Drug Safety

, Volume 40, Issue 9, pp 771–781 | Cite as

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

  • Lauren Hirsch
  • Jaeun Yang
  • Lauren Bresee
  • Nathalie Jette
  • Scott Patten
  • Tamara Pringsheim
Systematic Review



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.


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.


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.


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.


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.


Compliance with Ethical Standards


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.

Supplementary material

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Supplementary material 1 (PDF 44 kb)
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Supplementary material 2 (PDF 122 kb)
40264_2017_543_MOESM3_ESM.pdf (92 kb)
Supplementary material 3 (PDF 92 kb)
40264_2017_543_MOESM4_ESM.pdf (146 kb)
Supplementary material 4 (PDF 146 kb)


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Copyright information

© Springer International Publishing Switzerland 2017

Authors and Affiliations

  1. 1.Department of Community Health SciencesUniversity of CalgaryCalgaryCanada
  2. 2.Hotchkiss Brain InstituteUniversity of CalgaryCalgaryCanada
  3. 3.Department of Clinical NeurosciencesUniversity of CalgaryCalgaryCanada
  4. 4.O’Brien Institute of Public HealthUniversity of CalgaryCalgaryCanada
  5. 5.Canadian Agency for Drugs and Technologies in HealthOttawaCanada
  6. 6.Department of Clinical Neurosciences, Psychiatry, Pediatrics and Community Health SciencesUniversity of Calgary, Mathison Centre for Mental Health Research and EducationCalgaryCanada

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