OTC Options Help for the Sleepless
by Marian Segal

(This is the first in a series of articles on nonprescription
drugs.)
     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 sleep-aids 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 sleep-aid 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.) n

Marian Segal is a member of FDA's public affairs staff

The Doxylamine Dilemma
     In 1978, FDA approved a new drug application providing for OTC
marketing of doxylamine succinate for nighttime sleep-aid 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. n

--M.S.

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. 
--M.S.