MELATONIN IN PSYCHIATRIC AND SLEEP DISORDERS - THERAPEUTIC IMPLICATIONS

Melatonin is the major hormone produced by the pineal gland. The concentration of the hormone in blood is increased during the hours of darkness, while a low concentration occurs during daylight. Its secretion is controlled by an endogenous rhythm-generating system that is entrained by light. Melatonin has a role in cueing circadian rhythms (notably the sleep-wake rhythm) and promoting sleep and contributes significantly to the circadian rhythm in body temperature. Administration of melatonin or bright light treatment has established therapeutic actions in circadian rhythm sleep disorders, periodic sleep disorder in blindness, and sleep and behavioural disorders in children with multiple brain damage. The effects of bright light or melatonin treatment follow a phase-response curve. Evening bright light treatment causes a phase delay in the sleep-wake cycle and morning light causes a phase advance. Melatonin treatment produces effects that are nearly the mirror image of those caused by bright light. Few clinical trials have been done in insomnias that are not associated with circadian rhythm disorders. Large doses of melatonin may have a therapeutic effect in chronic insomnia. Insomnia that coincides with diminished melatonin secretion occurs in aging and following treatment with beta-adrenoceptor blockers. Trials of melatonin treatment for these sleep disorders have yet to be published. A decrease in melatonin concentration has been reported in most studies of depressed patients. Treatment with drugs that enhance noradrenergic transmission or with tryptophan or 5-methoxypsoralen cause both a therapeutic response and an increase in melatonin secretion; however, no treatment trials of melatonin have been reported in depressed patients. Treatment studies of disorders that are associated with diminished nocturnal melatonin secretion require a therapeutic formulation of the hormone that would reproduce the normal nocturnal increase in melatonin concentration. Although some formulations have been reported, they have yet to be used in treatment studies.