benzofurans and Bipolar-Disorder

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.

Topics: Antipsychotic Agents; Benzofurans; Bipolar Disorder; Circadian Rhythm; Cyclopropanes; Humans; Inappropriate Prescribing; Indenes; Melatonin; Off-Label Use; Patient Safety; Practice Patterns, Physicians'; Receptors, Melatonin; Risk Assessment; Risk Factors; Sleep; Treatment Outcome

Topics: Benzofurans; Bipolar Disorder; Humans; Male; Mania; Middle Aged; Receptors, Serotonin, 5-HT4

Lithium is an effective drug in the treatment of both manic and depressive episodes of bipolar disorder. Lithium has been shown to block the metabolism of the intracellular second messenger inositol-1,4,5-trisphosphate which is involved in the rise in ionic intracellular calcium [( Ca++]i) which triggers neurotransmitter release and other cellular changes in secretory cells. We have measured the effect of lithium on [Ca++]i dynamics in platelets from bipolar patients stabilized with lithium treatment, and from healthy controls. Both resting [Ca++]i and the thrombin stimulated increase in [Ca++]i were higher in bipolar patients than in controls. Lithium added in vitro tended to increase the thrombin-stimulated rise in [Ca++]i. The use of the fluorescent Ca++ probe fura-2 in human platelets provides a useful method to investigate the mechanism of lithium's action in bipolar disorder and to study Ca++ related systems which may be abnormal in bipolar disorders.

Topics: Adult; Aged; Benzofurans; Bipolar Disorder; Blood Platelets; Calcium; Female; Fluorescent Dyes; Fura-2; Humans; Lithium; Male; Middle Aged; Reference Values; Thrombin

Topics: Adolescent; Adult; Amitriptyline; Anthracenes; Antidepressive Agents; Azocines; Benzoates; Benzofurans; Bipolar Disorder; Clomipramine; Cyclothymic Disorder; Depression; Dibenzazepines; Dimethylamines; Dothiepin; Humans; Imipramine; Methylamines; Middle Aged; Personality Disorders; Propylamines; Schizophrenia