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August 1965

Extrapyramidal Side Effects and Therapeutic Response

Arch Gen Psychiatry. 1965;13(2):155-162. doi:10.1001/archpsyc.1965.01730020057007

A CONSISTENT observation in the burgeoning area of psychopharmacology has been that those drugs which are effective in the treatment of psychotic disorders typically tend also to produce extrapyramidal phenomena. Recent evidence indicates that this relationship is not peculiar to the phenothiazines, but holds as well for compounds of dissimilar structure such as the newer butyrophenone derivatives.1-5 Understandably, many clinicians have assumed this relation to be causal rather than casual. As early as 1953 Fluegel suggested that therapeutic response with chlorpromazine is contingent upon production of extrapyramidal side effects, and this view has since been restated in one form or another by a host of investigators.6-14 Relatively little controlled experimental work has been done on the problem. Those few methodologically adequate studies which have been conducted have consistently failed to demonstrate a significant correlation between extrapyramidal side reactions and therapeutic effect. Despite these negative findings,

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