Primary Research · 2015
Rhodiola rosea versus sertraline for major depressive disorder: a randomized placebo-controlled trial
Mao JJ, Xie SX, Zee J, et al. · Phytomedicine, 2015
Key finding
12-week three-arm RCT (n=57) found rhodiola produced smaller antidepressant effect than sertraline but with significantly fewer adverse events, supporting it as an option for milder depression.
Abstract
PubMed · PMID 25837277 →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.
Copyright © 2015 Elsevier GmbH. All rights reserved. Abstract sourced from PubMed, a database of the U.S. National Library of Medicine. Displayed in the authors’ own words for context; our critique is in the sections below.
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Rhodiola
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How to read a study like this
The same questions worth asking about any research paper, not just this one. Worth a minute even if you trust the grade.
Who was studied, and do you resemble them?
Supplement effects often depend on baseline status. Vitamin D helps people who are deficient; iron helps people who are anemic. A result in people unlike you may not apply to you.
What was measured, and does it matter in daily life?
A study that shows a blood marker moved isn't the same as a study that shows people felt or functioned better. Ask what the outcome means in practice.
How large was the effect — not just whether it was significant.
'Statistically significant' only means the effect is unlikely to be zero. It doesn't tell you the effect is large enough to notice. Look for effect sizes, not just p-values.
Who paid for the trial, and what did they stand to gain?
Industry-funded trials are several times more likely to report positive results than independent ones. It's not usually fraud — it's subtle design and reporting choices. Weight accordingly.
Has anyone else replicated this?
Single positive trials are hypotheses. Replication by independent groups is what turns a hypothesis into reliable evidence. If the only positive trial is the one you're reading, wait.
Does the dose in the trial match what's being sold?
Supplement marketing routinely cites trials that used 5–10× the dose in the product. If the effective dose was 2 g/day and the capsule has 200 mg, expect roughly no effect.
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