor.For RLS, the symptoms might get worse in the early morning, start earlier in the afternoon, or spread to your arms. For Parkinson's, you might have new or worse muscle movements.

Possible Side Effects While Using This Medicine

Call your doctor right away if you notice any of these side effects:

Allergic reaction: Itching or hives, swelling in your face or hands, swelling or tingling in your mouth or throat, chest tightness, trouble breathing.
Change in how much or how often you urinate, painful urination.
Changes in vision.
Extreme sleepiness or drowsiness.
Fever, chills, cough, sore throat, and body aches.
Lightheadedness, dizziness, fainting, or falling.
Numbness, tingling, or burning pain in your hands, arms, legs, or feet.
Problems with balance or walking.
Seeing, hearing, or feeling things that are not really there.
Slow heartbeat.
Swelling in your hands, legs, ankles, or feet.
Tremors, muscle stiffness, or slowed movements.
Trouble breathing, chest pain.
Twitching or muscle movements you cannot control.
Unusual tiredness or weakness.

If you notice these less serious side effects, talk with your doctor:

Anxiety, nervousness, trouble sleeping.
Confusion, memory problems, or unusual behavior.
Dry mouth.
Headache.
Increased appetite for food or sex.
Increased sweating.
Joint pain.
Nausea, vomiting, constipation, stomach pain or upset, diarrhea.
Pain in arms or legs.

Review Date: 8/4/2008

A.D.A.M. Copyright

adam.com

Source Doc: 45_0845

Migraine headaches

FitSugar — Wed, 08 Oct 2008 17:35:00 -0700

In This Report

Highlights
Introduction
Prognosis
Causes
Risk Factors
Diagnosis
Treatment Approaches
Medications Used for Treatm...
Prevention
Medications Used for Preven...
Resources
References

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

Migraine Surveys

About 17.1% of women and 5.6% of men suffer migraines, according to the 2007 American Migraine Prevalence and Prevention survey. Nearly a third of respondents reported 3 or more migraine attacks per month. Over half were severely impaired or needed bed rest during attacks. Although many patients met the criteria for preventive medication, only a small percentage actually received it.
About 20% of patients with migraine take potentially addictive opioid and barbiturate drugs, even though these drugs have not been approved by the Food and Drug Administration (FDA) for migraine treatment, according to a 2007 survey commissioned by the U.S. National Headache Foundation.

FDA Actions

The opioid drug fentanyl (Fentora) should not be prescribed "off-label" to patients with migraine or other severe headaches, warns the FDA, following several reports of drug-related deaths. Fentanyl is approved only for treating cancer pain.
In 2007, the FDA pulled 15 unapproved ergotamine preparations off the market because they lacked a warning label describing the risks for serious drug interactions.

Migraines in Adolescents

Many adolescents may stop having migraines, or transition to less severe types of headaches, when they reach adulthood, suggests a small 2006 study in Neurology.
Zolmitriptan (Zomig) nasal spray appears to be safe and effective for adolescent migraine, indicates a 2007 study in Pediatrics. Zolmitriptan, like all migraine drugs, is currently approved only for adults.

Sumatriptan-Naproxen Combination

A combination of the triptan drug sumatriptan (Imitrex) and the nonsteroidal anti-inflammatory drug naproxen (Aleve) works better for migraine pain relief than either drug alone, according to a 2007 study in the Journal of the American Medical Association.

Introduction

The pain from a headache does not start from inside the brain. (The brain itself can not feel pain.) Instead, headache pain begins in one or more of the following locations:

The tissues covering the brain
The structures at the base of the brain
Muscles and blood vessels around the scalp, face, and neck

Headache is generally categorized as primary or secondary.

Primary Headache. A headache is considered primary when a disease or other medical condition does not cause it.

Tension headache is the most common primary headache and accounts for 90% of all headaches. [See In-Depth Report # 11: Tension headaches.]
Neurovascular headaches are the second most common primary headaches. This type includes migraines and cluster headaches. [See In-Depth Report # 99: Cluster headaches.] Such headaches are caused by an interaction between blood vessel and nerve abnormalities.

Headaches are usually caused by muscle tension, vascular problems, or both. Migraines are vascular in origin, and may be preceded by visual disturbances, loss of peripheral vision, and fatigue. Over-the-counter pain medications can relieve most headaches.

Click the icon to see a depiction of migraine cause.

Secondary Headache. Secondary headaches are caused by other medical conditions, such as sinusitis, neck injuries or abnormalities, and stroke. About 2% of headaches are secondary headaches caused by abnormalities or infections in the nasal or sinus passages. [See "Causes of Secondary Headaches," in this report.]

It is not uncommon for someone to experience a combination of headache types.

Click the icon to see a comparison of headache symptoms.

Migraine is now recognized as a chronic illness, not simply as a headache. About 28 million people suffer from migraines annually. They are often classified by whether or not auras (seeing bright "spots" or "stars") accompany them:

Common migraines are without auras. About 75% of migraines are the common type.
Classic migraines are those with auras.

A person may experience one or the other at different times.

In general, there are four phases to a migraine (although they may not all occur in every patient): The prodrome phase, auras, the attack, and the postdrome phase.

Prodrome. The prodrome phase is a group of vague symptoms that may precede a migraine attack by several hours, or even a day or two. Prodrome symptoms include:

Sensitivity to light or sound
Changes in appetite
Fatigue and yawning
Malaise
Mood changes
Food cravings

Auras. Auras are sensory disturbances that occur before the migraine attack in 1 in 5 patients. Visually, auras are referred to as being positive or negative:

Positive auras include bright or shimmering light or shapes at the edge of their field of vision called scintillating scotoma. They can enlarge and fill the line of vision. Other positive aura experiences are zigzag lines or stars.
Negative auras are dark holes, blind spots, or tunnel vision (inability to see to the side).
Patients may have mixed positive and negative auras. This is a visual experience that is sometimes described as a fortress with sharp angles around a dark center.

Other neurologic symptoms may occur at the same time as the aura, although they are less common. They include:

Speech disturbances
Tingling, numbness, or weakness in an arm or leg
Perceptual disturbances such as space or size distortions
Confusion

Migraine Attack. If untreated, attacks usually last from 4 - 72 hours. A typical migraine attack produces the following symptoms:

Throbbing pain on one side of the head. The word migraine, in fact, is derived from the Greek word hemikrania, meaning "half of the head" because the pain of migraine often occurs on one side. Pain also sometimes spreads to affect the entire head.
Pain worsened by physical activity
Nausea, sometimes with vomiting
Visual symptoms
Facial tingling or numbness
Extreme sensitivity to light and noise
Looking pale and feeling cold

Less common symptoms include tearing and redness in one eye, swelling of the eyelid, and nasal congestion, including runny nose. (Such symptoms are more common in certain other headaches, notably cluster headaches. In one study, however, they occurred in over 40% of migraine sufferers.)

Postdrome. After a migraine attack, there is usually a postdrome phase, in which patients may feel exhausted and mentally foggy for a while.

In some cases, patients eventually experience on-going and chronic headaches. In fact, in an analysis using two different diagnostic methods, between 87 - 90% of daily chronic headaches were actually migraines. Some doctors believe that, unless otherwise demonstrated, any chronic headache consisting of episodes of disabling pain that recur regularly over years should be considered as a migraine.

Chronic migraines may occur from overuse of migraine medications (called a rebound headache) or may develop over time (called transformed migraine).

Rebound Headache. The most common cause of chronic migraine is the rebound effect, which is a cycle caused by overuse of migraine medications. The process involves the following:

Patients typically have taken pain medication for more than 3 days a week on an ongoing basis.
When the patients stop taking medication, they experience a rebound headache.
They start taking the drugs again.
Eventually the headache simply persists, and medications are no longer effective.

Medications implicated in rebound migraines include nonprescription painkillers (acetaminophen, aspirin, ibuprofen), barbiturates, sedatives, narcotics, and migraine medications, particularly those that also contain caffeine. (Heavy caffeine use can also cause this condition.)

Transformed Migraines. In some cases, migraines themselves evolve into chronic, daily headaches called transformed migraines. Such headaches resemble tension headaches but are more likely to be accompanied by gastrointestinal distress and mental or visual disturbances and, in women, to be affected by menstrual cycles. In one study, the risk for transformed migraines were associated with other factors, including allergies, asthma, hypothyroidism, hypertension, and a daily intake of caffeine.

Migraines are defined by the number and length of attacks and whether an aura is present.

Definition of Migraines without Auras (Common Migraine). To be defined as a migraine without aura, a patient should have at least five attacks that have the following characteristics:

A. Each untreated, or unsuccessfully treated, attack must last 4 - 72 hours.

B. It must have at least two of the following four characteristics:

Pain on one side of the head
Pulsing or throbbing pain
Pain severe enough to impair or prevent daily activities
Pain must be intensified by exertion, such as walking up stairs

C. During a headache at least one of the following symptoms must also be present:

Nausea, vomiting or both
Sensitivity to light and noise

In addition, other neurologic or medical conditions that might be causing this pain must be ruled out, or, if they do occur, they are not related in time to the suspected migraine.

Definition of Migraines with Auras (Classic Migraine). To be defined as a migraine with aura, the patients must have at least two attacks that have three out of four of the following events.

At least one fully reversible aura symptom suggesting the headache starts in the cerebral cortex or brain stem.
At least one aura symptom that develops gradually over more than 4 minutes ,or two or more aura symptoms that occur in succession.
No single aura symptom that lasts more than 1 hour. (There may be successive aura symptoms that extend that time, but each one should not last more than 60 minutes.)
The headache itself may begin before, at the same time, or at an interval of no more than an hour after the aura.

As with common migraines, other neurologic or medical conditions that might be causing this pain must be ruled out or if they occur, they are not related in time to the suspected migraine.

Click the icon to see a definition of a migraine.

Although migraine is considered to be a specific chronic illness, it has various presentations that occur in different individuals.

Menstrual Migraines. Migraines are often tied to a woman’s menstrual cycle. Researchers think that estrogen plays a role. About half of women with migraines report an association with menstruation. Compared to migraines that occur at other times of the month, menstrual migraines tend to be more severe, last longer, and not have auras. Triptan drugs can provide relief and may also help prevent these types of migraines.

The highest incidence of migraines typically occurs during the early follicular phase, (beginning of menstruation). A 2005 study found that women are 1.7 times more likely to have a migraine during the 2 days before menstruation begins. But, women are 2.5 times more likely to have a migraine during the first 3 days of menstruation. During this time, migraines are more likely to be severe, with symptoms that include vomiting.

Ophthalmoplegic Migraine. This very rare headache tends to occur in younger adults. The pain centers around one eye and is usually less intense than in a standard migraine. It may be accompanied by vomiting, double vision, a droopy eyelid, and paralysis of eye muscles. Attacks can last from hours to months. A computed tomography (CT) or magnetic resonance imaging (MRI) scan may be needed to rule out an aneurysm (a rupture blood vessel) in the brain.

Retinal Migraine. Symptoms of retinal migraine are short-term blind spots or total blindness in one eye that lasts less than an hour. A headache may precede or occur with the eye symptoms. Sometimes retinal migraines develop without headache. Other eye and neurologic disorders must be ruled out.

Basilar Migraine. Considered a subtype of migraine with aura, this migraine starts in the basilar artery, which forms at the base of the skull. It occurs mainly in young people. Symptoms may include vertigo (the room spins), ringing in the ears, slurred speech, unsteadiness, possibly loss of consciousness, and severe headaches.

Familial Hemiplegic Migraine. This is a very rare inherited genetic migraine disease. It can cause temporary paralysis on one side of the body, vision problems, and vertigo. These symptoms occur about 10 - 90 minutes before the headache.

Status Migrainosus. This is a serious and rare migraine. It is so severe and lasts so long that it requires hospitalization.

About 90% of people seeking help for headaches have a primary headache disorder. The balance of secondary headaches is caused by an underlying disorder that produces the headache as a symptom. Many conditions cause headaches as a symptom. Some of the most common are listed below.

Sinus Headache. Many primary headaches, including migraine, are misdiagnosed as sinus headaches. Nearly 9 in 10 patients who think they have sinus headaches actually have or probably have had a migraine. Sinus headaches occur in the front of the face, usually around the eyes, across the cheeks, or over the forehead. They are usually mild in the morning and increase during the day and are usually accompanied by fever, runny nose, congestion, and general debilitation. Sinus headaches spread over a larger area of the head than migraines, but telling the difference between these two kinds of headache is difficult, particularly if a headache is the only symptom of sinusitis. The two may even coexist in many cases. Often, the visual changes associated with migraine can rule out sinusitis, but such visual changes do not occur with all migraines. (Rarely, sinusitis can cause double vision and even vision loss, a sign of very serious infection.)

Headache Due to Neck Problems. Some headaches may be caused by abnormalities of the neck muscles resulting from prolonged poor posture (such as that caused by sitting in front of a computer keyboard or driving daily for long periods), arthritis, injuries of the upper spine, or abnormalities in the cervical spine (the spinal bones in the neck). Nerves in the neck converge in the trigeminal nerve in the face and can generate pain signals that the brain may interpret as headache. Pain is usually on one side. Even if it affects both sides of the head, it is usually more severe on one side. The quality of the headache may be similar to an aching tension headache or a mild migraine without aura.

Temporomandibular Joint Dysfunction. Temporomandibular joint dysfunction (TMJ) is caused by clenching the jaws or grinding the teeth (usually during sleep), or by abnormalities in the jaw joints themselves. The diagnosis is easy if chewing produces pain or if jaw motion is restricted or noisy. TMJ pain can occur in the ear, cheek, temples, neck, or shoulders.

Glaucoma. Acute glaucoma is caused by increased pressure in the eye and requires immediate medical attention. Throbbing pain may be felt around or behind the eyes or in the forehead. Patients have redness in the eye and may see halos or rings around lights.

Brain Tumor. Fear of having a brain tumor is common among people with headaches, but a headache is almost never the first or only sign of a tumor. Changes in personality and mental functioning, vomiting, seizures, and other symptoms are more likely to appear first. When the headache does develop, it is often worse early in the morning or may awaken sufferers during the night.

Neuralgia. Neuralgia is pain due to nerve abnormalities, which can occur in the facial area and resemble migraine or sinus headaches.

Hypertension. Although many people attribute headaches to high blood pressure, the two are rarely associated. An exception is malignant hypertension, an uncommon medical emergency, in which the blood pressure abruptly rises to extreme levels, causing damage to blood vessels in the brain, heart, and kidneys.

Strokes Caused by Blood Clots or Hemorrhages. A blood clot or hemorrhage in the brain leading to a stroke can cause a severe headache, sometimes referred to as a thunderclap headache when it is very sudden and severe. The onset of such a headache, particularly if it is associated with confusion, stupor, or other neurologic symptoms, mandates prompt medical attention. It is important to determine if a clot or bleeding is causing the stroke, since treatments are very different.

Head Injuries. It is obvious that a significant blow to the head will cause pain. Post-injury headaches, however, can reflect serious damage, ranging from skull fractures to internal bleeding.

Disorders of the Meninges. The meninges are the membranes covering the brain and the spinal cord. In very rare instances, ordinary physical strain may injure or weaken the meninges, causing a leakage of cerebrovascular fluid (the fluid that bathes the brain). This can cause severe headache and nausea, which are relieved by lying flat. The condition is very treatable. Meningitis, which is an infection or irritation of these membranes, is an uncommon but potentially serious cause of severe headache. Other symptoms include nausea and stiffness or pain in the neck.

Gynecologic Problems. Many clinicians have anecdotally linked gynecologic problems, such as ovarian cysts and menstrual disorders, to chronic headaches, and new data are emerging to support this association.

Temporal (Giant Cell) Arteritis. Certain causes of headaches are unique to the elderly, such as temporal arteritis, also called giant cell arteritis. Inflammation in arteries that carry blood to the head, neck, and sometimes the upper part of the body can cause very severe headaches. The risk for this headache is highest in people over age 70, especially among women, people of European heritage, and patients with polymyalgia rheumatica.

Miscellaneous Causes of Benign Headaches. Rapid consumption of ice cream or other very cold foods or beverages is the most common trigger of sudden headache pain. (It may be prevented by warming the food or drink for a few seconds in the front of the mouth before swallowing.) Other common benign causes of headache include eyestrain, dental problems, allergies, systemic infections, and caffeine withdrawal. Headaches may be induced by sexual activity or intense physical exertion. Leakage from spinal cord fluid is rare but can cause headaches that may be mistaken for brain tumors.

Click the icon to see an image of the sinuses.

Prognosis

For many people, migraines eventually go into remission and sometimes disappear completely, particularly as they age. Estrogen decline after menopause may be responsible for remission in some older women. One study reported that the following people with migraines (called migraineurs) have a better chance of remission if they have:

A family history of migraine with aura
Migraines that are not triggered by light
No other primary headaches

According to another study, a history of head trauma or oral contraceptive use predicted a poorer long-term outlook.

Migraine or severe headache is a risk factor for stroke in both men and women, especially before age 50. About 19% of all strokes occur in people with a history of migraine. Research indicates that migraine also increases the risk for other types of heart problems.

Migraine with aura carries a higher risk for stroke than without auras. A 2005 analysis of over 12,000 participants from an atherosclerosis risk study found that migraine with aura was significantly associated with higher risk for stroke and transient ischemic attacks. Another 2005 study suggested that people who experience migraine with aura tend to have more cardiovascular risk factors than people without migraine. These risk factors included worse cholesterol profile, higher blood pressure, early history of heart disease and stroke, and greater likelihood of using oral contraceptives.

Results from a 2005 study showed that women who have migraine with aura are at increased risk of ischemic stroke compared with those who do not have auras and those who have non-migraine headaches. Women under age 55 had the highest risk, with more than double the risk. A 2006 Women’s Health Study of women ages 45 and older found that migraine with aura also increases women’s risk for heart attack, angina, and death due to ischemic heart disease (in which blood flow is decreased due to narrowing of coronary arteries). Migraine without aura did not increase heart disease and stroke risks.

Studies suggest specific stroke risk factors for younger women with migraines, particularly those with auras. Smoking, high blood pressure, and birth control pills considerably raise one's risk 10 - 20 times.

Researchers are also studying the relationship between patent foramen ovale (PFO) and migraine. A PFO is a hole in the wall dividing the upper left and right heart chambers. About half of patients with PFO have severe migraines with aura. Researchers are investigating whether surgical repair of the PFO may help control migraines in patients with this heart condition.

Migraine and other headaches associated with aura may increase the risk for retina damage (retinopathy) among middle-aged people, suggests a 2007 study.

The negative impact of migraines on quality of life, families, and even work productivity is significant and often underrated as a serious complication. Studies indicate that people with migraines have poorer social interactions and emotional health than patients with chronic medical illnesses, including asthma, diabetes, and arthritis. Anxiety (particularly panic disorders) and major depression are also strongly associated with migraines.

A 2005 National Headache Foundation-sponsored survey of migraine sufferers reported that:

90% of people with migraines could not function normally on the day of a migraine attack
80% experienced abnormal sensitivity to light and noise
75% experienced nausea and vomiting
30% required bed rest
25% missed at least 1 day of work due to migraine in past 3 months

Effect of Pregnancy on Migraines. In one study, pregnant women with tension or migraine headaches experienced 80% fewer headaches, usually after the end of the first trimester.

Effect of Migraine on the Pregnant Woman or Fetus. Migraine headaches do not pose any added risks during pregnancy to the mother or the fetus, although women with migraines may be at higher risk for having smaller (but not premature) babies.

Causes

Until recently, the general theory on the migraine process rested solely on the idea that abnormalities of blood vessel (vascular) systems in the head were responsible for migraines. Now, however, doctors tend to believe that migraine starts with an underlying central nervous system disorder. When triggered by various stimuli, this disorder sets off a chain of neurologic and biochemical events, some of which subsequently affect the brain's vascular system. No experimental model fully explains the migraine process.

There is certainly a strong genetic component in migraine with or without auras. Researchers have located a single genetic mutation responsible for the very rare familial hemiplegic migraine, but several genes are likely to be involved in the great majority of migraine cases. Numerous chemicals, structures, nerve pathways, and other players involved in the process are under investigation.

Central Nervous Disorder. One theory that attempts to integrate many of the known events in the migraine process is as follows:

Stress or some unknown factor triggers the release of certain protein fragments called peptides (Substance P, calcitonin gene-related peptide, and others).
These peptides dilate blood vessels and produce an inflammatory response that triggers over-excitation of the nerve cells in the trigeminal pathway. [This nerve pathway runs from the brain stem to the head and face. These nerves spread to the meninges (the membrane covering of the brain).]
While the brain itself is insensitive to pain, the meninges and blood vessels around the brain are sensitive to pain. Some doctors suggest that pain occurs when blood drains from the center of the head to the blood vessels around the brain.
Auras are believed to be a response to blood flow changes that cause a rapid reduction in brain activity that reaches the cerebral cortex (the outer layer of the brain), referred to as spreading depression. This effect may be visualized as an electrical wave spreading through the brain just as a wave of water is caused by the dropping of a pebble. Some research suggests that in people with auras, the cortical spreading depression itself activates the inflammation in the trigeminal nerves that triggers pain in the meninges.

One theory of the cause of migraine is a central nervous system (CNS) disorder. The CNS consists of the brain and spinal cord. In migraine, various stimuli may cause a series of neurologic and biochemical events that affect the brain's vascular system.

Abnormal Calcium Channels. Some migraines may be due to abnormalities in the channels within cells that transport the electrical ions calcium, magnesium, sodium, and potassium. Calcium channels appear to play a particularly critical role in migraine:

Calcium channels regulate the release of serotonin, an important neurotransmitter in the migraine process. (A neurotransmitter is a chemical messenger that allows communication between nerves in the brain.)
Magnesium interacts with calcium channels, and magnesium deficiencies have been detected in the brains of patients with migraine.
Calcium channels also play a major role in cortical spreading depression, the brain event that appears to be important in migraine symptoms.

Some patients with migraines may inherit one or more factors that impair calcium channels, making them susceptible to headaches. For example, mutations in a gene that encodes calcium channels appears to be responsible for familial hemiplegic migraine.

Researchers are also investigating factors that are common to both migraines and tension-type headaches. Some research suggests that both problems may result from a continuum of abnormalities in the central nervous system (the nerves in the brain and spine). Such changes trigger a progression of symptoms starting with mild sensations, developing into tension headache, and finally, progressing in some people to a migraine.

Serotonin and Other Neurotransmitter Levels. Neurotransmitters are chemical messengers in the brain. Serotonin is a neurotransmitter (chemical messenger in the brain) that is important for sleep, well-being, and other factors that affect quality of life. Abnormalities in serotonin levels have been observed in both tension-type and migraine headache sufferers. Altered levels of other neurotransmitters, importantly dopamine and stress hormones, also occur with migraine and tension-type headaches.

Dopamine, for example, may act as a stimulant of the migraine process. Some evidence suggests that certain genetic factors make people over-sensitive to the effects of dopamine, which include nerve cell excitation. Such nerve-cell over-activity could trigger the events in the brain leading to migraine. The prodromal symptoms (mood changes, yawning, drowsiness), for example, have been associated with increased dopamine activity. Dopamine receptors are also involved in regulation of blood flow in the brain.

Reduced Magnesium Levels. Magnesium deficiencies have been observed in people with both tension-type and migraine headaches. Researchers have noted a drop in magnesium levels before or during a migraine attack. Magnesium plays a role in nerve cell function. Reduced levels could be a destabilizing factor, causing the nerves in the brain to misfire, possibly even accounting for the auras that many sufferers experience.

Nitric Oxide. Other research suggests that over-excitable neurons release nitric oxide, a small molecular messenger that may be important in triggering in most primary headaches (tension-type, cluster, and migraines). Elevated levels have been observed in blood cells of patients with tension-type headache. Some evidence suggests that the release of this molecule in blood vessels may activate nerve pathways in the brain, muscles, or elsewhere and increase pain.

Estrogen Fluctuations in Women. Tension-type headaches and migraine headaches are slightly more common in females during adolescence and adulthood. Most likely hormone fluctuations, rather than whether levels are elevated or low, trigger headaches. Some research suggests that fluctuations in estrogen levels may impact levels of serotonin and other pain-modulating substances that affect these headaches.

Inflammation in the Maxillary Nerve. Early studies suggest that some chronic tension-type and migraine headaches may be caused by inflammation in the nerve that runs behind the cheekbone (the maxillary nerve) -- not around the covering of the brain. In fact, some work using ice water for reducing swelling in areas of the gums above the last upper molars has relieved some severe migraine and tension-type headaches.

A wide range of events and conditions can alter conditions in the brain that bring on nerve excitation and trigger migraines. They include, but are not limited to:

Emotional stress
Intense physical exertion (exercise, lifting, and even bowel movements or sexual activity)
Abrupt weather changes
Bright or flickering lights
High altitude
Travel motion
Lack of sleep
Low blood sugar and fasting
Chemicals found in certain foods. More than 100 foods may potentially trigger migraine headache. Caffeine is one such trigger. Caffeine withdrawal can also trigger migraines in people who are accustomed to caffeine. Experts recommend that patients keep a headache diary to track which foods trigger migraine.

Risk Factors

About 30 million Americans suffer from migraine headaches. They affect about 17% of all women and 6% of men. In fact, 70% of all migraine sufferers are women. Migraine is more prevalent among women throughout the world and in every culture. Although the incidence of migraine is similar for boys and girls during childhood, it increases in girls after puberty. Most people with migraine have 1 - 4 attacks per month.

Hormone Fluctuations in Women. Most migraines in women develop during the hormonally active years between adolescence and menopause. Fluctuations of estrogen and progesterone, rather than their presence, appear to increase the risk for migraines and their severity in some women.

About half of women with migraines report headaches associated with their menstrual cycle, although true menstrual migraines may actually be less common. True menstrual migraines tend not to have auras and to increase in prevalence between 2 days before and 5 days after the onset of period.
The first 3 months of pregnancy can worsen migraines in some women, although one study reported that pregnancy had little effect one way or the other on severity in most women with chronic headaches.
Women whose migraines are affected by pregnancy or menstruation are also likely to have worse migraines if they take oral contraceptives or hormone replacement therapies.

General Age of Onset. More than 20% of adults with migraines report that their headaches started before age 10, and over 45% say they started before age 20. The incidence of migraine declines in both men and women after age 40.

Migraine in Children. Migraine headaches occur in all ages and can appear in children as young as 4 years of age. Migraines in children are equally prevalent in boys and girls. Studies estimate that about 4 – 10% of all children suffer from migraine. Research indicates that overweight children may be especially susceptible to headaches, although this association is most likely due to poor nutrition and lack of exercise rather than excess weight. Children who have sleep problems, especially difficulty falling asleep, may also be more prone to migraines.

A small 2006 study indicated that some adolescents with migraine may eventually grow out of their condition. By the end of the 10-year study, 38% of patients had stopped having migraines, and 20% had transitioned into less severe tension-type headache. Children with a family history of migraine were more likely to continue having migraines.

Migraine Onset in Older Adults. Although uncommon, late-life migraine occurs in about 1% of the population, usually in men. In such cases, it often occurs as migraine with visual disturbances but without headache.

Migraine headaches can be inherited. If both parents suffer from migraines, their children have a 75% chance of getting them. When only one parent gets migraines, there is a 50% chance that children will be afflicted.

Caucasians have a higher risk than either African-Americans or Asians. Worldwide, one study reported that migraines are most common in North America. They are slightly less prevalent in South America and Europe and far less common in Asia and Africa. Investigators believe that the differences are due to genetic variations, not lifestyle factors.

People with migraine have a higher incidence of other medical conditions, including:

Asthma and allergies. These conditions have also been associated with a higher risk for conversion from having periodic migraines attacks to a chronic form (transformed migraines).
H. pylori infection. People who are infected with the bacteria H. pylori, the major cause of peptic ulcers, are at higher risk for migraines.
Epilepsy. Patients with epilepsy are twice as likely to have migraines as the general population.
Fibromyalgia
Systemic lupus erythematosus
Raynaud syndrome
Mitral valve prolapse
Narcolepsy

One study suggested that women with migraines tend to over-respond to stressful situations. In the study, they were more likely than other women to be diligent, conscientious, and overly sensitive to pressure from others. More likely, however, a person's family history of migraine, rather than any personality trait, is the important risk factor.

Diagnosis

Anyone, including children, who has recurring or persistent headaches should consult a doctor. There are no blood tests or imaging techniques that can be used to diagnose migraine headaches. A diagnosis will be made on the basis of history and physical exam, and, if necessary, tests may be necessary to rule out other diseases or conditions that may be causing the headaches. It is important to choose a doctor who is sensitive to the needs of headache sufferers and aware of the latest advances in treatment.

For an accurate diagnosis, the patient should describe:

Duration and frequency of headaches
Recent changes in their character
Location of pain
Type of pain (throbbing or steady pressure)
Intensity of the headache
Associated symptoms, such as visual disturbances or nausea and vomiting
Behaviors during a headache. This may help distinguish between migraine and tension headaches. The predominant behavior with tension headaches is massaging the scalp, temples, or the nape of the neck. A person with migraines is more apt to use compression (such as tying a scarf around the forehead and temples) or to apply cold. They also tend to isolate themselves, lie down, induce vomiting, and use more pillows than usual. (None of these maneuvers do much good in relieving either headache, unfortunately.)

The presence of auras or other visual disturbances do not always identify migraine:

Patients with severe sinus infections may experience double vision or visual loss. (This is an emergency condition, since it indicates the infection has spread to areas around the eyes.)
Many migraine sufferers have no auras.
Many elderly people with late-onset migraine have auras but no pain.

The patient should try to recall what seems to bring on the headache and anything that relieves it. Keeping a headache diary is a useful way to identify triggers that bring on headaches. Some tips include:

Note all conditions, including any foods eaten, preceding an attack. Often two or more triggers interact to produce a headache. For example, a combination of weather changes and fatigue can make headaches more likely than the presence of just one of these events.
Keep a migraine record for at least three menstrual cycles. For women, this can help to confirm or refute a diagnosis of menstrual migraine.
Track medications. This is important for identifying possible rebound headache or transformed migraine.
Attempt to define the intensity of the headache using a number system, such as:

1 = Mild, barely noticeable

2 = Noticeable, but does not interfere with work/activities

3 = Distracts from work/activities

4 = Makes work/activities very difficult

5 = Incapacitating

The patient should report any other conditions that might be associated with headache, including but not limited to:

Any chronic or recent illness and their treatments
Any injuries, particularly head or back injuries
Any uncharacteristic dietary changes
Any current medications or recent withdrawals from any drugs, including over-the-counter or natural remedies.
Any history of caffeine, alcohol, or drug abuse.
Any serious stress, depression, and anxiety.

The doctor will also need a general medical and family history of headaches or diseases, such as epilepsy, that may increase their risk. Migraine tends to run in families.

In order to diagnose a chronic headache, the doctor will examine the head and neck and will usually perform a neurologic examination, which includes a series of simple exercises to test strength, reflexes, coordination, and sensation. The doctor may ask questions to test short-term memory and related aspects of mental function.

Diagnosing the cause of persistent daily headache is difficult, even for expert doctors. Studies report that people who visit the emergency room with disabling headache are often misdiagnosed as tension-type headaches instead of migraines. It is important to choose a doctor who is sensitive to the needs of headache sufferers and aware of the latest advances in treatment.

Extensive testing may be advised for anyone with a chronic, daily headache. Tracking times of medications, withdrawal, and headache, using the headache diary, is usually very helpful in diagnosis.

Differentiating Rebound Headaches from Transformed Migraines. Migraines that evolve to chronic headaches must be first differentiated between natural transformed migraines and rebound headaches (the most common cause of persistent migraines):

A transformed migraine is usually more consistent in its severity and its location than a rebound headache.
Transformed migraines are less sensitive to triggers than rebound headaches.

Differentiating Transformed from Tension Headaches. Once rebound headache is ruled out, the doctor must then differentiate natural transformed migraines from tension headaches:

In most cases of transformed migraine (but not tension headache), gastrointestinal or neurologic symptoms are present.
Transformed migraine is also frequently associated with menstrual fluctuations in women.

Imaging tests of the brain may be recommended under the following circumstances:

If the results of the history and physical examination suggest neurologic problems.
For patients with headaches that wake them at night.
For new headaches in the elderly. In this age group, it is particularly important to first rule out age-related disorders, including stroke, hypoglycemia, hydrocephalus, and head injuries (usually from falls).
For patients with worsening headaches.

They are not recommended for patients with migraine and with no other abnormal indications.

The following tests may be used:

A CT (computed tomography) scan may be ordered to rule out brain disorders or headaches caused by chronic sinusitis.
X-rays and other tests may also be used if sinusitis is strongly suspected.
A neck x-ray can reveal arthritis or spinal problems.
Other imaging tests include an MRI (magnetic resonance imaging), EEG (electroencephalogram), lumbar puncture, ultrasound testing, and cerebral angiography, positron emission tomography (PET), and single-photon emission computed tomography (SPECT). These tests are only performed if there is reason to suspect an underlying disease or as part of clinical studies.

A CT (computed tomography) scan is a much more sensitive imaging technique than x-ray, allowing high definition of not only the bony structures but also the soft tissues. Clear images of organs and structures, such as the brain, muscles, joints, veins and arteries, as well as of tumors and hemorrhages, may be obtained with or without the injection of contrasting dye.

Headaches indicating a serious underlying problem, such as cerebrovascular disorder or malignant hypertension, are uncommon. (It should again be emphasized that a headache is not a common symptom of a brain tumor.) People with existing chronic headaches, however, might miss a more serious condition by believing it to be one of their usual headaches. Such patients should call a doctor promptly if the quality of a headache or accompanying symptoms has changed. Everyone should call a doctor for any of the following symptoms:

Sudden, severe headache that persists or increases in intensity over the following hours, sometimes accompanied by nausea, vomiting, or altered mental states (possible hemorrhagic stroke).
Sudden, very severe headache, worse than any headache ever experienced (possible indication of hemorrhage or a ruptured aneurysm).
Chronic or severe headaches that begin after age 50.
Headaches in the back of the head accompanied by other symptoms, such as memory loss, confusion, loss of balance, changes in speech or vision, or loss of strength in or numbness or tingling in arms or legs (possibility of small stroke in the base of the skull).
Headaches after head injury, especially if drowsiness or nausea are present (possibility of hemorrhage).
Headaches accompanied by fever, stiff neck, nausea and vomiting (possibility of spinal meningitis).
Headaches that increase with coughing or straining (possibility of brain swelling).
A throbbing pain around or behind the eyes or in the forehead accompanied by redness in the eye and perceptions of halos or rings around lights (possibility of acute glaucoma).
A one-sided headache in the temple in elderly people; the artery in the temple is firm and knotty and has no pulse; scalp is tender (possibility of temporal arteritis, which can cause blindness or even stroke if not treated).
Sudden onset and then persistent, throbbing pain around the eye possibly spreading to the ear or neck unrelieved by pain medication (possibility of blood clot in one of the sinus veins of the brain).

Treatment Approaches

Many effective headache remedies are available for treating a migraine attack. Still, a study that analyzed over 800,000 cases of migraine reported that most migraines are not treated according to any recommended guidelines. In the study, 30% of patients were treated with potentially addictive opioids -- most often merepidine (Demerol). Furthermore, 70% of these patients were not offered effective and available anti-migraine drugs. Anti-nausea drugs that have no effect on headaches were used six times more often than drugs that reduce headaches.

A 2007 survey of migraine sufferers, commissioned by the U.S. National Headache Foundation, reported that 20% of patients are prescribed non-approved medications containing opioids or barbiturates. The survey also indicated that patients who take non-approved drugs are more likely to experience drug-related side effects. For mild migraines, non-prescription treatments (Excedrin Migraine, Advil Migraine, Motrin Migraine Pain) are the best first choice. For severe migraines, doctors recommend starting with a triptan drug.

Preventive treatment, used to stop migraine attacks before they happen, may help many patients. According to another 2007 survey, more than 1 in 4 patients with migraine are candidates for preventive therapy but most do not receive it.

As many as 30% of patients with migraine also have accompanying headaches resulting from tension, drugs, infections, or other causes. It is important to distinguish between headache types in order to determine appropriate treatment.

General Guidelines. The general goals of treatment are:

Choose drugs with as few side effects as possible. Patients should talk to their doctors about various methods for administering the medication (pills, injections, nasal spray, or rectal suppositories) and begin with the one they believe will be the least distressing.
Treat the attack rapidly, within an hour of symptom onset if possible. Start with low doses, and build up dosage slowly.
Try to minimize the use of back-up or "rescue medications." (A rescue medication is typically a narcotic opiate drug, which is used for pain relief when other medications fail.)
Try to guard against rebound effect. Nearly all drugs used for migraine can cause rebound headache, and patients should not take any the drugs for longer than 2 days per week.
It may take 2 - 4 months for any drug to be effective.

Stepped-Up Treatment Approach. Some doctors recommend a stepped-up treatment course for an acute migraine attack. This involves starting with the least potent treatments and taking increasingly more powerful drugs until the pain stops. In this approach, patients may need up to five different medications to achieve pain relief. A typical stepped-up approach is the following:

The patient should first use nonprescription pain relievers (NSAIDs, Excedrin Migraine) and stress-reduction techniques.
If these are not effective within 2 hours, the patient should take migraine-specific drugs. Triptans are the first choice, then ergot derivatives.
Patients with migraines associated with severe nausea or vomiting may use injected or rectally administered drugs. Nausea itself should be treated with specific anti-nausea drugs, such as metoclopramide (Reglan).
If migraine medications fail to relieve symptoms within 4 hours, rescue drugs (opioids, corticosteroids) may be used.

Stratified Approach. Many doctors and patients now prefer the stratified approach. The doctor first estimates the severity of the patient's condition based on his or her history. Then, depending on the severity of a typical attack, the doctor decides whether the patient should start with more or less powerful drugs at the first signs of the migraine:

Patients with less disabling migraines start with general pain relievers.
Patients with a history of moderate-to-severe migraines start with migraine-specific prescription medicine, such as a triptan, at the onset of mild pain.

Some studies report dramatic relief with the stratified approach. In one study, zolmitriptan, a newer triptan, reduced the intensity of headaches within 2 hours in 70% of patients with moderate pain but only in 44% of those with severe headaches.

Side effects can be severe with many migraine drugs, although newer drugs, such as the recent generation triptans, may provide effective early relief without significant side effects.

Studies estimate that between 5 - 10% of children have migraines but that the disorder is underdiagnosed in children. An interesting study reported that when children drew pictures in response to their doctors' questions about their migraines, the doctors were able to tell the difference between migraine and non-migraine headaches in the majority of cases.

Symptoms in Children. The standard diagnostic criteria for migraine in adults may apply to only about two-thirds of migraines in children and adolescents. For example, doctors have seen the following differences:

Headaches tend to last for a shorter time (as little as an hour) in children.
Migraine pain tends to occur in the face and on both sides of the head in two-thirds of child patients.
Children often have a form of migraine known as a migraine equivalent or abdominal migraine, which does not cause a headache at all. Instead, children experience periodic bouts of nausea and vomiting (called cyclic vomiting syndrome) or other secondary symptoms found in adult migraine, such as a reaction against light or sound. Cyclic vomiting may occur in nearly 2% of school-aged children with or without a migraine association.
Migraine triggers in children are similar to those in adults, but common ones in children are anxiety and fear, and eating ice cream.

Outlook in Children. Migraine in children is disabling, as it is in adults, and they tend to lose more school days than other children. Children with frequent headaches may also be at higher risk for headaches in adulthood and also for other physical and psychiatric problems. However, some children who have migraine eventually stop having attacks when they reach adulthood, or have less severe types of headaches.

Treatments in Children. Most children with migraines may need only mild pain relievers and home remedies (such as ginger tea) to treat their headaches. The American Academy of Neurology’s 2004 practice guidelines for children and adolescents recommend the following drug treatments:

For children age 6 years and older, ibuprofen (Advil) is recommended. Acetaminophen (Tylenol) may also be effective. Acetaminophen works faster than ibuprofen, but the effects of ibuprofen last longer.
For adolescents age 12 years and older, sumaptriptan (Imitrex) nasal spray is recommended.

Preventive Measures in Children. Non-medication methods, including biofeedback and muscle relaxation techniques may be helpful. In one study of children with migraines and poor sleep habits, who were taught how to sleep better instructions without using medications had significantly fewer migraine attacks.

If these methods fail, then preventive drugs may be used, although evidence is weak on the effectiveness of standard migraine preventive drugs in children.

If medication overuse causes rebound migraines develop, the patients cannot recover without stopping the drugs. (If caffeine is the culprit, a person may need only to reduce coffee or tea drinking to a reasonable level, not necessarily stop drinking it altogether.) The patient can usually stop abruptly or gradually. The patient should expect the following:

Most headache drugs can be stopped abruptly, but the patient should talk to their doctor first. Certain non-headache medications, such as anti-anxiety drugs or beta-blockers, require gradual withdrawal.
If the patient chooses to taper off standard headache medications, withdrawal should be completed within three days.
The patient may take other pain medicines during the first days. Examples of drugs that may be used include dihydroergotamine (with or without metoclopramide), NSAIDs (in mild cases), corticosteroids, or valproate.
The patient must expect their headache to get worse after they stop taking their medications, no matter which method they use. Most people feel better within 2 weeks, although headache symptoms can persist up to 16 weeks (and in rare cases even longer).
If the symptoms do not respond to treatment and cause severe nausea and vomiting, the patient may need to be hospitalized.

On the encouraging side, some patients experience dramatic long-term relief from all headaches afterward, and one study reported that 82% of patients significantly improved 4 months after medication withdrawal.

Medications Used for Treatment

Many different medications are used to treat migraines. However, the Food and Drug Administration (FDA) has specifically approved only the following types of drugs for migraine treatment:

Non-prescription drugs: Excedrin Migraine, Advil Migraine, Motrin Migraine Pain
Prescription drugs: Triptans and ergotamine

Other types of drugs, including opioids and barbiturates, are sometimes prescribed off-label for migraine treatment. Opioids and barbiturates have not been approved by the FDA for migraine relief, and they can be addictive.

All FDA-approved migraine treatments are approved only for adults. No migraine products have officially been approved for use in children.

Some patients with mild migraines respond well to over-the-counter (OTC) painkillers, particularly if they take the medicine at the very first sign of an attack.

The Food and Drug Administration has approved three OTC (nonprescription) products to treat migraine. Excedrin Migraine (a combination of aspirin, acetaminophen, and caffeine) was the first such medication approved for the temporary relieve of migraine and its symptoms. Studies have reported significant relief in nearly 70% of patients. It may also help menstrual migraines. Advil Migraine and Motrin Migraine Pain, both containing ibuprofen, are also approved to treat migraine headache.

Cooling Pads. Cooling pads may help during an attack. Some products (Migraine Ice, TheraPatch Headache Cool Gel) use a pad containing a gel that cools the skin for up to 4 hours and can be placed on the forehead, temple, or back of the neck.

Non-steroidal anti-inflammatory drugs (NSAIDs) include aspirin, ibuprofen, and naproxen. They were among the first types of drugs tried to treat mild-to-moderate migraines. Aspirin, ibuprofen (Advil, Motrin), and naproxen (Anaprox, Aleve) are all available without prescription. Naproxen may have specific benefits for migraine. A 2007 study indicated that a combination of naproxen and sumatriptan provides better migraine pain relief than either drug alone.

Other types of NSAIDs are available only by prescription. Some studies indicate that the NSAID combination diclofenac-potassium (Cataflam) may work faster than the migraine drug sumatriptan (Imitrex) and help reduce nausea. The combination is not appropriate for people allergic to aspirin or at risk for bleeding.

Injectable NSAIDs, particularly ketorolac (Toradol), may be very effective for severe and persistent migraines. A 2003 study found that intravenous ketorolac provided greater pain relief than nasal sumatriptan (Imitrex). A 2005 study presented at the annual meeting of the American Headache Society reported that intravenous ketorolac was more effective than opioid drugs for late-stage treatment of severe migraine attacks.

COX-2s are a class of prescription drugs that have the anti-inflammatory effects of NSAIDs, but do not upset most people's stomachs. However, most of these drugs have been withdrawn from the U.S. market due to increased risk for heart attack and stroke. Celecoxib (Celebrex) is the only available COX-2, and it has a strong warning label alerting users of the potential for heart attack, stroke, and serious gastrointestinal problems. (The warning is the same one the Food and Drug Administration recommended for the labels of prescription NSAIDs in 2005.)

NSAID Side Effects. High dosages and long-term use of NSAIDs can increase the risk for heart problems, kidney problems, and stomach bleeding. In April 2005, the FDA asked drug manufacturers of prescription NSAIDs to include with their products the same boxed warning used for the COX-2 inhibitor celecoxib (Celebrex). This boxed warning emphasizes an increased risk for cardiovascular events and gastrointestinal bleeding in people taking these drugs. The FDA also requested manufacturers of over-the-counter NSAIDs to revise their labels to include more specific language concerning potential cardiovascular and gastrointestinal risks. Due to its proven heart benefits, aspirin was excluded from these labeling revisions.

Triptans (also referred to as serotonin agonists) were the first drugs specifically developed for use against migraine. They are the most important migraine drugs currently available. They help maintain serotonin levels in the brain, and so specifically target one of the major components in the migraine process.

Triptans are recommended as first-line drugs for adult patients with moderate-to-severe migraines when NSAIDs are not effective. Triptans have the following benefits:

They are effective for most patients with migraine, as well as patients with combination tension and migraine headaches.
They do not have the sedative effect of other migraine drugs.
Withdrawal after overuse appears to be shorter and less severe than with other migraine medications

Sumatriptan. Sumatriptan (Imitrex) has the longest track record and is the most studied of all triptans. It is available as a fast-dissolving pill, nasal spray, or injection. Injected sumatriptan works the fastest of all the triptans and is the most effective, but it can cause pain at the injection site. The nasal spray form bypasses the stomach and is absorbed more quickly than the oral form. Some patients report relief as soon as 15 minutes after administration. The spray tends to work less well when a person has nasal congestion from cold or allergy. It may also leave a bad taste. Sumatriptan is effective for many patients, but headache recurs in 20 - 40% of people within 24 hours after taking the drug.

A 2007 study in the Journal of the American Medical Association suggested that a combination of sumatriptan and naproxen works better than either drug alone.

Other Triptans. Newer triptans include almotriptan (Axert), zolmitriptan (Zomig), naratriptan (Amerge), rizatriptan (Maxalt), frovatriptan (Frova), and eletriptan (Relpax). Comparison studies with sumatriptan suggest that some of the newer drugs have fewer side effects and are superior to sumatriptan for providing immediate, sustained, and consistent pain relief. Recurrence rates are also lower. They are also being investigated for prevention under certain circumstances, such as menstrual migraines, but benefits appear limited.

Studies on newer triptans indicate:

Almotriptan is as effective as oral sumatriptan and may have fewer side effects, particularly chest pain, than most other triptans.
Rizatriptan may have the most rapid effects of all oral triptans. Zolmitriptan also has a more rapid effect than sumatriptan (although there appears to be no significant difference in adverse effects). Both rizatriptan and zolmitriptan are also available as rapidly dissolving wafers.
Eleptriptan is also very rapidly effective at high doses, but at those levels may have significant adverse effects. (To date, it does not seem to have any advantages over other triptans in head-to-head comparisons.)
Naratriptan and frovatriptan have a delayed response but long duration, few side effects, and lower risk for recurrence than with sumatriptan. Some evidence suggests that they may have specific benefits for stopping prolonged migraines and may even play a role in prevention.
Frovatriptan: A large study of more than 500 women with an average 12-year history of menstrual migraines examined the use of frovatriptan for the short-term prevention of such headaches. Researchers found that the migraines disappeared in over half of the women on the higher dose (5 mg) of frovatriptan.
Zolmitriptan (Zomig): Several studies indicate that zomitriptan nasal spray may be safe and effective for adolescents. In one study, zolmitriptan relieved pain within 2 hours for nearly half of the children (aged 12 - 17 years) enrolled in the trial. Zolmitriptan nasal spray is approved only for adults.

Side Effects. Many of the newer triptans may have fewer severe side effects than sumatriptan. Side effects of most triptans, however, can include:

Tingling and numbness in the toes
Sensations of warmth
Discomfort in the ear, nose, and throat
Nausea
Drowsiness
Dizziness
Muscle weakness
Heaviness, pain, or both in the chest. (About 40% of patients taking sumatriptan experience these symptoms, and they are major factors in discontinuing the drug. Newer drugs, such as almotriptan, produce fewer chest symptoms.)
Rapid heart rate

Complications of Triptans. The following are potentially serious problems.

Complications of heart and circulation. Triptans narrow (constrict) blood vessels. Because of this effect, spasms in the blood vessels may occur and cause serious side effects, including stroke and heart attack. Such events are rare, but patients with an existing history or risk factors for these conditions should generally avoid triptans.
Serotonin syndrome. Serotonin syndrome is a life-threatening condition that occurs from an excess of the brain chemical serotonin. Triptan drugs used to treat migraine, as well as certain types of antidepressant medications, can increase serotonin levels. These antidepressant drugs include serotonin reuptake inhibitors (SSRIs) -- such as fluoxetine (Prozac), paroxetine (Paxil), and sertraline (Zoloft) -- and selective serotonin/norepinephrine reuptake inhibitors (SNRIs), such as duloxetine (Cymbalta) and venlafaxine (Effexor). It is very important that patients not combine a triptan drug with a SSRI or SNRI drug. Serotonin syndrome is most likely to occur when starting or increasing the dose of a triptan or antidepressant drug. Symptoms include restlessness, hallucinations, rapid heartbeat, tremors, increased body temperature, diarrhea, nausea, and vomiting. You should seek immediate medical care if you have these symptoms.

The following people should avoid triptans or take them with caution and only with the advisement of a doctor:

Anyone with a history or any risk factors for stroke, uncontrolled diabetes, high blood pressure, or heart disease.
People taking antidepressants that increase serotonin levels.
Children and adolescents. They may be safe, but controlled studies are needed to confirm this. (Triptans should not, in any case, be the first-line treatment for children.)
People with basilar or hemiplegic migraines. (Triptans are not indicated for these migraineurs.)
There is no evidence to date of any higher risk for birth defects in pregnant women who take triptans. Still, women should be cautious about taking any medications during pregnancy and discuss any possible adverse effects with their doctors.

Drugs containing ergotamine (commonly called ergots) constrict smooth muscles, including those in blood vessels, and are useful for migraine. They were the first anti-migraine drugs available. Ergotamine is available by prescription in the following preparations:

Dihydroergotamine (DHE) is an ergot derivative. It is administered as a nasal spray form (Migranal) or by injection, which can be performed at home.
Ergotamine is available tablets taken by mouth, tablets taken under the tongue (sublingual), and rectal suppositories. Some of the tablet forms of ergotamine contain caffeine.

Ergotamine’s role since the introduction of triptans is now less certain. Only the rectal forms of ergotamine are superior to rectal triptans. Injected, oral, and nasal-spray forms are all inferior to the triptans. Ergotamine may still be helpful for patients with status migrainous or those with frequent recurring headaches.

Side Effects. Side effects of ergotamine include:

Nausea
Dizziness
Tingling sensations
Muscle cramps
Chest or abdominal pain

The following are potentially serious problems:

Toxicity. Ergotamine is toxic at high levels.
Adverse effects on blood vessels. Ergot can cause persistent blood vessel contractions, which may pose a danger for people with heart disease or risk factors for heart attack or stroke.

Internal scarring (fibrosis). Scarring can occur in the areas around the lungs, heart, or kidneys. It is often reversible if the drug is stopped.

The following patients should avoid ergots:

Pregnant women. Ergots can cause miscarriage.
People over age 60.
Patients with serious, chronic health problems, particularly those of the heart and circulation.

Ergotamine can interact with other medications, such as antifungal drugs and some antibiotics. All ergotamine products approved by the Food and Drug Administration (FDA) contain a "black box" warning in the prescription label explaining these drug interactions. In 2007, the FDA pulled 15 unapproved older ergotamine products off the market, in part because they lacked this warning label. The five FDA-approved ergotamine products that remain on the market are:

Migergot suppository (marketed by G and W Labs)
Ergotamine Tartrate and Caffeine tablets (marketed by Mikart and West Ward)
Cafergot tablets (marketed by Sandoz)
Ergomar sublingual tablets (marketed by Rosedale Therapeutics)

Nasal drops containing lidocaine, a local anesthetic, can provide effective and quick pain relief within 15 minutes for many migraine sufferers. However, lidocaine has certain downsides:

It is rather difficult to administer. Patients must be lying down with their head dangling.
The headache often relapses in an hour, and other drugs must then be used.
Side effects include unpleasant taste, burning sensation, and facial numbness.

However, the drug does not cause drowsiness or heart rhythm disturbances as some other migraine treatments do. It should not be used for any other form of headache.

If the pain is very severe and does respond to other drugs, doctors may try painkillers containing opioids. Opioid drugs include morphine, codeine, meperidine (Demerol), and oxycodone (Oxycontin)]. Butorphanol is an opioid in nasal spray form that may be useful as a rescue treatment when others fail.

Opioids are not approved for migraine treatment and should not be used as first-line therapy. Nevertheless, many opioid products are prescribed to patients with migraine, sometimes with dangerous results. In 2007, following reports of several drug-related deaths, the Food and Drug Administration warned that the cancer pain pill fentanyl (Fentora) should not be used to treat patients with migraine or others conditions for which the drug is not specifically approved.

Side Effects. Side effects for all opioids include drowsiness, impaired judgment, nausea, and constipation. There is a risk for addiction, and these drugs can become ineffective with long-term use for chronic migraines. Doctors should not prescribe opioids to patients at risk for drug abuse, including those with personality or psychiatric disorders.

Metoclopramide (Reglan) is used in combinations with other drugs to treat the nausea and vomiting that occurs with other drugs and with migraine itself. Metoclopramide and other anti-nausea drugs, such as domperidone (Motilium), may help the intestine better absorb migraine medications.

New drugs in clinical trials include tonabersat (a gap junction blocker), trexima (a combination triptan and non-steroidal anti-inflammatory drug), GW274150 (a nitric oxide synthase inhibitor), and MK-0974 (a calcitonin gene-related peptide antagonist). Researchers are also investigating a nasal spray containing capsaicin, the chemical found in cayenne peppers.

Prevention

There are several ways to prevent migraine attacks. You should try a healthy diet, the right amount of sleep, and non-drug approaches, such as biofeedback, first for prevention.

Behavioral techniques that reduce stress and empower the patient may help some people with migraines. Studies report between 35 - 50% reduction in migraine and tension-type headaches with these approaches. They generally include:

Biofeedback therapy
Cognitive-behavioral therapy
Relaxation techniques

Behavioral methods may help counteract the tendency for muscle contraction and uneven blood flow associated with some headaches. They may be particularly beneficial for children, adolescents, and pregnant and nursing women, and anyone who cannot take most migraine medications.

Biofeedback. Studies have demonstrated some effectiveness from biofeedback for migraine headaches. Biofeedback training teaches the patient to monitor and modify physical responses, such as muscle tension, using special instruments for feedback.

Cognitive Behavioral Therapy. Behavioral therapy may be useful alone but is particularly beneficial for patients who are on preventive drug treatments. It typically uses the headache diary to track activities and headaches. The patient then works with the therapist to change or add behaviors or medications that will reduce the frequency and severity of attacks.

Alternative non-drug therapies used for headache management and prevention include hypnosis, meditation, visualization and guided imagery, acupuncture, acupressure, yoga, and other relaxation exercises. There is no clear evidence that any of these techniques have specific value for migraines.

Some studies report the following:

Acupuncture. Acupuncture is a Chinese medicine technique that uses thin needles to stimulate specific points aligned with energy pathways in the body. Studies have showed mixed results on the benefits of acupuncture for migraine. A 2005 study published in the Journal of the American Medical Association reported that acupuncture was no more effective than sham acupuncture (needles placed at non-acupuncture points) in preventing migraines. More than 300 people were enrolled in this randomized trial. A 2006 study of 960 people, published in Lancet Neurology, found that real acupuncture, sham acupuncture, and standard drug treatment were all equally effective in preventing migraine attacks.
Relaxation Techniques. Muscle relaxation techniques may be helpful. One study reported that relaxation treatments appeared to help adolescents with migraine but not tension headaches.

Hormonal drugs, such as oral contraceptives or hormone replacement therapy, have a mixed effect on women with migraines. Oral contraceptives have been associated with worse headaches in 18 - 50% of women and have also been linked to a higher risk for stroke in women with classic migraines (with auras). Young women should avoid or stop oral contraception if they have classic migraines, migraines that worsen or change character after oral contraceptives , if they have close relatives with stroke or heart disease, or if they smoke.

Some evidence suggests, however, that oral contraceptives may help prevent true menstrual migraines (which do not have auras). In such cases, their benefits may outweigh the low risk of a serious adverse event. Keeping a migraine record for at least three menstrual cycles can help confirm whether a woman actually has a true menstrual migraine.

Making a few minor changes in your lifestyle can make your migraines more bearable. Improving sleep habits is important for everyone, and especially those with headaches. What you eat also has a huge impact on migraines, so dietary changes can be extremely beneficial, too.

Avoiding Food Triggers. Avoiding foods that trigger migraine is an important preventive measure. Common food triggers include monosodium glutamate (MSG), processed lunch meats that contain nitrates, dried fruits that contain sulfites, aged cheese, alcohol and red wine, chocolate, and caffeine. However, people’s responses to triggers differ. Keeping a headache diary that tracks diet and headache onset can help identify individual food triggers.

Healthy Diet. One study indicated that a diet low in fat and high in complex carbohydrates may significantly reduce the frequency, severity, and duration of migraine headaches. Such a diet is healthy in general, in any case.

Eating Regularly. Eating regularly is important to prevent low blood sugar. People with migraines who fast periodically for religious reasons might consider taking preventive medications.

Fish Oil. Some studies suggest that omega-3 fatty acids, which are found in fish oil, have anti-inflammatory and nerve protecting actions. These fatty acids can be found in oily fish, such as salmon, mackerel, or sardines. They can also be obtained in supplements of specific omega-3 compounds (DHA-EPA).

Exercise is certainly helpful for relieving stress. An analysis of several studies reported that aerobic exercise in particular might help prevent migraines. It is important, however, to warm up gradually before beginning a session, since sudden, vigorous exercise might actually precipitate or aggravate a migraine attack.

Manufacturers of herbal remedies and dietary supplements do not need Food and Drug Administration approval to sell their products. Just like a drug, herbs and supplements can affect the body's chemistry, and therefore have the potential to produce side effects that may be harmful. There have been several reported cases of serious and even lethal side effects from herbal products. Patients should always check with their doctors before using any herbal remedies or dietary supplements.

Riboflavin (Vitamin B2). There is reasonable evidence on the benefits of vitamin B2 for migraine sufferers. In one study, patients who took 400 mg of vitamin B2 (riboflavin) reduced their migraine attacks by half, although the vitamin had no effect on the severity or duration of migraines that did occur. In another study, it helped increase the effectiveness of beta-blockers, drugs used to prevent migraines in some people. Vitamin B2 is generally safe, although some people taking high doses develop diarrhea.

Magnesium Supplements. Studies have reported a higher rate of magnesium deficiencies in some patients with migraine, such as those with menstrual migraines. Magnesium helps relax blood vessels. Some patients report relief from supplements.

Feverfew. Feverfew is the most studied herbal remedy for headaches and is effective in some cases. However, like all effective headache remedies, overuse can cause a rebound effect.

Ginger. In general, herbal medicines should never be used by children or pregnant or nursing women without medical counsel. One exception may be ginger, which has no side effects and can be eaten in powder or fresh form, as long as quantities are not excessive. Some people have reported less pain and frequency of migraines while taking ginger, and children can take it without danger.

Medications Used for Prevention

The Food and Drug Administration has approved four drugs for prevention of migraine:

Propanolol (Inderal)
Timolol (Blacadrene)
Divalproex sodium (Depakote)
Topiramate (Topamax)

Propanolol and timolol are beta-blocker drugs. Divalproex and topiramate are anti-seizure drugs. Many other drugs are also being used or investigated for preventing migraines.

Beta-blockers are usually prescribed to reduce high blood pressure. Some beta-blockers, however, are also useful in reducing the frequency of migraine attacks and their severity when they occur. Propranolol (Inderal) and timolol (Blocadren) have been approved specifically for prevention of migraine. Metoprolol (Toprol), atenolol (Tenormin), and nadolol (Corgard) are also being studied for migraine prevention.

Side Effects. Side effects may include:

Fatigue and lethargy are common.
Some people experience vivid dreams and nightmares, depression, and memory loss.
Dizziness and lightheadedness may occur upon standing.
Exercise capacity may be reduced.
Other side effects may include cold extremities, asthma, decreased heart function, gastrointestinal problems, and sexual dysfunction.

If side effects occur, the patient should call a doctor, but it is extremely important not to stop the drug abruptly. Some evidence suggests that people with migraines who have had a stroke should avoid beta-blockers.

Anti-seizure drugs, also called anti-epileptic drugs or anticonvulsants, affect the neurotransmitter gamma aminobutyric acid (GABA), which helps prevent nerve cells from over-firing. GABA may also have a role in migraines. These drugs are commonly used for epilepsy and bipolar disease. Anti-seizure drugs are more expensive than other drugs. They also have significant side effects. Divalproex sodium (Depakote) and topiramate (Topamax) are the only anti-seizure drugs that are approved for migraine prevention. However, if patients do not respond to either of these drugs, doctors may try other types of anti-seizure medications.

Divalproex Sodium (Depakote). Divalproex sodium (Depakote) was first approved in 1996 for migraine prevention. A once-a-day formulation of divalproex (Depakote ER) was approved in 2000. Doctors sometimes prescribe a similar drug, valproate (Depakene). Pregnant patients should not use these drugs, as they may cause birth defects.

Topiramate (Topamax). In 2004, the Food and Drug Administration approved topiramate for prevention of migraines in adults. Studies from 2006 indicated that the drug works well when used on a long-term basis. Patients in these studies experienced significantly fewer migraines for up to 14 months. Topiramate’s most common side effect is a tingling sensation in the arms and legs. Weight loss is also a side effect. In clinical trials, patients lost an average of 3.8% of their body weight.

Other Anti-Seizure Drugs Under Investigation. Researchers are studying other types of anti-seizure drugs for migraine prevention. These include levetiracetam (Keppra), gabapentin (Neurontin), pregabalin (Lyrica), zonisamide (Zonegran), tiagabine (Gabitril), and the investigational drug lacosamide (LCM).

Side Effects. Anti-seizure medication's side effects vary by drug but may include:

Nausea and vomiting
Diarrhea
Cramps
Hair loss
Dizziness
Sleepiness
Blurred vision
Weight gain
Valproate and divalproex can cause serious side effects of inflammation of the pancreas (pancreatitis) and damage to the liver

Amitriptyline (Elavil, Endep), a tricyclic antidepressant drug, has been used for many years as a first-line treatment for migraine prevention. It may work best for patients who also have depression or insomnia. Tricyclics can have significant side effects, including disturbances in heart rhythms, and can be fatal in overdose. Although other tricyclic antidepressants may have fewer side effects than amitritpyline, they do not appear to be particularly effective for migraine prevention.

Researchers have investigated newer types of antidepressants, including serotonin-reuptake inhibitors(SSRIs), such as fluoxetine (Prozac). However, studies to date do not indicate that SSRIs are helpful for migraine prevention.

Muscle Relaxants. Botulinum toxin A (Botox) injection, a common wrinkle treatment, causes small muscles to relax. This approach is now being used with some success for treating disorders that involve over-excited muscle activity, including myofascial pain syndrome and migraine. One study reported complete migraine relief in more than half of patients being tested and improvement of more than 50% in another 35% of patients. Relief lasted 3 - 4 months with no adverse effects. A study presented at the 2005 meeting of the American Headache Society reported that patients who regularly received Botox injections every 3 months reduced both the frequency of migraine attacks and their reliance on pain medications

Angiotensin Converting Enzyme Inhibitors. Commonly used for treating high blood pressure, angiotensin converting enzyme (ACE) inhibitors block the production of the protein angiotensin, which constricts blood vessels and may be involved in migraine. Studies using the ACE inhibitor lisinopril (Prinivil, Zestril) are reporting significant reduction in migraine attacks.

Angiotensin-Receptor Blockers. Angiotensin-receptor blockers (ARBs) have actions similar to ACE inhibitors, but may have fewer side effects. In one study, patients who took the ARB candesartan (Atacand) had significantly fewer headaches compared to patients who received placebo.

Neurostimulation Devices. Researchers are investigating a transcranial magnetic stimulation (TMS) device to help stop migraines before they occur. The hair dryer-size device is held to the back of the head and delivers quick magnetic pulses. The device is used when a patient experiences the first signs of a migraine. Other types of nerve stimulation devices are also under investigation.

Inhalation Devices. These devices use heat to vaporize a drug so that it can be inhaled into the lungs. Clinical trials are currently testing this device with procholorperazine (Compazine), a tranquilizer drug that is used to treat nausea and vomiting.

Nasal Devices. New types of nasal sprays and powders are being researched. Some of them use capsaicin, the chemical found in cayenne peppers, to help relieve pain.

Skin Patches. The Actyve transdermal patch uses a small battery-powered system to deliver a triptan drug through the skin.

Drugs. New drugs in development include tonabersat (gap junction blocker), trexima (combination triptan and non-steroidal anti-inflammatory drug), and GW274150 (nitric oxide synthase inhibitor).

Resources

www.headaches.org -- National Headache Foundation
www.americanheadachesociety.org -- American Headache Society
www.aan.com -- American Academy of Neurology
www.ninds.nih.gov -- National Institute of Neurological Disorders and Stroke
www.clinicaltrials.gov -- Find clinical trials
www.migraineinfo.org -- National Migraine Association

References

Brandes JL, Kudrow D, Stark SR, O'Carroll CP, Adelman JU, O'Donnell FJ, et al. Sumatriptan-naproxen for acute treatment of migraine: a randomized trial. JAMA. 2007 Apr 4;297(13):1443-54.

Lewis DW, Winner P, Hershey AD, Wasiewski WW; Adolescent Migraine Steering Committee. Efficacy of zolmitriptan nasal spray in adolescent migraine. Pediatrics. 2007 Aug;120(2):390-6.

Lipton RB, Bigal ME, Diamond M, Freitag F, Reed ML, Stewart WF; AMPP Advisory Group. Migraine prevalence, disease burden, and the need for preventive therapy. Neurology. 2007 Jan 30;68(5):343-9.

Monastero R, Camarda C, Pipia C, Camarda R. Prognosis of migraine headaches in adolescents: a 10-year follow-up study. Neurology. 2006 Oct 24;67(:1353-6.

Rose KM, Wong TY, Carson AP, Couper DJ, Klein R, Sharrett AR. Migraine and retinal microvascular abnormalities: the Atherosclerosis Risk in Communities Study. Neurology. 2007 May 15;68(20):1694-700.

Review Date:
11/1/2007
Reviewed By:
Harvey Simon, MD, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital.

A.D.A.M. Copyright

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Olanzapine (By mouth)

admin — Thu, 04 Sep 2008 19:55:09 -0700

Overview

Introduction
Brand Name(s)
When This Medicine Should Not Be Used
How to Use This Medicine
How to Store and Dispose of This Medicine
Drugs and Foods to Avoid
Warnings While Using This Medicine
Possible Side Effects While Using This Medicine

HEALTH GUIDE REFERENCE FROM A.D.A.M

Introduction

Olanzapine (oh-LAN-za-peen)

Treats psychotic mental disorders, such as schizophrenia or bipolar disorder (manic-depressive illness).

Brand Name(s)

Zyprexa, Zyprexa Zydis

There may be other brand names for this medicine.

When This Medicine Should Not Be Used

You should not use this medicine if you have had an allergic reaction to olanzapine.

How to Use This Medicine

Tablet, Dissolving Tablet

Your doctor will tell you how much of this medicine to use and how often. Your dose may need to be changed several times in order to find out what works best for you. Do not use more medicine or use it more often than your doctor tells you to.
You may take this medicine with or without food.
If you are using the disintegrating tablet, make sure your hands are dry before you handle the tablet. Do not open the blister pack that contains the tablet until you are ready to take it. Remove the tablet from the blister pack by peeling back the foil, then taking the tablet out. Do not push the tablet through the foil. Place the tablet in your mouth. It should melt quickly. After the tablet has melted, swallow or take a drink of water.

If a dose is missed:

If you miss a dose or forget to use your medicine, use it as soon as you can. If it is almost time for your next dose, wait until then to use the medicine and skip the missed dose. Do not use extra medicine to make up for a missed dose.

How to Store and Dispose of This Medicine

Store the medicine in a closed container at room temperature, away from heat, moisture, and direct light. Keep the disintegrating tablet in the original package until you are ready to take it.
Ask your pharmacist, doctor, or health caregiver about the best way to dispose of any leftover medicine after you have finished your treatment. You will also need to throw away old medicine after the expiration date has passed.
Keep all medicine away from children and never share your medicine with anyone.

Drugs and Foods to Avoid

Ask your doctor or pharmacist before using any other medicine, including over-the-counter medicines, vitamins, and herbal products.

You must be careful if you are also using other medicine that might cause similar side effects as olanzapine. This includes medicine that might cause low blood pressure, overheating, or liver problems. Make sure your doctor knows about all other medicines you are using.
Make sure your doctor knows if you are also using carbamazepine (Tegretol®), fluoxetine (Prozac®), fluvoxamine (Luvox®), levodopa (Sinemet®, Stalevo®), omeprazole (Prilosec®), or rifampin (Rifadin®).
Make sure your doctor knows if you are also using medicine to treat high blood pressure (such as atenolol, hydrochlorothiazide [HCTZ], lisinopril, metoprolol, quinapril, Accupril®, Cozaar®, Diovan®, Lotrel®, Norvasc®, Toprol®, Zestril®).
Make sure your doctor knows if you are using medicine to treat anxiety (such as alprazolam, diazepam, Valium®, Xanax®). Tell your doctor if you are using any medicines that make you sleepy. These include sleeping pills, cold and allergy medicine, narcotic pain relievers, and sedatives.
Do not drink alcohol while you are using this medicine.
Tell your doctor if you smoke. You might need a different amount of this medicine if you smoke.

Warnings While Using This Medicine

Make sure your doctor knows if you are pregnant or breastfeeding, or if you have diabetes, liver disease, prostate problems, or glaucoma. Tell your doctor if you have a history of seizures, breast cancer, or severe constipation.
Make sure your doctor knows about any heart or blood problems you have now or have had in the past. This includes heart rhythm problems or a stroke.
Tell your doctor if you have ever had neuroleptic malignant syndrome (NMS) caused by any medicine for psychiatric disorders.
This medicine may increase your cholesterol and fats in the blood. If this condition occurs, your doctor may give you some medicines that can lower the amount of cholesterol and fats in the blood.
This medicine may increase your weight. Your doctor may need to check your weight regularly during treatment with this medicine.
This medicine may raise or lower your blood sugar, or it may cover up symptoms of very low blood sugar (hypoglycemia).
Your doctor will need to check your blood at regular visits while you are using this medicine. Be sure to keep all appointments.
This medicine may make you dizzy or drowsy. Avoid driving, using machines, or doing anything else that could be dangerous if you are not alert. Sit or lie down until you no longer feel dizzy. Get up slowly.
This medicine might reduce how much you sweat. Your body could get too hot if you do not sweat enough. If your body gets too hot, you might feel dizzy, weak, tired, or confused. You might vomit or have an upset stomach. Do not get too hot while you are exercising. Avoid places that are very hot. Call your doctor if you are too hot and cannot cool down.
Some side effects are more likely to happen in elderly people who have memory problems or other reduced mental skills. Make sure the doctor knows if the person who will be using this medicine has Alzheimer's disease or similar problems (often called "dementia").
Zyprexa® Zydis® contains phenylalanine (aspartame). This is only a concern if you have a disorder called phenylketonuria (a problem with amino acids). If you have this condition, talk to your doctor before using this medicine.

Possible Side Effects While Using This Medicine

Call your doctor right away if you notice any of these side effects:

Allergic reaction: Itching or hives, swelling in your face or hands, swelling or tingling in your mouth or throat, chest tightness, trouble breathing.
Blurred or other changes in vision.
Change in how much or how often you urinate.
Fast or uneven heartbeat.
Fever, sweating, confusion, muscle stiffness.
Increased restlessness or excessive movements.
Jerky muscle movement you cannot control (often in your face, tongue, or jaw).
Lightheadedness or fainting.
Numbness or weakness in your arm or leg, or on one side of your body.
Severe sleepiness, slurred speech, trouble breathing.
Shakiness, problems with balance or walking.
Swelling in your hands, ankles, or feet.
Swollen breasts, or liquid discharge from your nipples (men or women).
Trouble swallowing.

If you notice these less serious side effects, talk with your doctor:

Back pain.
Constipation, upset stomach.
Dry mouth, increased thirst, watering of mouth.
Increased appetite.
Missed menstrual period.
Redness or swelling in your eye.
Sleepiness or unusual drowsiness.
Stuffy or runny nose.
Trouble sleeping.
Weakness.
Weight gain.

Review Date: 8/4/2008

A.D.A.M. Copyright

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Source Doc: 45_0769