A Double-Blind Randomized Controlled Trial of Augmentation and Switch Strategies for Refractory Social Anxiety Disorder

• Published in: The American journal of psychiatry 2014-01, Vol.171 (1), p.44-53
• Main Authors: Pollack, Mark H., Van Ameringen, Michael, Simon, Naomi M., Worthington, John W., Hoge, Elizabeth A., Keshaviah, Aparna, Stein, Murray B.
• Format: Article
• Language: English
• Subjects: Adult; Anti-Anxiety Agents - administration & dosage; Anti-Anxiety Agents - therapeutic use; Anxiety; Clonazepam - administration & dosage; Clonazepam - therapeutic use; Cyclohexanols - administration & dosage; Cyclohexanols - therapeutic use; Double-Blind Method; Drug Administration Schedule; Drug Therapy, Combination; Fear & phobias; Female; Humans; Male; Middle Aged; Phobic Disorders - drug therapy; Psychotropic drugs; Sertraline - administration & dosage; Sertraline - therapeutic use; Severity of Illness Index; Socialization; Treatment Outcome; Venlafaxine Hydrochloride
• ISSN: 0002-953X; 1535-7228
• DOI: 10.1176/appi.ajp.2013.12101353

Adding clonazepam increases the likelihood of response in patients with social anxiety disorder who remain symptomatic after a trial with an SSRI, supporting the common clinical practice of combining a benzodiazepine with an SSRI. Among 181 nonresponders to sertraline alone, those who had up to 3 mg/day of clonazepam added to sertraline had a response rate of 56% after 12 weeks, compared with 36% for those who continued to take sertraline alone and 46% for patients switched to venlafaxine. Remission rates were 27%, 17%, and 19%, respectively, but did not show a statistical difference. ObjectiveMost patients remain symptomatic after an initial intervention with approved treatments for generalized social anxiety disorder. This randomized controlled trial provides systematic, prospectively derived data on the relative benefits of “next-step” pharmacotherapies to improve outcomes for individuals with generalized social anxiety disorder who remain symptomatic after initial treatment.MethodThis three site, 12-week, double-blind randomized controlled trial compared the relative benefits of three strategies for patients remaining symptomatic (Liebowitz Social Anxiety Scale [LSAS] score >50) after a 10-week trial of sertraline alone: the addition of up to 3.0 mg/day of clonazepam (sertraline plus clonazepam), a switch to up to 225 mg/day of venlafaxine, or prolonged sertraline treatment with placebo (sertraline plus placebo).ResultsA total of 397 participants received at least one dose of sertraline; 181 nonresponders (LSAS score >50) at week 10 were randomly assigned to sertraline plus clonazepam, switch to venlafaxine, or sertraline plus placebo. Overall, 21% of patients achieved remission (LSAS score ≤30) at the endpoint, and 27% of patients assigned to sertraline plus clonazepam achieved remission compared with patients assigned to sertraline plus placebo (17%) or venlafaxine (19%), but the differences did not reach significance. Sertraline plus clonazepam was associated with a significantly greater drop in LSAS severity (p=0.020) and disability (p=0.0028) compared with sertraline plus placebo; no significant differences were observed on these parameters between venlafaxine and either sertraline plus placebo or sertraline plus clonazepam. In supplemental analysis, the overall response rate (LSAS score ≤50) was 46%, including a significantly greater proportion of patients in the sertraline plus clonazepam group (56%) compared with the sertraline plus placebo gro