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

Akathisia, suicidality, and fluoxetine.

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Department of Psychiatry, College of Physicians and Surgeons of Columbia University, New York.



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


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.


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


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.

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