Yohimbine to Enhance Cognitive Behavioral Therapy (CBT) for Social Anxiety

The primary aim is to determine the relative efficacy of exposure-based CBT for social
phobia when conducted with adjunctive acute (prior to four of five sessions) administration
of either Yohimbine hydrochloride (10.8 mg) or placebo during core exposure sessions. Based
on the available evidence, the investigators hypothesize that acute treatment with Yohimbine
hydrochloride prior to exposure-based CBT would facilitate the extinction of fear that
occurs with this treatment and would enhance treatment outcome.

Inclusion Criteria:

1. Male or female outpatients between 18 and 65 years of age with a primary psychiatric
diagnosis (designated by the patient as the most important source of current
distress) of non-generalized social anxiety disorder (SAD) or Generalized Social
Anxiety Disorder (GSAD) with a significant fear of public speaking as defined by
DSM-IV criteria.

2. Severity of the social phobia of at least 3 on the CGI scale rated for the severity
of public speaking anxiety

3. Willingness and ability to comply with the requirements of the study protocol.

Exclusion Criteria:

1. A lifetime history of bipolar disorder, schizophrenia, psychosis, delusional
disorders or obsessive-compulsive disorder; an eating disorder in the past 6 months;
organic brain syndrome, mental retardation or other cognitive dysfunction that could
interfere with capacity to engage in therapy; a history of substance (amphetamines,
benzodiazepines, barbiturates, cocaine metabolites, marijuana, narcotics, and
sedative hypnotics) abuse or dependence or alcohol abuse or dependence (other than
nicotine) in the last 6 months or otherwise unable to commit to refraining from
alcohol use during the acute period of study participation.

2. Patients with posttraumatic stress disorder within the past 6 months are excluded.
Entry of patients with other mood or anxiety disorders will be permitted if the
social anxiety disorder is judged to be the predominant disorder, in order to
increase accrual of a clinically relevant sample. Patients with significant suicidal
ideation (BDI item 9 score > 1) or who have enacted suicidal behaviors within 6
months prior to intake will be excluded from study participation and referred for
appropriate clinical intervention.

3. Given that Yohimbine hydrochloride is frequently used as an adjunctive medication in
order to decrease side effects commonly resulting from antidepressant use (Pollack &
Smoller, 1996), antidepressant and anxiolytic medications are acceptable if they are
stabilized for at least 8 weeks prior to the baseline assessments. However,
individuals taking monoamine oxidase inhibitors or tricyclic antidepressants will be
excluded from the study unless they are able and willing to discontinue these
medications prior to baseline screening.

4. Individuals taking antihistamines or strattera (atomoxetine) will be excluded from
the study unless they are able and willing to discontinue these medications prior to
baseline screening

5. Evidence through interview or physical exam of significant general medical condition
(e.g renal, endocrine, hepatic, respiratory, cardiovascular, hematologic, immunologic
or cerebrovascular disease, or malignancy) that may interfere with the interpretation
of safety and efficacy evaluations in the opinion of the prescribing physician.

6. Resting blood pressure ≥ 160 systolic and/or 100 diastolic. Individuals currently
being treated for high blood pressure and meeting these criteria are eligible.

7. Significant personality dysfunction likely to interfere with study participation.

8. Patients with a current or past history of seizures

9. Pregnant women, lactating women, and women of childbearing potential who are not
using medically accepted forms of contraception (e.g., IUD, oral contraceptives,
barrier devices, condoms and foam, or implanted progesterone rods stabilized for at
least 3 months). A urine pregnancy test will be performed on all female subjects of
child-bearing potential at the screening visit.

10. Any concurrent psychotherapy initiated within 3 months of baseline, or ongoing
psychotherapy of any duration directed specifically toward treatment of the SAD is
excluded. Prohibited psychotherapy includes CBT or psychodynamic therapy focusing on
exploring specific, dynamic causes of the phobic symptomatology and provides
management skills. General supportive therapy initiated > 3 months prior is
acceptable.

11. Prior non-response to adequately-delivered exposure (i.e., as defined by the
patient's report of receiving specific and regular exposure assignments as part of a
previous treatment) will exclude participants from the study.

12. Patients with a history of head trauma causing loss of consciousness, seizure or
ongoing cognitive impairment.

13. Patients unable to understand study procedures and participate in the informed
consent process.