Role of Melatonin with Antipsychotic Induced Metabolic Effects

Role of Melatonin With 

Antipsychotic Induced Metabolic Effects


The following three randomized, double-blind, parallel-group, placebo-controlled clinical trials evaluated the metabolic effect of melatonin in patients taking antipsychotics. 



Study 1: Bipolar Disord. 2014 Jun;16(4):410-21.

  • Duration: 8 weeks
  • n= total of 44 patients treated with antipsychotics (Second generation): 20 with bipolar disorder and 24 with schizophrenia, randomly received placebo (n = 24) or melatonin 5 mg (n = 20).


  • The melatonin group showed a decrease in diastolic blood pressure (5.1 versus 1.1 mmHg for placebo, p = 0.003) compared to placebo group.
  • The melatonin group showed a decrease in attenuated weight gain (1.5 versus 2.2 kg for placebo, F = 4.512, p = 0.040) compared to the placebo group.
  • This beneficial metabolic effects of melatonin 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.


Study 2: J Psychiatr Res. 2014 Jun;53:133-40.

  • n= 48 patients with first-episode schizophrenia who were eligible for olanzapine treatment
  • Patients were randomly assigned to olanzapine plus either melatonin 3 mg/day or matched placebo
  • Duration: eight weeks.


  • 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.


Study 3: Acta Med Iran. 2014;52(10):734-9.

  • Design: parallel-group, randomized, double-blind, placebo-controlled trial 
  • Duration: 12-week
  • n = 48 patients: 11-17-year-old adolescents with first time diagnosis of bipolar mood disorder. 
  • 24 patients were allocated to olanzapine (5-10 mg/day), lithium carbonate (3-4 mg/day), and melatonin (3 mg/day) and
  • 24 patients were allocated to olanzapine(5-10 mg/day), lithium carbonate(3-4 mg/day), and placebo.


  • Fasting blood sugar showed a greater increase in the placebo group compared to the melatonin group (but this was not statistically significant).
  • Mean triglyceride (TG) levels showed a greater increase in the placebo group compared to the melatonin group (but this was not statistically significant).
  • Mean cholesterol increased by 24.26 mg/dl in the placebo group compared to 6.84 mg/dl in the melatonin group.
  • Mean Systolic Blood Pressure (SBP) increased more slowly in the melatonin group compared with the placebo group (1.05mmHg vs. 6.36 mmHg) (F: 2.32; df: 36; P=0.023).


  • Administration of melatonin along with olanzapine and lithium carbonate could significantly inhibit the rise in cholesterol level and SBP compared to placebo.
  • The effect of melatonin on TG was more obvious in boys.
  • Melatonin was more effective in prevention of SBP rise.


Based on these results: Melatonin 3-6 mg/day can be used as an adjunctive treatment with second generation antipsychotics to reduce the risk of metabolic side effects. 

Please do post your questions or comments below. 

Dr. Harvinder Singh, M.D. (Admin)

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