FitSugar

Is Cod Liver Oil a Cure All?

FitSugar — Tue, 25 Mar 2008 07:30:00 -0700

I have a friend who swears by cod liver oil; she takes a teaspoon everyday, which to me sounds like a punishment meted out on Tom Sawyer by his Aunt Polly. My friend swears it helps her skin (which looks great and she is nearing 50), her joints, and her overall health. She tells me my fish oil supplement is not enough, so I decided to investigate.

Here's what I discovered. It is true that cod liver oil is high in vitamins A and D, which is why it was taken as a nutritional aid back in the days of Tom Sawyer and Huck Finn. Some holistic health practitioners think cod liver oil is still a great way to get these two vitamins, but others think that cod liver oil often provides too much vitamin A, which can be toxic and interfere with bone density.

Cod liver oil is also high in omega-3 fatty acids – the fat you should love, but so are my fish oil supplements. Additionally, cod liver oil being made from the organ that filters toxins out of blood, is more likely to contain toxins like PCB when compared to regular fish oil.

To see if there is any substance to the health claims of cod liver oil, read more.

While many of the health claims, like that cod liver oil prevents cancer and Alzheimer's have yet to be proven, the oil has been found to slow down the damage arthritis does to joints. There is also evidence that the oil may ward off depression, but it is believed that the omega-3s are responsible over any other element in the oil.

If you are interested in taking cold liver oil, you should limit your intake to one teaspoon a day and it seems the brand Carlson Labs is often recommended.

Me? I am going to stick with my fish oil capsules, and you?

Source

Got PMS? Try a Natural Remedy

FitSugar — Tue, 22 Jan 2008 14:30:00 -0800

Most women experience some sort of PMS, and certain symptoms can be easier to treat than others. Ibuprofen is great for cramps, and Midol can help with bloating, but battling PMS-related irritability or depression is more of a challenge.

I've been on the hunt for natural remedies, including vitamins and herbal supplements, that might help relieve my monthly moodiness. Of course, there's always good, old-fashioned exercise, but I've also found some other natural solutions that sound promising. To see the list, read more

Of course, you should consult your doctor before taking any new vitamins and supplements, but here are some I plan to talk to my OB/GYN about:

Magnesium and B-6: Recent studies have found that this vitamin cocktail can help with bloating and moodiness. WebMD recommends 200 mg per day of magnesium combined with 50 mg of vitamin B-6.

Vitamin E: In his book Natural Health, Natural Medicine, Dr. Andrew Weil writes that vitamin E supplements can treat both PMS and painful or heavy periods. He recommends a supplement with 80 mg of vitamin E complex, taken once a day with your largest meal. Again, please talk to your doctor before starting any supplement program; vitamin E should not be taken if you have heart disease or diabetes.
Dong quai: Another of Dr. Weil's suggestions, this Chinese herb, made from the root of a carrot-like plant, is sometimes called "female ginseng," since it treats irregular periods, PMS, and menopausal symptoms. Weil recommends a two-month trial taking it two to three times a day.
Chaste tree berry: I've seen this recommended on several sites. According to an article on About.com: "a study published in the British Medical Journal involving 178 women with PMS found that chaste tree berry significantly reduced PMS symptoms over three menstrual cycles." It was especially effective treating irritability and depression.

Have any of you tried one of these natural remedies? If so, I'd love to hear if they worked, so please share in the comments below.

Source

Coughing Kid? Try a Spoonful of Honey

FitSugar — Tue, 04 Dec 2007 02:00:00 -0800

Since the FDA released a public health advisory warning parents not to give their children cold medicine, kids sick with colds and associated coughs suffered many sleepless nights. So did their parents. Luckily a new study found that honey is close to nature's own cough syrup. Yep, a spoonful of honey eases nighttime coughing in children better than the cough syrup ingredient dextromethorphan. This is great news for parents and kids alike!

It is believed that honey helps ease coughs for a variety of reasons. It not only soothes sore throats, but honey is also high in antioxidants and has antimicrobial effects. I guess if you are using honey as cough syrup, you really won't need a "spoonful of sugar to help the medicine go down!"

If you are interested in the recommended dosage, just read more

Children ages two to five = 1/2 teaspoon
Children ages six to eleven = 1 teaspoon
Children twelve and older = 2 teaspoons

Source

Laxative, stimulant combination (By mouth)

admin — Thu, 04 Sep 2008 20:02:42 -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

Treats constipation by helping you have a bowel movement.

Brand Name(s)

Senokot S, Perdiem, Senna-S, Sennalax-S, The Medicine Shoppe Medi-Natural Plus, SennaLax-S, Peri-Colace, Senna-Time S, DR. Edward's Olive Laxative, Femintrol, Doc-Q-Lax, Mason Remedies Docusate Sodium with Sennosides, Dok Plus, Doxidan, Laxa-Basic Plus

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 senna, sennosides, docusate, casanthranol, or psyllium. Some brand names for these medicines are Correctol® stool softener, Ex-Lax®, Colace®, or Metamucil®. Make sure your doctor knows if you are allergic to any other laxative medicines.

How to Use This Medicine

Tablet, Liquid Filled Capsule, Liquid, Granule, Capsule, Powder for Suspension

Your doctor will tell you how much of this medicine to use and how often. Do not use more medicine or use it more often than your doctor tells you to.
If you have had a sudden change in your bowel movements in the past two weeks, ask your doctor before using this medicine.
If you are using this medicine without a prescription, follow the instructions on the medicine label.
Drink a full glass of water when you take this medicine. One full glass of water is about 8 ounces or 1 cup. Drinking 6 to 8 full glasses of water every day will help keep your bowel movements soft.
You might need to mix the granules or powder with water before you take each dose. Drink this mixture right away. Do not swallow the granules or powder dry unless the directions say you can.
Measure the oral liquid medicine with a marked measuring spoon, oral syringe, or medicine cup.
Use this medicine at bedtime, unless your doctor tells you otherwise.

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.
Ask your pharmacist, doctor, or health caregiver about the best way to dispose of any outdated medicine or medicine no longer needed.
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.

Make sure your doctor knows if you are also using mineral oil.
Some laxatives need to be taken 2 hours before or 2 hours after other medicines. If you need to take any other medicine, ask your health caregiver if you need to follow a special schedule.

Warnings While Using This Medicine

Make sure your doctor knows if you are pregnant or breast feeding.
Do not use this medicine if you have stomach pain, nausea, or vomiting, unless your health caregiver tells you to use it.
If you do not have a bowel movement after using this medicine, talk to your doctor. Most people will have a bowel movement within 6 to 12 hours after using this laxative.
You should not use this laxative for more than 1 week unless your doctor says it is okay. Laxatives may be habit-forming and can harm your bowels if you use them too long.

Possible Side Effects While Using This Medicine

Call your doctor right away if you notice any of these side effects:

Bleeding from your rectum.
Skin rash.
Urine turns a different color.

If you notice these less serious side effects, talk with your doctor:

Diarrhea, cramps, nausea, burping.

Review Date: 8/4/2008

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

Source Doc: 45_4799

Many Probiotics Short on Bacteria

FitSugar — Fri, 20 Nov 2009 03:00:09 -0800

With claims that they improve digestion, bolster immunity, and fight acne, it's no wonder that probiotic supplements are big business. Newsweek reports that sales of these supplements have more than quadrupled in the last 10 years. I will admit, I'm a fan these friendly bacteria found in yogurt and miso, but it's the quality of the supplements that's raising eyebrows.

Many popular probiotic supplements were tested by Consumer Lab, an independent agency that monitors vitamins, herbal remedies, and supplements not regularly tested by the government. The lab's findings are a bit startling. Some of the products contain as little as 13 percent of the amount of "viable bacteria" claimed on the products' labels, although most products do contain one billion organisms - the amount needed to register some health benefits.

When it comes to misleading marketing with these supplements, much of the problem stems from the fact that the term probiotics has no legal definition and can be used loosely by manufactures. Of the supplements tested, ConsumerLab ranked Advocare Probiotic Restore, GNC Nature Brand Best Super Acidophilus, and Jarrow Formulas Jarro-Dophilus as having the highest quality. You can buy a full review from Consumer Lab for $12.

Prevent Heartburn With These 5 Foods

FitSugar — Tue, 15 Sep 2009 10:00:25 -0700

If you suffer from heartburn or gastroesophageal reflux disease (GERD), the acid that's in your stomach comes back up through your esophagus, and results in burning and pain in your chest. It's often caused by the foods you eat, so here are some foods that will prevent these uncomfortable symptoms.

Oatmeal with bananas - Opt for this high fiber, lowfat food instead of a sugary, fried doughnut for breakfast since high fat foods often lead to symptoms. Bananas naturally fight stomach acid, so the combination is perfect.
Fresh ginger -This natural anti-inflammatory is an ancient remedy for digestive issues. Drink ginger tea, make your own ginger ale, suck on ginger candy, or grate some fresh ginger into your stir-fries.

To see the other foods, read more.

Whole wheat pasta with lowfat white sauce - Tomato sauce is acidic and a surefire way to serve you up some heartburn. So go for a light sauce made from milk, cheese, or broth instead. Choose whole wheat pasta over white pasta since high fiber foods can help alleviate symptoms.
Beans - They're not only good for the heart, but are also a good source of protein that's a great alternative to heartburn-causing meat.
Applesauce - Baking with oil or butter may trigger heartburn symptoms, so replace it with applesauce in your baked good recipes.

Insomnia

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

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

Multiple sclerosis

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

In This Report

Highlights
Introduction
The Autoimmune Disease Proc...
Symptoms
Causes
Risk Factors
Complications
Diagnosis
Treatment
Drug Treatment
Other Treatments
Treating the Complications...
Lifestyle Changes
Resources
References

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

Gender and Multiple Sclerosis (MS)

MS is increasingly affecting women, according to research presented at the 2007 annual conference of the American Academy of Neurology. Researchers found that in the 1940s, women were twice as likely as men to be diagnosed with MS. By 2000, women were about four times more likely than men to develop MS. Experts are uncertain why this ratio is growing.

Family History

If MS runs in your family, there’s a chance you may develop the disease at the same age that other family members did, suggests a 2007 Neurology study. However, family history does not predict disease course or severity.

Vitamin D

Higher blood levels of vitamin D may reduce the risk for MS, at least among Caucasians, indicates a 2007 study in the Journal of the American Medical Association. (The researchers found no protective effect for African-Americans or Hispanics.) However, until further research is conducted, doctors do not recommend taking vitamin D supplements for MS prevention.

Infections and Symptom Relapse

Both viral and bacterial systemic infections can trigger relapses, according to a study in Neurology. Researchers found that relapses and new brain lesions appeared within 2 weeks after an infection.

Drug Research

Natalizumab (Tysabri) may help reduce vision loss in patients with relapse-remitting MS, indicates a 2007 Neurology study. In 2006, the FDA enforced safety restrictions on the use of this drug due to cases of progressive multifocal leukoencephalopathy (PML), a rare brain disorder. Since the restrictions were put in place, no new cases of PML have been reported.
Glatiramer acetate (Copaxone) shows little benefit for primary progressive MS, according to a 2007 study in Annals of Neurology.
Testosterone gel may help men with relapse-remitting MS, suggests a small study published in 2007 in the Archives of Neurology.

Introduction

Multiple sclerosis (MS) is a disease of the central nervous system (CNS), the nerves that comprise the brain and spinal cord. It has two major features:

Destruction of myelin, a fatty insulation covering the nerve fibers, is the main characteristic of MS. The end results of this process, called demyelination, are multiple patches of hard, scarred tissue called plaques. (Multiple sclerosis is well named. Sclerosis comes from the Greek word skleros, which means hard.)
Destruction of axons, the long filaments that carry electric impulses away from a nerve cell, is also a major factor in the permanent disability that occurs with MS.

Myelin is the layer that forms around nerves. Its purpose is to speed the transmission of impulses along nerve cells.

The symptoms, severity, and course of MS vary widely depending partly on the sites of the plaques and the extent of the demyelination. Experts generally group multiple sclerosis into two major symptom categories:

Relapsing-remitting
Chronic-progressive

Chronic-progressive MS is often subcategorized as primary-progressive, secondary-progressive, and progressive-relapsing.

Recent evidence suggests that the disease process starts long before symptoms begin. By the time symptoms appear, there are often already signs of brain and spinal cord atrophy. The cause of MS is unknown, and it cannot be prevented or cured. It is not fatal, however, and great progress is being made in treating it and identifying underlying mechanisms that trigger this disease.

Relapsing-remitting multiple sclerosis generally occurs in younger people and is the most common form of MS. It generally follows this course:

Most patients first experience a single attack of symptoms called a clinical isolated syndrome, which typically occurs between the ages of 20 - 40 years. Once a second attack occurs, the patient is considered to have relapsing-remitting multiple sclerosis.
The characteristic feature of relapsing-remitting MS is the attack (also referred to as relapse, flare-up, or exacerbation), which is a bout of specifically MS symptoms (facial pain, Lhermitte’s sign, or bladder instability) that lasts at least 24 hours and typically several days. Such attacks are fairly mild in about half of patients with this form of MS.
The disease then goes into remission (when symptoms improve or disappear), usually for about 4 - 8 weeks. To be considered in remission, attacks need to be separated by at least 30 days. Remission periods may be spontaneous or induced by immunosuppressive drugs. A person with multiple sclerosis in remission may have subtle attacks and not realize it. For example, hands may be a little numb for a few days, or there may be slight awkwardness in gait or coordination.
Remissions are almost always followed by relapses, in which symptoms flare-up or the patient experiences a period of deteriorating ability.

About 20% of patients with relapsing-remitting MS experience little or no progression after a first attack for long periods of time, although by 25 years most patients have converted to a progressive phase.

The term chronic-progressive multiple sclerosis is used to describe cases in which symptoms continue to worsen slowly without remission. About 20% of multiple sclerosis patients (usually those whose first symptoms occur after age 45) have the chronic-progressive form without first developing relapsing-remitting MS. Chronic-progressive MS generally follows a downhill course, but its severity varies widely. Three variants are commonly used to define this patient group:

Secondary-Progressive MS (SPMS). SPMS is the natural evolution of relapsing-remitting MS and develops in about half of patients during the first 10 years and nearly all of them within 25 years. It follows a progressive course of nerve and muscle deterioration with occasional acute flare-ups, remissions, and plateaus.
Primary-Progressive MS (PPMS). PPMS progresses continuously and gradually from the first onset of symptoms and has no remissions. It occasionally levels off, and minor improvement is even possible. This occurs in about 10% of patients, who tend to be older than average at the time of diagnosis.
Progressive-Relapsing MS (PRMS). PRMS is progressive from the start with acute symptom flare-ups, but may have some relapses with continued deterioration between them. It occurs in less than 5% of patients.

Because the natural courses of primary-progressive and progressive-relapsing MS are similar, some experts believe this distinction is unnecessary.

Click the icon to see an image depicting multiple sclerosis.

The Autoimmune Disease Process

Multiple sclerosis is referred to as an autoimmune disease. The general theory for the development of MS is that a genetically damaged immune system is unable to distinguish between virus proteins and the body’s own myelin and so produces antibodies that attack. In other words, the body becomes allergic to itself, a condition known as autoimmunity.

Autoimmunity may develop when the body's immune system is damaged by genetic or environmental factors or both, causing it to attack its own tissues. In the case of MS, the immune system attacks the tissues that make up myelin:

Myelin is made from layers of cell membranes that are produced in the brain and spinal cord by specialized cells called oligodendrocytes. The destruction of this myelin sheath during the disease process is the hallmark for multiple sclerosis.
The myelin coat is distributed in segments along the axons, the long filaments that carry electric impulses away from a nerve cell.
The segments are separated from each other by tiny clusters called nodes of Ranvier, which house channels for sodium ions. These sodium ions are important for boosting the electrical charge required to pass signals from one nerve to another.
As the myelin insulation is destroyed, signals transmitted from nerve cell to nerve cell throughout the central nervous system are disrupted.
Experts once believed that axons themselves were spared during the disease process. Research, however, has shown that many are severed in MS and, in fact, axon destruction appears to start at an early stage in the disease and may be a major cause of its irreversibility.

The body often makes corrective actions to offset the effects of the nerve cell destruction:

For example, researchers have observed an increase in the density of the sodium channels, which carry electric charges. By increasing their numbers, the nerve cells can continue to communicate, in spite of the loss of myelin.
The nerves also retain some capacity to remyelinate (to restore the insulating myelin).

Such processes are probably responsible for the remissions that most patients experience. Unfortunately, the disease process nearly always eventually outpaces these corrective actions.

The Normal Immune Response.

The most important critical immune factors in the disease process are white blood cells called lymphocytes, which consist of T cells and B cells. These cells are the warriors in the immune defense system.
Receptors on T cells acquire the ability to recognize specific molecules called antigens. Antigens are typically proteins from infecting organisms, such as bacteria or viruses, and perceived as a threat to the body.
Once the antigen is identified, specific T cells, called helper T cells, trigger the B cells to release antibodies. These molecules are designed to attach to and destroy the targeted antigen.

Autoimmunity.

Multiple sclerosis, and probably all autoimmune diseases, involves an error in the education of T cells, which makes them unable to distinguish self from non-self.
In multiple sclerosis, the miseducated T cells mistake molecules in the body's own myelin as a foreign antigen. Such targets are referred to as self-antigens.
In response to detection of these self-antigens, the T cells set off the usual cascading immune events, including the release of B lymphocytes, to rid the body of the perceived threat.
The B lymphocytes fire off antibodies as usual, but in this case they are referred to as autoantibodies, because they are attacking antigens that belong to the body's own self.
In MS, the immune system is tricked into targeting self-antigens that are myelin proteins, the fatty insulation covering the nerve fibers. Another autoantibody target may be the oligodendrocytes themselves -- the specialized cells that make up myelin.
To make matters worse, the process perpetuates through a cascading series of events in which the B cells and T cells continue to interact, creating numerous different self-antigens. The attacks continue and, in the process, the original self-antigen is unrecognizable.

Cytokines and the Inflammatory Response. The inflammatory response is the product of an overactive immune system and is a major destructive force in an autoimmune disease.

Once the lymphocytes have launched a response to an antigen, they also release masses of other white blood cells to gather at the injured or infected site.
The major players in this response are white blood cells called leukocytes. Researchers are particularly interested in leukocytes called cytokines. These are small powerful proteins that, in tiny amounts, are indispensable for healing. When they are overproduced, however, which occurs in MS, they play a major role in the destructive process.
Their intensive convergence on the affected area causes it to become inflamed and injurious to the very cells they are designed to protect. Under normal conditions, this inflammatory process is controlled and self-limiting, but in people with autoimmune diseases such as multiple sclerosis, the process persists and damage occurs in the surrounding tissues.

Important cytokines in MS appear to be tumor necrosis factors, interleukin-12, and interferon-gamma. Other cytokines, including interleukin-10 and transforming growth factor beta, may play a protective role and help block inflammatory activity.

The inflammatory response may trigger the disease, but afterward a progressive course takes over that does not appear to be related to inflammation. Experts have found that destruction of axons, the long filaments that carry electric impulses away from a nerve cell, is a major feature of multiple sclerosis. In fact, it may be the major cause of permanent disability that occurs with this disease. Microscopic studies reveal that axons are injured early on as "bystanders" while myelin is being peeled off. As the disease progresses, these weakened and exposed axons degenerate further. Most of the damage occurs early in the disease process and decreases over time, although some destruction can still be observed years and decades afterward. Such evidence is having significant effect on approaches to treatment and research.

Symptoms

Most patients first experience multiple sclerosis as a single attack of symptoms called a clinical isolated syndrome, which typically occurs between the ages of 20 - 40 years. Once a second attack occurs, the patient is considered to have relapsing-remitting multiple sclerosis. Much less commonly, the disease is progressive from the start and symptoms are more or less continuous.

Early symptoms may include the following:

Optic neuritis and other problems in the eye. Optic neuritis, which is inflammation of the nerves in the eye, affects over 50% of patients and is the first symptom in about 16% of patients. Symptoms include unclear or doubled vision, usually in one eye. Some people see a shimmering effect. Patients may also experience pain or involuntary jerking or movement of the eye (called nystagmus). In 20% of people with this condition, MS develops within 2 years after the onset. In 45 - 80%, MS develops within 15 years. About 17% of people eventually experience impaired eye movement.
Fatigue. Fatigue is typically worse in the afternoon and may be accompanied by an increase in body temperature. At the onset, this occurs in about 20% of patients, but as the disease progresses, this is a significant symptom in nearly all patients.
Changes in sensations in the arms and legs. Patients can experience heaviness, weakness, or clumsiness in the limbs. Tingling or loss of sensations can also occur, most commonly in the legs. The first symptoms for patients with primary progressive MS often develop slowly in the upper legs.
Muscle weakness in the legs and poor coordination.
Lhermitte’s sign. This is an electrical sensation that runs down the back and into the legs, which is produced by bending the neck forward.
Spasticity. Spasticity is the inability to control muscle tone and leads to spasms and stiffness. It is very common in MS.
Disturbances in the bladder.

In addition to the persistence of early symptoms, some patients experience the following symptoms as the disease progresses:

Imbalance and dizziness.
Tremors.
Facial pain.
Spasm-related symptoms. They include burning, itching, aching, quivering sensations. They usually occur in the extremities and last seconds to minutes.
Speech difficulties.
Difficulty swallowing.
Symptoms in the gastrointestinal, urinary, and genital tracts. Possible sexual dysfunction and loss of bowel and bladder control in severe cases.
Emotional mood swings. Depression is very common. About 10% of patients suffer from psychosis (manic depression and paranoia). About 5% of patients with severe MS experience uncontrolled and extreme mood swings called the laughing/weeping syndrome.
Problems in concentration and memory.
Hearing loss.

Infections. Viral infections have long been known to worsen MS symptoms. An important 2006 study indicated that bacterial infections can also trigger MS relapses. In the study, relapses appeared within 2 weeks of a viral or bacterial infection.

Heat. Heat, whether generated by ambient temperature, infection, or physical activity, worsens MS symptoms in about 60% of patients.

Stress. There is a strong correlation between severe stress and exacerbation of MS symptoms. For example, in one study, 85% of instances of MS exacerbations were associated with stressful events that occurred within an average of 14 days before the episode. Stress is not a cause of MS, however.

Trauma. Some experts believe that injury (trauma) to the head, neck, or upper back may trigger new or recurrent symptoms by disrupting the blood-brain barrier and allowing immunological attacks on the brain. This is a highly controversial theory, however, with very little supporting evidence.

Causes

The cause, or causes, of multiple sclerosis remains a mystery. Genetic factors certainly play a role in MS. No single gene, however, is likely to be responsible for causing MS. Rather, the current theory is that the disease occurs in people with a genetic susceptibility who are exposed to some environmental assault (a virus or a toxin) that disrupts the blood-brain barrier. Immune factors converge in the nerve cells and trigger inflammation and an autoimmune attack (a self-attack) on myelin and axons. Still, a number of disease patterns have been observed in patients, and some experts believe that MS may prove to be not a single disorder, but may represent several diseases with different causes.

Some research suggests that all autoimmune diseases are basically due to the same genetic error. A 2001 study found, for example, that the T cell immune factors in type 1 diabetes target the same self-antigens as in multiple sclerosis (MS). Many questions are unanswered, however. It is not known why the diseases develop in different locations to cause separate disorders. Nor, why some autoimmune events occur in everyone but not everyone develops an autoimmune disease.

Genetic factors probably play some role in making a person susceptible to the disease process leading to multiple sclerosis. In particular, abnormalities in the human leukocyte antigen (HLA) region located on chromosome 6 appear to be more prevalent among people with MS. Researchers theorize, however, that a combination of genes (not a single gene) is implicated in the development of MS, and the risk for someone inheriting all of these genetic factors is less than 5%. Advanced techniques called microarray technologies are now making it possible to scan hundreds of genes and identify those most likely to be contributors to MS. Genetic research may also pave the way for the development of new drugs to treat this disease. For example, researchers have recently identified the Olig1 gene as a key regulator in repairing damaged myelin-producing cells.

Infectious organisms, most likely viruses, are the top suspects for triggering the autoimmune response in people genetically susceptible to MS. There are a number of reasons for this belief:

The geographical distribution of the disease. The number of MS cases increases the further one gets from the equator in either direction.
Multiple sclerosis clusters. Four separate clusters of multiple sclerosis outbreaks occurred between 1943 - 1989 in the Faroe Islands, located between Iceland and Scandinavia. During World War II, this region was occupied by British troops. The incidence of MS increased each year for 20 years after the war, leading some researchers to think that the troops might have brought with them some disease-causing organism. In fact, one theory suggests that these findings offer evidence that MS is a sexually transmitted infection that occurs during adolescence. For example, the disease clusters observed in the Faroe Islands could be related to high sexual activity between the troops and local young women. A high incidence of MS is found in countries with a high degree of sexual permissiveness. MS is very rare in traditional cultures, but increases in people from these regions when they immigrate to industrialized Western nations.
Viral similarity to myelin. Some viruses are strikingly similar to the myelin protein and may therefore cause confusion in the immune system, causing the T cells to continue to attack their own protein rather than the viral antigen. More than one antigen may be involved; some may trigger the disease, and others may keep the process going.

Infectious Organisms Under Suspicion. Although many infectious microorganisms have been investigated, no one organism has emerged as a proven trigger. It is possible that different patients may be affected by different organisms, and that infections cause some, but not all, cases of MS. Organisms that are at the top of the suspect list are those that can affect the central nervous system. The following are three primary suspects:

HHV-6. Herpesvirus 6 (a form of herpesvirus that causes roseola, a benign disease in children) is also known to cause encephalitis (brain inflammation) in patients with impaired immune systems. A number of studies have reported higher than normal rates of HHV-6 infection in patients, and some experts believe that may be important in MS. Other experts argue, however, that nearly everyone harbors this virus and there is still no evidence of a causal relationship. Other herpes viruses can also infect brain cells. They include herpes simplex 1 and 2 (the causes of oral and genital herpes), varicella-zoster virus (the cause of chicken pox and shingles), and cytomegalovirus.
Epstein-Barr virus (EBV). Evidence suggests an association between EBV, the cause of mononucleosis, and MS. EBV is an extremely common virus and another member of the herpes virus family. Nearly all people have been exposed to EBV. However, researchers have discovered that people who are especially sensitive to the virus and have unusually high levels of EBV antibodies may have a greater risk of developing MS. Scientists are still uncertain if EBV is a cause of MS. EBV has also been linked to other autoimmune diseases such as lupus.
Chlamydia Pneumoniae. This atypical bacterium has been associated with persistent inflammation. A few studies have reported significantly higher rates of previous Chlamydia infection in patients with MS than in individuals without MS. An important group of 2000 studies reported no connection at all between Chlamydia and MS, and any experts now believe there is no strong evidence linking the microbe to MS. It is still possible, however, that the infection, which can cause widespread inflammation, plays a role early in the course of the disease in some individuals.

Other viruses that have been investigated include measles virus, adenovirus, and the retroviruses (HIV, HTLV-I, and HTLV-II), but none have emerged as having any importance.

Note on Vaccinations: Concerns about a link between the hepatitis B vaccine and MS led France to halt a major vaccination program in 1998. Subsequent research investigating whether the hepatitis B vaccine is indeed associated with an increased risk of MS has yielded mixed results. It appears that the vaccine would be, at most, a contributing -- but not the sole -- factor in MS development. At present, the evidence has not warranted any change in American immunization policies. Research has ruled out a link between any other vaccinations, such as or influenza or tetanus, and relapses of MS.

Risk Factors

An estimated 400,000 Americans and 2.5 million people worldwide suffer from MS.

Age. Onset occurs between the ages of 20 - 40 years in 70% of patients with the average age being 30 and the peak incidence occurring in the mid-twenties. The disease can still occur in both younger and older individuals. It rarely develops before age 15 or after age 60, however.

Gender. MS is more common among women than men. The gender gap is strongest among people who develop MS at a younger age. According to research presented at the 2007 American Academy of Neurology annual conference, the ratio between women to men has been growing. Researchers found that in the 1940s, the ratio of women to men with MS was 2 to 1. By 2000, the ratio had grown to 4 to 1. However, some research indicates that men may be more disabled by the disease than women.

Ethnicity. Multiple sclerosis occurs worldwide but is most common in Caucasian people of northern European origin, especially those of Scottish descent. It is extremely rare among Asians, Africans, and Native Americans. Specific groups (gypsies, Eskimos, Bantus) have never reported a case. While the risk of MS for African-Americans is around half of that for Caucasians, a recent study suggested that African-Americans are more likely to develop a more aggressive form of the disease and to suffer impaired mobility.

Geography. The risk for MS is higher in different regions of the world. In general, MS is more prevalent in temperate regions than in the tropics. Specifically, prevalence is highest in northern and central Europe (except northern Scandinavia), Italy, southern Australia, and northern regions of North America. Middle-risk areas include southern Europe (except Italy), southern US, northern Australia, and northern Scandinavia. Low-risk areas include parts of Africa and Asia, the Caribbean, Mexico, and possibly northern South America. It is unclear whether this pattern is attributable to environmental factors, genetics, or both.

Family History. A family history of the disease also puts people at risk for MS, although the risk for someone inheriting all the genetic factors contributing to MS is only about 2 - 4%. A 2007 study indicated that family members who have MS tend to develop the disease at around the same age. However, family history does not predict whether one family member will experience the same disease severity as another family member.

Cow's Milk During Early Infancy. Breast milk contains factors that may help regulate the immune response, and there is some evidence that infants fed only on cow's milk may have a higher risk for either diabetes type 1 (another type of autoimmune disease) or multiple sclerosis later in life. Studies on national differences in diabetes suggest that the risk may vary with different milk proteins, suggesting that not all cow's milk is the same and that some proteins carry higher risks than others.

The Hygiene Theory: Early Infections as Protection Against Allergies and Autoimmune Diseases. Over the past decades, there has been a dramatic increase in asthma, allergies, and autoimmune diseases, such as multiple sclerosis, Crohn's disease, and type 1 diabetes. One theory blames this rise on the reductions in childhood infections that have occurred with modern hygiene and antibiotic use. Studies supporting this have observed a higher incidence of allergies and autoimmune diseases, including MS, among populations with good hygiene and in animals that have been raised in a germ-free environment. The basic theory rests on the idea that early infections stimulate production of specific immune factors that protect against allergies and autoimmune diseases. The exact mechanisms of these effects are as yet unknown.

Vitamin D. Higher blood levels of vitamin D have been associated with a lower risk for MS, at least among Caucasians. (Studies have not shown that vitamin D has a protective effect for other racial groups.) However, there is not yet enough evidence to indicate that taking vitamin D supplements can help prevent MS.

Exposure to Sunlight. In a 2003 study, higher exposure to sunlight during childhood and early adolescence was associated with a lower risk for MS, perhaps because UV radiation produces higher levels of vitamin D, which has been associated with protection against MS. The effect of sunlight during winter seemed to be more protective than summer light. Unfortunately, higher exposure to sunlight also coincides with a higher risk for skin cancer, which is far more common than MS.

Estrogen and Oral Contraceptives. Higher estrogen levels may temporarily lower the risk of developing multiple sclerosis. Studies indicate that oral contraceptives (which contain estrogen) and pregnancy delay the onset of multiple sclerosis. The risk for a first clinical attack increases, however, in the 6 months after a woman gives birth.

Complications

Multiple sclerosis is not a fatal disease. Some data suggest that it shortens the average life span by only about 6 or 7 years. Still, in about half of MS cases, patients die of complications of the disease, and the disease has significant negative emotional and physical consequences. Suicide rates among patients with MS are higher than average.

The severity of the disease varies widely from patient to patient and is unpredictable. About 20% of patients remain asymptomatic or become only mildly symptomatic after an initial clinical event. Another 20% experience a rapidly progressive condition. Most patients, however, will experience some degree of progression.

Women tend to have a better outlook than men. Factors the determine a higher risk for a severe condition include:

Age over 40 years at the time of onset of symptoms
Initial symptoms that affect motor control, mental functioning, or urinary control, or initial symptoms affect multiple regions
Attacks in the first years that are frequent or interval between the first two attacks is short
Incomplete remissions
Rapid progression to disability
MS that is progressive from the beginning or becomes progressive shortly after the onset

Doctors and researchers often use a scale called the Kurtzke Disability Status Scale to assess and predict future disability. The system uses a score of 1 to 10 to rate the degree of walking disability. Experts have used the scale to attempt to predict average times for progression from one stage to the next depending on whether patients have relapsing-remitting or chronic progressive MS.


Score	Disability Description	Relapsing-Remitting MS: Average time until onset of symptoms*	Chronic Progressive MS: Average time until onset of symptoms*
1	No disability and minimal neurologic symptoms.	11.4 years from Score 1 to Score 4	0 years from Score 1 to Score 4
2	Minimal disability in one or two functional areas. Slight weakness or stiffness, mild walking impairment or visual disturbances
3	Moderate disability in one functional area, such as vision or the urinary tract, and possibly more than one minimal disability in several others. Either a part of one of the limbs or a whole side can be partially paralyzed. May stagger at times.
4	Disability is relatively severe but there is full ability to walk without aid. Patients are self-sufficient and can be active 12 hours a day and carry on normal activities. Can walk without aid or rest for 300 to 500 meters.
5	Disability is severe enough to impair or even preclude a full day's activities. Able to walk unaided and without rest for 100 to 200 meters.	23.1 years from Score 1 to Score 6	7.1 years from Score 1 to Score 6
6	Can walk unaided for about 100 meters only with assistance or devices, such as two canes, crutches, or braces.	23.1 years from Score 1 to Score 6	7.1 years from Score 1 to Score 6
7	Mostly restricted to wheelchair, although can manage the wheelchair and leave it unassisted. Can walk with aids no further than about five meters.	33.1 years from Score 1 to Score 7	13.4 years form Score 1 to Score 7
8	Mostly restricted to wheelchair or even bed, but still has effective use of arms remains and able to perform many self-care functions.	(Data not available)	(Data not available)
9	Bedridden. Patient can communicate or eat.
10	Fatality occurs from complications.
* Data taken from Relapses and Progression of Disability in Multiple Sclerosis, The New England Journal of Medicine, November 16, 2000, Vol. 343, No. 20

Because the effects of nerve injury are widespread, complications can be very severe and affect all parts of the body. Although not all patients experience all of the following problems, any of them can negatively impair quality of life.

Fatigue. Fatigue is one of the most common and debilitating MS symptoms and affects at least two-thirds of patients with MS. Fatigue specifically attributed to MS and not to other causes is defined as abnormal fatigue that lasts at least half of the time or more than 6 weeks. It causes a general lack of energy that significantly limits daily functioning regardless of any neurologic symptoms or specific muscle weaknesses. Up to 40% of patients describe fatigue as the most disabling MS symptom, which is higher than weakness, spasticity, motor control, or bowel or urinary problems. Many conditions that are common in MS (sleep disorders, depression, hypersensitivity to sensation, hypothyroidism, medications, heat) may contribute to fatigue. None fully explain the consistent presence or severity of this problem in MS. Researchers using imaging techniques have identified possible changes in part of the brain in MS that may play a role in the fatigue of MS.

Loss of Mobility and Spasticity. Nearly every patient loses some mobility, which may take the form of less or impaired motor control, muscle weakness, impaired balance, and, importantly, spasticity. Spasticity is one of the primary symptoms of MS. It is characterized by weakness, loss of dexterity, and the inability to control specific movements. It is usually more severe in the legs and torso. (Ironically, mild spasticity actually helps improve muscle tone in the legs, which is important in supporting the patient’s weight when walking.) Mobility can be affected by many non-physical factors, including mental well-being, social networks, fatigue, and even the weather.

Pain. About two-thirds of patients experience pain at some point during the course of the disease, and 40% are never pain free. MS causes many pain syndromes; some are acute while others are chronic. Some worsen with age and disease progression. Pain syndromes associated with MS are trigeminal (facial) pain, powerful spasms and cramps, optic neuritis (pain in the eye), pressure pain, stiffened joints, and a variety of sensations, including feelings of itching, burning, and shooting pain.

Bowel Dysfunction. Bowel dysfunction, which can include constipation or fecal incontinence, is a serious problem for many patients. Constipation may be caused by the disorder itself or by medications used to treat spasms or other symptoms.

Sexual Dysfunction. Sexual dysfunction is a common problem, occurring in over 70% of patients. Men are likely to have impotence and women, problems with vaginal lubrication. It appears to be highly associated with urinary dysfunction.

The nerves that branch off the central nervous system (CNS) provide messages to the muscles and organs for normal function. When there is CNS damage, the function of these organs and tissues may be compromised. In multiple sclerosis, the demyelinization of nerve cells may lead to bowel incontinence, bladder problems and sexual dysfunction.

Urinary Dysfunction. Urinary problems from bladder dysfunction occur in two-thirds of patients. Some patients have difficulties in urinating at will, called urinary retention. Often it takes the form of urge incontinence (also called hyperactive or irritable bladder). People with urge incontinence need to urinate frequently or are unable to reach the bathroom before leakage. In such cases, the bladder is overactive. Complications in the urinary tract also produce a high rate of urinary tract infections.

Difficulty Swallowing. A third to a half of patients experience difficulty in chewing or swallowing, problems that may be caused or made worse by many MS medications.

Speech and Hearing Problems. Problems in speech may occur because of difficulty in controlling the quality of the voice and articulating words. (Problems with language itself, however, are very rare in MS.) Hearing problems also occur in MS and may affect speech.

Problems in the Lungs. As the muscles that control breathing weaken, the ability to cough is impaired and the patient is at higher risk for pneumonia and other complications in the lungs.

Osteoporosis. Osteoporosis (loss of bone density) and subsequent fractures are common and under-recognized problems among patients. Osteoporosis is caused and worsened by immobility and by some MS medications. Fractures caused by falls can be far more serious in patients than in the normal population, leading to problems, including deconditioning or even inability to walk, obstruction of the intestines (from pain-relieving medications), and respiratory complications.

Cognitive problems, such as having trouble concentrating and solving problems, affect about half of patients. More people with MS leave work because of such cognitive difficulties than because of physical problems, according to a 2000 study. In about 10% of cases, mental dysfunction may be severe and resemble dementia. The severity of such mental changes appears to be associated with the degree of loss of brain tissue. This offers another argument for early treatment as interferon medications may improve these symptoms.

Between 40 - 60% of patients suffer from depression at some point over the course of the illness, and studies have reported risks for suicide ranging from 3 - 15%. Some evidence suggests that depression in multiple sclerosis is not only due to the social and psychologic impact of MS but also to the disease process itself. Depression may have biologic effects, such as increasing production of inflammatory cytokines, that could exacerbate the disease itself. Doctors should assess patients for depression, even if there are no obvious signs of it. The risk for suicide may be present even in patients who are not obviously depressed. People at highest risk for suicide are those who live alone, those with a history of an emotional disorder (depression, anxiety, alcohol abuse), a family history of mental illness, and people with high social stress.

Diagnosis

Multiple sclerosis is characterized by recurring neurologic episodes that are due to multiple lesions (injured areas) in different locations in the central nervous system. The diagnostic challenges in multiple sclerosis are two-fold:

Making an initial diagnosis as early as possible in order to slow down the disease progression. Most patients first seek medical help after an initial inflammatory event (known as a clinically isolated syndrome) originating from demyelination in the eye, the spinal cord, or the brain. About 30% of these individuals will develop progressive MS within the year. At this time, however, experts cannot predict who among these patients are at highest risk for rapid progression.
Predicting the severity of the disease. Once MS has been diagnosed, the pattern of the disease is uncertain. It can be very benign to rapidly progressive and severe. Magnetic resonance imaging (MRI) is able to detect lesions in the brain indicating MS. But, the severity of the disease does not appear related to the number of lesions, the rate of their appearance, or their location. Researchers are hoping to identify some biologic marker, possibly certain antibodies, that will enable doctors to accurately determine the onset and severity of the problem once a diagnosis has been made.

The McDonald Criteria. There is no single test that can accurately diagnose MS, and a number of other conditions may mimic its symptoms. Some doctors use a set of factors, called the McDonald criteria, for diagnosing multiple sclerosis in early stages. The criteria include the presence of specific symptoms, spinal fluid evaluation, and magnetic resonance imaging techniques for detecting lesions within the central nervous system and tracking them over time. The criteria show high reliability in identifying MS in patients with a variety of disease stages or states, including having only one episode, a typical relapsing-remitting course, or a slow insidious progression without clear attacks or remissions. Depending on the MRI and other findings, the patient is then categorized as having MS, possible MS, or no MS.

The symptoms of MS are similar to a number of other diseases, which must be ruled out. These include stroke, alcoholism, emotional disorders, Lyme disease, chronic fatigue syndrome, fibromyalgia, AIDS, and certain other autoimmune disorders (hypothyroidism, scleroderma, Sjögren syndrome, and systemic lupus erythematosus).

Doctors and investigators generally use a test called the Expanded Disability Status Scale (EDSS) to rate the severity of symptoms. It is also used after a diagnosis to gauge the status of the disease, and score the effectiveness of treatments. The scale ranges from 0 to 10 with higher scores indicating more severe symptoms. These are subjective ratings that require doctor observation skills.

Objections to the use of the EDSS are that it assesses only limp and walking problems and does not assess other important complications, including fatigue, sexual function, and mental function.

No reliable single laboratory procedure or test can establish the diagnosis of multiple sclerosis. Several are necessary before a diagnosis can be made.

Analysis of Cerebrospinal Fluid (CFS). Obtaining a sample of spinal fluid requires a lumbar puncture, or spinal tap. Testing spinal fluid is becoming increasingly important for detecting abnormal proteins, tiny fragments of myelin, or specific white blood cells that can help in making a diagnosis. For example, high levels of the immunoglobulin IgG is useful for making a diagnosis and may be a marker for disease progression. (Immunoglobulins are protein chains that are part of the immune system.)

A lumbar puncture, or spinal tap, is a procedure to collect cerebrospinal fluid to check for the presence of disease or injury. A spinal needle is inserted, usually between the 3rd and 4th lumbar vertebrae in the lower spine. Once the needle is properly positioned in the subarachnoid space (the space between the spinal cord and its covering, the meninges), pressures can be measured and fluid can be collected for testing.

Evoked Potential (EP) Test. This is a simple and painless electrical test of nerve function that assesses how long it takes nerve impulses from the eye, ear, or skin to reach the brain.

Magnetic resonance imaging (MRI) scans are important diagnostic tools in MS and are used for diagnosing multiple sclerosis, tracking changes over time, and helping to determine treatment effectiveness.

Click the icon to see an image of a brain MRI.

Making a Diagnosis and Tracking the Disease. Magnetic resonance imaging (MRI) scans can detect bright patches that indicate injured tissue (lesions) caused by MS. Such lesions may also indicate other conditions, such as infections, migraines, or clots. Importantly, a very sensitive MRI technique using enhancement by a contrast material called gadolinium can indicate recent activity by showing if the blood-brain barrier has been broken down (the first step in the development of MS lesions). Detecting lesions and treating MS early in the disease process may help reduce progression. Many experts therefore now advocate performing a brain MRI as soon as symptoms appear.

Once diagnosed, periodic follow-up MRIs can be used to track the disease and effectiveness of treatments in two ways:

By distinguishing new lesions from old ones
Revealing increasing or decreasing numbers of lesions within the central nervous system over time

Unfortunately, neither the rate nor the number of new or growing lesions necessarily predicts whether symptoms will worsen or if the patient will develop secondary progressive MS.

Measuring Atrophy in Brain and Spinal Cord. As myelin, axons, oligodendrocytes, and neurons are destroyed, the brain begins to shrink. Processing MRI images to determine brain volume may be a useful way to monitor progression and treatment effects. MRI can also detect shrinkage in the spinal cord, which is proving to be a very strong marker of disease progression. A variation of MRI, magnetic resonance spectroscopy (MRS), provides information on the biochemistry of the brain, and may be particularly helpful in detecting this destructive aspect of MS.

Detecting Black Holes.Severe disease progression can be gauged by the presence of so-called "black holes.” These are lesions in the brain that emit very low signals on an MRI scan. Some evidence suggests that they may represent iron deposits in the brain.

Researchers are continuously searching for biologic markers that might help make an accurate diagnosis, predict outcome, or both. Promising markers are antibodies that target two key protein components of myelin: Myelin oligodendrocyte glycoprotein (MOG) and myelin basic protein (MBP). If future studies confirm the predictive value of these antibodies, scientists may be able to develop a blood test for MOG and MBP.

Treatment

Patients diagnosed with multiple sclerosis face great uncertainty, since the course of the illness varies so widely among patients. Experts recommend a multidisciplinary approach to the disease, which might involve a neurologist, a nurse or social worker expert in MS, and possibly a specialist in mental health (since depression is so common and the suicide rate is higher than average).

Evidence now strongly suggests that the most destructive changes from multiple sclerosis in the brain occur very early on in the disease process -- and may cause considerable damage even before symptoms begin.

Many experts are now urging treatment after a first episode of relapsing MS (a clinically isolated syndrome) using medication called disease-modifying drugs. They include three interferons -- IFN1b (Betaseron) and IFN1a (Avonex, Rebif) -- and glatiramer (Copaxone). These drugs are all effective and may help slow down or even prevent progression in some patients. Definitive studies comparing them are ongoing.

The best current approach is to use specific findings from advanced MRI techniques to help determine which patients are at highest risk for progression and would be likely candidates for early treatment with disease modifying drugs.

Interferons and other disease-modifying drugs can have significant side effects and are expensive. Furthermore, a significant number of patients have a mild course that can be managed with less toxic drugs. Nevertheless, strong evidence suggests that delaying treatment in most patients increases the risk for severe disability.

Corticosteroids are the standard drugs for treating an acute relapse and hastening recovery. Typically, intravenous methylprednisolone (IVMP) is given once a day for 3 days. Sometimes this is followed by oral prednisolone for a few days.

Disease Modifying Drugs. Since the introduction of disease modifying drugs -- interferons beta (Betaseron) and alpha (Avonex, Rebif) and glatiramer (Copaxone) -- relapsing-remitting multiple sclerosis is now considered a treatable disease. In patients with very active MS, some experts start with Betaseron or Rebif. For patients with possible or probable MS, they begin with Avonex. This drug is slightly less effective than Rebif and Betaseron but has fewer side effects. Copaxone is also a reasonable choice for early mild MS. It appears to have the fewest side effects, longer relapse-free rates than interferons, and its benefits persist for years.

The newest drug, the monoclonal antibody natalizumab (Tysabri), was approved in November 2004 for treatment of relapsing forms of MS. The FDA withdrew it from the market, however, in February 2005 following reports of serious neurological events. In June 2006, the FDA allowed natalizumab back on the market but with special restrictions (see Drug Treatment section).

Other Approaches. Some research has reported benefits from the use of pulsed administration of intravenous methylprednisolone (IVMP) or intravenous immunoglobulin, although there is not enough evidence for either approach to recommend them as first-line choices. Other drugs showing promise include azathioprine (an immunosuppressant) and laquinimod (an oral immune-modulating drug).

Treating Secondary Progressive Multiple Sclerosis (SPMS). Interferons and other standard treatments for relapsing-remitting MS may be helpful for patients with SPMS who are still experiencing relapses. It is not clear if they help those whose condition has become continuously progressive.

Mitoxantrone (Novantrone) was the first drug approved for SPMS. The drug is an immunosuppressant and is proving to delay relapse and progression. Side effects, however, can be serious in some cases. Some experts recommend using mitoxantrone when evidence suggests progression to SPMS, and continuing the interferons Betaseron or Rebif for maintenance.

Other immunosuppressants, such as cyclophosphamide, methotrexate, and cladribine, may help some patients with SPMS. They can have very toxic side effects, however, and there must be clear treatment indications for patients who take these drugs.

Treating Primary Progressive Multiple Sclerosis. No treatments have been proven yet to slow progressive multiple sclerosis. Studies using interferons and glatiramer are under way.

A number of treatments are available for managing symptoms and complications.

Drug Treatment

Corticosteroids (commonly called steroids) are mainstay treatments for acute relapses patients with relapse-remitting MS. High-dose methylprednisolone given intravenously (IVMP) is typically administered for major relapse, often followed by oral prednisone for a few days. Steroids reduce inflammation in the central nervous system and may help suppress the immune system's attack on myelin and even improve electrical conduction.

Steroids, in general, do not improve the long-term course of the disease and can lose effectiveness if overused. They are not generally used for maintenance therapy. Some research, however, is reporting benefits from the use of pulsed administration of intravenous methylprednisolone. Such an approach typically administers the steroid daily for 5 days every 4 months for 3 years, then every 6 months for 2 years. Some research suggests that this approach might reduce destruction in central nervous system, although more evidence is needed before it can be recommended. They can also have considerable adverse effects when used over time.

Side Effects. Side effects of long-term use of steroids include weight gain and facial fullness, hypertension, diabetes, osteoporosis, cataracts, intestinal bleeding, and increased susceptibility to infections. In addition, side effects of steroids on the central nervous system (sleeplessness, memory loss, anxiety, and depression) can be particular problems for patients. It is extremely important to taper withdrawal very carefully after continuously taking steroids for a prolonged period of time. This gives the body time to recover its own ability to produce natural steroids. A serious condition known as adrenal insufficiency can otherwise develop.

Interferons (so-called because they “interfere” with viral replication) both suppress important inflammatory factors in the immune system and have anti-viral properties. Interferons specifically block immune factors known as class II MHC molecules, which are associated with the attack on myelin and the breach in the blood-brain barrier that allows the destructive T cells to pass through.

Specific Interferons Used for MS. Interferon drugs used for MS are IFN1b (Betaseron) and IFN1a (Avonex, Rebif). They are now the treatments of choice for relapsing-remitting MS. Expert organizations urge that they be used early in the course of the disease and continued indefinitely, unless they produce no benefits or have severe side effects.

Successes and Drawbacks. Interferons can reduce flare-ups overall by 30% and have an even greater effect on reducing major relapses. Disease activity, as measured by MRI scanning, is reduced by over 80%. They appear to be about equal in reducing disability. To date, only Avonex has demonstrated slowing progression of mental impairment. It also appears to be better tolerated than other interferons. Studies on their effects on quality of life are limited. None of the interferons are a cure, in any case, and when the drug is discontinued, disease activity may increase. All of these drugs need to be injected. (Oral forms are under investigation.)

Side Effects and Complications. Side effects include:

Pain at the injection site. Many patients taking Betaseron complain of severe pain at the injection site caused by damaged tissue. Experts recommend taking acetaminophen (Tylenol) before the injection and then every 6 hours after each injection for 24 hours during the first 6 months of treatment.
Skin injury at the injection site. Black dead tissue may form around the site, and many patients taking Betaseron have reported severe skin eruptions. These skin injuries heal after the drug is withdrawn, but scarring can occur. This side effect is least severe with Avonex, followed by Rebif.
Other physical side effects. Both drugs cause flu-like symptoms, nausea, vomiting, headaches, and dizziness. Such side effects usually fade after 2 - 3 months.
Depression. Early studies associated taking interferon with a higher risk for depression during the first 2 - 6 months following initial therapy. More recent studies, however, have reported no greater risk for depression in patients taking any of these drugs. MS itself, in any case, is highly associated with depression.
Thyroid abnormalities. Interferon has been associated with autoimmune thyroiditis, a cause of hypothyroidism. Some experts recommend monitoring for thyroid function, particularly in the first year and in those with a history of thyroid problems. If there is no evidence of the condition during that period, the risk for its occurrence appears to be very low.
Liver damage. Interferon may cause liver damage and, in rare cases, liver failure. Patients should avoid alcohol and have regular liver function tests while taking this drug

Neutralizing Antibodies That Reduce Effectiveness. Over time, people taking interferons develop antibodies to the drugs, some of which can neutralize their effects. The risk for neutralizing antibodies (NAbs) increases with higher doses and greater frequency of use. Interferons injected under the skin (Betaseron, Rebif) are more likely to produce neutralizing antibodies than Avonex, which is injected into a muscle. Patients who experience this, however, often can be effectively treated with an alternative interferon or with glatiramer, which has an extremely low risk, for NAbs. In many cases, after switching drugs, NAb levels decline, and the patient may be able to return to the original interferon.

Glatiramer acetate (Copaxone) is a synthetic molecule that resembles a basic protein found in myelin. It is used as a decoy to trick white blood cells into attacking it instead of myelin. It is approved to help reduce the frequency of relapses in patients with relapse-remitting MS. The best results are in patients in early stages, but the longer patients remain on the drug, the greater the improvement. Benefits have persisted for years. Glatiramer acetate can also help reduce the number of new brain lesions.

Glatiramer acetate is also being studied for its effects in patients with primary progressive MS. A 2007 study indicated that while the drug had little benefit for most patients with this type of MS, it may help slow disease progression and delay disability in men with primary progressive MS.

Side Effects. Side effects occur in about 15% of patients, usually right after the injection. They include pain at the injection site, chest pain, rapid heartbeat, flushing, anxiety, and shortness of breath.

Monoclonal antibodies (MAbs) are drugs that target specific antibodies involved with the immune response. In 2004, natalizumab (Tysabri) became the only MAb approved for treatment of MS. Shortly afterwards, reports emerged of progressive multifocal leukoencephalopathy (PML) occurring among patients who took natalizumab for more than 2 years. PML is a rare neurological disease that can affect people with compromised immune systems. Based on these reports, the FDA suspended marketing of natalizumab in February 2005 and recommended that patients discontinue its use.

In June 2006, the FDA allowed natalizumab to return to the market with certain safety restrictions. Doctors can prescribe the drug only to patients who have failed to respond to or who cannot tolerate other MS treatments. Natalizumab can only be taken alone, not in combination with other immune-modifying drugs. Patients who take natalizumab must enroll in a special program called TOUCH, which is run by the drug’s manufacturer. Patients need to get magnetic resonance imaging (MRI) brain scans before they begin taking the drug, and they are evaluated regularly during drug treatment to make sure they are not at risk of developing PML. In the year after these restrictions were implemented, no new cases of PML were reported.

Clinical trials indicate that natalizumab’s benefits may outweigh its risks. Several studies published in 2006 in the New England Journal of Medicine showed that natalizumab, alone or in combination with IFN1a (Avonex) can help prevent disability in patients with multiple sclerosis. Another study suggested that the risk of PML is very low if patients use natalizumab for less than 18 months.

Natalizumab is also being studied for treating complications associated with MS. In a 2007 study, natalizumab helped reduce vision loss in patients with relapsing MS. Vision loss is one of the most common symptoms associated with MS.

Other MAbs under investigation for MS include daclizumab (Zenapax), alemtuzumab (Campath), and rituximab (Rituxan). Results from a 2005 phase II trial for alemtuzumab indicated that the drug helped prevent relapse but also caused serious side effects. Patients who took the drug had a high risk for developing a serious bleeding disorder caused by a low blood platelet count. Daclizumab is currently in phase II trials as is rituximab. Unlike other MAbs, which affect T cells, rituximab targets and depletes B cells. In several studies presented at the 2007 meeting of the American Academy of Neurology, rituximab showed promising results in reducing relapse frequency and number of brain lesions in patients with relapse-remitting MS.

Intravenous immunoglobulin treatments are monthly infusions of natural antibodies. They appear to have some modest benefits for relapsing-remitting MS. Studies suggests that intravenous immunoglobulin reduces relapse rates and occurrences of new lesions and slows disease progression in relapsing-remitting MS. It does not appear to reduce disability. It is extremely expensive and does not appear to have any benefits for patients with secondary progressive MS.

Many drugs being investigated for chronic progressive multiple sclerosis are immunosuppressants, which block certain factors in the immune system that contribute to the inflammatory process. Each of these drugs can produce serious side effects, including susceptibility to infection. Evidence on benefits is uncertain, mainly because of high toxicity or study limitations. Still, some immunosuppressants may help certain patients with severe MS. Among immunosuppressant drugs or procedures that have been investigated with little or no obvious benefits or unacceptably high side effects are total lymphoid irradiation, sulfasalazine, cyclosporine, acyclovir, and oral bovine myelin.

Mitoxantrone. Mitoxantrone (Novantrone) was the first drug approved specifically for secondary progressive MS. Studies suggest that it may help reduce progression and relapse rates. Cumulative doses can have toxic effects on the heart, however, so the drug is only used for a limited period. Mitoxantrone is also being studied in combination with glatiramer acetate. In one preliminary study, initial treatment with mitoxantrone, followed by maintenance treatment with glatirimer acetate, helped reduce relapses for up to 5 years.

Methotrexate. In some patients, low doses of the immunosuppressant methotrexate may slow the course of chronic-progressive MS, particularly in those with secondary progressive MS. To date, studies have found beneficial effects only on the upper body, however. Although this drug, like all immunosuppressants, can have toxic side effects, it may be taken in low doses for MS and so side effects are generally minimal.

Cyclophosphamide. Cyclophosphamide (Cytoxan) blocks cell growth and also suppresses the immune system. Some studies, but not all, have reported benefits for patients with chronic progressive MS. Small studies suggest that monthly intravenous administration or a combination with interferon-beta may help some patients with rapidly deteriorating MS. Cyclophosphamide has many side effects, including hair loss, nausea, vomiting, infertility, lung scarring, and blood abnormalities, and should be used for patients who do not respond to methotrexate.

Azathioprine. Azathioprine (Imuran) is designed to suppress the immune system and reduce the number of cells attacking the CNS myelin. It is used with or without steroids and is sometimes used as an alternative to patients with relapsing-remitting MS who do not respond to either interferon beta or glatiramer acetate. One study reported that 40% of patients had not experienced a relapse after taking the drug for 3 years, although others report only modest benefits. The drug has no effect on progression of disability.

Cladribine. Cladribine (Leustatin) may be effective in delaying progression in patients with chronic progressive MS. It has no significant effect on relapsing-remitting MS.

A number of treatments are under investigation that may prove to be helpful for multiple sclerosis. Those discussed below are only some of them.

Immune-Modulating Drugs. Most MS drugs are injected, but researchers are developing several new drugs that can be taken by mouth. Four of the most promising candidates are cladibrine (Mylinax), fingolimod (FTY720), teriflunomide, and fumarate (BG00012). In late-stage clinical trials, these drugs have shown positive results in the treatment of relapse-remitting MS.

Sex Hormones. Women with MS have a reduced risk of experiencing relapses during pregnancy, probably because of their high levels of the female sex hormones estrogen and progesterone. Because of this association, researchers have investigated whether oral estrogen therapy (estriol) can help prevent relapses. Some small studies have indicated that estriol treatment may help reduce lesions and disease activity, but the overall evidence is still inconclusive. The male sex hormone testosterone is also being studied as a treatment for men with relapse-remitting MS. A small 2007 pilot study suggested that treatment with testosterone gel is safe and may help improve cognitive function, slow brain degeneration, and increase muscle mass.

Cannabinoids. Cannabinoids are compounds in marijuana (cannabis), which may have properties that protect nerve cells. Cannabis has been found to improve pain, mobility, tremor, mood, appetite, fatigue, vision, sexual and urinary function, and memory. In a 2003 study, patients reported less pain and improved mobility (although spasticity itself did not improve). Not all patients respond. The drug may also worsen balance and posture in patients with spasticity. Synthetic versions are being investigated that allow rapid delivery without the unwanted side effects of natural cannabis.

Potassium Channel Blockers. Aminopyridines are potassium-blocking compounds that appear to improve nerve conduction through demyelinated areas. In small, preliminary trials, 4–aminopyridine (also called AP) was associated with mild-to-marked improvement in vision, strength, and coordination and was well tolerated. Beneficial effects, however, lasted only a few hours. A related compound, 3,4–diaminopyridine, or DAP, is being studied for relieving fatigue associated with MS.

Statins. Statins are currently the most important drugs for lowering cholesterol. They are also showing additional possible benefits, including anti-inflammatory and nerve protecting properties, which may help patients with neurologic conditions, including multiple sclerosis.

Plasmapheresis. Plasmapheresis with plasma exchange is a procedure in which blood is removed from the body. Blood cells are separated from plasma (the liquid portion of blood) and mixed with replacement plasma, which is then returned to the body. The replacement plasma is thought to dilute antibodies and other immunologically active substances that may trigger MS. Small studies suggest this procedure may have significant benefits for some patients with severe MS, particularly if they are younger and have an early response to this treatment. Side effects include risk of infection and blood clotting problems.

Stem Cell Transplantation. Investigators are studying the benefits of stem-cell transplantation procedures. Stem cells are produced in the bone marrow and are the early forms for all blood cells in the body (including red, white, and immune cells). Early studies indicate that stem cell transplantation may slow progression, although at this point it is not a cure.

Oligodendrocyte Implants. A newly developed, minimally invasive method to transplant modified oligodendrocyte cells directly into the brain is under investigation. Such cells stimulate nerve and axon growth. If feasible, this approach might be helpful in patients whose MS is not caused by an autoimmune response (where the new cells would be attacked, just as the patient's own cells were).

Other Treatments

Nearly 60% of patients try some form of nontraditional remedies. Research on any benefits is slim, and there may be some danger with many remedies commonly used by patients. The following are a few alternative remedies sometimes used for MS.

Relaxation and Meditation Techniques. Generally harmless, and possibly helpful, nontraditional therapies for MS are relaxation and meditation techniques and Eastern martial art exercises. Such techniques include biofeedback, music therapy, yoga, tai chi, and massage therapy.

Acupuncture. Some patients report benefit from acupuncture, which does carry a very small risk, usually for infection.

Acupuncture, hypnosis, and biofeedback are all alternative ways to control pain. Acupuncture involves the insertion of tiny sterile needles, slightly thicker than a human hair, at specific points on the body.

Electromagnetic Stimulation. A few centers have studied pulses of weak electromagnetic fields applied to the brain. Very small studies have reported improvement in fatigue, tremors, depression, and other symptoms in patients who were severely affected by MS. In one controlled study, this approach relieved symptoms more effectively than placebo. The effect was small however and more research is needed.

Linoleic Acid. Linoleic acid, commonly known as evening primrose oil, is a polyunsaturated fatty acid believed by some people to be helpful because myelin is composed of fatty acids. No study has proven that it is beneficial, but supplements sold in health food stores do not appear to be harmful.

Oral Enzymes. Oral drugs containing various natural enzymes, including bromelain, trypsin, papain, and rutin, have been used overseas to treat arthritic pain. They appear to reduce inflammation and are also being studied in patients with MS. Such enzymes have been marketed alone and in combinations (Wobenzym, Phlogenzym). In one small study, Phlogenzym was associated with a decline in complications and longer remission. They are not painkillers; any benefits derived from them may take several weeks. As with any natural remedy, there are few clinical studies on these products and no U.S. regulation of quality, safety, or effectiveness.

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 check with their doctor before using any herbal remedies or dietary supplements

The following warnings are of particular importance for people with multiple sclerosis:

Antioxidants. Some patients use antioxidant vitamins or supplements (A, E, C, Q10, pycnogenol, OPC, grape seed extract), since the destruction in the MS disease process may be partly due to oxidation (chemical damage from particles called oxygen-free radicals). Theoretically, however, antioxidants can trigger T cells and macrophages (inflammatory components of the immune system) and, therefore, may pose some danger to patients. Small studies to date have not found any worsening of the disease from taking vitamin supplements, but patients should be cautious. No vitamins studied for MS, including carotenoids, vitamin C, vitamin E, B12 injections or vitamin D, have been proven to be beneficial.

Gingko. Although the risks for gingko appear to be low, there is an increased risk for bleeding at high doses. Ginkgo can also interact with high doses of vitamin E, anti-clotting medications, aspirin, and NSAIDs. Large doses have also been known to cause convulsion. Commercial gingko preparations may contain colchicine, a drug that can be harmful in pregnant women and people with kidney or liver problems.

Bee Venom. For years, anecdotal reports have claimed that bee stings relieve some MS symptoms, although a study on mice indicated that it may worsen MS. Bee venom contains many chemicals, some of which can cause severe and sometimes deadly allergic reactions in some people.

Other Remedies. Herbal or natural remedies that supposedly boost the immune system (echinacea, ginseng, garlic, zinc) may worsen MS. Melatonin has been associated with worsening of some autoimmune diseases. Toxic effects have also been reported with herbal remedies such as borage seed oil, chaparral, and comfrey.

Treating the Complications

Fatigue affects at least two-thirds of patients. It is among the most disabling problems in MS and is difficult to treat. Treating any problem (depression, hypothyroidism) that may be causing fatigue is important. Aerobic exercise programs scheduled early in the day have been helpful for patients who can participate. Preventing overheating can improve fatigue.

Modafinil (Provigil, Alertec) is a promising drug that promotes long-lasting wakefulness and is currently used in narcolepsy. Small studies report that it is effective in reducing fatigue and sleepiness, with lower doses (200 mg) being more effective than higher ones. Studies also suggest that the antiviral drug amantadine (Symmetrel) may be helpful.

Managing pain and spasticity in the lower limbs can be difficult. Although many drugs are used to reduce spasticity and lower-limb pain, most studies investigating these drugs have been poorly designed and no treatment has emerged as a front-runner.

Exercise. Mild spasticity actually helps improve muscle tone in the legs, which is important in supporting the patient’s weight when walking. This benefit can be lost with drug treatment. Mild spasticity, then, should be treated with exercises several times a day that improve range of motion.

Drugs Used for Spasticity.

Baclofen (Lioresal) has long been the drug of choice to alleviate more severe spasticity. It is available both orally and infused through an implanted pump. Distressing side effects include confusion, drowsiness, and a rubbery-like sensation in the legs that makes it hard to stand.
Antiseizure medications, such as gabapentin (Neurontin) or levetiracetam (Keppra), may help reduce spasticity without increasing fatigue or impairing concentration. Studies on gabapentin also suggest that it also have other specific benefits for patients, including reducing facial pain and improving vision.
Tizanidine (Zanaflex) is an oral drug that works after one week. In one study, 75% of patients taking tizanidine reported improvement without the leg-muscle weakness experienced using baclofen. The drug does not appear to be any more effective than baclofen, however. Side effects include dizziness, drowsiness, dry mouth, and fatigue. Liver function must be monitored.
Diazepam (Valium) is also used for spasticity and may be particularly useful for patients who also experience anxiety. Drug dependence is the primary problem with diazepam, as well as dizziness, drowsiness, and confusion. The medication should not be used by people who are seriously depressed.
Botulinum toxin (Dysport) injections are being investigated for spasticity in specific regions such as the hip.
Dantrolene (Dantrium) may be an effective alternative for patients who cannot tolerate diazepam or baclofen. Because dantrolene causes muscle weakness, however, it is best suited for either patients who are wheelchair bound but still suffer from spasticity, or for those whose muscles are still strong so that the drug-induced weakness isn't unduly debilitating. It also causes nausea, vomiting, and anorexia, and with high dosages it can cause dangerous liver damage.

Surgery. In very severe cases where medication and exercise are not helpful, surgery may be considered. In such cases, the surgeon cuts the tendons that are involved with spasticity.

Spinal Injections. In very severe cases, administering phenol using spinal injections in the lower back may reduce pain and spasms for some patients with severe conditions. Most patients are not appropriate candidates for this approach.

Other Treatments. Researchers are also investigating non-drug treatments for spasticity. Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive method that uses a magnet placed on the scalp to generate a magnetic field that stimulates the cortex of the brain. In a small 2007 study, rTMS showed promise in improving lower-limb spasticity in patients with relapse-remitting MS.

Urge Incontinence. Urge incontinence (the need to urinary frequently) is common in patients. To help reduce social difficulties, patients should not drink fluids before going to places where restrooms are not easily available. When possible, they should urinate every 3 - 4 hours. A number of medications are available for urge incontinence, including anticholinergic drugs, such as propantheline bromine (Pro-Banthine), tolterodine (Detrol), or oxybutynin (Ditropan). Sacral nerve stimulation (InterStim) sends electrical pulses to help retrain nerves in the pelvic area, and is also proving to be helpful. Botulinum toxin injection into the urinary tract muscles is being investigated and may be helpful for incontinence caused by spasticity. [See In-Depth Report #50: Urinary incontinence.]

Urinary Retention. Urinary retention occurs in some patients. Sometimes urination can be stimulated simply by pressing the bladder area with the fist or hand, by tapping against it, or by straining. Drugs being tried with some success for this problem are desmopressin (DDAVP), ordinarily used for bed wetting in children, and maprotiline (Ludiomill), an antidepressant. If medication is ineffective, a catheter may be needed, either one used intermittently by the patient or placed in the urinary tract. Various new surgical procedures that reconstruct the bladder or divert urine flow may be effective in severe cases of bladder dysfunction. Because urinary symptoms usually remain intermittent for years, treatment approaches for bladder dysfunction should be limited to medications and other reversible therapies, for as long as possible.

Urinary Tract Infections. Urinary tract infection is common in patients, and a urinalysis should be performed with any symptom flare-ups, fever, or change in bladder symptoms. Treatment uses appropriate antibiotic regimens. Some evidence suggests that cranberry juice may help prevent infections. [See In-Depth Report #36: Urinary tract infection.]

In addition to maintaining a high-fiber diet and drinking plenty of fluids, bulk fiber such as psyllium (Metamucil), with or without a stool softener, may be needed. Going to the bathroom the same time every day, particularly after a meal and waiting there for a movement, reduces the risk of losing control later in the day. Exercise helps patients avoid becoming dependent on laxatives, enemas, or colonic irrigation, which can eventually slow down the bowel and cause imbalances in electrolytes. Biofeedback techniques may be helpful in some patients with limited multiple sclerosis.

Major tremors can be very distressing and are particularly hard to treat. Carbamazepine and glutethimide have some possible benefits, but in general drug therapy has been disappointing. Weight applied to the affected limb has been beneficial in about 20% of cases. Surgery is very controversial.

Trigeminal neuralgia is facial pain, usually on one side, that can be very severe and may be triggered by an event as mild as a breeze or teeth brushing. If nonprescription painkillers fail to alleviate facial pain, it can be treated with anticonvulsive medications. Carbamazepine (Tegretol) is currently the drug of choice. Carbamazepine is also effective on other types of MS pain and spasm-related symptoms, including itching and aching. Another antiseizure drug, gabapentin (Neurontin), however, may be particularly effective for MS. This drug also appears to improve blurred vision associated with MS and may help spasticity in general.

Other drugs used for this symptom include phenytoin (Dilantin), diazepam (Valium), or pimozide (Orap), and the antidepressant amitriptyline (Elavil). If severe pain persists and interferes with function, some patients elect to have a section of a nerve surgically removed or blocked. This relieves pain but causes numbness. Before patients commit to such a procedure, they should ask the doctor to temporarily block the nerve with an anesthetic in order to experience the effect of numbness before undergoing irreversible surgery.

A small percentage of patients suffer from pseudobulbar affect (uncontrollable laughing or crying). Neurodex is an investigative drug that is showing promise in controlling these symptoms. The drug combines dextromethorphan (an ingredient contained in many cough suppressants) and the enzyme inhibitor quinidine.

Sildenafil (Viagra) may help improve sexual dysfunction in some patients. Corticosteroids, which are sometimes used for other MS symptoms, also improve sexual function. Other treatments are available that might be very beneficial. Patients should not be shy about discussing sexuality with their doctor. [See In-Depth Report # 15: Erectile dysfunction.]

Techniques for helping patients with swallowing problems include using specific head and tongue positions to assist swallowing, and preparing pureed food. Patients may need to work with otolaryngologists (doctors specializing in ear, nose, and throat disorders) to address swallowing problems. Left untreated, swallowing problems can increase a patient's risk of aspiration pneumonia, malnutrition, dehydration, and other problems.

MS is a strong risk factor for osteoporosis. In addition to calcium and vitamin D supplements, a number of drugs are now available to help prevent bone loss and reduce the risk of fractures due to osteoporosis. [See In-Depth Report #18: Osteoporosis.]

Treating Depression. Treating depression may not only improve mood but may also have direct benefits for patients.

Antidepressants known as tricyclics may have specific benefits for MS in addition to managing severe depression. Amitriptyline (Elavil), for example, may be effective in alleviating the extreme mood swings that frequently occur in patients. This “emotional incontinence,” the inability to control emotions, can distress some patients more than physical symptoms. Other tricyclics include desipramine (Norpramin, Pertofrane) and imipramine (Tofranil), which have additional effects that improve bladder symptoms in some patients. These drugs, however, can have severe side effects.
Newer antidepressant drugs, known as SSRIs (serotonin-reuptake inhibitors), which include fluoxetine (Prozac), sertraline (Zoloft), and paroxetine (Paxil), may be better tolerated. A study on sertraline suggested that it may also reduce the immune system's inflammatory response.

Stress Reduction and Supportive Measures. Stress can worsen symptoms, and may worsen the disease itself. Reducing stress is an important part of general health maintenance. Studies on methods for reducing stress report improved well-being in patients. A sense of control and connection appears to be extremely important for patients. Relaxation or meditation exercises can be beneficial, although cognitive-behavioral methods may be more effective in these patients. [See In-DepthReport # 31: Stress.]

Support for Caregivers. Many patients require long-term physical, financial, and psychological support from family and friends. The physical and mental health of the caregiver are critical. In one study, caregivers reported that among the most distressing aspects were the psychological impact of MS on the patient and the incurability of the disease. Most caregivers identified the best form of support to be practical help, cooking, cleaning, and better availability of medical and financial advice. Therapeutic help for family members may also be helpful.

Interferon, used to treat MS, may improve mental function. Other medications and therapies may also be helpful. For example, drugs called cholinesterase inhibitors, such as donepezil (Aricept), which are used for Alzheimer's disease, may help improve mental functioning. Vocational programs for the patient may also be helpful. Therapeutic programs for both patients and their families can help them better understand and cope with cognitive weaknesses such as concentration and problem solving.

Lifestyle Changes

People with multiple sclerosis should make every effort to preserve their general health. A healthy diet, sufficient rest, establishing priorities to conserve energy, and developing emotional support networks can all be very helpful.

Some dietary suggestions for patients with MS include:

Drink two quarts of water a day and avoid caffeine-containing beverages, which are actually dehydrating. This helps avoid constipation (although may cause difficulties in patients who also have urge incontinence).
Eat a diet rich in fiber, particularly from whole grains (especially bran, oats, or flax), fruits (particularly prunes), and vegetables.
Low-fat diets have not proven to have much effect on MS but are, in any case, generally healthy.
Fish and fish oil. Omega-3 fatty acids, which are found in oily fish, have been associated with protection against inflammation and some reduction in symptoms in people with various autoimmune conditions. Such fatty acids are also available in supplements as docosahexaenoic (DHA) and eicosapentaenoic (EPA) acids. Standards for optimal amounts and forms of omega-3 fatty acids have not yet been established, however. Some experts recommend that people with MS eat three fish meals a week.

Special diets, such as those that are gluten- or yeast-free, have not shown to have any direct effect on the symptoms or course of MS.

Exercise is an important component in managing MS. An active patient with MS is less likely to develop certain complications, such as bladder and bowel dysfunction, osteoporosis, permanent muscle contractions, ulcerations of the skin, or abnormal blood clotting. MS symptoms can temporarily worsen during physical activity, however, so any program must be planned carefully. A health professional should be consulted to determine the best form of physical activity. One study reported that physical rehabilitation for 3 weeks in a hospital setting was significantly more effective in achieving functional independence than home exercise. It is not known if the same benefits can be achieved with a similar program outside the hospital.

Some suggestions include:

Exercise programs must be designed to stimulate working muscles, but at the same time avoid overload and overheating, which can block nerve conduction.
Stretching and range-of-motion exercises are important because they can relieve muscle spasticity.
Pool exercises are particularly helpful. Water supports the body, and cool water dissipates heat.
Specific exercises that strengthen and increase the endurance of muscles that control breathing functions may be helpful. However, it is unclear if such exercises reduce lung complications over the long-term.
Gradually, patients may be able to build up to more complex exercise programs.

Body overheating causes demyelinated nerves to function less efficiently than usual. Although this effect is resolved within a few hours of regaining normal body temperature, active cooling can help reduce fatigue and improve stability. As a result, researchers are studying the effectiveness of cooling suits.

The following measures may be helpful:

Use air conditioners in the summer.
Keep the home slightly cool in winter.
Avoid swimming in heated pools.
A portable helmet that uses cold liquid to cool the head and neck and therefore lower core body temperatures may help MS symptoms during daily activities.

MS symptoms worsen during a cold or the flu, probably because of increased immune system activity. Experts recommend that patients with MS receive a flu shot in the fall. However, experts warn that patients should not take the nasal spray version of the flu vaccine (FluMist Intranasal). Unlike the flu injection vaccine, which uses an inactivated virus, FluMist contains a live virus. Live virus vaccinations may be harmful for people with MS, especially those who take immune-suppressing drugs.

Resources

www.ninds.nih.gov -- National Institute of Neurological Disorders and Stroke
www.aan.com -- American Academy of Neurology
www.msaa.com -- Multiple Sclerosis Association of America
www.nmss.org -- National Multiple Sclerosis Society
www.msfacts.org -- Multiple Sclerosis Foundation
www.www.fda.gov/cder/drug/infopage/natalizumab -- FDA information on natalizumab (Tysabri)
www.myelin.org -- The Myelin Project
www.abledata.com -- National database of assistive devices and rehabilitation equipment

References

Balcer LJ, Galetta SL, Calabresi PA, Confavreux C, Giovannoni G, Havrdova E, et al. Natalizumab reduces visual loss in patients with relapsing multiple sclerosis. Neurology. 2007 Apr 17;68(16):1299-304.

Boggild M. .Rationale and experience with combination therapies in multiple sclerosis. J Neurol. 2006 Nov;253 Suppl 6:vi45-vi51.

Centonze D, Koch G, Versace V, Mori F, Rossi S, Brusa L, et al. Repetitive transcranial magnetic stimulation of the motor cortex ameliorates spasticity in multiple sclerosis. Neurology. 2007 Mar 27;68(13):1045-50.

Correale J, Fiol M, Gilmore W. The risk of relapses in multiple sclerosis during systemic infections. Neurology. 2006 Aug 22;67(4):652-9. Epub 2006 Jul 26.

Hensiek AE, Seaman SR, Barcellos LF, Oturai A, Eraksoi M, Cocco E, et al. Familial effects on the clinical course of multiple sclerosis. Neurology. 2007 Jan 30;68(5):376-83.

Kappos L, Antel J, Comi G, Montalban X, O'Connor P, Polman CH, et al. Oral fingolimod (FTY720) for relapsing multiple sclerosis. N Engl J Med. 2006 Sep 14;355(11):1124-40.

Munger KL, Levin LI, Hollis BW, Howard NS, Ascherio A. Serum 25-hydroxyvitamin D levels and risk of multiple sclerosis. JAMA. 2006 Dec 20;296(23):2832-8.

Sicotte NL, Giesser BS, Tandon V, Klutch R, Steiner B, Drain AE, et al. Testosterone treatment in multiple sclerosis: a pilot study. Arch Neurol. 2007 May;64:683-688.

Wolinsky JS, Narayana PA, O'Connor P, Coyle PK, Ford C, Johnson K, et al. Glatiramer acetate in primary progressive multiple sclerosis: results of a multinational, multicenter, double-blind, placebo-controlled trial. Ann Neurol. 2007 Jan;61(1):14-24.

Review Date:
5/26/2007
Reviewed By:
Harvey Simon, M.D., Editor-in-Chief, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital

A.D.A.M. Copyright

adam.com

Menopause

FitSugar — Wed, 08 Oct 2008 17:34:57 -0700

In This Report

Highlights
Introduction
Complications
Symptoms
Lifestyle Changes
Medications
Resources
References

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

Black Cohosh Doesn’t Help Hot Flashes

The herbal remedy black cohosh is no better than placebo for treating hot flashes and night sweats, according to a 2006 study in the Annals of Internal Medicine.
Most complementary and alternative medicines are ineffective for relieving menopausal symptoms, according to a 2006 review in the Archives of Internal Medicine.

Hormone Replacement Therapy (HRT)

Short-term use of HRT remains an option for recently menopausal women who have a low risk for stroke, according to a 2007 statement from the North American Menopause Society (NAMS). However, NAMS recommends that women who are at risk for heart disease or breast cancer should consider other approaches for managing hot flashes.
For women who want to discontinue HRT, gradually tapering off the medication or stopping it abruptly appears to make little difference in the recurrence of symptoms, suggests a 2006 study. A gradual approach may delay the reappearance of symptoms, but does not prevent them from returning.

HRT and Heart Disease: Timing Counts

Women who begin HRT within 10 years of menopause have a much lower risk for heart disease and heart attack than women who start HRT later on, indicates a 2007 study in the Journal of the American Medical Association. Experts suggest that HRT is relatively safe for younger women (under age 60) but should not be used by older women. HRT should never be used for prevention of heart disease, and HRT increases the risk for stroke regardless of a woman’s age or when she begins taking it.

HRT and Cancer

A dramatic fall in breast cancer rates has accompanied the decline in HRT use, according to a 2007 study in the New England Journal of Medicine.
Women who use HRT for more than 5 years have a 20% greater risk of developing and dying from ovarian cancer than women who have never used HRT, indicates a 2007 Lancet study of nearly 1 million women.

Introduction

The ovaries contain 200,000 - 400,000 follicles, tiny sacks that contain the materials needed to produce mature eggs, or ova. The ovaries produce two major female hormones: estrogen and progesterone.

The uterus is a hollow muscular organ located in the female pelvis between the bladder and rectum. The ovaries produce the eggs that travel through the fallopian tubes. Once the egg has left the ovary it can be fertilized and implant itself in the lining of the uterus. The main function of the uterus is to nourish the developing fetus prior to birth.

Estrogen. Estrogens have an effect on about 300 different tissues throughout a woman's body:

They are essential for the reproductive process and for the development of the female organs.
Estrogens determine the characteristic female distribution of body fat on the hips and thighs, which develops during adolescence.
They also are involved in tissues in the central nervous system (including the brain), the bones, the liver, and the urinary tract.

Estrogen has different forms:

The most potent form is estradiol.
The other important, but less powerful, estrogens are estrone and estriol.

Most of the estrogens in the body are produced by the ovaries, but they can also be formed by other tissues, such as body fat, skin, and muscle.

Progesterone. Progesterone, the other major female hormone, is necessary for thickening and preparing the uterine lining for the fertilized egg.

As a woman ages, her supply of eggs declines. Menopause occurs naturally after the woman's supply of follicles has been depleted and menstruation ends completely. (Menopause may also be induced if the ovaries are surgically removed.)

Perimenopause. Menopause does not occur suddenly. A period called perimenopause usually begins a few years before the last menstrual cycle. Some experts believe there are three stages in the transition:

Early Stage. The beginning of perimenopause can begin in some women in their 30s, but most often it starts between ages 40 - 44. It is marked by changes in menstrual flow and in the length of the cycle. There may be sudden surges in estrogen.
Middle Stage. In the middle cycle, periods become irregular but they are not skipped.
Late Stage. In the late stages, women begin missing the periods until they finally stop. About 6 months before menopause estrogen levels drop significantly. The fall in estrogen triggers the typical symptoms of vaginal dryness and hot flashes (which can last from half a year to more than 5 years after onset of menopause).

Menopause. At the point at which menopause occurs, the following hormonal changes occur:

Ovarian secretion of estrogen and progesterone ends.
Once the ovaries have stopped producing estrogens, however, they still continue to produce small amounts of the male hormone testosterone, which can be converted to estrogen (estradiol) in body fat.
In addition, the adrenal gland continues to produce androstenedione (a male hormone), which is converted to estrone and estradiol in the body fat.

Click the icon to see an image of the adrenal glands.

The total estrogen produced after menopause, however, is far less than that produced during a woman's reproductive years.

The average age of women at menopause today is 51.4 years although it can occur as early as age 40 to as late as the early 60s. Women now have a life expectancy of more than 80 years. Currently, women can expect to live some 30 or 40 years of their life in the postmenopausal state.

Menopause is not a disease. However, many conditions are associated with estrogen depletion, including heart disease, osteoporosis, and other complications. Fortunately, effective treatments are available for these conditions.

In a number of studies, most women have reported menopause as a positive experience and have welcomed it with relief and as a sign of a new stage in life.

Complications

After a woman reaches menopause, her average life expectancy is 30 - 40 years. During those years, however, she faces certain health risks due to lower levels of estrogen that cause accelerated bone loss and an increase in LDL cholesterol (the so-called bad cholesterol). Her risks for serious disorders are estimated at 46% for heart disease, 20% for stroke, and 15% for hip fracture. In addition, about 8% of people over 75 have dementia, with postmenopausal women having 1.4 - 3 times the risk for Alzheimer's disease compared to men.

Heart disease is the number one killer of women. In 2003, more than 480,000 women died from diseases of the heart and circulation (cardiovascular diseases). Although young women have a much lower risk for cardiovascular disease than young men, after menopause women catch up. After age 51, women’s risk of dying from heart disease is very close to that of men. Estrogen loss is believed to play a major role in this increased risk.

Some studies indicate that women who reach menopause at an early age are at increased risk of heart disease. However, recent research suggests that the reverse may also be true. A 2006 study suggested that women who have heart disease risk factors (smoking, high total cholesterol levels, high blood pressure) during premenopause may enter menopause earlier than women with healthier heart profiles. [See In-Depth Report #3: Coronary artery disease.]

Estrogen has the following effects:

Harmful Effects on Cholesterol and Other Lipids (Fats in the Blood). About 2 years before menopause, as estrogen levels begin to decline, the levels of the harmful low-density lipoprotein (LDL) cholesterol begin to rise, and the advantageous high-density lipoprotein (HDL) levels decrease.
Positive Effect on Blood Flow. Estrogen has significant effects on smoothing, relaxing, and opening blood vessels, thereby increasing blood flow and reducing pressure.
Antioxidant Actions. Estrogen is also an antioxidant. That is, it helps clean up particles called oxygen-free radicals that are released by natural chemical processes in the body, which can cause significant damage, including harm to the arteries.
Mixed Effects on Blood Pressure. The effects of estrogen on blood pressure are not clear. Oral contraceptives, for instance, which contain estrogen, appear to increase pressure slightly.

Blood pressure is the force applied against the walls of the arteries as the heart pumps blood through the body. The pressure is determined by the force and amount of blood pumped and the size and flexibility of the arteries.

Mixed Effects on Blood Clotting. Estrogen affects many blood-clotting factors in the liver: It reduces blood viscosity (stickiness) and may enhance fibrinolysis, the natural process for breaking down blood clots. Unfortunately, estrogen also has other actions that increase the risk for blood clots. Women who take hormone replacement therapy are at risk for thromboembolism -- blood clots that block a vessel.

Click the icon to see an image of thromboembolism.

This action may explain the higher rates of adverse heart events now observed in women with heart disease who take HRT.

Osteoporosis is a disease of the skeleton in which bones become brittle and prone to fracture. In other words, the bone loses density. At age 65, about 30% of women have osteoporosis, and nearly all of them are unaware of their condition. After age 80, up to 70% of women develop osteoporosis. Osteoporosis is a major risk factor for fracture in the spine and hip. The lifetime risk of spinal fracture in women is about 1 in 3 and that for hip fracture is 1 in 6. Furthermore, between 10 - 20% of women who experience a hip fracture die within a year and about 25% require nursing home treatment.

Click the icon to see an image of osteoporosis.

Experts are still puzzled by the extreme speed-up of bone breakdown (resorption) after menopause. Estrogen may have an impact on bone density in various ways:

Estrogen's most important effect on osteoporosis appears to be prevention of bone break down (resorption). Some research suggests that estrogen may control the lifespan of osteoclasts, the cells responsible for bone breakdown.
Part of estrogen's beneficial actions may involve maintaining normal levels of vitamin D, an important nutrient in bone protection.

Risk factors for osteoporosis include:

Being tall and thin
Being Caucasian
Smoking
Taking thyroid hormone
Being sedentary
Early menopause or surgical menopause (removal of ovaries)

Women at risk for osteoporosis should have a bone density test to measure their bone mass and then make a decision about treatment after consulting their doctor. [See In-Depth Report #18:Osteoporosis.]

Depression may occur as a woman transitions into menopause (perimenopause), even among women with no history of clinical depression. Hormonal changes and declines in estrogen levels are probably involved in this process. Research suggests that a depressive disorder is 2.5 times more likely to develop during perimenopause than premenopause. Women who transition to menopause at a younger age are at increased risk of a first episode of depression.

Symptoms of clinical depression include:

Loss of interest or pleasure in activities once enjoyed
Persistent (longer than 2 weeks) sad mood
Decreased energy
Sleep problems (insomnia or oversleeping)
Feelings of guilt, worthlessness, and hopelessness
Difficulty concentrating

Some of these symptoms may overlap with other symptoms that typically accompany perimenopause. Women who experience these symptoms should talk to their doctor. Depression is treatable. [See In-Depth Report #8: Depression.] For many women, depression eases once they reach menopause.

Estrogen, the primary female hormone, appears to have properties that protect against the memory loss and lower mental functioning associated with normal aging. Estrogen's effects on the brain include:

Laboratory studies suggested that estrogen may help block production of beta-amyloid, the source of the sticky plaques found in Alzheimer's brains.
Estrogen may trigger the temporary growth of nerve pathways in the memory portion of the brain.
Estrogen may stimulate production of the neurotransmitters acetylcholine and serotonin, which are depleted in Alzheimer's patients.
Estrogen also appears to smooth, relax, and open blood vessels, which may help blood flow in the brain.
Estrogen is an antioxidant. That is, it helps clean up free-oxygen radicals, the unstable particles thought to play a role in Alzheimer's.
Studies have been mixed on the association between natural estrogen levels and mental functioning in older women.

Estrogen therapy has been associated with reduced gum bleeding and with decreased bone loss around the teeth, and women who take estrogen are less likely to lose their teeth. Thus, the same principle that helps prevent bone loss in osteoporosis is also at work in preventing bone loss in the mouth.

Estrogen, progesterone, or both appear to protect against cataracts.

Click the icon to see an image of a cataract.

Studies also indicate that estrogen helps prevent glaucoma and macular degeneration.

Click the icon to see an image of glaucoma.

Click the icon to see an image of macular degeneration.

The drop in body estrogen levels brought on by menopause may contribute to both urinary stress and urge incontinence.

Women are at increased risk for recurrent urinary tract infections after menopause. Research suggests that estrogen may prevent infection by increasing the number of lactobacilli, a microorganism that fights infection by preventing bacteria from adhering to vaginal cells.

Estrogen may help prevent slackness and dryness in the skin and reduce wrinkles.

Menopause is associated with more sleeping problems, including inability to fall asleep and nighttime wakefulness.

Symptoms

The most prominent symptoms of the transition to menopause include:

Hot flashes and night sweats. Women often experience hot flashes as an intense build-up in body heat, followed by sweating and chills. Some women report accompanying anxiety as the sensation builds. In most cases, hot flashes resolve within 2 years of menopause, although in some women they may persist for years. Women who have a hysterectomy (surgical removal of the uterus) are less likely to experience hot flashes than women who have a natural menopause. However, women who have surgical removal of both ovaries, and who do not receive hormone replacement therapy, may have more severe hot flashes than women who enter menopause naturally.
Heart pounding or racing can occur, with or without hot flashes.
Difficulty sleeping. Insomnia is common during perimenopause. It may be caused by the hot flashes or it may be an independent symptom of hormonal changes. A 2006 study indicated that severe hot flashes are frequently associated with chronic insomnia.
Mood changes. Mood changes are most likely to be a combination of sleeplessness, hormonal swings, and psychological factors as a woman undergoes this intense passage in her life. Once a woman has reached a menopausal state, however, depression is no more common than before, and women with a history of premenstrual depression often experience significant mood improvement.
Sexuality. Sexual responsiveness tends to decline in most women after menopause, although other aspects of sexual function, including interest, frequency, and vaginal dryness vary. It is useful to remember that the symptoms of menopause eventually go away.
Forgetfulness. This appears to be one of the few symptoms that are common across most cultural and ethnic groups.
Urine leakage.
Vaginal dryness.
Joint stiffness.

Women from different ethnic and or cultural groups report different menopausal symptoms. For example, in one study hot flashes occurred in about 30% of Caucasians and 45% of African-Americans. Hispanic women tended to complain of urine leakage, vaginal dryness, and heart pounding. Japanese and Chinese women experienced far fewer menopausal symptoms, except for forgetfulness. All groups complained about this symptom.

Lifestyle Changes

Simple changes in lifestyle and diet can help control menopausal symptoms such as hot flashes. Avoid hot flash triggers like spicy foods, hot beverages, caffeine, and alcohol. Dress in layers so that clothes can be removed when a hot flash occurs. For vaginal dryness, moisturizers, and non-estrogen lubricants, such as KY Jelly, Replens, and Astroglide are available.

When women reach menopause, they are at increased risk for heart disease. A heart-healthy diet is an important way to control cholesterol and blood pressure levels. [See In-Depth Report #42: Heart-healthy diet.]

In 2007, the American Heart Association (AHA) issued revised diet and lifestyle recommendations. The current guidelines recommend:

Balancing calorie intake and physical activity to achieve or maintain a healthy body weight. (Controlling weight, quitting smoking, and exercising regularly are essential companions of any diet program. Try to get at least 30 minutes, and preferably 60 – 90 minutes, of daily exercise.)
Consuming a diet rich in a variety of vegetables and fruits. Vegetables and fruits that are deeply colored (spinach, carrots, peaches, berries) are especially recommended as they have the highest micronutrient content.
Choosing whole-grain, high-fiber foods. These include fruits, vegetables, and legumes (beans). Good whole grain choices include whole wheat, oats/oatmeal, rye, barley, brown rice, buckwheat, bulgur, millet, and quinoa.
Eating fish, especially oily fish, at least twice a week (about 8 ounces/week). Oily fish such as salmon, mackerel, and sardines are rich in the omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). Consumption of these fatty acids is linked to a reduced risk of sudden death and death from coronary artery disease. Women with existing heart disease may also consider taking a daily dietary supplement of 850 – 1,000 mg of EPA and DHA.
Limiting daily intake of saturated fat (found mostly in animal products) to less than 7% of total calories, trans fat (found in hydrogenated fats, commercially baked products, and many fast foods) to less than 1% of total calories, and cholesterol (found in eggs, dairy products, meat, poultry, fish, shellfish) to less than 300 mg per day. Choose lean meats and vegetable alternatives (such as soy). Select fat-free and low-fat dairy products. Grill, bake, or broil fish, meat, and skinless poultry.
Using little or no salt in your foods. Reducing salt can lower blood pressure and decrease the risk of heart disease and heart failure.
Cutting down on beverages and foods that contain added sugars (corn syrups, sucrose, glucose, fructose, maltrose, dextrose, concentrated fruit juice, honey).
If you consume alcohol, do so in moderation. The AHA recommends limiting alcohol to no more than 1 drink per day for women.
The AHA does not recommend antioxidant supplements (such as vitamin E, C, or beta carotene) or folic acid supplements for prevention of heart disease.

Soy is an excellent food. It is rich in both soluble and insoluble fiber, omega-3 fatty acids, and provides all essential proteins. Soy proteins have more vitamins and minerals than meat or dairy proteins. They also contain polyunsaturated fats, which are better than the saturated fat found in meat. The best sources of soy protein are soy products (tofu, soy milk, soybeans).

For many years, soy was promoted as a food that could help lower cholesterol and improve heart disease risk factors. But an important 2006 review of studies found that soy protein and isoflavone supplement pills do not really have any effects on cholesterol or heart disease prevention. The AHA still recommends soy foods, but not supplements, as a healthy food choice. The benefits of soy on menopausal symptoms are mixed, according to research (see below in Alternative Therapies). A 2006 study reported that increased soy intake does not help reduce the frequency or severity of hot flashes and night sweats.

Soy is high in estrogen-like plant chemicals called isoflavones, which may improve bone health in older women. A 2005 review of 15 clinical trials found that, although the results were mixed, isoflavones appeared to decrease bone loss, especially in younger postmenopausal women. Soy food products, such as tofu, that also contain calcium may be particularly beneficial.

A combination of calcium and vitamin D is important for helping to prevent bone loss. [See In-Depth Report #18: Osteoporosis.]

Calcium. Women should be sure they have sufficient calcium and vitamin D in their diet by consuming low-fat dairy products or calcium-enriched orange juice. Calcium supplements may be another option for some women. For calcium supplements, calcium citrate (Citracal) is better absorbed than calcium carbonate (Tums, Os-Cal) and other types of calcium compounds. Calcium citrate was the first calcium supplement reported to preserve bone density after menopause.

Click the icon to see an image of the benefits of calcium.

The standard recommended calcium dose for adults age 50 years and older is 1,000 – 1,500 mg per day, depending on risk factors. High doses (over 2,500 mg per day) of calcium supplements may increase the risk for kidney stones. (Because many commercial foods are now fortified with calcium, this upper limit may be easier to reach than people think.)

Click the icon to see an image of calcium sources.

For years, doctors have recommended that women take supplements of calcium plus vitamin D to help maintain bone density and reduce the risk for fractures. However, a 2006 New England Journal of Medicine study raised some questions about this approach. In the Women’s Health Initiative study, women were randomly assigned to receive either 1,000 mg of calcium carbonate plus 400 IU of vitamin D a day or placebo. The results indicated that daily calcium and vitamin D supplements:

Improve hip bone density slightly (by 1%)
Prevent hip fracture, but only for women who consistently take the supplements. (Another 2006 study supported this finding.)
Do not prevent spine or other types of fractures
Produce a slight increase in the risk of kidney stones

The medical community has differing views on how to interpret these findings. Some doctors recommend that women over age 60 should still consider taking calcium and vitamin D for bone health. Other doctors feel that due to the risks of kidney stones, supplements are beneficial only for women (especially those over age 70) who do not get enough calcium in their diets. Ask your doctor whether you should take calcium supplements.

Vitamin D. Vitamin D is necessary for the absorption of calcium in the stomach and gastrointestinal tract and is the essential companion to calcium in maintaining strong bones. Some studies suggest that vitamin D protects against osteoporosis only in combination with calcium.

Vitamin D is manufactured in the skin using energy from the ultraviolet rays in sunlight. It can also be obtained from dietary supplements. As a person ages, vitamin D levels decline. Levels also fall during winter months and when people have inadequate sunlight. Pollution may also contribute to less sunlight and declining vitamin D levels.

Click the icon to see an image of vitamin D sources.

Daily dosage guidelines vary. General recommendations include:

400 IU for people age 50 - 60
600 IU for those over age 70 who do not have sufficient exposure to sunlight. (Some evidence suggests that higher doses of vitamin D -- up to 800 IU per day -- may help prevent fractures in people with osteoporosis.)
800 – 1,000 IU for adults over age 50 (the amount recommended by the National Osteoporosis Foundation)

Drinking milk fortified with vitamin D and sunlight exposure supply most people's need for vitamin D. (One cup of whole milk provides about 100 IU of vitamin D.) Oily fish (sardines especially, as well as salmon, fresh tuna, and mackerel) are also important dietary sources of vitamin D. Wild salmon has a much higher vitamin D content than farmed salmon.

Effect on the Heart. One drink a day in women who are not at risk for alcohol abuse may be beneficial for the heart. Red wine in particular contains a substance called resveratrol, which is classified as a phytoestrogen and has estrogen-like effects.

Effect on Bones. Alcohol has different effects on bones depending on how much is consumed. A 2004 study found that moderate wine consumption was linked to improved bone mineral density in postmenopausal women. Alcohol, in moderate amounts, may increase estrogen levels. Excessive drinking, however, has been associated with brittle bones.

Effect on Breast Cancer. Women who drink face an increased risk for breast cancer, but the risk associated with mild-to-moderate drinking is small.

Many women need to increase physical activity and reduce caloric intake before and after menopause. Weight gain is common during these years, and it can be sudden and distressing, particularly when habitual exercise and eating patterns are no longer effective in controlling weight. Gaining weight around the abdomen (the so-called apple shape) is a specific risk factor for heart disease and diabetes and many other health problems. A 2007 study suggested that calcium and vitamin D supplements may help prevent weight gain in postmenopausal women. The benefit was greatest for women who had not been getting enough daily calcium in their diets.

Click the icon to see an image of different types of weight gain.

For protection against all aging diseases, women, whether or not they are taking hormone replacement therapy, should pursue a lifestyle that includes a balanced aerobic and weight resistance exercise program appropriate to their age and medical conditions. Brisk walking, stair climbing, hiking, dancing, and tai chi are all helpful. Several studies report that exercise can help control hot flashes. A healthy diet plus regular, consistent exercise can also help ward off the weight gain associated with menopause. Weight-bearing exercises are specifically helpful for protecting against bone loss. Women should strive for at least 30 minutes of exercise each day (for weight loss, 60 – 90 minutes is preferred). While more exercise is better, any exercise is helpful. A 2007 study showed that postmenopausal sedentary women who exercised only 75 minutes a week experienced improvement in fitness levels.

If a woman smokes, she should quit. Smoking is linked to a decline in estrogen levels. Women who smoke experience menopause about 2 years earlier than nonsmokers. Smoking doubles a woman’s odds of developing coronary heart disease and is a major risk factor for osteoporosis.

Aspirin. The American Heart Association recommends daily low-dose aspirin for all women age 65 years and older who can safely take aspirin. High-risk women may require 75 – 325 mg per day; lower-risk women may benefit from 81 mg a day or 100 mg every other day.

There are many unproven methods for relieving menopausal symptoms, some more effective than others. Acupuncture, meditation, and relaxation techniques are all harmless ways to reduce the stress of menopause, and some people report great benefit from these practices.

Women often try herbal or so-called natural remedies to treat menopausal symptoms. There have been numerous studies conducted on various herbal products and other complementary and alterative therapies. These studies have not found that these approaches have any benefit. Some can have adverse side effects.

Many studies have researched plant estrogens (phytoestrogens), which are generally categorized as isoflavones (found in soy and red clover) and lignans (found in whole wheat and flaxseed). No evidence to date indicates that phytoestrogen supplements provide any benefit for hot flashes or other menopausal symptoms. Nevertheless, foods containing them may be healthful.

Supplements containing specific isoflavones found in soy -- typically the estrogen-like compounds genistein and daidzein -- do not appear to provide any benefits compared to the whole soy protein. Taking them separately may, in fact, cause harm, including a possible increase in estrogen-related cancers.

The following herbs are sometimes use for menopausal symptoms and carry certain risks:

Black cohosh (Cimicifuga racemosa), also known as squaw root, is the herbal remedy most studied for menopausal symptoms. Although it contains a plant estrogen, this substance does not act like an estrogen in the human body. Studies have shown mixed results in preventing hot flashes. A rigorous 2006 study found that black cohosh worked no better than placebo for treating hot flashes and night sweats. While it may be ineffective, black cohosh appears to be safe. Headaches and gastrointestinal problems are common side effects.
Dong quai (Angelica sinensis) does not appear helpful for hot flashes or other menopausal symptoms. Do not use dong quai with blood-thinning drugs, such as warfarin, because it may cause bleeding complications.
Ginseng (Panax ginseng) may help menopausal symptoms of depression and sleep problems, but it has no effect on hot flashes.
Kava (Piper methysticum) may relieve anxiety but it does not help hot flashes. This herb is generally considered unsafe, due to several reports of liver failure and death, especially in people with liver disease.
Wild yam (Dioscorea villosa) is an herb sometimes used for menstrual problems as well as menopausal symptoms. It contains a plant progesterone. However, like black cohosh, there is no evidence that the human body can convert this substance into a hormone. Patients should be aware that some commercial herbal wild yam products contain prescription progesterones.
Dehydroepiandrosterone (DHEA) is a weak male hormone secreted by the adrenal gland. It is available as a dietary supplement. DHEA has no benefit for hot flashes and may increase the risk of breast cancer.

Generally, manufacturers of herbal remedies and dietary supplements do not need FDA approval to sell their products. Just like with drugs, 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 check with their doctors before using any herbal remedies or dietary supplements.

Medications

Doctors used to believe that HRT could help reduce the risk of heart disease and other health risks in addition to treating menopausal symptoms. The results of an important study, called the Women's Health Initiative (WHI), led doctors to revise their recommendations regarding HRT.

The WHI, started in 1991, enrolled 161,809 women between the ages of 50 - 79 in 40 different medical centers. Part of the study was intended to examine the health benefits and risks of hormone replacement therapy, including the risks of breast cancer, heart attacks, strokes, and blood clots.

In 2002, one component of the WHI, which studied the use of estrogen and progestin in women who had a uterus, was stopped early because the health risks exceeded the health benefits. The main reason for stopping the estrogen-progestin study was a 26% increase in breast cancer. This combination therapy study also showed an increased risk for heart attack, stroke, blood clots, and dementia. There was a reduced risk for colorectal cancer and bone fractures, but these benefits did not outweigh the considerable risks.

In 2004, a second component of the WHI, which studied estrogen-only therapy in women who no longer have a uterus, was stopped early. This was primarily because of an increase in the risk for strokes and blood clots. The study also found the estrogen-only therapy had no effect on heart attack or colorectal cancer risk. An update in 2006 suggested that estrogen-only therapy does not increase breast cancer risk over the short term (average 7 years) but may increase risk when taken for a longer time (15 years or more). Another WHI update, from 2007, indicated that estrogen-only therapy can help reduce calcium deposits in the coronary arteries (a sign of heart disease) for women in their 50s who have had a hysterectomy. However, women who have a uterus cannot take estrogen-only HRT because it increases the risk for uterine cancer. Combination estrogen-progestin HRT does not have the same benefits for cholesterol reduction as estrogen-only HRT.

While the WHI studies indicate that HRT should not be prescribed for prevention of chronic diseases, many doctors still accept its use for short-term treatment of moderate-to-severe hot flashes and other menopausal symptoms, and in women undergoing premature menopause for medical or other reasons. Current guidelines recommend using the lowest possible dose for the shortest duration of time. A 2007 position statement from the North American Menopause Society (NAMS) supports short-term use of HRT for treatment of hot flashes and other vasomotor symptoms in recently menopausal women who have a low risk for stroke. However, NAMS recommends that women who are at risk for heart disease or breast cancer should avoid hormone therapy and try other options to manage symptoms.

When a woman stops taking HRT, perimenopausal symptoms may recur. There is some debate about whether it is better to abruptly stop the medication or to taper it off gradually. A 2006 study suggested that gradual discontinuation of HRT delays -- but does not prevent -- the reappearance of symptoms. However, when a woman reaches full menopause, symptoms will eventually go away.

Hormones Used in HRT. Hormone replacement therapy uses either estrogen alone (known as ET or unopposed estrogen) or in combination with forms of progesterone (known as combined hormone therapy or EPT). Progesterone is referred to by one of several names:

Progesterone is the name for the natural hormone.
Progestin is the term for any hormone, natural or synthetic, that causes progesterone effects.
Progestogen is any hormone that has effects similar to progesterone.

Both ET and EPT are available in many forms, including oral tablets, skin patches, and vaginal and skin applications. A new form approved by the FDA in 2004 is a topical estrogen gel that is applied to the arm.

HRT is mainly recommended for relieving menopausal symptoms, including hot flashes, night sweats, vaginal dryness, sleep problems, and mild depression. HRT does not prevent certain other problems associated with menopausal changes, such as thinning hair.

Oral hormonal medications and skin patches are equally effective in reducing hot flashes, mild depression, and sleep problems. Progestins may sometimes be prescribed alone for hot flashes and other acute menopausal symptoms, though they can cause side effects, such as mood swings, bloating, and breast tenderness. Estrogen creams, rings, or vaginal tablets restore vaginal elasticity and lubrication and improve sexual pleasure.

HRT may be useful for some women at high risk for osteoporosis, although other drugs, such as bisphosphonates, should be considered first. It increases bone density and also appears to improve balance and protects against falling. Studies also report reductions in fractures (especially hip fractures) among women taking HRT, but the benefits may not outweigh the risks of HRT. It appears that the beneficial effects wear off soon after therapy is stopped. Estrogen must be taken life long for maximum protection against osteoporosis, which then increases the risk for adverse health effects.

Heart Disease. HRT does not prevent heart disease and can increase the risk for heart disease and heart attack, especially in older women. An important 2007 Women’s Health Initiative study in the Journal of the American Medical Association indicated that this risk is time and age dependent. The study found that women who began HRT within 10 years of menopause had less risk of heart disease than women who begin HRT later on. This study suggests that HRT may be safest for women younger than age 60, and should be avoided by women older than age 60. Any woman who is considering HRT should be sure to have her blood pressure and cholesterol levels evaluated.

Another 2007 study, published in the New England Journal of Medicine (NEJM), also indicated that timing is important. The NEJM study found that that estrogen-only HRT may help reduce calcium deposits in coronary arteries in younger women (age 50 - 59) who have had a hysterectomy. (Because of the increased risk for uterine cancer, estrogen-only HRT is only appropriate for women who no longer have a uterus. Women who have a uterus need to take estrogen-progestin HRT. And, estrogen can increase the risk for heart attack in women who have advanced heart disease.) Although the NEJM study found some heart benefits for estrogen-only HRT for younger women, experts still advise that HRT should be used for only a few years. Any woman who is considering HRT should be sure to have her blood pressure and cholesterol levels evaluated.

Stroke. HRT increases the risk of stroke, regardless of years since menopause. In addition, HRT appears to worsen the outlook for women who have had a stroke.

Mental Decline. Observational studies had suggested that hormone replacement therapy (HRT) helped prevent mental decline and even Alzheimer's disease after menopause. Other studies have found no differences in mental performance and no protection from Alzheimer's disease in women taking HRT compared to non-users. A 2004 review of the Women’s Health Initiative Memory Study found that combined HRT did not reduce the risk of cognitive impairment, and actually increased the risk of dementia among women ages 65 and over.

Thromboembolism. HRT is associated with a higher risk for thromboembolism, in which blood clots form in deep veins. This places women at risk for pulmonary embolism, in which the blood clot travels to the lungs.

Click the icon to see an image of a pulmonary embolism.

Breast Cancer. Because breast tissue growth is highly sensitive to estrogens, the more a woman is exposed to estrogen over her lifetime, the higher the risk for breast cancer. A number of studies have reported a higher risk for breast cancer in postmenopausal women taking HRT that contains both estrogen and progestin. A combination of estrogen and testosterone also increases breast cancer risk. A 2005 study suggested that HRT with no or low progestin is safer than standard estrogen-progestin combination therapy.

Several 2006 studies of women who had a hysterectomy indicated that estrogen alone does not increase overall breast cancer risk when the drug is used for 7 years or less. However, women who take the drug for 15 years or more do have an increased risk. Women who are at low risk for breast cancer tend to have fewer breast cancers with estrogen alone, while women at higher risk tend to have more breast cancers. In addition, estrogen therapy may cause abnormal mammogram results. Breast tissue density increases with HRT, which makes mammograms more difficult to read and leads to more breast biopsies. Women who take estrogen HRT should be aware that they need frequent mammogram screenings.

As further evidence of the association between HRT and breast cancer, a 2007 New England Journal of Medicine study noted that breast cancer rates have fallen as HRT use has declined.

Endometrial (Uterine) Cancers. Estrogen overstimulates the tissue lining the uterus (the endometrium) and causes uncontrolled cell growth, a condition known as hyperplasia, which is a strong risk factor for cancer. Taking unopposed estrogen replacement therapy (ERT) increases the risk of endometrial cancer at least five-fold. Adding progestin to HRT appears to pose no risk for this cancer. However, a 2007 study indicated that short-term treatment (3 years) with ERT is associated with a relatively low risk of endometrial cancer. Women who take ERT should anticipate uterine bleeding, especially if they are obese, and may need endometrial biopsies and other gynecologic tests.

Ovarian Cancer. HRT appears to increase the risk for ovarian cancer. A 2007 UK study of nearly 1 million women found that women who used HRT for more than 5 years were 20% more likely to develop and die from ovarian cancer than women who had never taken HRT.

Gallstones. HRT is associated with a higher risk for gallstones.

Despite its risks, hormone replacement therapy appears to be the best treatment for hot flashes. Nonhormonal treatments for hot flashes and other menopausal symptoms include:

Antidepressants. The antidepressants known as selective serotonin-reuptake inhibitors (SSRIs) are sometimes used for managing mood changes and hot flashes. They include fluoxetine (Prozac), sertraline (Zoloft), venlafaxine (Effexor), and paroxetine (Paxil, Asimia). A 2006 review of nonhormonal therapies, found that paroxetine in particular may help hot flashes. However, paroxetine, like other antidepressants, can cause headache, anxiety, and sexual problems. A 2007 study suggested that the antidepressant citalopram (Celexa), given alone or with HRT, may help treat hot flashes.

An investigational antidepressant, desvenlafaxine (Pristiq), is also being studied for treatment of hot flashes, night sweats, and perimenopausal sleep problems. Research presented at the 2007 meeting of the American College of Obstetricians and Gynecologists indicated that desvenlaxafine, which is related to venlaxafine, showed promise in improving symptoms.

Gabapentin.Several small studies suggest that gabapentin (Neurontin), a drug used for seizures and nerve pain, may relieve hot flashes. Gabapentin may cause drowsiness, dizziness, fatigue, and swelling of the hands and feet.

Clonidine. Clonidine (Catapres) is a drug used to treat high blood pressure. Studies show it may help manage hot flashes. Side effects include dizziness, drowsiness, dry mouth, and constipation

Testosterone. Some doctors prescribe combinations of estrogen and small amounts of the male hormone testosterone to improve sexual function and increase bone density. Side effects of testosterone include increased body hair, acne, fluid retention, anxiety, and depression. Testosterone also adversely affects cholesterol and lipid levels. A 2006 study indicated that combined estrogen and testosterone can increase the risk of breast cancer.


HRT Form	Brand Name	Active Ingredient	Side Effects
Oral Estrogens	Premarin	Natural conjugated estrogen, which is a mixture of estrogens derived from the urine of pregnant mares	Bleeding after withdrawal. It is a primary reason why many women stop treatment, although usually lighter or shorter compared to before menopause. If it is distressing, patient should consider continuous estrogen and progestin therapy. Irregular bleeding. This should be checked with the doctor for possible problems. Nausea and vomiting. If it occurs, usually does so only during the first 3 months and is minimal. Rarely with low doses. Headaches. Cramps. Risk for blood clots.
	Cenestin	Synthetic conjugated estrogen, which is a mixture of estrogens derived from compounds found in yams and soy
	Estratab, Menest	Plant-derived estrogens, called esterified estrogens. Usually made from modified soy
	Estrace (oral)	Estradiol, the most potent natural estrogen
	Ogen, Ortho-Est	Estropipate, a version of estrone, which is a weaker form of estrogen
	Estrovis	Quinetrol, a synthetic estrogen
	Estinyl	Synthetic form estradiol, the most potent estrogen

Oral Progestins	Provera, Amen, Curretab, Cycrin	Medroxyprogesterone, a synthetic progestin	Breast tenderness. Usually subsides in 3 - 4 months and can be relieved with over-the-counter painkillers and possibly by decreasing caffeine intake and adding vitamin E. Headache. Fluid build-up. Bloating. Fatigue, unusual tiredness, weakness. Depression, irritability, or other mood changes.
	Norlutin, Aygestin, Norlutate	Norethindrone and norethindrone acetate, synthetic progestins
		Norgestrel

Oral Combinations of Estrogen and Progestin	Prempro, Premphase	Conjugated estrogens plus medroxyprogesterone	May have some of the side effects of both estrogen and progestin. Continuous regimens eliminate menstrual bleeding in more than half of women. Investigators are studying the use of higher progestin doses or a lower estrogen doses and comparing combinations for further reduction of bleeding risk.
	Activelle, Femhrt	Estradiol and norethindrone or norethindrone acetate
	Ortho-Prefest	Estradiol and norgestimate
	Angeliq	Estradiol and drospirenone

Skin Patch Administration of HRT	Estraderm, Alora, Climara, Vivelle, FemPatch, Evorel	Estradiol	Skin irritation where the patch is applied most common. Hormonal side effects associated with formulation of patch.
Skin Patch Administration of HRT	CombiPath	Estradiol plus norethindrone (a progestin)

Vaginal Creams for dryness and irritation	Estrace (cream)	Estradiol (potent estrogen)	Hormonal side effects associated with estrogen or progestins, depending on formulation.
	Ogen (cream)	Estropipate (weaker estrogen.)
	Premarin (cream)	Conjugated natural estrogens
	Ortho-dienestrol (cream)	Dienestrol (synthetic estrogen)
	Crinone (cream)	A natural progesterone
Other forms of vaginal administration	Vagifem (vaginal tablet)
	Estring (vagina Ring)	Estradiol
	Other forms: injections, nasal sprays, and as pellets inserted under the skin twice a year.
Topical Gel	EstroGel	Estradiol	Hormonal side effects associated with estrogen.

Resources

www.menopause.org -- North American Menopause Society
www.acog.com -- American College of Obstetricians and Gynecologists
www.nia.nih.gov -- National Institute on Aging
www.nhlbi.nih.gov/whi/recommend.htm -- Women's Health Initiative Study
www.nih.gov/PHTindex.htm -- National Institutes of Health -- Menopausal Hormone Therapy Information
http://nccam.nih.gov/health/menopauseandcam -- National Center for Complementary and Alternative Medicine

References

Beral V; Million Women Study Collaborators; Bull D, Green J, Reeves G. Ovarian cancer and hormone replacement therapy in the Million Women Study. Lancet. 2007 May 19;369(9574):1703-10.

Caan B, Neuhouser M, Aragaki A, Lewis CB, Jackson R, Leboff MS, et al. Calcium plus vitamin d supplementation and the risk of postmenopausal weight gain. Arch Intern Med. 2007 May 14;167(9):893-902.

Church TS, Earnest CP, Skinner JS, Blair SN. Effects of different doses of physical activity on cardiorespiratory fitness among sedentary, overweight or obese postmenopausal women with elevated blood pressure: a randomized controlled trial. JAMA. 2007 May 16;297(19):2081-91.

Haimov-Kochman R, Barak-Glantz E, Arbel R, Leefsma M, Brzezinski A, Milwidsky A, et al. Gradual discontinuation of hormone therapy does not prevent the reappearance of climacteric symptoms: a randomized prospective study. Menopause. 2006 May-Jun;13(3):370-6.

Jackson RD, LaCroix AZ, Gass M, Wallace RB, Robbins J, Lewis CE, et al. Calcium plus vitamin D supplementation and the risk of fractures. N Engl J Med. 2006 Feb 16;354(7):669-83.

Kalay AE, Demir B, Haberal A, Kalay M, Kandemir O. Efficacy of citalopram on climacteric symptoms. Menopause. 2007 Mar-Apr;14(2):223-9.

Manson JE, Allison MA, Rossouw JE, Carr JJ, Langer RD, Hsia J, et al. Estrogen therapy and coronary-artery calcification. N Engl J Med. 2007 Jun 21;356(25):2591-602.

Mosca L, Banka CL, Benjamin EJ, Berra K, Bushnell C, Dolor RJ, et al. Evidence-based guidelines for cardiovascular disease prevention in women: 2007 update. Circulation. 2007 Mar 20;115(11):1481-501.

Nedrow A, Miller J, Walker M, Nygren P, Huffman LH, Nelson HD. Complementary and alternative therapies for the management of menopause-related symptoms: a systematic evidence review. Arch Intern Med. 2006 Jul 24;166(14):1453-65.

Newton KM, Reed SD, LaCroix AZ, Grothaus LC, Ehrlich K, Guiltinan J. Treatment of vasomotor symptoms of menopause with black cohosh, multibotanicals, soy, hormone therapy, or placebo: a randomized trial. Ann Intern Med. 2006 Dec 19;145(12):869-79.

North American Menopause Society. Estrogen and progestogen use in peri- and postmenopausal women: March 2007 position statement of The North American Menopause Society. Menopause. 2007 Mar-Apr;14(2):168-82.

North American Menopause Society. The role of local vaginal estrogen for treatment of vaginal atrophy in postmenopausal women: 2007 position statement of The North American Menopause Society. Menopause. 2007 May-Jun;14(3 Pt 1):355-69.

Ohayon MM. Severe hot flashes are associated with chronic insomnia. Arch Intern Med. 2006 Jun 26;166(12):1262-8.

Ravdin PM, Cronin KA, Howlader N, Berg CD, Chlebowski RT, Feuer EJ, et al. The decrease in breast-cancer incidence in 2003 in the United States. N Engl J Med. 2007 Apr 19;356(16):1670-4.

Rossouw JE, Prentice RL, Manson JE, Wu L, Barad D, Barnabei VM, et al. Postmenopausal hormone therapy and risk of cardiovascular disease by age and years since menopause. JAMA. 2007 Apr 4;297(13):1465-77.

Steiner AZ, Xiang M, Mack WJ, Shoupe D, Felix JC, Lobo RA, et al. Unopposed estradiol therapy in postmenopausal women: results from two randomized trials. Obstet Gynecol. 2007 Mar;109(3):581-7.

Tamimi RM, Hankinson SE, Chen WY, Rosner B, Colditz GA. Combined estrogen and testosterone use and risk of breast cancer in postmenopausal women. Arch Intern Med. 2006 Jul 24;166(14):1483-9.

Review Date:
6/25/2007
Reviewed By:
Harvey Simon, MD, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital.

A.D.A.M. Copyright

adam.com

Headaches - tension

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

In This Report

Highlights
Introduction
Prognosis
Causes
Risk Factors
Diagnosis
Managing Tension-Type Heada...
Medications
Treatment
Lifestyle Changes
Resources
References

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

Global Prevalence of Tension-Type Headache

Tension-type headaches account for nearly half of all headaches, according to a 2007 study in Cephalagia. The researchers estimated that more people are disabled by tension-type headache than by migraine.

Causes of Tension-Type Headaches

Doctors are not really sure why tension-type headaches occur. Possible causes include muscle contractions or changes in brain chemicals. Several studies in 2006 and 2007 presented the theory that tension-type headaches may be due to myofascial trigger points in the shoulders and neck, as well as poor head posture. Some researchers suggest that tension-type headaches may be related to fibromyalgia, a condition that is also characterized by myofascial pain.

Tension-type headaches may be triggered by:

Chronic poor posture
Overwork and stress
Lack of sleep
Dental problems, including temporomandibular joint disorder (TMJ)
Certain types of foods
Skipping meals
Medication overuse
Hormonal changes related to menstruation

Managing Tension-Type Headaches

Acetaminophen (Tylenol) or non-steroidal anti-inflammatory drugs (NSAIDs) such as aspirin, ibuprofen (Motrin, Advil), naproxen (Aleve), or ketoprofen (Actron, Orudis KT) can usually provide pain relief for tension-type headache attacks. Patients who have chronic headaches sometimes take amitriptyline (Elavil), a prescription tricyclic antidepressant, to help prevent attacks. Exercise, stress reduction, and relaxation techniques are very important lifestyle approaches for controlling tension-type headaches.

Introduction

Most people are familiar with headaches, the all too common affliction marked by throbbing, piercing, or vise-like pain around much or a part of the head. There are many different kinds of headaches, and they range from being an infrequent annoyance to a persistent, severe, and disabling medical condition.

The brain itself is insensitive to pain, so that is not what hurts when a headache arises. The pain, instead, occurs in the following locations:

The tissues covering the brain
The attaching structures at the base of the brain
Muscles and blood vessels around the scalp, face, and neck

Doctors categorize headaches as either primary or secondary, which helps to distinguish the many different kinds of headaches and to determine appropriate treatments for each.

Primary Headaches. A headache is considered primary when a disease or other medical condition does not cause it. Most primary headaches fall into three main types: Tension-type, migraine, and cluster headaches.

Tension headache is the most common primary headache and accounts for 90% of all headaches.
Neurovascular headaches are the second most frequently occurring primary headaches and include migraines (the more common) and cluster headaches. Such headaches are caused by an interaction between blood vessel and nerve abnormalities. [See In-Depth Report #97: Migraine headaches and In-DepthReport #99: Cluster headaches.]

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.

Symptoms of migraine and tension-type headaches often overlap, and a diagnosis is sometimes difficult.

Secondary Headaches. Secondary headaches are caused by other medical conditions, such as sinus infections, neck injuries, and strokes. About 2% of headaches are secondary to abnormalities or infections in the nasal or sinus passages, and they are commonly referred to as sinus headaches.

Chronic Daily Headaches. The International Headache Society's classification system includes a category called chronic daily headaches. They may originate as tension headaches, migraines, or a combination of these or other headache types. Chronic daily headaches affect 4 - 5% of the population.

Click the icon to see an image of the different types of headache.

Chronic daily headaches are defined as any benign headache that occurs at least 15 days a month and is not associated with a serious neurologic abnormality. Most people with these headaches have them daily, or almost daily, and they can be quite debilitating.

Chronic daily headaches are, in turn, subdivided into two categories:

Short-duration headaches last fewer than 4 hours. The most common short-acting chronic headaches are cluster headaches.
Long-duration headaches last more than 4 hours. Tension-type headaches are the most common type of long-duration chronic (recurring) headaches and, in fact, the most common type of chronic headaches in general.

General Description. Tension-type headaches, also called muscle contraction headaches or simply tension headaches, are the most common of all headaches. Tension-type headaches can last minutes to days and have the following characteristics:

The pain is commonly described as a tight feeling, as if the head were in a vise. It usually occurs on both sides of the head and is often experienced in the forehead, in the back of the head and neck, or in both regions. Soreness in the shoulders or neck is common.
Depression, anxiety, and sleeping problems may accompany persistent headaches.
Sufferers of tension-type headaches may also have migraine-like symptoms, including being sensitive to light or noise (but not both). Some patients also may suffer from visual disturbances. (Such symptoms in tension headaches, however, tend to be less severe than in migraine. Tension headaches also do not cause nausea or limit activities to the degree that migraines do.)

Types of Tension Headache. In 2004, the International Headache Society updated its original 1988 classification criteria. Tension-type headaches are now divided into the following four classifications:

Frequent episodic tension-type headache. Headaches occur at least once but not more than 15 days per month for at least 3 months (a minimum of 12 days but not more than 180 days per year). Headaches last from at least 30 minutes to 7 days.
Infrequent episodic tension-type headache. At least 10 episodes of headache that occur less than 1 day per month (12 days per year). Because these headaches occur infrequently, they do not impact a patient's quality of life as severely as frequent episodic headaches and may not require attention from a medical professional.
Chronic tension-type headache. Headaches occur at least 15 days per month for at least 3 months (180 days per year). The headache persists for hours at a time and may be continuous.
Probable tension-type headache. Probable tension headaches may be classified as probable frequent episodic, probable infrequent episodic, or probable chronic. They have most, but not all, of the symptoms of tension-type headaches and are not attributed to migraine without aura or other neurological disorders. Probable chronic tension-type headache may be related to medication overuse.

Migraine Headache: General Description of Its Course. Migraine is now recognized as a chronic illness, not simply as a headache. These headaches are often classified by whether or not auras 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 symptom 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 between 20 - 25% of 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 four to 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.

Cluster Headache. Cluster headaches are very painful events. Patients typically awaken a few hours after they go to sleep with the following symptoms:

Very severe, stabbing pain centered in one eye.
Excessive tearing, a drooping eyelid, and one stuffy or runny nostril, all on the same side as the pain.
Feelings of intense restlessness are common. People in the throes of a cluster headache may pace the floor or may even bang their heads against the wall in an attempt to cope with the pain.
Cluster headaches often have a cycle with the following pattern:
Attacks themselves are usually brief, lasting 30 - 90 minutes, although they can persist for up to 3 hours.
During an active period, sufferers can experience as few as one attack every other day to one or more daily. In a rare form of cluster headache, known as chronic paroxysmal hemicrania, as many as six attacks per day can occur.
An active period of recurrent cluster attacks typically extends over 4 - 12 weeks.
Headache-free periods last several months to even years.

Hemicrania Continua. Hemicrania continua is a rare form of chronic headache. Such headaches occur on one side of the face, mostly in women. The patient generally experiences continuous low-level headache with periodic attacks that can last days to weeks. (About 10% of patients experience remissions.) The actual attacks can be mild to severe, and may resemble migraines. The headaches can usually be treated successfully with NSAIDs such as indomethacin (Indocin). Migraine medications are typically not as helpful.

Prognosis

Both episodic tension-type headache and chronic daily headache affect quality of life. Tension-type headache episodes are rarely disabling, however, and rarely require emergency treatment. If they do, usually there is a migraine component occurring with the tension-type headache.

Nevertheless, although they are not medically dangerous, chronic tension headaches have a negative impact on quality of life, families, and work productivity. Several studies have reported lower quality of life with any chronic daily headache compared to those with no headaches or who have only episodic ones. In one study, people with tension-type headaches tended to have higher anxiety and lower quality of life during a headache attack than people with migraines (who, however, were less able to cope during a migraine attack).

In one study, two-thirds of patients with chronic tension-type headaches reported daily or near daily headaches for an average of 7 years. Only 12% reported headaches occurring less than 20 days a month. In the study, 74% of the patients had to take some time off from work because of the headaches, and about a third reported impaired sleep, less energy, and reduced emotional well-being on 10 or more days a month. Most were able to carry out their daily responsibilities even when in pain, although at lower than normal capacity. This and other studies report a strong association between anxiety and depression and chronic tension-type headaches.

Causes

There does not appear to be a single cause of chronic tension-type headache. Many factors are likely involved.

One of the most popular theories on the cause of tension-type headaches involves muscle contraction in the head, neck, and shoulders. There are several ideas about how muscle tension may produce these headaches.

The most common cause of tension-type headaches is muscle contraction in the head, neck or shoulders.

Studies have suggested that tension-type headache sufferers may have higher-than-average muscle tenderness in the face and head that make them more susceptible to headache after muscle contractions. A few studies suggest that some patients with chronic headaches may be overly sensitive to pain in general or may overestimate muscle contraction pain.

One theory suggests that sustained tension or stress that produces muscle contractions in the tender areas around the skull constrict blood vessels. Blood flow is reduced so oxygen is blocked and waste matter builds up, resulting in pain.

Still, pain can last long after the muscles have relaxed, and clear evidence is lacking on how or even if muscle contractions are a major cause of tension headache.

Researchers are increasingly finding evidence to support factors that are common to both migraine and tension-type headache. 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 oversensitive 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, which 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 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.

Genetic factors appear to play a role in predisposing people to recurrent tension headaches. One study of twins suggested that the chances of inheriting the susceptibility to recurring headaches (both migraine and tension) were about 70% in close relatives. The trait is equal in both boys and girls. Because such headaches tend to occur more in females, however, hormonal, social, psychological, or other factors must play a role in their development.

Tension-type headache has been highly associated with an intense response to stress. Some studies suggest that patients with chronic tension-type headaches have more general feelings of anxiety or depression and are less able to express their emotions. One study indicated that patients with tension headaches tend to perceive everyday events as more stressful than those without headaches. Some research even suggests that tension-type headache victims may have some biological predisposition for translating stress into muscle contraction. Still, the link between stress and tension-type headaches is not fully understood, and some evidence challenges any causal association.

Whiplash, concussions, and other head and neck injuries, even mild ones, may result in persistent tension-type or migraine headaches in both adults and children. Such headaches should be treated as if they were the primary types. The risk for tension headaches may persist for years after the injury.

Myofascial pain involves the fascia (connective tissue) and muscles. Some researchers think that tension-type headaches may be linked to myofascial trigger points in the neck and shoulder muscles. Trigger points are knots in the muscle tissue that can cause tightness, weakness, and intense pain in various areas of the body. (For example, a trigger point in the shoulder may result in headache.) Because fibromyalgia is also characterized by myofascial pain, researchers are exploring whether there may be an association between this condition and tension-type headache. [See In-Depth Report #76: Fibromyalgia.]

Medication Overuse (Rebound) Headache. About a third of persistent headaches -- whether chronic migraine or tension-type -- are medication-overuse headaches. These are the result of a rebound effect caused by the regular overuse of headache medications. Nearly any headache medication can produce this effect. In one study of headache sufferers, medication-overuse headaches developed after an average of 1.7 years of regular use of triptans (18 doses a month), after 2.7 years of ergot use (37 doses as month), and after 4.8 years using painkillers (114 doses a month). Regular use of painkillers for any chronic problem (such as arthritis) poses a 2% risk for medication-overuse headache, with risk being highest in people who already have primary headaches, especially migraines.

Chronic Migraines. In some cases, migraines naturally evolve into chronic, daily headaches referred to as transformed migraines.

About 90% of people seeking help for headaches have a primary headache. The rest are secondary headaches, caused by an underlying disorder that produces headache as a symptom. More than 300 conditions can cause headaches. Some of the most common are listed below.

Sinus Headaches. Many primary headaches, including migraines, are misdiagnosed as sinus headaches. Sinus headaches can 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 it is often difficult to tell them apart, particularly if headache is the only symptom of sinusitis. They 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. (In rare cases, sinusitis can cause double vision and even vision loss, a sign of very serious infection.)

Headaches that Originate in the Neck. Some headaches may be caused by abnormalities of the neck muscles (called cervicogenic headaches). Nerves in the neck converge in the trigeminal nerve, which is the largest nerve in the skull. It originates in the brain stem and supplies sensation to the face. This nerve can generate pain signals to the facial area 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 difficult to distinguish from an aching tension headache or a mild migraine without aura. Cervicogenic headaches can result 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).

Temporomandibular Joint Disorder. Muscle contractions that cause headaches may be a result of temporomandibular joint dysfunction (TMJ, also known as TMD), which 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. This condition often coexists with chronic tension headache.

Click the icon to see an image of temporomandibular joint dysfunction.

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 brain tumor is common among people with headaches, but 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 migraines or sinus headaches.

Hypertension. Although many people attribute headaches to high blood pressure, evidence suggests that hypertension does not cause headaches. 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.

Epilepsy. Severe headaches that can last 12 hours or longer are very common in epilepsy. Migraine is particularly associated with epilepsy.

Head Injuries. It is obvious that a significant blow to the head will cause pain. In most cases, the pain is similar to tension-type headache and is treated in the same way as the primary headache. Post-injury headaches, however, can reflect serious damage, ranging from skull fractures to internal bleeding, and monitoring is important.

Disorders of the Meninges. The meninges are the membranes covering the brain and the spinal cord. 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, which 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.

Risk Factors

Tension-type headaches are the most common headaches, accounting for nearly half of all headaches. According to one study, nearly 40% of Americans have at least one episode of tension headache during the course of a year. Some reports estimate that over 85% of women and about 63% of men will have a tension-type headache at some point during a year. Nearly everyone has at least one tension-type headache during their lifetime.

Surveys indicate that about 3 - 5% of the general population has chronic tension-type headache, with the prevalence being higher in women.

About 40% of people with tension-type headaches first have them before they are age 20, and another 40% first experience them between ages 20 - 40. Most of the remaining headache sufferers first have tension-type headaches in the decade between ages 40 - 50. Chronic tension-type headache tends to occur in older adults.

Headaches in Children. Headaches are rare before age 4 but increase in prevalence throughout childhood, reaching a peak around age 13. In one large study, about 7% of seven year olds and 15% of 11 year olds had headaches. Ten percent of these childhood headaches were recurrent. In many of these patients, chronic headaches persist into adulthood. In addition, as adults these patients have a tendency to develop multiple physical or psychiatric complaints, such as back pain, muscle aches, digestive complaints, and depression.

Studies have found that only a minority of chronic childhood headaches are due to physical conditions, such as head injuries or medical problems. In one study, over 62% of children with tension-type headache episodes suffered some form of emotional disorder. In the study, every child reported the presence of a stress factor.

Psychological factors associated with childhood tension-type headaches include:

Sleep problems. According to one study, more than two-thirds of children who experience chronic daily headaches suffer from sleep disturbances, especially difficulty falling asleep.
Moderate or severe depression.
Emotional rigidity in a child and more repressed anger than their peers.
Family stress. This includes maternal illness or separation, family bereavement, relationship problems, mental illness in a family member, and other stressful family events.
Problems at school. According to a National Headache Foundation survey, nearly 30% of children miss school because of headaches. For many children, the start of the school season can be a particularly stressful time.

The National Headache Foundation recommends these tips for parents:

Keep a diary of child’s headaches noting time of onset, length and intensity of attack, location of pain, and food triggers.
Make sure child gets plenty of sleep at regular times.
Avoid changes in child’s eating routing (hunger and eating at irregular times can trigger headaches).
Discuss any headache concerns with child’s doctor.

The following conditions can make people susceptible to tension-type headaches.

Chronic poor posture
Chronic overwork
Upper respiratory tract infections, such as colds and flu
Sleep disorders. Sleep problems, such as insomnia, sleep apnea, or habitual snoring, are common in all primary headaches. Headache can disturb sleep, but sleep disorders may also contribute directly to tension headache, particularly those that occur at night or early morning. (In one study, treating people who had chronic headaches for sleep apnea cured the headaches in many cases.)
Obesity
Hypothyroidism (decreased thyroid function)
Dental problems
Allergies
Substance or alcohol abuse
Temporomandibular joint dysfunction (TMJ, also called TMD). This is a condition in which there are abnormalities in the jaw joints. TMJ itself can cause headache, and it also often coexists with chronic tension headache.

Certain triggers, including the following, may cause headache episodes in people with chronic tension-type headaches:

Specific stressful events
Not eating on time
Fatigue or lack of sleep
Crying. In one study, only stress, anxiety, and menstruation were more important headache triggers in women.
Withdrawal from over-used substances (caffeine, nicotine, alcohol, pain relievers)
Eyestrain
Intense physical exertion, including sexual activity. Athletes are at higher risk for headaches. Patients with tension-type headaches should not avoid exercise, however. Ordinary levels of physical activity do not usually precipitate these headaches. Furthermore, a sedentary lifestyle may increase the risks for stress and obesity and thereby for tension headaches in susceptible people.
Certain foods, such as chocolate, cheese, and the flavor enhancer monosodium glutamate (MSG), are commonly cited as triggers for tension headaches as they are for migraines.
Medications (overuse of headache medications, nitrates, certain anti-depressants, some drugs used to treat high blood pressure, and many others.)
Hormonal changes, such as specific menstrual phases, in women.

Weather conditions, certain smells, smoke, and light, which can set off migraines, are not common triggers for tension-type headaches.

The rapid consumption of ice cream or other very cold foods or beverages is a well-known trigger of sudden headache pain -- the so-called "ice cream" headache. It can be easily prevented by warming the food or drink for a few seconds in the front of the mouth before swallowing. Drinking a glass of room-temperature water quickly relieves the pain.

Diagnosis

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.

According to the International Headache Society, a diagnosis of tension-type headache is suggested by the following symptoms:

Pressing or tightening (but non-pulsating) feeling
Mild-to-moderate pain on both sides of the head
Not aggravated by routine physical activity (walking, etc.)

In episodic tension-type headaches:

No nausea or vomiting
Photophobia (intolerance of light) or phonophobia (intolerance of sound) may be absent or one of these symptoms (but not both) may be present

In chronic tension-type headaches:

No vomiting
No moderate or severe nausea
No more than one of the following symptoms: Mild nausea, photophobia, or phonophobia
Some types of chronic tension headache may include tenderness upon manual palpitation of the head (pericranial tenderness).

Differentiating Medication-Overuse (Rebound) Headache from Tension-Type Headache. About a third of persistent headaches are the result of the rebound effect caused by the overuse of headache medications (formerly called rebound headaches).

Usually in such cases, medications have been taken on an ongoing basis for more than 3 days each week. If patients stop taking these drugs, the headaches come back. The patient then starts taking the drugs again. Eventually the headache simply persists and medications are no longer effective. Even after successful medication withdrawal, relapse is common, particularly with drugs that contain caffeine, so doctors should check for this type of headache even in patients who have previously been treated.

Medications implicated in medication-overuse headache include barbiturates, sedatives, narcotics, and migraine medications, particularly those that also contain caffeine. (Heavy caffeine use can also cause this condition.) Simple painkillers, such as aspirin or ibuprofen, are less likely causes of medication-overuse headaches.

Differentiating Tension Headaches from Chronic Migraines. It is often difficult to differentiate between chronic migraine and chronic tension-type headaches. The McGill Pain Questionnaire may be useful for ruling out migraine. According to a 2003 study, patients with migraine who answer the questionnaire report significantly more severe specific symptoms (throbbing, stabbing, gnawing, hot, sickening, exhausting) than those with tension-type headaches. There is very little difference between these headaches, however, in scores of overall severity of the pain.

For an accurate diagnosis, the patient should describe the following:

Duration and frequency of headaches
Recent changes in their character
Location of the pain
Type of pain (throbbing or steady pressure)
Intensity of the headache
Associated symptoms, such as visual disturbances or nausea and vomiting. (These are seen most often with migraines.)
Behaviors during a headache. Different behaviors may help distinguish between migraine and tension headaches. People with tension headaches tend to relieve pain by massaging the scalp, temples, or the nape of the neck. People with migraines are more likely to compress the forehead and temples (tying a scarf around the head) or to apply cold to the area. 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 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. Be sure to include all events preceding an attack. Often two or more triggers interact to produce a headache.

Researchers are investigating triggers of headaches to determine if certain ones are more likely to set off different primary headaches. In general, however, the same stimuli seem to trigger any of the primary headaches, although people with migraines may be more sensitive to some of them (weather, certain smells, light, and smoke) than people with tension headaches.

Tracking medications is an important way of identifying medication-overuse headache or transformed migraine.

Be sure to attempt to define the intensity of the headache. There are different scoring symptoms available that help communicate the severity of the pain to the doctor. For instance, the following is a number system that can be helpful:

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 the following:

Any chronic or recent illness and their treatments
Any injuries, particularly head or back injuries
An uncharacteristic dietary changes
Any current medications or recent withdrawal 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 the patient's general medical and family history, particularly concerning headaches or other diseases such as epilepsy. Migraine, in particular, 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 will also examine the eyes to rule out pressure build-up in the eye as a cause of headache. The doctor may ask questions to test short-term memory and related aspects of mental function.

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 headache that wakes 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 headache.

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 other conditions, particularly chronic sinusitis, which, in one study, occurred in 20% of patients with chronic headache. Other findings include aneurysms, benign or cancerous growths, and other abnormalities in the brain.
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 tests include an MRI (magnetic resonance imaging), EEG (electroencephalogram), lumbar puncture, ultrasound testing, and cerebral angiography, which are only performed if there is reason to suspect an underlying disease.

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 believing it to be one of their usual headaches. Such patients should immediately call a doctor 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).

Managing Tension-Type Headaches

Given the very high prevalence of tension-type headaches, some experts express frustration over the lack of serious scientific attention given to this problem. Unfortunately, few tension headache sufferers seek medical help for their problem, and 60% of those with severe headaches use only over-the-counter medications. Many patients fear that they will not be taken seriously by their doctor or believe the widespread misperceptions that their problem is due solely to stress. With medications, relaxation training, lifestyle changes, and other therapies, over 90% of patients can be helped.

Fortunately, most acute tension-type headaches get better without any treatment, and simple over-the-counter pain relievers such as acetaminophen or non-steroidal anti-inflammatory drugs (NSAIDs) can treat mild symptoms.

The most common pain relievers are:

Acetaminophen (Tylenol, Anacin-3, Panadal, Phenaphen, Valadol)
Over-the-counter NSAIDs include aspirin, ibuprofen (Motrin IB, Advil, Nuprin, Rufen), naproxen (Aleve), ketoprofen (Actron, Orudis KT)
Prescription NSAIDs include ibuprofen (Motrin), naproxen (Naprosyn, Anaprox), diclofenac (Voltaren), tolmetin (Tolectin), ketoprofen (Orudis, Oruvail)

Acetaminophen may be effective for moderate-to-severe headaches only at high doses (1,000 mg), while NSAIDs can be effective at lower doses. One study indicated that ibuprofen and naproxen were more effective than aspirin or acetaminophen.

There are few proven therapies for treating or preventing chronic tension-type headaches, and studies are weak. To date, the major treatments used for chronic tension-type headache are a group of antidepressants called tricyclics, and cognitive-behavior therapy. Used alone either of these approaches achieves modest benefits, at best. A combination, however, may be very helpful in some cases.

Some research suggests the following steps in treating this condition:

Because many chronic daily headaches are due to over-use of headache medications, withdrawal from such drugs is the first action. (NSAIDs or other painkillers should not be used to prevent chronic tension-type headaches.)
Cognitive behavioral therapies, including relaxation and stress-reduction techniques, should be used next for managing headaches. They should be the first option for children and adolescents with chronic headaches.
If medication withdrawal and psychological methods fail to bring improvement, tricyclic antidepressants are tried next in combination with cognitive therapy.
Physical therapy, massage therapy, or acupuncture may help some people.

If headaches develop because of medication overuse, the patients cannot recover without stopping the drugs. (If caffeine is the culprit, a person may only need to reduce coffee or tea drinking to a reasonable level, not necessarily stop drinking it altogether.) The patient usually has the option of stopping abruptly or gradually and should expect the following course:

Most headache drugs can be stopped abruptly, but the patient should be sure to check with the doctor before withdrawal. 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 or shorter. Otherwise the patient may become discouraged.
No matter which approach is used for stopping medication, the patient must expect a period of worsening headache for a few days afterward. Alternative pain relievers may be administered during the first days to help withdrawal.
Most people feel better within 2 weeks, although headache symptoms can persist up to 16 weeks (and in rare cases even longer).

Studies suggest that nearly half of patients with medication-overuse headaches relapse. According to one study, the relapse rate may be much higher for tension headaches (73%) than for migraine headaches (22%). More research is needed to determine the optimal methods for drug withdrawal. On the encouraging side, some patients experience dramatic long-term relief from all headaches afterward.

Medications

The standard treatments for tension-type headaches are non-steroidal anti-inflammatory drugs (NSAIDs) such as aspirin and ibuprofen, and tricyclic antidepressants, usually amitriptyline (Elavil, Endep).

Several pain relievers are helpful for mild-to-moderate headaches. They should not be used to prevent headaches, however.

Nonsteroidal Anti-Inflammatory Drugs (NSAIDs). NSAIDs are common pain relievers that block prostaglandins, substances that dilate blood vessels and cause inflammation and pain. NSAIDs are usually the first drugs tried for almost any kind of headache. There are dozens of NSAIDs. Aspirin is the most common, but it is not as effective for acute tension-type headache as other NSAIDs. Common NSAIDs include:

Over-the-counter NSAIDs. Aspirin, ibuprofen (Motrin), naproxen (Aleve), ketoprofen (Actron, Orudis KT)
Prescription NSAIDs. Diclofenac (Voltaren, Cataflam, Solaraze), tolmetin (Tolectin), indomethacin (Indocin)

Patients should be aware that long-term use of high-dose NSAIDs may increase the risk for stomach bleeding and heart problems, including heart attack and stroke.

Acetaminophen. Acetaminophen (Tylenol) is a good alternative to NSAIDs when stomach distress, ulcers, or allergic reactions prohibit their use. A high dose (1,000 mg), however, is needed for this drug to be effective for headaches. Midrin (a combination of a drug that narrows blood vessels, a mild sedative, and acetaminophen) may be very helpful for tension-type headaches.

Acetaminophen does have some adverse effects, however, and the daily dose should not exceed 4 grams (4,000 mg). Patients who take high doses of this drug for long periods are at risk for liver damage, particularly if they drink alcohol and do not eat regularly. Acetaminophen may cause serious kidney problems in people who already have kidney disease. It also may interact with certain medications, including the blood thinner warfarin.

Antidepressants known as tricyclics are most often used for prevention of severe chronic tension-type headaches. Newer selective serotonin-reuptake inhibitors (SSRIs) antidepressants are also sometimes used in milder cases.

Tricyclic Antidepressants. Tricyclics are not only useful for depression but also appear to help relieve muscle pain and improve sleep. They are sometimes classified in one of two categories: tertiary or secondary amines:

Tertiary amines include amitriptyline (Elavil) and imipramine (Tofranil). Amitriptyline is the tricyclic most commonly used for tension-type headache. These drugs tend to cause more drowsiness than secondary amines, which may be helpful for patients with sleep problems.)
Secondary amines include desipramine (Norpramin) and nortriptyline (Pamelor, Aventyl). Secondary amines may have fewer side effects than tertiary amines, but they are just as toxic in high amounts.

Less commonly used tricyclics include doxepin (Sinequan), amoxapine (Asendin), maprotiline (Ludiomill), protriptyline (Vivactil), trimipramine (Surmontil), mianserin (Bolvidon), and dothiepin (Prothiaden).

Unfortunately, these drugs can lose effectiveness over time. Side effects are also fairly common with these medications. Drowsiness is the most common, but may vary by specific drug. In addition, side effects most often reported include dry mouth, constipation, blurred vision, sexual dysfunction, weight gain, trouble urinating, heart rhythm problems, and dizziness. Blood pressure may also drop suddenly when sitting up or standing.

Tricyclics can have serious, although rare, side effects, including heart rhythm problems, which can be dangerous for some patients with certain heart diseases. These drugs can be fatal with overdose.

Selective Serotonin-Reuptake Inhibitors. Selective serotonin-reuptake inhibitors (SSRIs) work by increasing levels of serotonin in the brain. SSRIs include fluoxetine (Prozac), sertraline (Zoloft), paroxetine (Paxil), fluvoxamine (Luvox), and citalopram (Celexa). Because they act on serotonin specifically, they have fewer side effects than the older antidepressants, such as monoamine oxidase inhibitors (MAOIs), which affect a number of chemicals in the body. SSRIs take 2 - 4 weeks to be effective in most adults and sometimes longer, up to 12 weeks, so their value for treating headaches is limited.

Side effects may include nausea, stomach problems, agitation, insomnia, mild tremor, impulsivity, temporary weight gain or loss, and sexual dysfunction. Death from overdose is extremely rare. Serious interactions can occur with other antidepressants, such as tricyclics and MAOIs.

Designer Antidepressants. Several drugs target other neurotransmitters, such as norepinephrine, alone or in addition to serotonin, and are showing promise for prevention of tension-type headache. The following are some examples:

In one study, bupropion (Wellbutrin) was as effective as a tricyclic in preventing tension-type headaches.
Nefazodone (Serzone), a fast-acting designer antidepressant, was particularly beneficial in a study of patients with chronic daily headaches. After 3 months of treatment, symptoms were reduced by half in over 70% of patients. Nearly 60% of them said their symptoms improved over 75%.
Venlafaxine (Effexor), a designer antidepressant that targets both serotonin and the brain chemical norepinephrine, is showing promise for preventing chronic tension-type headaches (as well as migraines). In one study, patients who took the extended-release form of the drug for 6 months went from an average of 24 tension headaches a month to 15.
Mirtazapine (Remeron) is a unique antidepressant known as a 5-HT2 blocker. It may indirectly enhance the affects of both serotonin and norepinephrine. In one study, it was as effective in treating chronic tension-type headache as the tricyclic Elavil. Mirtazapine has significantly fewer side effects than tricyclics, although it may slightly raise cholesterol and triglyceride levels. It may also cause blurred vision and slight weight gain.

Mild anti-anxiety drugs are occasionally used as an adjunct in treating chronic headaches to decrease muscle contraction or to calm anxiety symptoms during periods of extreme stress. They include alprazolam (Xanax) and clonazepam (Klonopin). They tend to be highly addictive, however, and patients should therefore use them only on a short-term basis.

Tramadol. Tramadol (Ultram) is a pain reliever that has been used as an alternative to opioids. It has opioid-like properties but is not as addictive. (Dependence and abuse have been reported, however.) It can cause nausea, but does not cause severe gastrointestinal problems, as NSAIDs can. Some patients experience severe itching. A combination of tramadol and acetaminophen (Ultracet) is now available and provides more rapid pain relief than tramadol alone and more durable relief than acetaminophen alone. Side effects are the same as for each of these drugs.

Opioids. Opioids, such as codeine or hydrocodone, are sometimes prescribed for severe headaches, although their use is controversial because of the risk for addiction. Methadone is showing promise for patients who do not respond to standard treatments. These drugs are narcotics, however, and may be subject to abuse. Patients must be monitored and reevaluated regularly. Overuse of these drugs can reduce their effectiveness and lead to medication-overuse headaches, so it is important for a doctor to supervise this type of medication. Long-term, high-dosage use of some of these drugs can also lead to kidney disease and ulcers. Other, less serious side effects include gastrointestinal upset, dizziness, and ringing in the ears (tinnitus).

Sedatives. Barbiturates, particularly butalbital (Butalan) and its combinations (Fioricet, Axocet), are occasionally prescribed if other medications fail to provide relief. These drugs are sedatives that also contain pain relievers. Because they pose a very high risk for alcohol-like intoxication, dependence and drug-induced headaches during withdrawal, they should be used very sparingly. Some experts believe they should not be used at all for headaches.

Valproate. In some studies, the anticonvulsant medication valproate has been effective for stopping headaches in some patients with persistent migraines and tension-type chronic daily headaches. In one study, 75% of patients with either type of headache experienced at least a 50% reduction in headache frequency and severity. Minor side effects occurred in a third of the patients. Other anti-seizure medications are under investigation.

Botulinum Toxin. Botulinum toxin A (Botox) injections are now widely used to relax muscles and reduce skin wrinkles. They are also being investigated for chronic daily headaches, which include tension-type headache. This potentially deadly toxin is very safe when tiny amounts are injected into small muscles. In a 2003 study of various headache types (including tension-type headache), over 85% of all the patients had fewer headaches per month and the intensity of the pain. Several 2005 studies reported that Botox injections every 3 months might help patients with chronic daily headaches have fewer headaches. However, other studies have reported no benefit. Botox is not approved for headache treatment.

It should be noted that Botox also causes headaches in about 1% of cases. In some cases, the headaches can be very severe and long lasting (from 8 days to a month). Some researchers suggest that either a contaminated batch of Botox or a specific injection technique may be the cause, but additional investigation is needed.

Tizanidine. Tizanidine (Zanaflex) is a muscle relaxant that is emerging as a possible effective preventive drug in chronic tension-type headaches. Called an alpha2-adrenergic agonist, it blocks the release and effectiveness of a stress chemical in the body called norepinephrine and may also help prevent muscle spasms. Studies have reported that nearly 70% of patients with chronic tension-type headaches experienced a reduction in headache symptoms of 50% or more. It also appears to help patients experiencing medication-overuse headache to withdraw from medications. Side effects are usually minor and include fatigue and dry mouth, although patients taking the drug need to be monitored periodically for potential liver damage.

Nitric Oxide Synthase Inhibitors. Nitric oxide synthase inhibitors block nitric oxide, which may play a role in increasing nerve activity that leads to headache. Drugs being investigated include L-NG methyl arginine hydrochloride (L-NMMA) and L-NG-nitro-arginine. Studies suggest they may be very helpful in reducing chronic tension-type pain.

Treatment

In cases where abnormalities or injuries in the cervical spine (the spinal bones in the neck) cause headaches, a cervical epidural nerve block may be beneficial in treating and preventing further pain. This procedure involves injecting small amounts of a corticosteroid and anesthetic into spaces between the vertebrae in the neck to block the nerves. Some patients have reported significant pain relief from this procedure.

Dental Adjustment. Some reports suggest that dental adjustment to help teeth bite down evenly might help some people with temporomandibular joint disorder and chronic headaches. The results indicated that dental adjustments may be helpful. A systematic review in 2003, however, reported no headache relief from this approach.

Nociceptive Trigeminal Inhibition. A dental device called the NTI (nociceptive trigeminal inhibition) tension suppression system has been approved for relief of headaches due to jaw clenching during the night. The small plastic mouthpiece is fitted by a dentist and slips over the two front teeth, preventing teeth clenching at night. Preliminary studies report some benefits for relief of migraines and associated tension-type headaches.

Techniques using acupuncture points on the body have become popular for managing pain. Studies do show some benefits.

Standard Acupuncture. A major 2001 analysis of 26 trials of acupuncture suggested that it may have some benefit for tension headache, but the evidence to date is not completely convincing. Some studies comparing short-term acupuncture to sham (dummy) procedures report no benefits. A 2005 study suggested that acupuncture may help tension-type headache, but needling at non-acupuncture points worked just as well. This suggests a placebo effect may account for the headache relief experienced by acupuncture patients.

Acupuncture, hypnosis and biofeedback are all alternative ways to control pain. Acupuncture involves the insertion of tiny sterile needles, slightly thicker than a human hair, at specific points on the body.

Percutaneous Electrical Nerve Stimulation. A technique called percutaneous electrical nerve stimulation (PENS) uses low-level electrical pulses delivered through acupuncture needles into soft tissue. Patients are barely aware of the sensation. Some studies are showing some benefits, but strong evidence is still lacking to confirm or refute its benefits.

Acupressure. One acupressure practitioner reports that pressing for 60 seconds on the web space between the forefinger and thumb of the dominant hand erases headache in patients with migraine and tension-type headaches. The specific spot pressed should be the most tender point in the web area. The patient should then lie down for about 15 minutes.

Two investigational procedures called automated or electrical twitch obtaining intramuscular stimulation (ATOIMS or ETOIMS) are showing promise. ATOIMS uses an automated mechanical device that vibrates the muscle using a tiny pin. (The sensation is described as similar to a mosquito bite.) ETOIMS uses an extremely mild electrical current. They can also be used together. Both approaches cause the muscles to twitch and relax, and then the process is stopped. Discomfort is minimal. Small studies are reporting some help in relieving a number of conditions that cause chronic pain, including tension headache.

Spinal manipulation by chiropractors or osteopaths may have some benefits for preventing tension-type headaches. Evidence is stronger on benefits of spinal manipulation for patients with headaches originating from nerve or muscular problems in the neck. Some researchers believe that tension-type headaches relieved by spinal manipulation are probably really caused by neck problems.

In a small 2006 study, daily relaxation exercises combined with three sessions of osteopathic treatment helped reduce the frequency -- but not the intensity -- of tension-type headaches. Another 2006 study suggested that physical therapy that incorporates a craniocervical (head and neck) training program may help reduce tension-type headache frequency, intensity, and duration as well as reduce the need for pain medication. In the 6-week program, patients performed 10-minute exercises twice a day. The exercises were designed to retrain muscles in the head, neck, and shoulders. The benefits of these exercises lasted up to 6 months after the program had ended.

Lifestyle Changes

Good health habits -- including adequate sleep, healthy diet, regular exercise, and good stress management -- are important, along with the following specific measures for headache management. Quitting smoking is essential in reducing the risks for all headaches.

An ancient and potentially effective remedy for tension headaches uses pressure applied to the head (such as a headband or a towel wrapped around the head) plus either heat or cold. In one study, 87% of headache sufferers experienced significant relief, and the rest reported moderate relief while they were wearing special headbands that could be tightened. They applied packs that were frozen or heated in a microwave. (Either heat or cold packs were useful, although people with tension headaches generally preferred cold packs.)

A healthy diet rich in fresh fruits and vegetables and whole grains and low in saturated fats (animal fats) is important to everyone. Fish (particularly oily fish, such as salmon and tuna) and soy are protein sources that may be a good alternative to red meats.

Caffeine. In some people with headaches, caffeine appears to be an excellent companion to medications. One study found that the caffeine equivalent of two and a half of cups of coffee can help treat a tension-type headache by itself. Many medications contain combinations of pain or anxiety relievers and caffeine, which boosts pain-relieving potency and counters drowsiness. Taking ibuprofen along with caffeine is even more effective than either substance alone. (It should be noted that in some people with migraines, the tannin found in coffee or tea may be a trigger for the headache. In addition, withdrawal from caffeine is a major cause of headache.)

Headaches that occur during the night and early morning may be related to sleep disorders. One study reported that treating an underlying sleep disorder, such as sleep apnea or insomnia, in patients who also had headaches resulted in headache cure or improvement in all patients except those who suffered from restless legs syndrome.

Several stress-reduction methods are available that may help counteract the tendency for muscle contraction and uneven blood flow associated with some headaches. Such approaches may be especially helpful for children and pregnant women with chronic headaches. (For information on acupuncture and spinal manipulation, see the Treatment section of this report.)

Among the stress reduction techniques that may be helpful are:

Guided imagery. (This uses body awareness and visualization of pleasant or positive images.)
Biofeedback. This technique works when patients develop awareness of their physical responses and learn to feed this information back to the brain for the purpose of replicating that response. It is often used to reduce muscle tension. One interesting and sometimes effective technique for headaches is called thermal biofeedback. It is based on the concept that hand-warming reduces blood flow to the brain and so relieves headache. The patient learns techniques (such as using specific images) that can raise the temperatures of the hand during a headache. Studies suggest the approach has been helpful in children with tension and migraine headaches.
Autogenic training. This approach combines elements of meditation, relaxation, and self-hypnosis. In one study, it reduced headache frequency and use of medications in patients with tension-type and migraine headaches. It was more successful for tension-type headache.
Massage therapy. In one study, massage therapy of the neck and shoulder muscles reduced the frequency of chronic daily tension-type headaches within the first week of treatment. (It did not have any effect on the intensity of headaches, however.)
Reflexology, an alternative massage method that manipulates the feet, was associated with improvement in 81% of patients with tension or migraine headaches. Patients reported an improvement in energy, well-being, and increased ability to understand the cause of the headaches. In the study, 19% went off medication.
Muscle relaxation exercises.
Self-hypnosis.
Breathing exercises. Studies have reported that correct and rhythmic breathing from the diaphragm can sometimes relieve tension-type headaches. Such breathing exercises may be particularly beneficial when performed with physical movements. (Yoga, in fact, is a practice that combines both and has been helpful in people with headaches.)

Any of these therapies may be used in conjunction with drug therapy.

Numerous herbal remedies are promoted for tension-type headache. It is important that anyone taking herbal or so-called natural remedies be aware of the lack of regulations governing their quality and effectiveness.

Essential Oils. Some patients find relief using two drops of peppermint, eucalyptus, or lavender oil added to one cup of water. The patient soaks a cloth in the solution and applies it as a compress to the head.

Herbs. Generally, manufacturers of herbal remedies and dietary supplements do not need approval from the Food and Drug Administration (FDA) 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. Always check with your doctor before using any herbal remedies or dietary supplements.

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

Feverfew is the most studied herbal remedy for headaches. It does appear to help some people. However, like all effective headache remedies, long-term use can cause a rebound effect. Some experts recommend purchasing feverfew in dried leaf form. Feverfew is generally safe, but side effects can be distressing, particularly canker sores in the mouth (5 - 15% of cases) and stomach distress. Pregnant women or women hoping to become pregnant should not take this herb. People with any blood-clotting disorders should not take it.
Valerian has sedative qualities and is listed on the FDA's list of generally safe products. However, its effects can be dangerously increased if it is used with pharmaceutical sedatives. High doses of valerian can cause blurred vision, excitability, vivid dreams, and changes in heart rhythm.
Comfrey is an herbal remedy used to treat several inflammatory problems. Evidence suggests that comfrey is toxic to the liver. Animal studies have reported a possible cancer risk. It is banned in several countries.

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.i-h-s.org -- International Headache Society

References

Anderson RE, Seniscal C. A comparison of selected osteopathic treatment and relaxation for tension-type headaches. Headache. 2006 Sep;46(:1273-80.

Fernandez-de-Las-Penas C, Alonso-Blanco C, Cuadrado ML, Gerwin RD, Pareja JA. Myofascial trigger points and their relationship to headache clinical parameters in chronic tension-type headache. Headache. 2006 Sep;46(:1264-72.

Fernandez-de-Las-Penas C, Cuadrado ML, Pareja JA. Myofascial trigger points, neck mobility, and forward head posture in episodic tension-type headache. Headache. 2007 May;47(5):662-72.

Lenaerts ME, Gill PS. At the crossroads between tension-type headache and fibromyalgia. Curr Pain Headache Rep. 2006 Dec;10(6):463-6.

Stovner Lj, Hagen K, Jensen R, Katsarava Z, Lipton R, Scher A, et al. The global burden of headache: a documentation of headache prevalence and disability worldwide. Cephalalgia. 2007 Mar;27(3):193-210.

van Ettekoven H, Lucas C. Efficacy of physiotherapy including a craniocervical training programme for tension-type headache; a randomized clinical trial. Cephalalgia. 2006 Aug;26(:983-91.

Zissis NP, Harmoussi S, Vlaikidis N, Mitsikostas D, Thomaidis T, Georgiadis G, et al. A randomized, double-blind, placebo-controlled study of venlafaxine XR in out-patients with tension-type headache. Cephalalgia. 2007 Apr;27(4):315-24. Epub 2007 Mar 7.

Review Date:
10/29/2007
Reviewed By:
Harvey Simon, MD, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital.

A.D.A.M. Copyright

adam.com