Metabolic adverse effects of off-label use of second-generation antipsychotics in the adult population: a systematic review and meta-analysis.

Abstract

Prescription rates of second-generation antipsychotics (SGAs) are rapidly increasing for non-indicated (i.e., off-label) usage. SGAs used for approved indications are associated with significant metabolic adverse effects, including weight gain. The objective of this systematic review and meta-analysis is to evaluate the metabolic adverse effects of SGA use for off-label management of psychiatric illnesses in the adult population. We performed a systematic database search to identify randomized controlled trials (RCTs) that reported on weight and other metabolic outcomes with off-label use of SGAs among adults. Thirty-eight RCTs met inclusion criteria for this review; 35 of these studies, with a total of 4930 patients, were included in the quantitative meta-analysis. Patients treated with olanzapine, risperidone, and quetiapine were more likely to report weight gain as a side effect and experience clinically significant (≥7%) weight gain compared to those treated with a placebo. Among studies that reported weight as a continuous outcome, olanzapine was associated with significantly greater weight gain across all disorders (mean difference (MD) = 3.24 kg, 95% CI: 2.57-3.90 p = 0.001, N = 12 studies). Similar trends were noted with quetiapine and risperidone. A meta-regression analysis revealed a positive dose-response association between olanzapine dose and weight gain (regression coefficient: 0.36, p = 0.001). This review demonstrates that off-label use of SGAs, and particularly olanzapine, is associated with significant weight gain among adult patients. Our findings are concerning given the widespread off-label use of SGAs. Further studies are required to better understand the effects of off-label SGA use on other metabolic parameters. The study was registered with the PROSPERO international database of prospectively registered systematic reviews (PROSPERO #143186).

• Authors: Nicolette Stogios, Emily Smith, Sylvie Bowden, Veronica Tran, Roshanak Asgariroozbehani, William Brett McIntyre, Gary Remington, Dan Siskind, Sri Mahavir Agarwal, Margaret K Hahn
• Journal: Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology (Neuropsychopharmacology) Vol. 47 Issue 3 Pg. 664-672 (02 2022) ISSN: 1740-634X [Electronic] England
• PMID: 34446830 (Publication Type: Journal Article, Meta-Analysis, Research Support, Non-U.S. Gov't, Systematic Review)
• Copyright: © 2021. The Author(s), under exclusive licence to American College of Neuropsychopharmacology.

Chemical References

• Antipsychotic Agents
• Quetiapine Fumarate
• Risperidone
• Olanzapine

Topics

• Adult
• Antipsychotic Agents (adverse effects)
• Humans
• Off-Label Use
• Olanzapine
• Quetiapine Fumarate
• Risperidone (therapeutic use)