L-theanine adjunct to sertraline for major depressive disorder: A randomized, double-blind, placebo-controlled clinical trial

Background: Unsatisfactory responses to major depressive disorder (MDD) therapeutics available necessitated up-to-date treatment approaches. This study sought to investigate the efficacy and tolerability of adjunctive L-the-anine, a green tea constituent with neuropsychotropic effects, for MDD.Methods: Sixty MDD (DSM-5) patients were equally assigned to receive sertraline (100 mg/d) plus either L-the-anine (200 mg/d) or matched placebo in a six-week randomized, parallel-group, double-blind, placebo -controlled study. The participants were assessed using the Hamilton depression rating scale (HDRS) at base-line and weeks 2, 4, and 6. Changes in scores, early improvement, response and remission rates, and adverse events were compared between the groups.Results: Twenty-five participants in each group, a total of 50 patients, completed the study. All baseline char-acteristics were similar between the groups. The general linear model repeated-measures analysis demonstrated a significant time-treatment interaction effect for HDRS during the trial (p-value = 0.014), indicating more remarkable symptom improvement in the L-theanine group. A greater reduction in HDRS scores was observed in the L-theanine group from baseline to weeks 2, 4, and 6 (p-values = 0.02, 0.03, and 0.01, respectively). All patients responded to sertraline plus L-theanine until week 6. L-theanine was superior to placebo regarding response to treatment and remission rates at week 6 (p-values = 0.05 and 0.02, respectively). The frequency of side effects was comparable between the groups.Limitations: The small sample size and short study period were the limitations. Conclusions: L-theanine adjunct to sertraline outperforms placebo in treating MDD in a safe manner. Further long-term, large-scale studies are recommended to confirm this evidence.