Correlation Between Plasma Chlorpromazine and its Metabolites and Clinical Ratings in Patients with Acute Relapse of Schizophrenic and Paranoid Psychosis

Abstract

Nine patients diagnosed as having acute schizophrenic psychosis were treated with chlorpromazine. Their clinical response to drug treatment was measured by the use of a clinical rating scale developed from the Present State Examination, and a nurses rating scale. Plasma levels of chlorpromazine (CPZ), 7-hydroxychlorpromazine (7OHCPZ), monodesmethylchlorpromazine (NOR1CPZ) and chlorpromazine sulphoxide (SOCPZ), were monitored during the period of hospital treatment. Correlations were made between the increase in plasma levels of drug or metabolites and improvement in the different PSE scores. These showed that the most significant correlations occurred when symptoms with high diagnostic significance for schizophrenia (Group 1) and symptoms rating perceptual disorders (P) were correlated with plasma 7OHCPZ levels in plasma samples taken before the first morning dose of CPZ. The ratio of 7OHCPZ to CPZ in these samples increased significantly as clinical ratings improved, this correlation being most highly significant against the Group 1 and P scores. The ratio of 7OHPCZ to SOCPZ increased significantly only in the case of Group 1 and P scores. This indicates a preferential shift of CPZ metabolism towards the formation of the active 7OHCPZ during the period of clinical improvement.