Comparison of pimozide and chlorpromazine in acute schizophrenia.
A four week double-blind study comparing pimozide and chlorpromazine was designed to test the hypothesis that pimozide, a powerful dopamine receptor blocker, is more effective in the treatment of acute schizophrenia than chlorpromazine. Twenty patients, 13 males and 7 females ranging in age from 21 to 53 years (mean age 33 years) admitted to ST. Mary's Hospital with acute schizophrenia were placed on the study. They were treated on an individual titrated dosage of either chlorpromazine 300 mg to 2100 mg, or pimozide 10 to 70 mg. The results revealed that on the Brief Psychiatric Rating Scale, the chlorpromazine group significantly improved after one week, whereas the pimozide group showed no statistical improvement until the third week. By the end of the study no significant differences were apparent between the two groups. In the Clinical Global Impression Scale, a significant difference between the two groups was found at week 4 showing a greater improvement in the chlorpromazine group. In terms of adverse reactions, the chlorpromazine group had significantly fewer extrapyramidal symptoms than the pimozide group (Simpson and Angus Scale) and in addition 15 adverse reactions were noted for the pimozide group as compared with 8 for the chlorpromazine group. This study shows that chlorpromazine has an earlier onset of action than pimozide in the acute schizophrenic patient despite the fact that it has a weaker effect on the dopamine receptor than has pimozide. In view of this finding, the dopamine theory of schizophrenia should be critically re-examined.
Overall the quality of evidence is limited, poor and dated. Where drugs that have been better evaluated are available, it may be best to avoid use of chlorpromazine. Where chlorpromazine is used for acute aggression or where choices are limited, relevant trials are possible and urgently needed.