Melatonin attenuates antipsychotic metabolic effects: an eight-week randomized, double-blind, parallel-group, placebo-controlled clinical trial

• Published in: Bipolar disorders Vol. 16; no. 4; pp. 410 - 421
• Main Authors: Romo-Nava, Francisco, Alvarez-Icaza González, Dení, Fresán-Orellana, Ana, Saracco Alvarez, Ricardo, Becerra-Palars, Claudia, Moreno, Julia, Ontiveros Uribe, Martha P, Berlanga, Carlos, Heinze, Gerhard, Buijs, Ruud M
• Format: Journal Article
• Language: English
• Published: Denmark Blackwell Publishing Ltd 01.06.2014
• Subjects: Adult; Analysis of Variance; Anthropometry; Antioxidants - therapeutic use; bipolar disorder; Bipolar Disorder - complications; Bipolar Disorder - drug therapy; blood pressure; Double-Blind Method; fat mass; Female; Follow-Up Studies; Humans; Male; melatonin; Melatonin - therapeutic use; Mental Disorders - complications; Mental Disorders - drug therapy; metabolic; Metabolic Diseases - drug therapy; Metabolic Diseases - etiology; Retrospective Studies; schizophrenia; second-generation antipsychotic; weight; Young Adult; blood pressure; bipolar disorder; second-generation antipsychotic; fat mass; weight; schizophrenia; melatonin; metabolic
• ISSN: 1398-5647; 1399-5618
• DOI: 10.1111/bdi.12196

Objective Second‐generation antipsychotics (SGAs) are among the first‐line treatments for bipolar disorder and schizophrenia, but have a tendency to generate metabolic disturbances. These features resemble a metabolic syndrome for which a central autonomic imbalance has been proposed that may originate from the hypothalamic suprachiasmatic nuclei. In a clinical trial, we hypothesized that melatonin, a hormone that regulates the suprachiasmatic nucleus, could attenuate SGA‐induced adverse metabolic effects. Methods In an eight‐week, double‐blind, randomized, placebo‐controlled, parallel‐group clinical trial, we evaluated the metabolic effect of melatonin in SGA‐treated patients in terms of weight, blood pressure, lipid, glucose, body composition, and anthropometric measures. A total of 44 patients treated with SGAs, 20 with bipolar disorder and 24 with schizophrenia, randomly received placebo (n = 24) or melatonin 5 mg (n = 20). Results The melatonin group showed a decrease in diastolic blood pressure (5.1 versus 1.1 mmHg for placebo, p = 0.003) and attenuated weight gain (1.5 versus 2.2 kg for placebo, F = 4.512, p = 0.040) compared to the placebo group. The strong beneficial metabolic effects of melatonin in comparison to placebo on fat mass (0.2 versus 2.7 kg, respectively, p = 0.032) and diastolic blood pressure (5.7 versus 5.5 mmHg, respectively, p = 0.001) were observed in the bipolar disorder and not in the schizophrenia group. No adverse events were reported. Conclusions Our results show that melatonin is effective in attenuating SGAs' adverse metabolic effects, particularly in bipolar disorder. The clinical findings allow us to propose that SGAs may disturb a centrally mediated metabolic balance that causes adverse metabolic effects and that nightly administration of melatonin helps to restore. Melatonin could become a safe and cost‐effective therapeutic option to attenuate or prevent SGA metabolic effects.