Nonprescription Hypnotic Agents
Antihistamines: Most over-the-counter drug treatments for insomnia contain the antihistamines diphenhydramine, doxylamine or hydroxyzine. Individuals with insomnia report that these agents cause drowsiness and help them fall asleep. The most prominent disadvantage is the next-day “hang-over” effects of psychomotor impairment and anticholinergic side effects that can be intolerable. These agents are less effective for treating insomnia than are the benzodiazepines. Also, they typically are not effective for chronic insomnia because tolerance to the sleep-inducing effects often develops after one to two weeks of continuous use.
Melatonin: Melatonin is a naturally occurring hormone secreted by the pineal gland, which is located in the center of the brain. The pineal gland is connected to the retina via a nerve pathway that runs through the suprachiasmatic nucleus of the hypothalamus, the body’s circadian clock. The pineal gland produces melatonin (a byproduct of serotonin metabolism) only during the nocturnal phase of the circadian cycle and only in relative darkness. Exogenous melatonin has been promoted and studied as a treatment for insomnia, under the theory that rising melatonin levels “fool” the brain into sleep.
Melatonin currently has no established place in the treatment of insomnia, according to the International Consensus Conference on the Treatment of Insomnia. Melatonin has not demonstrated efficacy comparable to that of established hypnotics in relieving primary insomnia. Preliminary data suggest melatonin may be useful for treating abnormalities of the circadian clock, such as shift work, delayed-sleep phase syndrome (a persistent inability lasting more than six months to fall asleep and arise at conventional times — e.g., sleeping 1 AM to 9 AM instead of 11 PM to 7 AM), jet lag, and the recurring insomnia of the blind. (Loss of sight interferes with visual cues for natural circadian sleep regulation. People with blindness experience nocturnal sleep disruption and have a higher incidence of involuntary daytime naps and insomnia.) However, the only randomized double-blind trial of placebo and three regimens of melatonin (5 mg at bedtime, 0.5 mg at bedtime, and 0.5 mg taken on a shifting schedule) for jet lag found no difference in symptoms across all four groups.
Before pharmacists can recommend melatonin, important questions regarding its safety must be addressed. Emerging data regarding a vasoconstrictive effect on coronary arteries dictate a cautious approach. Depression and liver disease associated with melatonin have also been described in case reports. In addition, high doses of melatonin appear to have contraceptive effects in some women. Other alternative remedies, such as valerian and kava-kava, are used to treat insomnia even though evidence for efficacy, purity and safety is lacking.