The purpose of this study is to determine the effectiveness of St. John’s Wort as compared
to placebo (an inactive substance) in the treatment of outpatients with social phobia.
Social Phobia is a prevalent and debilitating condition, with a lifetime prevalence rate to
be 13.3 percent. Socially phobic patients have been found to be functionally impaired in the
areas of education, employment and social relationships, to have poorer quality of life, and
increased suicidal ideation and psychiatric comorbidity. Double-blind studies have found
benzodiazepines, selective and non-selective MAOI inhibitors, several SSRIs, and the
anticonvulsants pregabalin and gabapentin to be effective. However, side effects with these
compounds suggests the need for better tolerated compounds, e.g., in the paroxetine
multi-center trial (the only drug with an FDA approved indication), 27 percent reported
somnolence, 26 percent nausea, and 37 percent of males reported delayed ejaculation; 34
percent of patients discontinued the trial early. There has been considerable worldwide
interest in St. John's Wort (SJW) (Hypericum perforatum) as a treatment of mild to moderate
depression. There have been 23 randomized trials suggesting SJW is more effective than
placebo for the treatment of outpatients with mild to moderate depression. SJW is very well
tolerated with mild side effects observed in only 2.5 percent of cases in a large (3250
patients) drug monitoring study. Pharmacokinetic studies have found Hypericum to have
affinity for serotonin, dopamine and GABA alpha and GABA beta receptors, each of which have
been implicated in social phobia, thus there is a suggestion that SJW may be effective for
This will be a 12-week, double blind, placebo-controlled trial, designed to generate effect
size data that will be used to determine sample size needed to power a definitive study.
Forty patients will be randomized to either SJW (LI 160) or matching placebo. This will be a
flexible-dose design, starting at 300 mg tid to a maximum of 1800 mg total per day. An
intent-to-treat analysis will be employed. Subjects will be evaluated weekly for two weeks,
then bi-weekly thereafter. The primary outcome measure will be the change from baseline to
endpoint on the Liebowitz Social Anxiety Scale.
- Female patients: at least 2 years post-menopausal, surgically sterile, or practicing
a medically acceptable method of contraception.
- Meets DSM-IV criteria for Social Phobia, generalized subtype, lasting 12 months in
duration (phone screening will determine)
- Primary diagnosis of major depression, dysthymia, panic disorder, schizophrenia,
schizo-affective disorder, bipolar disorder, or PTSD
- Substance abuse or dependence in the past 6 months
- Vascular dementia or primary degenerative dementia of the Alzheimer’s type
- Treatment with MAOIs, TCAs, SSRIs, venlafaxine, nefazodone, remeron, citalopram, or
bupropion within 14 days of first visit.
- Fluoxetine within 14 days of first visit.
- Failure to respond to at least two adequate antidepressant trials for social anxiety.
- Investigational drugs within 30 days of baseline
- Known allergy or hypersensitivity to St. John’s Wort
- Currently in behavior therapy for Social Phobia
ALL INQUIRIES WILL UNDERGO A PHONE SCREENING TO DETERMINE WHETHER THEY MEET ELIGIBLITY