Antipsychotic-induced extrapyramidal side effects: A systematic review and meta-analysis of observational studies

PLoS One. 2021 Sep 10;16(9):e0257129. doi: 10.1371/journal.pone.0257129. eCollection 2021.


Background: Antipsychotic agents are the basis for the pharmacological management of acute and chronic schizophrenia, bipolar disorders, mood disorders with psychotic feature, and other psychotic disorders. Antipsychotic medication use is frequently associated with unfavorable adverse effects such as extrapyramidal side effects (EPSEs). Hence, this systematic review and meta-analysis was aimed to determine the magnitude of antipsychotic-induced EPSEs.

Method: A literature search was conducted using legitimate databases, indexing services, and directories including PubMed/MEDLINE (Ovid®), EMBASE (Ovid®), google scholar and WorldCat to retrieve studies. Following screening and eligibility, the relevant data were extracted from the included studies using an Excel sheet and exported to STATA 15.0 software for analyses. The Random effects pooling model was used to analyze outcome measures at a 95% confidence interval. Besides, publication bias analysis was conducted. The protocol has been registered on PROSPERO with ID: CRD42020175168.

Result: In total, 15 original articles were included for the systematic review and meta-analysis. The pooled prevalence of antipsychotic-induced EPSEs among patient taking antipsychotic medications was 37% (95% CI: 18-55%, before sensitivity) and 31% (95% CI: 19-44%, after sensitivity). The prevalence of antipsychotic-induced parkinsonism, akathisia, and tardive dyskinesia was 20% (95% CI: 11-28%), 11% (95% CI: 6-17%), and 7% (95% CI: 4-9%), respectively. To confirm a small-study effect, Egger's regression test accompanied by funnel plot asymmetry demonstrated that there was a sort of publication bias in studies reporting akathisia and tardive dyskinesia.

Conclusion: The prevalence of antipsychotic-induced EPSEs was considerably high. One in five and more than one in ten patients experienced parkinsonism and akathisia, respectively. Appropriate prevention and early management of these effects can enhance the net benefits of antipsychotics.

Publication types

  • Meta-Analysis
  • Systematic Review

MeSH terms

  • Antipsychotic Agents / adverse effects*
  • Geography
  • Humans
  • Movement Disorders / etiology*
  • Observational Studies as Topic*
  • Outcome Assessment, Health Care
  • Publication Bias
  • Tardive Dyskinesia / chemically induced


  • Antipsychotic Agents

Grant support

The author(s) received no specific funding for this work.