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

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

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.

Study Overview

• Status: Completed
• Conditions: Social Anxiety Disorder
• Intervention / Treatment: Behavioral: Group Cognitive Behavioral Therapy; Drug: Sugar Pill; Drug: Yohimbine Hydrochloride

Detailed 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.

• Study Type: Interventional
• Enrollment (Actual): 40
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Boston University
  • Texas
    • Dallas, Texas, United States, 75206
      • Southern Methodist University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 61 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Sugar Pill; Participants will receive placebo (sugar pill) augmented Group Cognitive Behavioral Therapy	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: 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.
Experimental: Yohimbine Hydrochloride; Participants will receive Yohimbine Hydrochloride augmented Group Cognitive Behavioral Therapy	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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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

Collaborators and Investigators

• Sponsor: Southern Methodist University
• Investigators: Principal Investigator: Michael W Otto, Ph.D., Boston University; Principal Investigator: Jasper Smits, Ph.D., Southern Methodist University

Publications and helpful links

General Publications

• 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.
• Smits JA, Rosenfield D, Davis ML, Julian K, Handelsman PR, Otto MW, Tuerk P, Shiekh M, Rosenfield B, Hofmann SG, Powers MB. Yohimbine enhancement of exposure therapy for social anxiety disorder: a randomized controlled trial. Biol Psychiatry. 2014 Jun 1;75(11):840-6. doi: 10.1016/j.biopsych.2013.10.008. Epub 2013 Oct 16.

Helpful Links

• BU Center for Anxiety and Related Disorders

Study record dates

Study Major Dates

• Study Start: March 1, 2009
• Primary Completion (Actual): January 1, 2013
• Study Completion (Actual): January 1, 2013

Study Registration Dates

• First Submitted: August 12, 2009
• First Submitted That Met QC Criteria: August 12, 2009
• First Posted (Estimate): August 13, 2009

Study Record Updates

• Last Update Posted (Estimate): November 11, 2013
• Last Update Submitted That Met QC Criteria: September 6, 2013
• Last Verified: September 1, 2013

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Phobic Disorders; Anxiety Disorders; Phobia, Social; Physiological Effects of Drugs; Adrenergic Antagonists; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Urological Agents; Adrenergic alpha-Antagonists; Mydriatics; Adrenergic alpha-2 Receptor Antagonists; Yohimbine
• Other Study ID Numbers: KS09-088