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

Mao et al., 2016 | Phytomedicine | Rct

Citation

Mao Jun J, Xie Sharon X, ... Amsterdam Jay D. Long-term chamomile (Matricaria chamomilla L.) treatment for generalized anxiety disorder: A randomized clinical trial. Phytomedicine. 2016-Dec-15;23(14):1735-1742. doi:10.1016/j.phymed.2016.10.012

Abstract

BACKGROUND: 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. PURPOSE: To evaluate long-term chamomile (Matricaria chamomilla L.) use for prevention of GAD symptom relapse. METHODS: 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 ClinicalTrials.gov, identifier NCT01072344. RESULTS: 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. CONCLUSIONS: 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.

Key Findings

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

Outcomes Measured

• anxiety
• blood pressure

Population

MeSH Terms

• Adult
• Anti-Anxiety Agents
• Anxiety
• Anxiety Disorders
• Blood Pressure
• Double-Blind Method
• Female
• Humans
• Male
• Matricaria
• Middle Aged
• Phytotherapy
• Plant Extracts
• Recurrence
• Time Factors
• Treatment Outcome
• Young Adult

Evidence Classification

• Level: Rct
• Publication Types: Journal Article, Randomized Controlled Trial
• Vertical: chamomile-anxiety

Provenance

• PMID: 27912875
• DOI: 10.1016/j.phymed.2016.10.012
• PMCID: PMC5646235
• Verified: 2026-04-09 via PubMed E-utilities API

Source extracted via PubMed E-utilities API on 2026-04-09