Efficacy and safety of tipepidine as adjunctive therapy in major depressive disorder: A randomized, double-blind, placebo-controlled clinical trial.

Aim: Tipepidine, a synthetic, non-opioid expectorant, has been shown to improve depressive-like behavior in animal models of depression. In this study, we assessed the efficacy and tolerability of tipepidine combination therapy with citalopram in treatment of major depressive disorder (MDD).
Methods: In a randomized, double-blinded, placebo-controlled clinical trial, 62 patients with MDD were assigned into two parallel groups to receive citalopram (up to 40 mg/day) plus placebo or citalopram plus tipepidine (30 mg twice daily) for 6 weeks. Participants were assessed with the Hamilton Rating Scale for Depression (HAM-D) at baseline and Weeks 2, 4, and 6.
Results: Fifty-six patients completed the trial. The tipepidine group showed greater improvement in HAM-D scores from baseline to all three study time points (P = 0.048 for all). The remission and response-to-treatment rates were significantly higher in the tipepidine group (53.6% and 100%) compared to the placebo group (25.0% and 75%) at the study end-point (P = 0.029 and 0.005, respectively). The remission and response times in patients in the tipepidine group were also shorter compared with the placebo group (log-rank P = 0.020 and 0.004). There was no significant difference between the two groups in baseline parameters or frequency of side-effects.
Conclusion: Tipepidine combination therapy with citalopram can effectively improve symptoms of patients with MDD in a shorter period of treatment. However, further studies with larger sample sizes and longer follow-up treatment are needed to confirm our findings.
(© 2020 The Authors Psychiatry and Clinical Neurosciences © 2020 Japanese Society of Psychiatry and Neurology.)