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Clinical Trial
, 22 (3), 394-9

Rhodiola Rosea Versus Sertraline for Major Depressive Disorder: A Randomized Placebo-Controlled Trial

Clinical Trial

Rhodiola Rosea Versus Sertraline for Major Depressive Disorder: A Randomized Placebo-Controlled Trial

Jun J Mao et al. Phytomedicine.


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.

Trial registration: NCT01098318.

Keywords: Botanical psychopharmacology; Complementary and alternative medicine; Depression; Rhodiola rosea; Sertraline.

Conflict of interest statement

Financial Disclosures

None of the authors are a member of any pharmaceutical or industry-sponsored advisory board or speaker’s bureau, and none of the authors have any financial interest in any pharmaceutical or herbaceutical company.


Figure 1
Figure 1
Screening, Randomization and Completion of 12-Week Evaluations
Figure 2
Figure 2
Mean change in HAM-D 17 scores among treatment groups
Figure 3
Figure 3
Mean change in BDI scores among treatment groups

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