Improving Treatment Outcomes in Pharmacotherapy of Generalized Social Anxiety Disorder

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.