AUGMENTATION STRATEGIES FOR TREATMENT-RESISTANT ANXIETY DISORDERS: A SYSTEMATIC REVIEW AND META-ANALYSIS

Abstract

Background: A systematic review and meta-analysis was conducted to explore the efficacy of medication augmentation strategies compared to control treatments in patients who have had a partial or no response to initial treatment for generalized anxiety disorder, social anxiety disorder, and panic disorder.

Methods: Double-blind controlled trials of medication augmentation in adult treatment-resistant anxiety disorders conducted between January 1990 and January 2015 were systematically reviewed and evaluated by two independent raters. The search identified 625 articles; 610 were excluded following abstract review and 15 had full-text screening. Studies had to include a definition of treatment resistance, exclude concomitant medications, and have a parallel or crossover design. Data extraction forms were completed in duplicate.

Results: Six studies were included in the meta-analysis. Effect estimates were calculated using random effects modeling; heterogeneity was assessed and subgroup and sensitivity analyses were completed. Primary outcome was response, defined by Clinical Global Impression-Improvement score of ≤2. Augmentation was not associated with an increased risk of response, as compared with placebo (RR = 1.08, 95% CI = 0.94-1.24). A small significant effect was found in reduction in symptom severity: standard mean difference = -0.32, 95% CI = -0.56 to -0.08. No significant differences between augmentation with medication versus placebo were found in ratings of functional impairment and dropouts due to adverse events.

Conclusions: Augmentation does not appear to be beneficial in treatment-resistant anxiety disorders. These results may be limited by small study samples, and a small number of overall studies in the analysis.

Keywords: GAD/generalized anxiety disorder; SAD/social anxiety disorder/social phobia; antidepressants; anxiety/anxiety disorders; clinical trials; panic attacks/agoraphobia; pharmacotherapy; treatment resistance.