Adjunctive tianeptine treatment for bipolar disorder: A 24-week randomized, placebo-controlled, maintenance trial.

OBJECTIVE: The purpose of this study was to assess the efficacy and tolerability of tianeptine as an adjunctive maintenance treatment for bipolar depression. METHODS: This is a multicenter double-blind randomized placebo-controlled maintenance trial of adjunctive tianeptine 37.5 mg/day. Participants ( n=161) had a Montgomery-Asberg Depression Rating Scale ⩾12 at entry. After eight weeks of open-label tianeptine treatment, those who responded to tianeptine ( n=69) were randomized to adjunctive tianeptine ( n=36) or placebo ( n=33) in addition to usual treatment. Kaplan-Meier estimates and the Mantel-Cox log-rank test were used to evaluate differences in time to intervention for a mood episode between the tianeptine and placebo groups. We also assessed overall functioning, biological rhythms, quality of life, rates of manic switch and serum brain-derived neurotrophic factor levels. RESULTS: There were no differences between adjunctive tianeptine or placebo regarding time to intervention or depression scores in the 24-week double-blind controlled phase. Patients in the tianeptine group showed better performance in the letter-number sequencing subtest from the Wechsler Adult Intelligence Scale at the endpoint ( p=0.014). Tianeptine was well tolerated and not associated with higher risk for manic switch compared to placebo. CONCLUSION: Tianeptine was not more effective than placebo in the maintenance treatment of bipolar depression. There is preliminary evidence suggesting a pro-cognitive effect of tianeptine in working memory compared to placebo.

Placebo-controlled study of tianeptine in major depressive episodes.

The efficacy and safety of tianeptine were compared, in the course of a multicentre randomised, double-blind, parallel group study, to those of placebo in the treatment of Major Depressions and Bipolar Disorder, Depressed with or without melancholia, without psychotic features. After a 1-week run-in placebo period, 126 depressed out-patients presenting DSM-III-R Major Depression or Bipolar Disorder, Depressed, with a total MADRS score of at least 25, were treated for 42 days with either tianeptine (25-50 mg/day) or placebo. Efficacy assessments were MADRS, CGI, HARS, Zung Depression Self Rating Scale and a VAS. Better efficacy of tianeptine was shown, and confirmed by covariance analyses, in final MADRS scores of the intention-to-treat population, of patients treated for at least 14 days and of completers; also in CGI items 1 and 2, MADRS item 10, and VAS. The results confirmed the efficacy of tianeptine (mean dosage: 37.5 mg/day) in the treatment of Major Depression and Bipolar Disorder, Depressed, with or without melancholia, compared to placebo. Tianeptine's acceptability did not differ from that of placebo. For adverse events, a higher incidence of headaches was found with tianeptine.