Clinical trial NCT01072344: Long Term Chamomile Therapy for Anxiety
Official title: Long-Term Chamomile Therapy for Generalized Anxiety Disorder (GAD)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Generalized Anxiety Disorder
Keywords: Anxiety
Chamomile
Herbal Remedy
Complementary and Alternative Medicine
Lead sponsor: University of Pennsylvania
Sponsor class: OTHER
First posted: 2010-02-22
Enrollment: 180
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Prior research has shown that chamomile may be an effective, short-term anti-anxiety treatment. This study will examine the initial and long-term benefits of chamomile extract therapy for the prevention of recurrent anxiety disorder.

Detailed description: Anxiety disorders are among the most common psychiatric conditions. They affect up to 25% of the US adult population. Generalized anxiety disorder (GAD) is a chronic, recurrent form of the disorder. Although benzodiazepines and serotonin reuptake inhibitors have become the mainstay therapy of GAD, these drugs are often associated with unwanted side effects, habituation, and withdrawal symptoms. Many individuals decline using conventional drug therapy for financial, cultural, or personal reasons such as the stigma of mental illness. As a result, many individuals will seek alternative therapy for their anxiety symptoms. The identification of effective alternative therapies for GAD would be of particular relevance. Among alternative therapies for anxiety, chamomile has been used as a traditional herbal medicine for its calming effect. It is well tolerated and demonstrates pharmacological activity in animal models of anxiety. Despite its widespread use and availability, there has been only one clinical trial of chamomile safety and efficacy in GAD. The current application seeks to build upon the results of that prior chamomile study. In that 8-week, double-blind, placebo-controlled trial, we found a significant superiority of chamomile (vs. placebo) in reducing GAD symptoms. We also found chamomile to be exceedingly well tolerated (vs. placebo). The current application seeks to extend these promising preliminary results by conducting a randomized, double-blind, parallel group, placebo-substitution, long-term safety and efficacy study of chamomile in preventing GAD relapse. For specific aim #1 we will ask: "Does long-term chamomile therapy (vs. placebo) prolong the time to relapse of anxiety symptoms following recovery from GAD?" To answer this question, 180 patients with moderate to severe GAD will receive open-label chamomile extract 500-1,500 mg daily for 8 weeks. Responders to chamomile, who remain well for 4 additional weeks of consolidation therapy, will be randomized to double-blind continuation therapy with chamomile 500-1,500 mg daily or placebo for an additional 26 weeks. We hypothesize that continuation chamomile therapy will result in a prolonged time to relapse (vs. placebo). For specific aim #2 we will ask: "What is the relative safety and tolerability of long-term chamomile therapy (vs. placebo) in patients who have recovered from GAD?" To answer this question, we will examine the following outcome measures: (i) the proportion of patients in each treatment condition who relapse; (ii) the frequency, severity, and duration of treatment-emergent adverse events; (iii) the frequency of discontinuation symptoms during initial double-blind therapy; and, (iv) the frequency of early study discontinuation. We hypothesize that chamomile therapy will result in a lower proportion of anxiety relapses and a lower study discontinuation rate (vs. placebo). We further hypothesize that chamomile therapy will result in a similar frequency of discontinuation symptoms and treatment-emergent adverse events (vs. placebo).

Eligibility criteria: Inclusion Criteria:

* Men and women at least 18 years old (all races and ethnicity)
* DSM IV diagnosis of GAD as the primary anxiety disorder
* Baseline GAD-7 score ≥ 10
* Baseline CGI/S score at least 4
* Not taking anti-anxiety medication (e.g., Benzodiazepines, buspirone, antidepressants)
* Not taking antidepressant, mood stabilizer, or tranquilizer therapy for a prior DSM IV Axis I mood disorder that is in remission
* Able to understand and provide informed consent
* Able to participate in a 38-week study

Exclusion Criteria:

* Patients \< 18 years old
* Primary DSM IV Axis I anxiety disorder other than GAD (e.g., panic disorder with or without agoraphobia, phobia disorder, acute stress disorder, social anxiety disorder, obsessive-compulsive disorder, post-traumatic stress disorder, substance-induced anxiety disorder)
* Current DSM IV Axis I psychotic disorder
* Substance abuse or dependence within the prior 3 months
* Current DSM IV Axis I bipolar or major depressive disorder \[Note: Patients with co-morbid depressive disorder NOS (e.g., minor depression, recurrent brief depressive disorder, or premenstrual dysphoric disorder (PMDD)\] will not be excluded
* Unstable medical condition
* Allergy to chamomile
* Documented allergy to plants of the asteraceae family (e.g., ragweed, asters, chrysanthemum)
* Allergic to mugwort or birch pollen
* Concurrent anti-anxiety tranquilizer, antidepressant or mood stabilizer therapy
* Concurrent use of over-the-counter anti-anxiety and/or antidepressant preparations (e.g., chamomile, St. John's Wort, kava kava)
* Concurrent use of established antidepressant, mood stabilizer, or tranquilizer therapy for pre-existing affective disorder. \[Note: Patients with a history of affective disorder (in remission) who are not currently taking antidepressant, mood stabilizer, or tranquilizer therapy are not excluded from the trial\]
* Women of child-bearing potential not willing to use a medically proven form of contraception
* Positive pregnancy test
* Actively suicidal or suicide attempt within the preceding 12 months

Primary outcomes:
measure: Time to Relapse in Each Treatment Condition.
timeFrame: 26 weeks
Secondary outcomes:
measure: The Proportion of Subjects in Each Treatment Condition Who Relapse.
timeFrame: 26 weeks
measure: Frequency, Severity, and Duration of Treatment-emergent Adverse Events.
timeFrame: 26 weeks
measure: Frequency of Discontinuation Symptoms at the Start of Double-blind Therapy in Each Treatment Condition.
timeFrame: 26 weeks
measure: Frequency of Early Study Discontinuation in Each Treatment Condition.
timeFrame: 26 weeks
Other outcomes:
Locations:
city: Philadelphia
country: United States
facility: Depression Research Unit
state: Pennsylvania
Study officials:
affiliation: University of Pennsylvania
name: Jun J Mao, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Keefe JR, Guo W, Li QS, Amsterdam JD, Mao JJ. An exploratory study of salivary cortisol changes during chamomile extract therapy of moderate to severe generalized anxiety disorder. J Psychiatr Res. 2018 Jan;96:189-195. doi: 10.1016/j.jpsychires.2017.10.011. Epub 2017 Oct 16.
citation: Mao JJ, Xie SX, Keefe JR, Soeller I, Li QS, Amsterdam JD. 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. Epub 2016 Oct 24.
citation: Keefe JR, Amsterdam J, Li QS, Soeller I, DeRubeis R, Mao JJ. Specific expectancies are associated with symptomatic outcomes and side effect burden in a trial of chamomile extract for generalized anxiety disorder. J Psychiatr Res. 2017 Jan;84:90-97. doi: 10.1016/j.jpsychires.2016.09.029. Epub 2016 Sep 30.