Efficacy of tianeptine vs placebo in the long-term treatment (16.5 months) of unipolar major recurrent depression

To compare the efficacy and acceptability of tianeptine vs placebo in the long-term treatment of unipolar major recurrent depression, 268 hospitalized and ambulatory patients meeting DSM III-R criteria for major depression with a 21-item Hamilton depression rating scale (HDRS) score greater than or equal to 17 and at least one episode in the previous 5 years received tianeptine in a 6-week multicenter open study. At D42, 185 responders (intention-to-treat population) were randomized for ethical reasons into two unbalanced groups to receive tianeptine 37.5 mg/day (n=111) or placebo (n=74) for 16.5 months; 173 of the 185 responders were defined as strict responders (per-protocol population) by an HDRS score which was both <15 and at least halved vs D1, combined with clinical confirmation by the investigator. The groups were similar at baseline except in the severity of the depressive episode (greater in the tianeptine group: 33 vs 18%, p=0.018). Relapse (before 6 months) and recurrence (after 6 months) were defined by an HDRS score <greater than or equal to>15 and/or clinical global impression score greater than or equal to4, and clinical confirmation by the investigator. Visits were at D63 and M3, M6, M9, M12, M15, and M18. Efficacy was measured by the number of relapses and recurrences and their time of onset (Kaplan-Meier survival curve analysis). Between D42 and M18 (intention-to-treat population), relapse and recurrence were less frequent on tianeptine us placebo (16 vs 36%, p = 0.002). Comparison over time also showed a higher proportion of patients without relapse or recurrence on tianeptine (p <0.001); the intergroup difference increased with follow-up duration. Secondary analysis of relapse in the intention-to-treat group showed a higher proportion on placebo (p=0.002); secondary analysis of recurrence over time showed that the difference in the percentages of recurrence-free patients was nonsignificant in the intention-to-treat population (p = 0.067) but significant in the per-protocol population (p = 0.036) in favor of tianeptine. Acceptability did not differ between the groups. Treatment-induced adverse events were rare and mild in both groups. These data support the use of tianeptine in the long-term treatment of unipolar major recurrent depression. Relapse and recurrence were decreased two- to threefold on tianeptine vs placebo with no difference in acceptability between the two groups. Copyright (C) 1997 Doin Editeurs.