Atypical
antipsychotics (AAPs) are increasingly used for the treatment of
psychotic disorders but are known to be associated with metabolic abnormalities. This study is a systematic review and meta-analysis of randomized controlled trials (RCTs) studying the effectiveness of
melatonin for the amelioration of
AAP-induced
metabolic syndrome. The MEDLINE (accessed via PubMed), Cochrane Central Register of Controlled Trials (CENTRAL), ClinicalTrials, PsycINFO, LILACS, CINAHL, and OpenGrey databases were searched for RCTs without language restrictions. Inclusion criteria were randomized, double-blind clinical trials comparing
melatonin or
melatonin agonists with placebo for the amelioration of
AAP-induced effects at any age with selected components of
metabolic syndrome as outcome measures. Two reviewers independently selected articles and assessed quality using Cochrane risk of bias and concealment tools. Of 53 records, five RCTs were eligible for the systematic review and three for the meta-analysis. The meta-analyses showed no statistically significant difference in any anthropometric or metabolic variable considered. Analysis according to
psychiatric diagnosis from one RCT showed significant decreases in diastolic blood pressure (5.5 vs. -5.7 mmHg for the placebo and
melatonin groups, respectively; p =0.001), fat mass (2.7 vs. 0.2 kg, respectively; p =0.032), and
triglycerides (D) (50.1 vs. -20 mg/dl, respectively; p =0.08) in the bipolar group but not the
schizophrenia group. Although limited to five RCTs with small sample sizes, evidence from RCT indicates that
melatonin improves
AAP-induced
metabolic syndrome. This beneficial effect seems more significant in patients with
bipolar disorder than those with
schizophrenia. Further RCTs are needed to definitively establish the potential ameliorative effect of
melatonin and to justify its efficacy as an add-on
therapy to curtail
AAP-induced
metabolic syndrome.