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Melatonin for prevention of metabolic side-effects of olanzapine in patients with first-episode schizophrenia: Randomized double-blind placebo-controlled study
Journal of Psychiatric Research, 03/14/14
Modabbernia A, et al. – The authors aimed to determine the efficacy of melatonin 3 mg/day in prevention of olanzapine–induced metabolic side–effects. In patients treated with olanzapine, short–term melatonin treatment attenuates weight gain, abdominal obesity, and hypertriglyceridemia. It might also provide additional benefit for treatment of psychosis.
  • In a randomized double-blind placebo-controlled study, 48 patients with first-episode schizophrenia who were eligible for olanzapine treatment, were randomly assigned to olanzapine plus either melatonin 3 mg/day or matched placebo for eight weeks.
  • Anthropometric and metabolic parameters as well as psychiatric symptoms using The Positive and Negative Syndrome Scale (PANSS) were assessed at baseline, week 4, and 8.
  • Primary outcome measure was the change from baseline in weight at week 8.

  • Data were analyzed using t-test, Mann–Whitney U test, and mixed-effects model.
  • Thirty-six patients had at least one post-baseline measurement.
  • At week eight, melatonin was associated with significantly less weight gain [mean difference (MD)=3.2 kg, P=0.023], increase in waist circumference [MD=2.83 cm, P=0.041] and triglyceride concentration [MD=62 mg/dl, P=0.090 (nearly significant)] than the placebo.
  • Changes in cholesterol, insulin, and blood sugar concentrations did not differ significantly between the two groups.
  • Patients in the melatonin group experienced significantly more reduction in their PANSS scores [MD=12.9 points, P=0.014] than the placebo group.
  • No serious adverse events were reported.

Author Commentary Exclusive

Amirhossein Modabbernia 03/18/2014
Olanzapine is one of the most effective antipsychotics, but at the same time is associated with high frequency of weight gain and several other metabolic disturbances. The results of this study underscore the efficacy of low dose melatonin in preventing weight gain and hypertriglyceridemia following olanzapine treatment. Unlike several other medications used to counteract the metabolic side effects of olanzapine, melatonin is associated with minimal side effects. Interestingly and unexpectedly we also show an additional antipsychotic effect of melatonin in treatment of schizophrenia, a finding that needs to be replicated in future studies. Importantly, our results are confined to short term treatment and long term effects of melatonin treatment in patients taking olanzapine has not been studied yet.

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