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

Phytomedicine. 2015 Mar 15;22(3):394-9. doi: 10.1016/j.phymed.2015.01.010. Epub 2015 Feb 23.


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: ClinicalTrials.gov NCT01098318.

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

Publication types

  • Clinical Trial, Phase II
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antidepressive Agents / therapeutic use*
  • Depressive Disorder, Major / drug therapy*
  • Double-Blind Method
  • Female
  • Humans
  • Male
  • Middle Aged
  • Phytotherapy
  • Plant Extracts / adverse effects
  • Plant Extracts / therapeutic use*
  • Psychiatric Status Rating Scales
  • Rhodiola / chemistry*
  • Sertraline / therapeutic use


  • Antidepressive Agents
  • Plant Extracts
  • Sertraline

Associated data

  • ClinicalTrials.gov/NCT01098318