Rhodiola rosea versus sertraline for major depressive disorder: A randomized placebo-controlled trial

Abstract Background : We performed a proof of concept trial to evaluate relative safety and efficacy of Rhodiola rosea ( R. rosea) versus sertraline for mild to moderate major depressive disorder. Hypothesis : We hypothesize that R. rosea would have similar therapeutic effects as sertraline but with less adverse events. Study design : Phase II randomized placebo controlled clinical trial. Methods : 57 subjects were randomized to 12 weeks of standardized R. rosea extract, sertraline, or placebo. Changes over time in Hamilton Depression Rating (HAM-D), Beck Depression Inventory (BDI), and Clinical Global Impression Change (CGI/C) scores among groups were examined using mixed-effects models. Results : Modest, albeit statistically non-significant, reductions were observed for HAM-D, BDI, and CGI/C scores for all treatment conditions with no significant difference between groups ( p  = 0.79, p  = 0.28, and p  = 0.17, respectively). The decline in HAM-D scores was greater for sertraline (−8.2, 95% confidence interval [CI], −12.7 to −3.6) versus R. rosea (−5.1, 95% CI: −8.8 to −1.3) and placebo (−4.6, 95% CI: −8.6 to −0.6). While the odds of improving (versus placebo) were greater for sertraline (1.90 [0.44–8.20]; odds ratio [95% CI]) than R. rosea (1.39 [0.38–5.04]), more subjects on sertraline reported adverse events (63.2%) than R. rosea (30.0%) or placebo (16.7%) ( p  = 0.012). Conclusions : Although R. rosea produced less antidepressant effect versus sertraline, it also resulted in significantly fewer adverse events and was better tolerated. These findings suggest that R. rosea , although less effective than sertraline, may possess a more favorable risk to benefit ratio for individuals with mild to moderate depression.