Efficacy and tolerability of pharmacological interventions on metabolic disturbance induced by atypical antipsychotics in adults: A systematic review and network meta-analysis

J Psychopharmacol. 2021 Sep;35(9):1111-1119. doi: 10.1177/02698811211035391. Epub 2021 Jul 27.


Background: There have been a few systematic reviews and conventional meta-analyses reporting effect of drugs on metabolic disturbance induced by atypical antipsychotics (AAPs). However, few of them provided sufficient and comprehensive comparisons between pharmacological interventions.

Aims: We aimed to qualitatively compare drugs' effect on AAPs-induced metabolic abnormalities by using network meta-analysis (NMA).

Methods: We searched PubMed, EMBASE, Web of Science, Cochrane Controlled Register of Trials (CENTRAL), and PsycINFO on March 26, 2019. Of 5889 records identified, 61 randomized clinical trials including 3467 participants were included. We estimated weighted mean difference (WMD) and odds ratio (OR) using NMA. We assessed the risk of bias of individual studies with the Review Manager 5.3. Primary outcomes included change of body weight and body mass index (BMI). Secondary outcomes included change of other cardiometabolic risk factors, acceptability, and tolerability.

Results: For body weight, topiramate (WMD -5.4, 95% CI -7.12 to -3.68), zonisamide (-3.44, 95% CI -6.57 to -0.36), metformin (-3.01, 95% CI -4.22 to -1.83), glucagon-like peptide-1 receptor agonists (GLP-1RAs) (-3.23, 95% CI -5.47 to -0.96), and nizatidine (-2.14, 95% CI -4.01 to -0.27) were significantly superior to placebo. Results regarding to BMI were similar to that of body weight. With respect to tolerability, only topiramate (OR 24, 95% CI 3.15 to 648) was inferior to placebo.

Conclusions: Considering both efficacy and tolerability, evidence from this NMA indicates zonisamide, metformin, GLP-1RAs, and nizatidine in adults should be the first-line treatment for alleviating AAPs-induced weight gain or elevated BMI.

Keywords: Atypical antipsychotics; PRISMA; metabolic disturbance; network meta-analysis; pharmacological interventions.

Publication types

  • Comparative Study
  • Meta-Analysis
  • Systematic Review

MeSH terms

  • Adult
  • Antipsychotic Agents / administration & dosage
  • Antipsychotic Agents / adverse effects*
  • Body Mass Index
  • Body Weight / drug effects
  • Cardiometabolic Risk Factors
  • Humans
  • Metabolic Diseases / chemically induced*
  • Network Meta-Analysis
  • Weight Gain / drug effects


  • Antipsychotic Agents