Relationships among clinical response, extrapyramidal syndrome and plasma chlorpromazine and metabolite ratios

Shortening of handwriting (micrographia) developed in nine out of 50 schizophrenic patients on a double blind chlorpromazine vs. placebo study (33 of the patients received active medication). Another nine showed excellent clinical response but never exhibited shortening of handwriting. There was a wide interpatient variability in chlorpromazine plasma levels in agreement with previous reports, which did not differentiate between the two groups. However, patients with shortening of handwriting had higher 7hydroxy-chlorpromazine (7OHCPZ) plasma levels and two of them went on to develop clinically manifest Extra-Pyramidal Syndrome (EPS).