Melatonin and melatonin‐agonists for metabolic syndrome components in patients treated with antipsychotics: A systematic review and meta‐analysis

Objective Metabolic side effects are a limiting factor in the use of antipsychotics, which remain the cornerstone of long‐term management of patients with severe mental illness. There is contrasting evidence on a possible role of melatonin and melatonin‐agonists in attenuating antipsychotic‐induced metabolic abnormalities. Design We conducted a systematic review (PubMed, PsycInfo, Cochrane databases, up to August 2020) and a random‐effect meta‐analysis of double‐blind, randomized placebo‐controlled trials (RCTs) involving melatonin and melatonin‐agonists in the treatment of antipsychotic‐induced metabolic changes. The primary outcome was the standardized mean difference (SMD) of composite metabolic outcomes built with metabolic syndrome components. Secondary outcomes were individual metabolic syndrome components, and other anthropometric, glucose metabolism, lipid profile, and psychopathology measures. Results Out of the initial 41 studies, six documented five separate RCTs randomizing 248 patients (126 to melatonin/ramelteon, 122 to placebo) affected by schizophrenia‐spectrum disorders and bipolar disorder. Melatonin/ramelteon outperformed placebo on the primary outcome (SMD −0.28, 95% CI = −0.39 ÷ −0.168), as well as on all individual components of metabolic syndrome (systolic blood pressure MD −3.266, 95% CI = −6.020 ÷ −0.511; fasting glucose MD −3.766, 95% CI = −5.938 ÷ −1.593; triglycerides MD −9.800, 95% CI = −19.431 ÷ −0.169; HDL MD 2.995, 95% CI = 0.567 ÷ 5.423), except waist circumference. Conclusions Melatonin/ramelteon augmentation may be beneficial for non‐anthropometric metabolic syndrome components in patients treated with antipsychotics.