Objective: To assess existing reported human trials of Withania somnifera (WS; common name, ashwagandha) for the treatment of anxiety.

Design: Systematic review of the literature, with searches conducted in PubMed, SCOPUS, CINAHL, and Google Scholar by a medical librarian. Additionally, the reference lists of studies identified in these databases were searched by a research assistant, and queries were conducted in the AYUSH Research Portal. Search terms included "ashwagandha," "Withania somnifera," and terms related to anxiety and stress. Inclusion criteria were human randomized controlled trials with a treatment arm that included WS as a remedy for anxiety or stress. The study team members applied inclusion criteria while screening the records by abstract review.

Intervention: Treatment with any regimen of WS.

Outcome measures: Number and results of studies identified in the review.

Results: Sixty-two abstracts were screened; five human trials met inclusion criteria. Three studies compared several dosage levels of WS extract with placebos using versions of the Hamilton Anxiety Scale, with two demonstrating significant benefit of WS versus placebo, and the third demonstrating beneficial effects that approached but did not achieve significance (p=0.05). A fourth study compared naturopathic care with WS versus psychotherapy by using Beck Anxiety Inventory (BAI) scores as an outcome; BAI scores decreased by 56.5% in the WS group and decreased 30.5% for psychotherapy (p<0.0001). A fifth study measured changes in Perceived Stress Scale (PSS) scores in WS group versus placebo; there was a 44.0% reduction in PSS scores in the WS group and a 5.5% reduction in the placebo group (p<0.0001). All studies exhibited unclear or high risk of bias, and heterogenous design and reporting prevented the possibility of meta-analysis.

Conclusions: All five studies concluded that WS intervention resulted in greater score improvements (significantly in most cases) than placebo in outcomes on anxiety or stress scales. Current evidence should be received with caution because of an assortment of study methods and cases of potential bias.