Conventional treatment options for people with depression are limited to pharmaceutical agents even though a 2010 meta-analysis featured in JAMA demonstrated that, in the majority of patients, pharmaceuticals don’t work any better than placebo. In a 2015 phase II randomized, placebo-controlled study by researchers from the Pennsylvania Perelman School of Medicine, the botanical Rhodiola rosea was compared to the drug, sertraline (Zoloft), and placebo.  While sertraline had a slightly better effect than Rhodiola, as expected there were fewer side effects with the botanical.
Participants in this study were randomized to receive either 340 mg of rhodiola standardized to contain 3.7% rosavin (n =20), 50 mg of sertraline (n = 19), or placebo (n = 18) for 12 weeks. The primary outcomes measurement was the HAM-D with the Beck Depression Inventory. Assessments were made at 2, 4, 6, 8 and 12 weeks. The most significant finding was regarding adverse events. More than 63% of the study participants taking sertraline suffered adverse reactions compared to 30% of the Rhodiola participants and nearly 17% of the placebo participants. In addition, even though efficacy was not statistically significant in either category, there were trends to reduced HAM-D scores over time for both Rhodiola and sertraline.
While the Rhodiola did not perform as well as the sertraline, the researchers concluded that based on the risk to benefit ratio, Rhodiola may be an appropriate first line treatment choice for individuals with mild to moderate depression. This is the depression category in which pharmaceuticals have generally not performed well. The researchers point out that this is the first study to do a direct comparison of Rhodiola with a prescription antidepressant. Rhodiola may be a viable alternative treatment for mild to moderate depression especially in cases where the prescription drug is not well tolerated.
Mao JJ, Xie SX, Zee J, et al. Rhodiola rosea versus sertraline for major depressive disorder: A randomized placebo-controlled trial. Phytomedicine. 2015;22(3):394-399. 

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