Clinical response and plasma levels: effect of dose, dosage schedules, and drug interactions on plasma chlorpromazine levels

Plasma chlorpromazine (CPZ) levels of 50 psychotic inpatients were measured by gas liquid chromatography; the clinical progress of 29 of these patients with acute psychoses was also assessed. CPZ levels of 50- 300 ng/ml were usually associated with clinical improvement; there was also a relationship between CPZ levels and increases in certain symptoms. The 50-300 ng/ml level was best attained by doses of 400-800 mg/day. Trihexyphenidyl decreased plasma CPZ by a mean of 44.7% in 12 of 15 patients. A single 400-800-mg dose of CPZ at bedtime produced steady states equal to or better than those achieved with multiple doses. Those patients who failed to attain CPZ levels of more than 70 ng/ml despite doses of 400-1000 mg/day were receiving lithium throughout the study and had discharge diagnoses of manic-depressive psychosis, manic type, and schizo-affective schizophrenia--a finding with implications for future research.