• combination;
  • major depressive disorder;
  • tianeptine;
  • treatment resistance


The goal of this study was to assess the efficacy and tolerability of tianeptine in combination with selective serotonin re-uptake inhibitor (SSRI) in partial responders or non-responders to SSRI monotherapy.


In this prospective, open-label, 6-week study, 150 patients with major depressive disorder who had previously not responded or partially responded to SSRI monotherapy were recruited. Tianeptine was given in combination with an SSRI for 6 weeks.


Significant improvements were observed in the mean scores of the Hamilton Depression Rating Scale (HDRS), Montgomery–Åsberg Depression Rating Scale (MADRS), and Clinical Global Impression–Severity (CGI-S). The change in the mean HDRS, MADRS, and CGI-S scores was significant from week 1. The response rates were 64.7% (HDRS) and 68.7% (MADRS), and the remission rates were 34.0% (HDRS) and 42.0% (MADRS) at week 6. Thirty-six patients (24.0%) reported adverse events that were determined by the investigator to be related to one of the study drugs. The tianeptine and SSRI combination was generally well-tolerated.


A combination strategy with tianeptine may be an effective and well-tolerated tool for patients who have failed to adequately respond to SSRI monotherapy.