Long Term Chamomile Therapy for Anxiety

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).

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