Bipolar disorders (BD) present with abnormalities of circadian rhythmicity and sleep homeostasis, even
during phases of remission. These abnormalities are linked to the underlying neurobiology of genetic susceptibility to BD. Melatonin is a
pineal gland secreted neurohormone that induces circadian-related and sleep-related responses. Exogenous melatonin has demonstrated
efficacy in treating primary insomnia, delayed sleep phase disorder, improving sleep parameters and overall sleep quality, and some psychiatric
disorders like autistic spectrum disorders. In order to evaluate the efficacy of melatonin among patients with BD, this comprehensive
review emphasizes the abnormal melatonin function in BD, the rationale of melatonin action in BD, the available data about the
exogenous administration of melatonin, and melatonin agonists (ramelteon and tasimelteon), and recommendations of use in patients with
BD. There is a scientific rationale to propose melatonin-agonists as an adjunctive treatment of mood stabilizers in treating sleep disorders
in BD and thus to possibly prevent relapses when administered during remission phases. We emphasized the need to treat insomnia, sleep
delayed latencies and sleep abnormalities in BD that are prodromal markers of an emerging mood episode and possible targets to prevent
future relapses. An additional interesting adjunctive therapeutic effect might be on preventing metabolic syndrome, particularly in patients
treated with antipsychotics. Finally, melatonin is well tolerated and has little dependence potential in contrast to most available
sleep medications. Further studies are expected to be able to produce stronger evidence-based therapeutic guidelines to confirm and delineate
the routine use of melatonin-agonists in the treatment of BD.
Keywords: Bipolar disorders, circadian rhythms, melatonin, ramelteon, sleep, tasimelteon.
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