Long-term antipsychotic use and brain changes in schizophrenia - a systematic review and meta-analysis

Hum Psychopharmacol. 2017 Mar;32(2). doi: 10.1002/hup.2574.


Objective: The association between long-term antipsychotic treatment and changes in brain structure in schizophrenia is unclear. Our aim was to conduct a systematic review and a meta-analysis on long-term antipsychotic effects on brain structures in schizophrenia focusing on studies with at least 2 years of follow-up between MRI scans.

Design: Studies were systematically collected using 4 databases, and we also contacted authors for unpublished data. We calculated correlations between antipsychotic dose and/or type and brain volumetric changes and used random effect meta-analysis to study correlations by brain area.

Results: Thirty-one publications from 16 samples fulfilled our inclusion criteria. In meta-analysis, higher antipsychotic exposure associated statistically significantly with parietal lobe decrease (studies, n = 4; r = -.14, p = .013) and with basal ganglia increase (n = 4; r = .10, p = .044). Most of the reported correlations in the original studies were statistically nonsignificant. There were no clear differences between typical and atypical exposure and brain volume change. The studies were often small and highly heterogeneous in their methods and seldom focused on antipsychotic medication and brain changes as the main subject.

Conclusions: Antipsychotic medication may associate with brain structure changes. More long-term follow-up studies taking into account illness severity measures are needed to make definitive conclusions.

Keywords: MRI; adverse effect; aetiology; brain; follow-up; psychotic disorders.

Publication types

  • Meta-Analysis
  • Review
  • Systematic Review

MeSH terms

  • Antipsychotic Agents / adverse effects*
  • Antipsychotic Agents / therapeutic use
  • Brain / drug effects*
  • Brain / pathology*
  • Dose-Response Relationship, Drug
  • Humans
  • Magnetic Resonance Imaging
  • Schizophrenia / drug therapy*
  • Schizophrenia / pathology*


  • Antipsychotic Agents