Improving Treatment Outcomes in Pharmacotherapy of Generalized Social Anxiety Disorder

Social Phobia Clinical Trial

Official title:

Improving Outcomes in Pharmacotherapy of Social Phobia

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00282828
• Other study ID #: R01MH070919
• Secondary ID: R01MH070919PA-01
• Status: Completed
• Phase: Phase 4
• First received: January 25, 2006
• Last updated: August 8, 2013
• Start date: March 2006
• Est. completion date: December 2011

Study information

• Verified date: August 2013
• Source: Massachusetts General Hospital
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal GovernmentCanada: Health Canada
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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 22.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 397
• Est. completion date: December 2011
• Est. primary completion date: December 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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, with the exception of psychostimulants to treat ADHD; 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)

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Anxiety Disorders
• Social Phobia

Intervention

Drug:
• Sertraline

• Venlafaxine

• Placebo

• Clonazepam

Locations

Country	Name	City	State
Canada	McMaster University Medical Centre Anxiety Disorders Clinic	Hamilton	Ontario
United States	Center for Anxiety and Traumatic Stress Disorders	Boston	Massachusetts
United States	University of California San Diego	La Jolla	California

Sponsors (2)

Lead Sponsor	Collaborator
Massachusetts General Hospital	National Institute of Mental Health (NIMH)

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Rates of Remission (LSAS=30) After 12 Weeks of Randomized Treatment During Phase II, Among Phase I Non-responders	The Liebowitz Social Anxiety Scale (LSAS) is a 24-item scale assessing fear and avoidance in social and performance situations; it is widely used in studies of pharmacological treatment of Generalized Social Anxiety Disorder (GSAD). Scores on the LSAS range from 0 to 144, with higher scores indicating greater pathology.	Measured at Week 22 (Endpoint)	No
Secondary	Post-treatment Social Phobia Severity as Defined by Endpoint LSAS Scores	The Liebowitz Social Anxiety Scale (LSAS) is a 24-item scale assessing fear and avoidance in social and performance situations; it is widely used in studies of pharmacological treatment of Generalized Social Anxiety Disorder (GSAD). We analyzed the overall change in LSAS (last Phase II LSAS minus Week 10 LSAS). Higher numbers reflect greater drops in social anxiety disorder severity. Scores on the LSAS range from 0 to 144, with higher scores indicating greater pathology.	Change from Week 10 to Week 22	No

External Links

•   Click here for the Anxiety Disorders Association of America website
•   Click here for the Center for Anxiety and Traumatic Stress Disorders at Massachusetts General Hospital website
•   Please click here for UCSD Anxiety and Traumatic Stress Disorders Research Program