Twenty-Four Week, Randomized, Double-Blind, Placebo-Controlled Trial of Metformin for Antipsychotic-Induced Weight Gain in Patients with First-Episode Psychosis: A Pilot Study

Excessive weight gain and cardiometabolic dysfunction are common and clinically relevant side effects of antipsychotic medications. In this pilot study, we aimed to establish the feasibility of using metformin and its effectiveness in managing antipsychotic-induced weight gain in patients with first-episode psychosis (FEP) on follow-up with the Singapore Early Psychosis Intervention Programme in a 24-week, randomized, double-blind, placebo-controlled trial, to ascertain the effects of metformin discontinuation on body weight and evaluate the safety and tolerability of metformin. Participants between the ages of 16 and 40 with FEP assessed as clinically stable and who had gained ≥5% of their pre-drug weight after initiation of the antipsychotic treatment were recruited from outpatient clinics between April 2015 and April 2018. Seventeen participants met all the inclusion criteria and were randomized to receive metformin (n = 8) or the placebo (n = 9) at Week 0, with follow up assessments at Weeks 3, 6, 12, 24, and 36. Metformin was generally well-tolerated. Participants in the metformin arm were able to control their weight better than participants receiving the placebo, an effect that did not persist after discontinuation. Our results support the use of metformin as a safe and tolerable weight control measure in a typical outpatient sample of young people with FEP.