title: Melatonin attenuates antipsychotic metabolic effects: an eight-week randomized, double-blind, parallel-group, placebo-controlled clinical trial.
abstract: 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.
authors.affiliation: Departamento de Psiquiatría y Salud Mental, Facultad de Medicina, UNAM, Mexico City, DF, Mexico; Clínica de Trastornos Afectivos, Instituto Nacional de Psiquiatría "Dr. Ramón de la Fuente", Mexico City, DF, Mexico; Hypothalamic Integration Mechanisms Laboratory, Departmento de Biologia Celular y Fisiologia, Instituto de Investigaciones Biomédicas, UNAM, Mexico City, DF, Mexico.
authors.forename: Francisco
authors.initials: F
authors.lastname: Romo-Nava
authors.forename: Dení
authors.initials: D
authors.lastname: Alvarez-Icaza González
authors.forename: Ana
authors.initials: A
authors.lastname: Fresán-Orellana
authors.forename: Ricardo
authors.initials: R
authors.lastname: Saracco Alvarez
authors.forename: Claudia
authors.initials: C
authors.lastname: Becerra-Palars
authors.forename: Julia
authors.initials: J
authors.lastname: Moreno
authors.forename: Martha P
authors.initials: MP
authors.lastname: Ontiveros Uribe
authors.forename: Carlos
authors.initials: C
authors.lastname: Berlanga
authors.forename: Gerhard
authors.initials: G
authors.lastname: Heinze
authors.forename: Ruud M
authors.initials: RM
authors.lastname: Buijs
mesh_terms: D000328:Adult; D000704:Analysis of Variance; D000886:Anthropometry; D000975:Antioxidants / Q000627:therapeutic use*; D001714:Bipolar Disorder / Q000150:complications / Q000188:drug therapy; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008550:Melatonin / Q000627:therapeutic use*; D001523:Mental Disorders / Q000150:complications* / Q000188:drug therapy; D008659:Metabolic Diseases / Q000188:drug therapy* / Q000209:etiology*; D012189:Retrospective Studies; D055815:Young Adult
chemical_list: D000975:Antioxidants; D008550:Melatonin
keywords: bipolar disorder; blood pressure; fat mass; melatonin; metabolic; schizophrenia; second-generation antipsychotic; weight