A double-blind six months comparative study of milnacipran and clomipramine in major depressive disorder.

Milnacipran is a new antidepressant with similar effects on the reuptake of noradrenaline and serotonin in vivo and in vitro. The present study was designed to study the efficacy and tolerability of long-term treatment of depressed patients with milnacipran in comparison with clomipramine. The study was designed as a double-blind, randomized parallel group comparison at 10 different hospitals in The Netherlands. The duration of treatment was 6 weeks, with an extension period of 20 weeks. The entire study period of 26 weeks was done under double-blind conditions. There was 1 week of dose escalation after which the patients received either treatment with milnacipran 200 mg/day or clomipramine 150 mg/day in fixed doses during weeks 2 to 10. This was followed by flexible dosing with 200, 150, or 100 mg/day milnacipran or 150, 100 or 75 mg/day clomipramine during weeks 11 to 26. Both milnacipran and clomipramine showed poor antidepressant activity in this patient sample. There were no significant differences between the two treatment groups with respect to antidepressant efficacy. Several methodological reasons might explain the lack of antidepressant efficacy in the present study. In 45% of the patients in the present study, the duration of the current episode of depression was longer than 6 months, whereas 48% of the patients used antidepressants before the study and 73% of these appeared to be non-responders. This raises the possibility that the present sample consisted of treatment-resistant depressive patients.