Doxylamine

When your head hits the pillow but your body refuses to sleep, lying in the dark counting sheep just might induce tossing and turning instead of heavy eyelids.

Often, simple remedies can solve the problem of an occasional restless night. For some people, just a few minutes' reading or television gazing will lull the mind to sleep. Others coax slumber by taking a warm bath or light snack just before bedtime. Over-the-counter (OTC) nighttime sleep-aids, regulated by the Food and Drug Administration, are another option.

According to a 1993 report to Congress by the National Commission on Sleep Disorders Research, "frequent or chronic insomnia, estimated to affect more than 60 million Americans--about one of every three adults--is a severe problem for approximately half of those individuals."

Insomnia lasting just a few days--what the American Sleep Disorders Association (ASDA) calls "transient insomnia"--is a common aftermath of stress or excitement. It's not unusual to lose one or two days' sleep worrying about a spat with a spouse or a report due at work. Good things sometimes keep people awake, too, like an exciting sports event or anticipation of the start of a vacation.

"Short-term insomnia"--lasting two or three weeks--may result from ongoing stress. A job setback, illness, or death of a loved one can upset normal sleep habits for a while. If unresolved, "chronic insomnia"--defined by the ASDA as "poor sleep every night, most nights, or several nights a month"--may ensue.

There are a lot of questions about sleep that scientists can't answer--why it's necessary, what its purpose is, how it's regulated, or what the brain does during sleep. But you don't have to be a scientist to recognize the effects of going without sleep. Anyone who has slept poorly for a few nights running knows that's the reason they are tired and irritable, and have trouble concentrating and staying alert.

Chronic insomnia can have more serious consequences. In a March 24, 1993, commentary in the Journal of the American Medical Association, sleep expert William C. Dement, M.D., Ph.D., notes that drowsiness is blamed for some 200,000 to 400,000 automobile accidents a year, accounting for almost half of all accident-related deaths in the United States.

The commission's report to Congress links sleep deprivation to increased psychosocial problems and illness and death, and to diminished productivity and performance. It names fatigue and drowsiness as contributors to accidents in hospitals, military operations, and the nuclear industry, and to major air, rail, road, and sea transportation disasters. The Challenger space shuttle explosion, the Exxon Valdez grounding, and the collision of two Conrail freight trains resulting in four deaths and $6 million dollars in damages are among several catastrophes cited.

So, while researchers want to learn more about sleep for many reasons, we plain folk who lie awake nights simply want to know how we can get more of it.

Professional or Self-Help?

People with chronic insomnia should see a doctor for treatment, which may include short-term use of prescription sleeping pills. Poor sleep for extended periods may be a symptom of an underlying disorder, such as depression, sleep apnea (repeated interruptions of breathing during sleep), pain from arthritis or other illness, or a neurological disease.

But if all that's needed is a little help to overcome a restless night or two, a do-it-yourself approach is sensible. Experts have come up with many useful tips to help people fall asleep and develop and maintain good sleeping habits (see "Tricks for the Tired").

Used appropriately, OTC and prescription sleep-aids also can help provide sounder sleep, the ASDA advises. The association cautions, however, that for some types of insomnia, such as that caused by breathing disorders, the products may be dangerous.

"Before taking any OTC drug product, you should read the label for directions on how and when to use it, and whether you should check with a doctor before taking it," says FDA regulatory review pharmacist Michael Benson. "Antihistamines are the ingredients in OTC nighttime sleepaids that make you nod off, and some contain other ingredients, like an analgesic for pain," he says.

FDA allows three antihistamines--diphenhydramine hydrochloride (HCl), diphenhydramine citrate, and doxylamine succinate--to be used as the active ingredient in OTC nighttime sleep-aids.

In the early 1970s, FDA began a review of OTC drug products. Manufacturers were requested to submit data on the safety and effectiveness of the active ingredients for their intended uses. Expert panels on various classes of drug products were convened to review the data and make recommendations to the agency.

In 1978, FDA approved a new drug application providing for OTC marketing of doxylamine succinate for nighttime sleepaid use. In 1982, the agency authorized the initial marketing of diphenhydramine HCl and diphenhydramine citrate for this use. These two drugs were the only ones included in the agency's final monograph on OTC nighttime sleep-aids, issued in 1989. After the monograph's publication, products containing active ingredients other than doxylamine succinate, diphenhydramine HCl, or diphenhydramine citrate had to be reformulated or taken off the market.

Read the Label

Consumers can find out what ingredients are in an OTC drug product by reading the label. Unisom contains doxylamine succinate, for example, while Nytol contains diphenhydramine HCl. Some products, such as Sominex Pain Relief Formula and Bufferin AF Nite Time contain an analgesic for pain relief as well as an antihistamine. You may find that one works better for you than another. Because of the different product ingredients, the label warnings and directions for use vary.

Most OTC sleep-aid product labels caution patients with certain conditions to check with a doctor before taking the product. Such conditions include shortness of breath, asthma, emphysema, chronic pulmonary disease, glaucoma, and difficulty urinating due to enlarged prostate gland. The labels also warn against taking the product along with alcohol or other central nervous system depressants, such as sedatives or tranquilizers, because they heighten the depressant effect.

(Recently approved revisions in wording will appear on all labels by April 11, 1995: The words "breathing problems" will be used to describe shortness of breath and difficulty breathing related to obstructive pulmonary disease; "chronic bronchitis" will replace "chronic pulmonary disease"; and the word "asthma" will be removed. These changes will help consumers recognize respiratory distress symptoms more readily.)

Sleep-aids that contain aspirin must carry a warning to consult a doctor about Reye syndrome before giving the product to children and teenagers who have chickenpox or flu symptoms. Reye syndrome is a rare but serious disease that has been associated with use of aspirin in children with these conditions. This warning may also appear on products containing other salicylates. These drugs should not be given to children under 12, and they should not be used for more than two weeks unless under a doctor's direction. Pregnant and nursing women should check with a doctor before taking these products.

OTC nighttime sleep-aids can provide welcome relief from a night of wide-eyed wakefulness. OTC status does not, however, guarantee the product is hazard-free. Just like prescription drugs, OTC drug products must be used with care.

"The bottom line for all OTC drug products," says FDA's Benson, "is to read the label and follow the instructions."

(For more on insomnia, see "Why Aren't You Asleep Yet? A Bedtime Story" in the October 1989 FDA Consumer. Also, write to the American Sleep Disorders Association, 1610 14th St., N. W., Rochester, MN 55901.)

Tricks for the Tired

If you're having trouble sleeping, you may want to try modifying some behaviors that might be keeping you awake. The American Sleep Disorders Association suggests one or more of the following practices might help:

* Get up about the same time every day, regardless of when you go to bed.

* Go to bed only when sleepy.

* Establish relaxing pre-sleep rituals, such as a warm bath, light bedtime snack, reading, or watching television.

* Exercise regularly. Get vigorous exercise--such as jogging or squash--in the late afternoon, and mild exercise--such as simple stretching or walking--two or three hours before bedtime.

* Don't eat or drink caffeine-containing products within six hours of bedtime. It's better not to smoke at all, but if you do, avoid smoking at bedtime. Caffeine and nicotine are both stimulants. Even if they don't interfere with falling asleep, they may trigger awakenings later.

* Don't drink alcoholic beverages at bedtime. A nightcap may induce sleep, but it can interfere with sound sleep through the night.

* Don't nap, unless you find that naps don't interfere with sleep later on.

* If you often worry at bedtime, reserve another time of day for working on problems.

* If you can't sleep, get out of bed and go to another room to read or watch television.

You may want to try sleep restriction. This strategy is based on the finding that many insomniacs spend excessive time in bed, hoping to make up for lost sleep.

Go to bed later than usual, and get up at the same time each morning. Stay in bed only as long as you actually sleep, even if it's only a few hours. When you sleep at least 90 percent of your allotted time in bed for five days in a row, go to bed 15 minutes earlier. After a week or two you should be sleeping better and, after a few months, as long as you want.

While you can try this on a do-it-yourself basis, ASDA says, it is generally more easily done under the supervision of a sleep specialist.

The Doxylamine Dilemma

In 1978, FDA approved a new drug application providing for OTC marketing of doxylamine succinate for nighttime sleepaid use.

Subsequently, the National Cancer Institute found that methapyrilene, an antihistamine similar to doxylamine, was a potent cancer-causing agent in rats. As a result, methapyrilene was removed from the market in 1979. This prompted FDA's National Center for Toxicological Research to study doxylamine for carcinogenicity and chronic toxicity.

The scientists gave mice and rats variable doses of doxylamine in their feed for two years and then examined their tissues.

"We got the study results in 1991, and they were inconclusive," says FDA microbiologist Katharine Freeman. "There were no significant differences in survival in the treated or nontreated rats or mice, and it was impossible to say if the changes seen in some animals--like tumors and liver toxicity--were species-specific, or if the findings were relevant to human use. We were left with the problem of how to deal with such nebulous findings."

At FDA's request, the Pulmonary-Allergy Drugs Advisory Committee evaluated the data and concluded doxylamine would not likely cause cancer in humans. It recommended OTC status, but suggested the rodent findings be included in the product labeling.

Concerned about how to present the information in a way that would be useful to consumers, FDA in 1993 asked its newly formed Nonprescription Drugs Advisory Committee for recommendations about doxylamine and its labeling.

This committee agreed with the pulmonary-allergy panel that doxylamine is unlikely to cause cancer in humans and is safe for OTC use. It recommended, however, that there be no statement about tumors in the labeling, but that FDA present the information in an agency talk paper and FDA Consumer article. In January 1994, FDA amended the monograph for OTC antihistamine drug products to include doxylamine succinate.

COPYRIGHT 1994 U.S. Government Printing Office
COPYRIGHT 2004 Gale Group