Long Term Chamomile Therapy for Anxiety

Phase 3

Completed

Conditions: Generalized Anxiety Disorder

Interventions: Drug: Chamomile (Matricaria recutita)

Registration Number: NCT01072344

Lead Sponsor: University of Pennsylvania

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).

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 180

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Chamomile Extract	Chamomile (Matricaria recutita)	Pharmaceutical grade oral chamomile extract.
Placebo	Chamomile (Matricaria recutita)	Pharmaceutical grade lactose monohydrate.

Primary Outcome Measures

Name	Time	Method
Time to Relapse in Each Treatment Condition.	26 weeks	The primary outcome was time to relapse during continuation therapy, analyzed using Cox proportional hazards. Relapse is dichotomously defined as an increase in CGI/S (a clinician-rated global measure of anxiety's severity) score from ≤ 3 (at study visit 6) to ≥ 4 (on two consecutive scheduled or unscheduled study visits ≥ 2 weeks apart) plus meeting DSM IV-TR criteria for GAD (minus the 6-month time criterion).

Secondary Outcome Measures

Name	Time	Method
The Proportion of Subjects in Each Treatment Condition Who Relapse.	26 weeks	The proportion of subjects in each treatment condition who relapsed after randomization
Frequency of Early Study Discontinuation in Each Treatment Condition.	26 weeks	This is the # of subjects who discontinued the study during randomization phase due to other reasons.
Frequency, Severity, and Duration of Treatment-emergent Adverse Events.	26 weeks	We will report the frequency, severity, and duration of treatment-emergent adverse events by treatment arm.
Frequency of Discontinuation Symptoms at the Start of Double-blind Therapy in Each Treatment Condition.	26 weeks	Discontinuation emergent signs and symptoms checklist (DESS) is a patient-rated measure of the presence and severity of discontinuation symptoms occurring after medication discontinuation. %