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Am J Psychiatry 1958;115:167-168.
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Psychiatry & Neurology Service, VA Hospital, Oakland, Calif.

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Four schizophrenic patients receiving chlorpromazine in doses adequate to produce a Parkinsonian syndrome but with no history or physical findings of other neurological disease showed elevation of cerebrospinal fluid protein ranging from 51 to 108 mg.%.Further studies are, of course, indicated and are under way. Besides confirming these findings in a larger series and investigating related drugs in the phenothiazine group, it is planned to evaluate the effect of dosage and duration of administration. Thus far the opportunity has been granted to examine spinal fluids before and after chlorpromazine on 3 non-psychiatric patients; all were on lower doses than those ordinarily employed in the treatment of psychosis.After 30 days of chlorpromazine (average daily dose 400 mg.) during which time none of the patients showed Parkinsonian manifestations, the spinal fluid levels rose in one case from 21 to 47 mg.%, in another from 27 to 55 mg.% and in the third from 45 to 57 mg.%.It is not now possible to say whether an increase in the cerebrospinal fluid protein content is related to an alteration in barrier permeability, or whether it indicates some degree of breakdown of tissue. The findings are here presented in a preliminary form solely to alert physicians working with this drug to a hitherto undescribed effect. It is hoped that dissemination of this information may prove helpful in evaluating spinal fluid data where certain complications or questions of differential diagnosis may arise in individuals undergoing long-term therapy with this drug.

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