Quetiapine augmentation of paroxetine CR for the treatment of refractory generalized anxiety disorder: Preliminary findings
Rationale: More data are needed to guide "next step" strategies for patients with generalized anxiety disorder (GAD) remaining symptomatic despite initial pharmacotherapy. Objective: This study prospectively examined the relative efficacy of quetiapine versus placebo augmentation for individuals with GAD remaining symptomatic with initial paroxetine CR pharmacotherapy. Materials and methods: Adult outpatients with GAD were recruited from 2004 to 2007 at two academic centers. Phase 1 consisted of 10 weeks of open-label paroxetine CR flexibly dosed to a maximum of 62.5 mg/day. Those remaining symptomatic (Hamilton Anxiety Scale [HAM-A]≥7) at week 10 were randomized to quetiapine or placebo augmentation flexibly dosed from 25 to 400 mg/day. Results: For participants receiving paroxetine CR (n=50), there was a significant reduction in HAM-A scores (baseline mean±SD=22.4±4.2 to endpoint mean±SD=11.2±6.9; paired t=12.1, df=49, t<0.0001) with 40% (n=20) achieving remission. Counter to our hypothesis, we did not find significant benefit for quetiapine augmentation of continued paroxetine CR (HAM-A reduction mean±SD=2.6±5.8 points quetiapine, 0.3±5.5 points placebo; t=0.98, df=20, p=n.s.) in the randomized sample (n=22) with relatively minimal additional improvement overall in phase 2. Conclusions: Although conclusions are considered preliminary based on the relatively small sample size, our data do not support the addition of quetiapine to continued paroxetine CR for individuals with GAD who remain symptomatic after 10 weeks of prospective antidepressant pharmacotherapy and suggest that further research examining strategies for GAD refractory to antidepressants is needed. © 2008 Springer-Verlag.
Simon, NM; Connor, KM; Lebeau, RT; Hoge, EA; III, JJW; Zhang, W; Davidson, JRT; Pollack, MH
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