Clinical trial NCT00958880: Yohimbine to Enhance Cognitive Behavioral Therapy (CBT) for Social Anxiety
Official title: Placebo-Controlled Evaluation of the Efficacy of Yohimbine Hydrochloride for Enhancing the Effects of CBT for Social Phobia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Social Anxiety Disorder
Lead sponsor: Southern Methodist University
Sponsor class: OTHER
First posted: 2009-08-13
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: The Liebowitz Social Anxiety Scale (LSAS)
timeFrame: LSAS means at 1 month follow-up
Secondary outcomes:
measure: Social Phobic Disorders Severity and Change Form
timeFrame: CGI change scores from baseline to 1 month follow-up
Other outcomes:
Locations:
city: Boston
country: United States
facility: Boston University
state: Massachusetts
city: Dallas
country: United States
facility: Southern Methodist University
state: Texas
Study officials:
affiliation: Southern Methodist University
name: Jasper Smits, Ph.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Boston University
name: Michael W Otto, Ph.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.