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Second-Generation Antipsychotics and Metabolic Side Effects: A Systematic Review of Population-Based Studies

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Abstract

Introduction

There is strong evidence from randomized controlled trials (RCTs) that second-generation antipsychotic (SGA) medications are associated with metabolic adverse events. However, with the recent increases in the use of SGAs worldwide and frequent off-label use, it is unclear whether these associations are generalizable to populations beyond those included in RCTs.

Objectives

This review aims to characterize the impact of SGAs on the population through a systematic review of population-based studies of SGA users. Studies could examine the use of any SGA medication and any comparator group. Studies also needed to include at least one metabolic outcome such as type 2 diabetes mellitus, dyslipidemia, obesity, hypertension, or metabolic syndrome.

Methods

A systematic search process was used to identify studies for inclusion in this review. Included studies had to be population-based studies of users of any SGA medication with at least one reported metabolic outcome. Study quality was also assessed using the AMSTAR tool, and evidence was synthesized by both metabolic outcome and specific SGA medication.

Results

In total, 15 studies were included in this review. Type 2 diabetes mellitus was the most frequently reported outcome; clozapine and olanzapine were most strongly associated with type 2 diabetes mellitus. Evidence was mixed for a moderate association between type 2 diabetes mellitus and risperidone or quetiapine. Few studies examined other metabolic outcomes, and therefore it is difficult to estimate the true effect in the population.

Discussion

Population-based evidence for other SGAs and metabolic outcomes was limited. However, clozapine and olanzapine were consistently more strongly associated with metabolic adverse events than were other SGAs currently available.

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Author information

Authors and Affiliations

  1. Department of Community Health Sciences, University of Calgary, Calgary, AB, Canada

    Lauren Hirsch, Lauren Bresee, Nathalie Jette & Scott Patten

  2. Hotchkiss Brain Institute, University of Calgary, Calgary, AB, Canada

    Lauren Hirsch, Nathalie Jette & Scott Patten

  3. Department of Clinical Neurosciences, University of Calgary, Calgary, AB, Canada

    Jaeun Yang, Nathalie Jette & Scott Patten

  4. O’Brien Institute of Public Health, University of Calgary, Calgary, AB, Canada

    Lauren Hirsch, Lauren Bresee, Nathalie Jette & Scott Patten

  5. Canadian Agency for Drugs and Technologies in Health, Ottawa, ON, Canada

    Lauren Bresee

  6. Department of Clinical Neurosciences, Psychiatry, Pediatrics and Community Health Sciences, University of Calgary, Mathison Centre for Mental Health Research and Education, 3280 Hospital Drive NW, Calgary, AB, T2N 4Z6, Canada

    Tamara Pringsheim

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  1. Lauren Hirsch
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Corresponding author

Correspondence to Tamara Pringsheim.

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Funding

No sources of funding were used to assist in the preparation of this study.

Conflict of interest

Lauren Hirsch, Jauen Yang, Lauren Breese, and Tamara Pringsheim have no conflicts of interest that are directly relevant to the content of this study. Nathalie Jette is the holder of a Canada Research Chair in Neurological Health Services Research for work not related to this project. Scott Patten holds a competitive, peer-reviewed grant from HBI/Pfizer that is not connected to this project.

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Hirsch, L., Yang, J., Bresee, L. et al. Second-Generation Antipsychotics and Metabolic Side Effects: A Systematic Review of Population-Based Studies. Drug Saf 40, 771–781 (2017). https://doi.org/10.1007/s40264-017-0543-0

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  • DOI: https://doi.org/10.1007/s40264-017-0543-0

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