Clinical trial NCT00282828
Conditions: Social Phobia
Keywords: Social Anxiety Disorder Pharmacotherapy Genetics Treatment Refractory
Sponsor: Massachusetts General Hospital
Start date: 2006-03-01; Completion date: 2011-12-01
Enrollment: 397 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief 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.

Detailed 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.

Arms: arm 1: Phase I non-responders randomized to this group remained on sertraline at the same dose level as at entry into Phase 2 with the addition of clonazepam up to 3.0mg per day.

Dosing was flexible, permitting clinicians to slow or suspend the titration of the medication because of side effects or response, but patients had to receive no less than 0.5mg of clonazepam per day in order to remain in the study. arm 2: Phase I non-responders randomized to this group switched to venlafaxine with flexible titration up to 225 mg per day.

Dosing was flexible, permitting clinicians to slow or suspend the titration of the medication because of side effects or response, but patients had to receive no less than 75 mg venlafaxine per day in order to remain in the study. arm 3: Phase I non-responders randomized to this group remained on sertraline at the same dose level as at entry into Phase 2 with the addition of placebo.

Dosing was flexible, permitting clinicians to slow or suspend the titration of the medication because of side effects or response, but patients had to receive no less than 1 capsule of placebo per day in order to remain in the study.
Interventions: intervention 1: Sertraline intervention 2: Venlafaxine intervention 3: Placebo intervention 4: Clonazepam
Intervention descriptions: intervention 1: None intervention 2: None intervention 3: None intervention 4: None

Protocol documents: