A systematic review of licensed weight-loss medications in treating antipsychotic-induced weight gain and obesity in schizophrenia and psychosis

Abstract

Background: Schizophrenia and antipsychotic use are associated with clinically significant weight gain and subsequent increased mortality. Despite weight loss medications (WLMs) licensed by regulatory bodies (FDA, EMA, and MHRA) being available, current psychiatric guidelines recommend off-label alternatives, which differ from non-psychiatric guidelines for obesity.

Objective: Evaluate the efficacy of licensed WLMs on treating antipsychotic-induced weight gain (AIWG) and obesity in schizophrenia and psychosis (OSP).

Method: A literature search was conducted using Medline, EMBASE, PsycINFO and Cochrane Library online databases for human studies using licensed WLMs to treat AIWG and OSP.

Results: Three RCTs (two liraglutide, one naltrexone-bupropion), one unpublished open-label trial (naltrexone-bupropion), and seven observational studies (five liraglutide, one semaglutide, one multiple WLMs) were identified. Results for liraglutide showed statistically significant improvement in weight, BMI, waist circumference, HbA1c, cholesterol, and LDL readings on meta-analysis. Evidence was mixed for naltrexone-bupropion with no detailed studies conducted for setmelanotide, or stimulants.

Conclusion: Evidence is strongest for liraglutide compared to other licensed WLMs. The findings, particularly the inclusion of human trial data, provide evidence for liraglutide use in treating AIWG and OSP, which would better align psychiatric practice with non-psychiatric practices around obesity. The findings also identify continued literature gaps regarding other licensed WLMs.

Keywords: Antipsychotic; Obesity; Schizophrenia; Weight gain; Weight-loss medication.