Double-blind trial with oral versus intravenous clomipramine in primary depression

Intravenous clomipramine and oral clomipramine at a daily dose of 2 mg/kg body weight were compared in a double-blind study of 40 inpatients with primary depressive illness. No significant differences between the two routes of clomipramine administration were found, either in response or in side effects. Steady state was not attained at the 4th week of treatment in 30% of patients. However, combined plasma levels of clomipramine (CI) plus desmethylclomipramine (DMCI) were similar in the two groups at all stages of treatment. The only significant pharmacokinetic difference that was found was in the ratio of DMCI to CI, which was higher among the patients who received the drug orally, but this did not correlate with clinical response. Conversely, Day 28 plasma concentrations of CI, DMCI, and the sum CI + DMCI were significantly related to clinical outcome in the patients treated orally. Among the patients who received the drug intravenously only CI was significantly associated with the percentage reduction of symptoms. By pooling the two groups, CI, DMCI, and their sum all bore relationships to clinical response significant at the 0.01 level.