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

The purpose of this study is to investigate the utility of Yohimbine hydrochloride for facilitating fear extinction in a sample of patients with social phobia who will be treated with CBT.

Southern Methodist University
Principal Investigator: 
Jasper Smits, Ph.D., Southern Methodist University; Michael W Otto, Ph.D., Boston University
Eligibility Criteria: 

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


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


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

Exclusion Criteria: 

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


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


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


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


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


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


Significant personality dysfunction likely to interfere with study participation


Patients with a current or past history of seizures


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


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


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


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


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

Pamela R Handelsman, B.A., 214-768-4310, anxiety@smu.edu; Angela C Berry, Ph.D., 617-358-4307, autschig@bu.edu
Boston, MA

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