Variation in plasma concentrations of clomipramine and desmethylclomipramine during clomipramine therapy

To determine steady-state plasma concentrations of clomipramine and desmethylclomipramine and their 24-hour variability, 17 depressed patients meeting certain defined criteria have been given clomipramine at stated dosages, and blood samples taken for measurement of these concentrations by gas-liquid chromatography. Response to treatment has been recorded by serial Hamilton-rating-scale and Beck-inventory scores. The complete results available for 13 patients indicate considerable variation both within and between individual patients. After three weeks' treatment plasma clomipramine concentrations ranged more widely than those of desmethylclomipramine, and some patients failed to reach steady state after five weeks' therapy. No correlation between concentration profiles and clinical response has yet emerged, but patients responding best had plasma clomipramine levels between 80 and 100 ng/ml.