Official Title: “Improving Outcomes in Pharmacotherapy of Social Phobia”

This study will compare the effectiveness of either adding clonazepam or placebo to standard treatment or switching to venlafaxine in treating generalized social anxiety disorder in individuals who have not responded to treatment with sertraline.

Study Type: Interventional

Study Design: Treatment, Randomized, Double Blind (Subject, Investigator, Outcomes Assessor), Dose Comparison, Parallel Assignment, Safety/Efficacy Study

Study Primary Completion Date: March 2011

Generalized social anxiety disorder (GSAD) is one of the most common psychiatric disorders, and often causes significant distress and dysfunction in affected individuals. Although currently available treatments for GSAD are effective, most individuals have residual symptoms after initial psychosocial or psychopharmacologic intervention. Further treatment is necessary for such individuals, but sufficient research has not been done to guide clinicians on what the safest and most effective next step may be. This study will compare the effectiveness of either combining clonazepam or placebo with sertraline or completely switching to venlafaxine in treating GSAD in individuals who have not responded to treatment with sertraline. This study will also examine predictors of treatment response, including factors such as age at disease onset, duration of illness, comorbidities, and genes that influence serotonin and catecholamine metabolism.

Participants in this double-blind study will first partake in an initial 10-week phase in which they will be treated with sertraline. Participants who do not respond to sertraline treatment will proceed to phase two of the study, in which they will be randomly assigned to one of three treatment groups. One group will receive both sertraline and clonazepam, another group will receive both sertraline and placebo, and the third group will receive only venlafaxine. All treatments will continue for 12 weeks. Sertraline and venlafaxine are both FDA-approved for the treatment of GSAD. Clonazepam is widely used for the treatment of anxiety, but is not FDA-approved for the treatment of GSAD. All participants will attend weekly study visits at Weeks 1, 2, 4, 6, 8, and 10. Participants who continue into phase two will attend weekly study visits at Weeks 11-14, 16, 18, 20, and 22. Symptom remission rates and post-treatment social phobia severity will be assessed at Week 20.

Intervention(s) in this Clinical Trial

• Drug: Clonazepam
  • Participants take 0.5 to 3 mg per day of clonazepam for 12 weeks.
• Drug: Venlafaxine
  • Participants take 37.5 to 225 mg per day of venlafaxine for 12 weeks.
• Drug: Sertraline
  • All participants take 50 to 200 mg per day of sertraline for the initial 10 weeks of treatment. Then some participants continue with sertraline and placebo or sertraline and clonazepam for 12 more weeks.
• Drug: Placebo
  • Participants take placebo with the sertraline for 12 weeks.

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: B1
  • Participants will take both sertraline and clonazepam
• Experimental: B2
  • Participants will take venlafaxine only
• Experimental: B3
  • Participants will take both sertraline and placebo

Primary Measures

• Remission rates less than 30 on the Liebowitz Social Anxiety Scale (LSAS)
  • Time Frame: Measured at Week 22
    Safety Issue?: No
• Post-treatment social phobia severity as defined by endpoint LSAS scores
  • Time Frame: Measured at Week 22
    Safety Issue?: No

Secondary Measures

• Treatment response
  • Time Frame: Measured at Week 10
    Safety Issue?: No

Inclusion Criteria:

• Primary psychiatric diagnosis of GSAD as defined by DSM-IV criteria and a score above 60 on the LSAS
• Agrees to use an effective form of contraception throughout the study

Exclusion Criteria:

• Clinically significant abnormalities found upon physical examination, electrocardiogram, and laboratory tests
• History of more than two unsuccessful, adequate treatment trials, indicated by a lack of response to over 10 weeks of any of the following: SSRIs (e.g., 40 mg of paroxetine or its equivalent per day); benzodiazepine (e.g. at least 2.5 mg of clonazepam per day) plus antidepressant (adequate dose as above); monoamine oxidase inhibitors (e.g., 60 mg of phenelzine or its equivalent per day); or a single failed trial of over 10 weeks of venlafaxine ( at least 150 mg per day)
• Pregnant or breastfeeding
• Simultaneous use of other psychotropic medications; participants must discontinue regular benzodiazepine or antidepressant therapy at least two weeks (5 weeks for fluoxetine) prior to study entry; beta-blockers must be discontinued unless they are indicated medically (e.g., for hypertension)
• DSM-IV diagnosis of any of the following: lifetime history of schizophrenia or any other psychosis, mental retardation, organic medical disorder, bipolar disorder, or obsessive compulsive disorder; eating disorder in the past 6 months; alcohol or substance abuse in the past 3 months or dependence within the past 6 months (entry of participants with major depression, dysthymia, panic disorder, generalized anxiety disorder, or post-traumatic stress disorder will be permitted if the social anxiety disorder is judged to be the predominant disorder)
• Significant suicidal ideation as indicated by a score greater than 3 on the Montgomery-Asberg Depression Rating Scale or suicidal behaviors within 6 months prior to study entry
• Significant personality dysfunction that could interfere with study participation
• Serious medical illness or instability for which hospitalization may be likely during the study
• Seizure disorders, with the exception of a childhood history of isolated, non-recurrent febrile seizures
• Any concurrent psychotherapy initiated within 3 months of study entry, or ongoing psychotherapy of any duration directed specifically toward treatment of GSAD (prohibited psychotherapy includes cognitive behavioral therapy or psychodynamic therapy that focuses on exploring specific, dynamic causes of the phobic symptomatology and that provides management skills; general supportive therapy for more than 3 months is acceptable)

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: National Institute of Mental Health (NIMH)

Overall Clinical Trial Officials and Contacts

Mark H. Pollack, MD Principal Investigator Massachusetts General Hospital  

Overall Contact: Nannette N. Herlands, BA 617-726-1570 nherlands@partners.org

Information obtained from ClinicalTrials.gov on November 19, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00282828

Study ID Number: R01 MH70919

ClinicalTrials.gov Identifier: NCT00282828

Health Authority: United States: Federal Government

Click here for the Center for Anxiety and Traumatic Stress Disorders at Massachusetts General Hospital website

Click here for the Anxiety Disorders Association of America website