Melatonin for Drug-Induced Metabolic Syndrome

Summary and Comment |
April 23, 2014

Melatonin for Drug-Induced Metabolic Syndrome

  1. Jonathan Silver, MD

In an early study, melatonin seems to decrease the weight gain that occurs with atypical antipsychotics.

  1. Jonathan Silver, MD

Weight gain and other adverse metabolic consequences are common with atypical antipsychotics. Based on results from animal studies, researchers receiving industry support hypothesized that melatonin could help to attenuate these effects.

The 50 participants had been taking clozapine, olanzapine, risperidone, or quetiapine for <3 months and were randomized to 8 weeks of slow-release melatonin (5 mg) or placebo at 8 pm. Among the 24 patients with schizophrenia and 20 with bipolar disorder who completed the study (mean age, 29; 22 men), those taking melatonin had significantly lower mean diastolic blood pressure (BP), gained less weight (mean, 1.5 vs. 2.2 kg), and had less of an increase in waist circumference. After adjustment for baseline factors, melatonin in patients also taking mood stabilizers improved BP and yielded greater benefit on fat mass.

In disorder-specific analyses, melatonin-associated changes in fat mass percentage, fat mass, and diastolic blood pressure were found only in the bipolar group. Melatonin was associated with significant differences in diastolic BP with medium-risk atypicals and in changes in lean mass and total body water with high-risk atypicals.


One possibility for the as-yet unknown mechanism of this finding is melatonin's effects on the suprachiasmatic nucleus and circadian rhythm, as circadian rhythm disturbances can have adverse metabolic consequences (NEJM JW Psychiatry Feb 14 2011). This study population is relatively small, and further studies are warranted. Also, melatonin did not reverse adverse changes, but only decreased them. Two important issues are whether starting melatonin when antipsychotic use is initiated would be more effective than starting later and whether immediate-release melatonin (which is what is generally available in the U.S.) would have different effects. However, slow-release melatonin is a promising and apparently low-risk strategy that may be helpful and should be considered.

Editor Disclosures at Time of Publication

  • Disclosures for Jonathan Silver, MD at time of publication Editorial boards Journal of Neurology, Neurosurgery and Psychiatry; Journal of Neuropsychiatry and Clinical Neuroscience; UpToDate Leadership positions in professional societies North American Brain Injury Association (Board Member) Editorial Boards Journal of Neurology, Neurosurgery & Psychiatry; Journal of Neuropsychiatry and Clinical Neurosciences


Reader Comments (3)

Dr. V Kantariya MD Physician, Family Medicine/General Practice

The findings supports a possible pathogenic role of melatonin neurothanssmition in delirium.Antipsychotic agents provide protection against delirium but have many advese effects.Melatonin prevents delirium in high-risk patients without side effects.

Dr. V Kantariya MD Physician, Family Medicine/General Practice

Melatonin not only attenuates antipsychotic metabolic effects, administered to hospitalized patients Ramelteon 8mg/d reduced incidence of delirium in elderly ICU patients.Melatonin was associated with a 10-fold difference in the rates of incidence of deliruim(3%vs32%;p=0.003).


Worthwhile looking at this strategy for primary prevention of metabolic syndrome in subjects on continuous 'night shifts'.

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