Akathisia, suicidality, and fluoxetine

J Clin Psychiatry. 1992 Nov;53(11):401-6.


Background: The propose link between fluoxetine and suicidal ideation is explained by fluoxetine-induced akathisia and other dysphoric extrapyramidal reactions.

Method: The following literature is reviewed: (1) the subjective response of schizophrenics to akathisia, including evidence that akathisia gives rise to suicidal ideation; (2) the subjective reports of patients taking fluoxetine; and (3) preclinical studies describing the role of serotonin in the extrapyramidal system and suggesting a mechanism whereby fluoxetine can induce extrapyramidal side effects.

Results: The literature suggests that fluoxetine-induced extrapyramidal reactions may be a mediator of de novo suicidal ideation.

Conclusion: We propose a syndrome which we name Extrapyramidal-Induced Dysphoric Reactions, one extreme manifestation of which is the emergence of suicidal ideation. We further propose a heuristic "Four Neuron Model of the Extrapyramidal Motor System" in which increased serotonin activity, by inhibiting the nigrostriatal dopamine tract, is capable of inducing extrapyramidal side effects.

Publication types

  • Review

MeSH terms

  • Akathisia, Drug-Induced / etiology
  • Akathisia, Drug-Induced / psychology*
  • Basal Ganglia Diseases / chemically induced
  • Basal Ganglia Diseases / physiopathology
  • Basal Ganglia Diseases / psychology
  • Depression / chemically induced
  • Depression / physiopathology
  • Depression / psychology
  • Fluoxetine / adverse effects*
  • Humans
  • Models, Neurological
  • Models, Psychological
  • Serotonin / physiology
  • Suicide / psychology*


  • Fluoxetine
  • Serotonin