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Phytomedicine. 2016 Dec 15;23(14):1735-1742. doi: 10.1016/j.phymed.2016.10.012. Epub 2016 Oct 24.

Long-term chamomile (Matricaria chamomilla L.) treatment for generalized anxiety disorder: A randomized clinical trial.

Author information

Bendheim Center for Integrative Medicine, Memorial Sloan Kettering Cancer Center, 1429 First Avenue, New York, NY 10021, United States. Electronic address:
Department of Biostatistics and Epidemiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States.
Department of Psychology, School of Arts and Sciences, University of Pennsylvania, Philadelphia, PA, United States.
Department of Family Medicine and Community Health, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States.
Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States.



Generalized Anxiety Disorder (GAD) is one of the most common anxiety disorders treated in primary care, yet current therapies have limited efficacy and substantial side effects.


To evaluate long-term chamomile (Matricaria chamomilla L.) use for prevention of GAD symptom relapse.


Outpatients from primary care practices and local communities with a primary diagnosis of moderate-to-severe GAD were enrolled for this two-phase study at a large US academic medical center. During Phase 1, eligible participants received 12 weeks of open-label therapy with chamomile pharmaceutical grade extract 1500mg (500mg capsule 3 times daily). During Phase 2, treatment responders were randomized to either 26 weeks of continuation chamomile therapy or placebo in a double-blinded, placebo-substitution design. The primary outcome was time to relapse during continuation therapy, analyzed using Cox proportional hazards. Secondary outcomes included the proportion who relapsed, treatment-emergent adverse events, and vital sign changes. This study is registered at, identifier NCT01072344.


Between March 1, 2010, and June 30, 2015, we enrolled 179 participants. Of those, 93 (51.9%) were responders and agreed to continue in the double-blind randomized controlled trial. A numerically greater number of placebo-switched (n=12/47; 25.5%) versus chamomile-continuation (n = 7/46; 15.2%) participants relapsed during follow-up. Mean time to relapse was 11.4 ± 8.4 weeks for chamomile and 6.3 ± 3.9 weeks for placebo. Hazard of relapse was non-significantly lower for chamomile (hazard ratio, 0.52; 95% CI, 0.20-1.33; P = 0.16). During follow-up, chamomile participants maintained significantly lower GAD symptoms than placebo (P = 0.0032), with significant reductions in body weight (P = 0.046) and mean arterial blood pressure (P = 0.0063). Both treatments had similar low adverse event rates.


Long-term chamomile was safe and significantly reduced moderate-to-severe GAD symptoms, but did not significantly reduce rate of relapse. Our limited sample size and lower than expected rate of placebo group relapse likely contributed to the non-significant primary outcome finding. Possible chamomile superiority over placebo requires further examination in large-scale studies.


Chamomile; Clinical trials; Generalized anxiety disorder; Herbal medicine

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