There remains significant debate about the use of melatonin in psychiatry and sleep disorders. Evidence continues to emerge, but studies are limited by the lack of consistent methodology and attention to both the chronobiotic and hypnotic effects of the molecule. Dosing and timing of melatonin can play a large role in its efficacy and can lead to variable effects. A low dose (1 to 3 mg) 3 to 4 hours before the preferred bedtime will help with a delayed sleep-wake phase, while higher doses (3 to 9 mg) given 60 to 90 minutes before the desired bedtime will help with jet lag sleep disorder or primary insomnia. However, significant clinical evaluation is frequently required to understand the roots of insomnia and the proper timing of melatonin administration.
Unfortunately, in the United States, melatonin is considered a dietary supplement; hence, the quality of the source of melatonin is always a concern. Melatonin receptor agonists address some of these concerns about purity and quality, but fewer data are available with these agents.
It is clear that forms of exogenous melatonin (especially controlled-release) and melatonin receptor agonists have a role in the treatment of circadian rhythm sleep disorders in patients with insomnia (especially in the elderly) and in those with comorbid depressive disorders. The safety and tolerability of melatonin, especially compared with other hypnotic agents, suggests a very favorable cost-benefit ratio and is one of the primary considerations in the treatment of insomnia.
Increasing sleep latency through a hypnotic or sedative effect has long been a paradigm that has been overemphasized in the treatment of insomnia and psychiatric illness. Although sleep is necessary, the increase in sleep latency must be balanced with the risk of next day hangover and cognitive effects, which can often be far more detrimental to a patient’s quality of life than the actual insomnia. Melatonin and its receptor analogues appear to be moving away from this traditional “knock out” paradigm of a sleeping pill. It appears that the actual sleep induction effect of melatonin and its receptor analogues is quite modest and their mechanism of action is more sophisticated: amplifying natural circadian differences in alertness and possibly creating a more biologically normal sleep pattern.
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