Relationship between the plasma concentration of clomipramine and desmethylclomipramine in depressive patients and the clinical response

Abstract

Thirty one in-patients suffering from depression were treated orally with clomipramine (C1) at various dosage, for 28 days, after a "wash-out" period of three days. In 17 patients receiving 75 mg per day of C1, steady state plasma levels of C1 were reached at Day 14, and steady state plasma levels of its active metabolite, desmethylclomipramine (DMC1), were reached at Day 21. In contrast, in 7 other patients receiving a dosage increasing to 150 mg per day at Day 7, mean plasma levels of C1 and DMC1 continued to rise during the entire treatment period. At the steady state, a correlation was found between C1 dosage expressed as mg kg body weight and the plasma concentration of C1 and DMC1. Factors such as tobacco and alcohol consumption seem to modify the C1/DMC1 ratio. A comparison of clinical response with plasma levels of C1, DMC1 and C1 + DMC1 showed a significant negative linear correlation.