Metabolic-Protective Strategies for Antipsychotic-Associated Weight Gain in Children and Adolescents: A Systematic Review
Abstract
Second-generation antipsychotics are effective for a range of pediatric psychiatric and behavioral conditions but are commonly associated with weight gain and metabolic dysfunction. Metformin is the most extensively studied pharmacological strategy for preventing or treating this adverse effect; however, the randomized evidence base has evolved substantially with the publication of recent large trials. This study aimed to systematically review and meta-analyze randomized controlled trials of metformin and other metabolic-protective strategies, including topiramate, melatonin, and antipsychotic switching, for preventing or treating antipsychotic-associated weight gain in children and adolescents. PubMed/MEDLINE, Scopus, Web of Science, and Cochrane Central Register of Controlled Trials were searched for records published between January 2000 and June 2026. Randomized controlled trials enrolling participants aged 19 years or younger who were receiving a second-generation antipsychotic were eligible. Risk of bias was assessed using the Cochrane Risk of Bias 2 tool. Random-effects meta-analyses using restricted maximum likelihood estimation with the Hartung-Knapp adjustment pooled mean differences and risk ratios when at least two trials contributed comparable data; prevention and treatment indications were analyzed separately. Seven unique randomized controlled trials reported across eight publications met eligibility criteria, including 1,871 participants: five trials…
How strong is the evidence?
Evidence Hub reads this as a systematic review, done in people. Its evidence level is 1 of 5 (Highest · pooled evidence). Pooled evidence from several studies sits at the top of the evidence pyramid. Reported size: 1,871 participants or records.
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