Extrapyramidal Reactions Associated with Serotonergic Antidepressants

Ann Pharmacother. 2015 Oct;49(10):1136-52. doi: 10.1177/1060028015594812. Epub 2015 Jul 16.

Abstract

Objective: Extrapyramidal reactions (EPRs) associated with serotonergic antidepressant treatments have been reported since 1958. These reactions can be distressing for patients and complicate treatment. Our objective was to complete a follow-up review of published EPR cases reported for serotonergic antidepressants.

Data sources: Published cases between January 1998 and May 2015 were collected through a medical literature search. Citation reference lists were also searched manually.

Study selection and data extraction: Identified cases were reviewed for patient age, gender, psychiatric diagnosis, dosage, time to reaction onset, concurrent medications, and EPR description. Cases were excluded when there was not a clear description, if descriptions were not consistent with accepted definitions, or if the written English was poor. We included cases of akathisia, dystonia, dyskinesia, parkinsonism, or mixed EPRs. Authors scored each case using the Naranjo adverse drug reaction probability scale.

Data synthesis: We identified 86 published reports involving 91 patients; selective serotonin reuptake inhibitors were implicated in 80.2% of cases. All EPR types were reported: 17 akathisia cases, 18 dyskinesia cases, 27 dystonia cases, 19 parkinsonism cases, and 10 mixed EPR cases. EPRs typically occurred within 30 days of either treatment initiation or dose increase. Age, gender, antidepressant dosing, or concurrent antipsychotic treatment did not appear to broadly contribute to EPR risk. Naranjo scores ranged from 2 to 8.

Conclusions: Case reports associating serotonergic antidepressants with EPRs continue to be published. Practitioners are advised that monitoring for such is important. Rigorous research efforts are needed to better understand the clinical risk factors for these adverse drug reactions.

Keywords: akathisia; antidepressive agents; dyskinesia; dystonia; humans; parkinsonism; serotonin reuptake inhibitors.

Publication types

  • Review

MeSH terms

  • Adrenergic Uptake Inhibitors / adverse effects
  • Age Factors
  • Akathisia, Drug-Induced / etiology
  • Akathisia, Drug-Induced / physiopathology
  • Antidepressive Agents / adverse effects*
  • Antipsychotic Agents / adverse effects
  • Dyskinesia, Drug-Induced / etiology
  • Dyskinesia, Drug-Induced / physiopathology
  • Extrapyramidal Tracts / drug effects*
  • Extrapyramidal Tracts / physiopathology
  • Female
  • Humans
  • Male
  • Parkinson Disease, Secondary / etiology
  • Parkinson Disease, Secondary / physiopathology
  • Psychomotor Agitation / drug therapy
  • Risk Factors
  • Selective Serotonin Reuptake Inhibitors / adverse effects*
  • Sex Factors

Substances

  • Adrenergic Uptake Inhibitors
  • Antidepressive Agents
  • Antipsychotic Agents
  • Serotonin Uptake Inhibitors