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

Abstract

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.

Management of cognitive impairment in bipolar disorder: a systematic review of randomized controlled trials

“…The majority of studies included participants diagnosed with BD I/II as defined by the DSM-IV. Other studies included participants with BD I/II or BD-NOS, 24 , 36 BD as defined by the ICD-10, 25 , 30 BD with psychosis, 47 or restricted participants to BD-I 32 . The mood state of participants in the included studies was highly variable.…”

Effect of Pharmacological and Neurostimulation Interventions for Cognitive Domains in Patients with Bipolar Disorder: A Systematic Review and Network Meta-Analysis of Randomized Controlled Trials

“…Adjunctive creatine monohydrate, high-and lowfrequency rTMS, infliximab, tianeptine and mifepristone were the interventions used (compared with TAU) in the 6 studies including patients with BD experiencing depressive episodes. [43][44][45][46][47][48] Across these studies, attention and social cognition were not measured, and only one evaluated problem-solving. Across the 5 domains included in the NMA (Supplementary Figure S3), none of the adjunctive therapies revealed significant benefits compared with TAU.…”

Adjunctive antidepressant treatment among 763 outpatients with bipolar disorder: Findings from the Bipolar CHOICE and LiTMUS trials

“…Other smaller RCTs found similar treatment efficacies between different adjunctive antidepressants (Frye et al, 2009;Kauer-Sant'Anna et al, 2019;Post et al, 2006;Sachs et al, 1994;Schaffer, Zuker, & Levitt, 2006;Shelton & Stahl, 2004), but those different antidepressants differed on rates of treatment-emergent manic switches (Post et al, 2006). Another recent study (N = 98) found that patients using adjunctive antidepressant drugs at discharge had lower rates of 12-month rehospitalization with no differences in mania hospitalization rates (Shvartzman et al, 2018).…”

“…Two large studies from the Systematic Treatment Enhancement Program for Bipolar Disorder trial investigated antidepressant use adjunctive to mood‐stabilizing treatment in a randomized (Sachs et al, 2007) and a nonrandomized fashion (Goldberg et al, 2007), finding no differences between antidepressant users and nonusers. Other smaller RCTs found similar treatment efficacies between different adjunctive antidepressants (Frye et al, 2009; Kauer‐Sant'Anna et al, 2019; Post et al, 2006; Sachs et al, 1994; Schaffer, Zuker, & Levitt, 2006; Shelton & Stahl, 2004), but those different antidepressants differed on rates of treatment‐emergent manic switches (Post et al, 2006). Another recent study ( N = 98) found that patients using adjunctive antidepressant drugs at discharge had lower rates of 12‐month rehospitalization with no differences in mania hospitalization rates (Shvartzman et al, 2018).…”