title: Melatonin and Melatonin Agonists as Adjunctive Treatments in Bipolar Disorders.
abstract: 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.
authors.affiliation: Service de Psychiatrie Adulte (Pr. Frank BELLIVIER), Groupe Hospitalier Saint-Louis-Lariboisière- Fernand Widal, 200 rue du Faubourg Saint Denis, 75475 Paris Cedex 10 France. pierre.a.geoffroy@gmail.com.
authors.forename: Pierre Alexis
authors.initials: PA
authors.lastname: Geoffroy
authors.forename: Bruno
authors.initials: B
authors.lastname: Etain
authors.forename: Jean-Arthur Micoulaud
authors.initials: JA
authors.lastname: Franchi
authors.forename: Frank
authors.initials: F
authors.lastname: Bellivier
authors.forename: Philipp
authors.initials: P
authors.lastname: Ritter
mesh_terms: D014150:Antipsychotic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001572:Benzofurans / Q000009:adverse effects / Q000627:therapeutic use*; D001714:Bipolar Disorder / Q000175:diagnosis / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology / Q000523:psychology; D002940:Circadian Rhythm / Q000187:drug effects; D003521:Cyclopropanes / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D057970:Inappropriate Prescribing; D007192:Indenes / Q000009:adverse effects / Q000627:therapeutic use*; D008550:Melatonin / Q000009:adverse effects / Q000627:therapeutic use*; D056687:Off-Label Use; D061214:Patient Safety; D010818:Practice Patterns, Physicians'; D044094:Receptors, Melatonin / Q000819:agonists* / Q000378:metabolism; D018570:Risk Assessment; D012307:Risk Factors; D012890:Sleep / Q000187:drug effects; D016896:Treatment Outcome
chemical_list: D014150:Antipsychotic Agents; D001572:Benzofurans; D003521:Cyclopropanes; D007192:Indenes; D044094:Receptors, Melatonin; C495910:ramelteon; D008550:Melatonin; C478745:tasimelteon