Milnacipran efficacy in the prevention of recurrent depression: a 12-month placebo-controlled study

To compare the efficacy and assess the tolerability of milnacipran 50mg p.o. b.i.d. to placebo in the prevention of recurrence in depressed patients who had responded an acute treatment and had remained in remission during a 4-month continuation phase. Remission criteria were: a Hamilton Depression Rating Scale (HDRS) (21-item) < or = 8, improvement or disappearance of the initial symptoms, and an assessment of 'very much improved' or 'much improved' on the Clinical Global Impression (CGI) Subscale: Global Improvement. Recurrence was defined by a major depressive episode according to DSM-III-R criteria and a minimum score of 18 on the HDRS, with the need to treat the recurrence. The primary analysis was the rate of recurrence as a function of time in the intent-to-treat population. Groups were compared using the Cox model. Absolute recurrence rates were 16.3% (17/104) in milnacipran-treated patients and 23.6% (26/110) in placebo-treated patients, with a significant difference in the reduction of recurrence as a function of time (Kaplan Meier Survival Analysis analysis, P < 0.05). There was no difference in tolerability between groups. This study demonstrates that milnacipran is effective with good tolerability in preventing recurrence in major depressive disorder over 1 year in patients with recurrent depression who responded to acute treatment with milnacipran and continued their response for 18 weeks.