Melatonin may help insomniacs

Healthfacts, Sept, 1995

The synthetic form of the hormone melatonin, which can be purchased at most health food stores, continues to show some effectiveness in treating insomnia. The latest preliminary study involved 12 elderly people (average age 76 years) who suffered chronic sleep disturbances and were receiving various medications for chronic illness.

Participants were given either a controlled-release form of melatonin (2 mg per night taken two hours before bedtime) or a placebo (a look alike inactive pill) in a study conducted by D. Garfinkel, M.D., and colleagues at various medical centers in Israel (The Lancet, 26 August 1995). The seven-week study was designed to make sure that the participants were unaware of whether they were taking the melatonin or the placebo.

The quality of sleep was monitored with a small computerized device worn on the wrist of each participant to track sleep-wake patterns based on wrist movements. At the end of the study, "sleep efficiency" was found to be significantly greater when the participants were taking melatonin.

Although the finding of improved sleep quality was judged "statistically significant," the results were relatively modest. For example, the hormone had no effect on total sleep time. But even a small benefit provides hope where it concerns insomnia which has no satisfactory treatment. In fact, the drugs most commonly prescribed for sleep disorders, such as Valium, Xanax, Librium, and Halcion, can cause more harm than good, particularly to people over age 60. (Sleep disturbances increase with age.) All are benzodiazepines, a class of drugs to be avoided by people over age 60 because the odds of experiencing side effects are significantly higher.

According to Worst Pills, Best Pills II (published by Public Citizen/Health Research Group, 1993), all of the above benzodiazepines can cause unsteady gait; dizziness, falling, with an increased risk of hip fractures; injurious automobile accidents; impairment of thinking and memory loss; and addiction. Ironically, benzodiazepines also cause sleep disturbances. Dr. Garfinkel and colleagues note that these drugs actually impair sleep by interfering with melatonin production. Similarly, drugs, such as beta blockers for hypertension (e.g., Inderal), commonly prescribed to elderly people, can also interfere with sleep by inhibiting melatonin production.

Melatonin, a hormone secreted by the pineal gland in the brain, has fascinated some researchers for the last decade. Blood levels of melatonin are low in the daytime, start rising at dusk, and peak after midnight. Production is dependent on the light-dark cycle, and any disruptions in the cycle, such as working the night shift or traveling quickly across many times zones, can cause sleep disturbances. Earlier studies have suggested that taking melatonin at bed time can alleviate symptoms of jet lag and aid people who have difficulty falling asleep.

In one study, 20 young men with no sleep disorders were given various doses of melatonin or placebo, placed in a dark room at midday, and told to close their eyes for 30 minutes. The men on the placebo took 25 minutes to fall asleep; whereas those on melatonin took five or six minutes. This study was conducted by Dr. Richard J. Wurtman, professor of neuroscience at Massachusetts Institute of Technology, who, in the 1960s, had conducted pioneering research showing how darkness stimulates the pineal gland to secrete melatonin.

Why Controlled Release?

Now researchers are searching for the best way to administer melatonin. It can be taken orally, intranasally, or intravenously. The new Israeli study used an oral time-released formulation of melatonin because Dr. Garfinkel and colleagues found that the regular oral formulation stays in the blood only about 40-50 minutes, peaking about 20 minutes after ingestion and falling rapidly thereafter.

Last year, The Wall Street Journal reported an interesting turf struggle over the sale of melatonin. The synthetic form can be purchased at most stores that sell vitamins. Yet if Interneuron Pharmaceuticals Inc. has its way, melatonin will become a prescription drug. At the heart of the struggle is Dr. Richard Wurtman, the pioneer researcher at MIT. After the 1994 media coverage of his study of the 20 young men, melatonin sales hit an all time high and Dr. Wurtman was deluged with letters from insomniacs and frequent flyers wanting more information.

The Wall Street Journal reported that these people received a form letter in return from Dr. Wurtman warning that the melatonin sold in health food stores is not controlled for purity and strength. He reminded them of amino acid L-tryptophan, also sold in health food stores until 1989, when impurities linked to a blood disorder caused 38 deaths and more than 1,000 injuries.

What Dr. Wurtman didn't mention, according to The Wall Street Journal, was his financial interest in melatonin. In 1993, he had applied for a patent with MIT on the use of melatonin to treat insomnia. In March, 1994, rights to the patent application were obtained by Interneuron Pharmaceuticals Inc., a small company co-founded by Dr. Wurtman, who owns nearly one million of its shares.