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

Social Anxiety Disorder Clinical Trial

Official title:

Placebo-Controlled Evaluation of the Efficacy of Yohimbine Hydrochloride for Enhancing the Effects of CBT for Social Phobia

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00958880
• Other study ID #: KS09-088
• Secondary ID: KS09-088
• Status: Completed
• Phase: Phase 3
• First received: August 12, 2009
• Last updated: September 6, 2013
• Start date: March 2009
• Est. completion date: January 2013

Study information

• Verified date: September 2013
• Source: Southern Methodist University
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 40
• Est. completion date: January 2013
• Est. primary completion date: January 2013
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

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.

Study Design

Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Anxiety Disorders
• Phobic Disorders
• Social Anxiety Disorder

Intervention

Behavioral:
• Group Cognitive Behavioral Therapy
5 weeks of group CBT for Social Anxiety. The aim of CBT is to help participants become more comfortable with social situations One arm will receive placebo augmented Group Cognitive Behavioral Therapy and the other will receive yohimbine hydrochloride augmented cognitive behavioral therapy.

Drug:
• Yohimbine Hydrochloride
Participants in the Yohimbine augmented arm will receive 4 doses of Yohimbine Hydrochloride before 4 of the 5 group cognitive behavioral therapy sessions.
• Sugar Pill
Participants in the placebo (sugar pill) augmented arm will receive 4 doses of a sugar pill before 4 of the 5 group cognitive behavioral therapy sessions.

Locations

Country	Name	City	State
United States	Boston University	Boston	Massachusetts
United States	Southern Methodist University	Dallas	Texas

Sponsors (1)

Lead Sponsor	Collaborator
Southern Methodist University

Country where clinical trial is conducted

United States, 

References & Publications (1)

Powers MB, Smits JA, Otto MW, Sanders C, Emmelkamp PM. Facilitation of fear extinction in phobic participants with a novel cognitive enhancer: a randomized placebo controlled trial of yohimbine augmentation. J Anxiety Disord. 2009 Apr;23(3):350-6. doi: 10.1016/j.janxdis.2009.01.001. Epub 2009 Jan 15. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The Liebowitz Social Anxiety Scale (LSAS)	The Liebowitz Social Anxiety Scale (LSAS) is a self-report measure of social anxiety symptom severity. Scores range from 0 to 144, with higher scores indicating more social anxiety symptoms severity (i.e., a worse outcome).	LSAS means at 1 month follow-up	No
Secondary	Social Phobic Disorders Severity and Change Form	Social Phobic Disorders Severity and Change (SPDSC) Form is a version of the Clinical Global Improvement-Severity scale adapted specifically for clinician ratings of social anxiety disorder symptom severity. The scale ranges from 0 to 5, with higher scores indicating more social anxiety symptoms severity (i.e., worse outcomes). We examined the change in SPDSC scores from baseline to a 1 month follow-up.	CGI change scores from baseline to 1 month follow-up	No

External Links

•   BU Center for Anxiety and Related Disorders