Reviewed: Amsterdam JD, Li Y, Soeller I, Rockwell K, Mao JJ, Shults J. Randomized, double-blind, placebo-controlled trial of Matricaria recutita (Chamomile) extract therapy for generalized anxiety disorder. J Clin Psychopharmacol. 2009;29:378-382.
Generalized anxiety disorder (GAD) is a chronic disorder often treated with pharmaceuticals. These pharmaceuticals can produce unwanted adverse effects and dependence. Chamomile (Matricaria recutita, Asteraceae; syn. Chamomilla recutita) has long been used as a traditional herbal remedy for its relaxing and calming effects. Although there have been no controlled clinical trials evaluating chamomile’s effect on people with GAD, the authors hypothesized that chamomile would have superior anxiolytic efficacy, yet a similar safety profile, when compared with placebo.
Fifty-seven patients (≥ 18 years of age) were referred by the Department of Family Medicine and Community Health outpatient clinic at the University of Pennsylvania Medical Center in Philadelphia for participation in this randomized, double-blind, placebo-controlled trial. These patients had a Diagnostic and Statistical Manual of Mental Disorders, 4th Edition (DSM-IV) Axis I diagnosis of GAD and a baseline total Hamilton Anxiety Rating (HAM-A) score ≥ 9. Patients with minor depression were not excluded if the depression was not a primary disorder. Patients were excluded if they had a diagnosis of major depressive disorder, bipolar disorder, panic disorder, phobic disorder, obsessive-compulsive disorder, post-traumatic stress disorder, acute stress disorder, substance-induced anxiety disorder, psychosis, dementia, or substance abuse or dependence within the preceding 3 months. Participants were not allowed to use other anxiolytics, antidepressants, mood stabilizers, sedatives, or complementary and alternative medicine (CAM) remedies during the study.
Patients were randomized to receive either placebo (n = 29) containing lactose monohydrate (National Formulary) or pharmaceutical grade German chamomile extract (n = 28) standardized to contain 1.2% apigenin (Spectrum Pharmacy Products; New Brunswick, NJ).
Chamomile aroma was blinded by inserting a disk impregnated with 1 drop of chamomile oil (for placebo) or 1 drop of neutral oil (for chamomile) into the lid of each airtight medication container. Chamomile therapy was initiated at 220 mg/day for the first week and increased to 440 mg/day during the second week of therapy. Patients with ≤ 50% reduction in total HAM-A score (vs. baseline) were increased to 660 mg/day during week 3 and 880 mg/day during week 4 of therapy. Patients who continued to have ≤ 50% reduction in baseline HAM-A score were increased to 1100 mg/day during weeks 5 through 8 of therapy. To maintain blinding, patients in both treatment groups had increases in the number of capsules consumed each week when patients had ≤ 50% reduction in total HAM-A score vs. baseline. Dose reductions could occur at any time based upon tolerability of the material. Outcome measurements occurred at baseline and after 2, 4, 6, and 8 weeks of treatment.
There were no significant differences between treatment groups in any baseline variable. There was no significant difference between groups in the mean daily capsule intake.
Patients treated with chamomile had a significantly greater reduction over time in the mean total HAM-A score (primary outcome measure) compared with placebo-treated patients (P = 0.047; 57% and 38%, respectively). According to the authors, the study was not powered to detect small to moderate group differences in secondary outcomes, but rather to find trends. There were clinically meaningful improvements in the chamomile-treated patients according to the Beck Anxiety Inventory, Psychological General Well Being Index, and Clinical Global Impression Severity Score, and more chamomile-treated patients than placebo-treated patients showed improvement on most of these scales.
One patient in each group discontinued due to an adverse event (AE). The chamomile-treated patient discontinued due to stomach discomfort. There were 11 AEs in the chamomile group and 22 in the placebo group that were rated as possibly, probably, or definitely related to treatment (no significant differences between groups). The specific AEs were not listed or described. There was no increase in AEs at higher chamomile doses.
The authors conclude that chamomile was clinically meaningful and statistically superior to placebo in reducing total HAM-A scores in patients with mild to moderate GAD. The authors chose the starting dose of chamomile based on authoritative reviews. It is possible that higher daily doses would be more effective.
The dose-escalating design of the study is typical for studies that evaluate novel psychopharmaceuticals. It is also known that clinical trials of psychopharmaceuticals report a strong placebo effect. It is possible that a larger population size and longer duration of action would produce a more robust effect in favor of chamomile. The authors had a unique method of blinding the well-known smell of chamomile; it is unknown whether there has been prior testing to evaluate the effectiveness of essential oil-impregnated disks in masking placebo.
The researchers used careful methodology in the study design, presentation of findings, and rigorous statistical analysis. This is the first randomized, double-blind, placebo-controlled study to demonstrate that the use of chamomile can lead to modest improvement in symptoms of anxiety in patients with mild to moderate GAD. It also demonstrates safety and tolerability. Although the results are limited by the small size, variability in dosing regimen, and short duration of the study (8 weeks), the positive findings of efficacy support the use of chamomile as a complementary treatment in mild to moderate GAD and indicate the need for further studies.
—Heather S. Oliff, PhD