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Problems in Therapeutic Blood Monitoring of Chlorpromazine

Summary: Chlorpromazine (CPZ) therapeutic drug monitoring is beset by inconclusive and controversial evidence on the positive correlation of plasma CPZ concentration and psychiatric improvement. Failure to establish meaningful correlation between plasma concentration and clinical benefit may be explained by chemical assay problems; differences in the pharmacokinetic plasma CPZ and metabolite profile due to age, acuteness or chronicity of the disease; drug interactions; and duration of neuroleptic treatment. At the other end, measurement of clinical effects in psychiatry suffers such draw-backs as less distinct and specific clinical end points, the patient's subjectiveness of symptoms and the investigator's subjectiveness on clinical scoring, and the ethical consideration of placebo use. Our data showed the following: (1) Plasma levels of CPZ parent compound correlated better with improvement in thought disorders and paranoid delusion than with total Brief Psychiatric Rating Scale; there were no correlations with depression and withdrawal retardation. (2) Chronically treated patients achieved significantly lower plasma CPZ compared to acutely treated patients on oral CPZ dose but not those treated with an intramuscular dose. (3) Children, in comparison to adults, require higher doses to achieve similar plasma CPZ levels and have a lower response threshold, both for clinical improvement and toxicity. (4) The plasma concentration of CPZ can be diminished by concomitant use of anticholinergics. (5) A drug “holiday” increases peak plasma concentration of CPZ and may benefit the nonresponders.