Comparative effects of pharmacological treatment for weight gain in patients treated with antipsychotics. A systematic review and network meta-analysis.

BACKGROUND: Weight gain induced by antipsychotic treatment is a significant cardiometabolic risk factor associated with increased mortality. METHODS: Following PRISMA criteria Medline, Cochrane Central Register of Clinical Trials and Science Direct were systematically searched. Only randomised placebo-controlled trials evaluating pharmacological interventions to reduce antipsychotic drug-induced weight gain in adults were included. Data on mean change in weight from baseline were extracted, together with parameters defining variability or dispersion. A fixed effects model and random effects mode were used. Treatments were ranked using SUCRA. OUTCOMES: 27 studies including 17 medications were included. The studies were divided into two groups with a time horizon of less or more than 12 weeks. A comparison of the short-term interventions showed significant advantages of nizatidine (MD -6,82; CI -13,36 to -0,55) and metformin (MD -4,17; CI -8,02 to -0,64) over placebo. For longer-term interventions, significant benefits were shown for liraglutide (MD -5,3; Cl -6,93 to -3,75), exenatide (MD -4,17; Cl -7,4 to -1,14), metformin (MD -2,08; Cl -2,86 to -1,35) and samidorphan (MD -1,91; CL -3,31 to -0,51) as compared to placebo. Liraglutide was superior to other drugs according to the SUCRA analysis. INTERPRETATION: Our network meta-analysis presents a comparison of pharmacological interventions to address weight gain associated with antipsychotic treatment. Metformin and liraglutide appear to have the strongest evidence for treating weight gain in the target group. FUNDING: This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sector.