Review ArticlesTreating Generalized Anxiety Disorder With Second Generation Antipsychotics: A Systematic Review and Meta-AnalysisLalonde, Carlos D. MD, FRCPC*; Van Lieshout, Ryan J. MD, FRCPC†Author Information From the *Homewood Health Centre, Guelph; and †Department of Psychiatry and Behavioural Neurosciences and Offord Centre for Child Studies, McMaster University, Hamilton, Ontario, Canada. Received February 4, 2010; accepted after revision March 17, 2011. Reprints: Ryan J. Van Lieshout, MD, FRCPC, Department of Psychiatry and Behavioural Neurosciences, McMaster University, Hamilton Health Sciences, Chedoke Division, Box 2000, Central Building Rm 304, 1200 Main Street W, Hamilton, Ontario, Canada L8N 3Z5 (e-mail: email@example.com). Dr Lalonde has no sources of support to declare. Dr Van Lieshout is supported by a Canadian Institutes of Health Research Fellowship. Supplemental digital contents are available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Web site (www.psychopharmacology.com). Journal of Clinical Psychopharmacology: June 2011 - Volume 31 - Issue 3 - p 326-333 doi: 10.1097/JCP.0b013e31821b2b3f Buy SDC Metrics AbstractIn Brief Most individuals with generalized anxiety disorder (GAD) fail to achieve remission despite standard treatments. As a result, we examined the efficacy and tolerability of second-generation antipsychotics (SGAs) as (a) augmentation or (b) monotherapy for GAD. We searched MEDLINE, EMBASE, PsycINFO, the Cochrane Library, controlled trials databases, and the abstracts of scientific meetings for all trials of GAD treatment with SGAs in adults. Randomized, double-blind, parallel-group trials examining SGA augmentation and monotherapy were meta-analyzed. Five augmentation studies containing 912 adults with refractory GAD indicated that SGA augmentation was not more likely to produce clinical response or remission than placebo and was associated with an increased risk of all-cause discontinuation (relative risk [RR] = 1.43; 95% confidence interval [CI], 1.04-1.96). There was no difference in the Hamilton Anxiety Rating Scale on change from baseline or weight gain between groups. Four SGA monotherapy studies containing 1383 patients with GAD indicated that treatment with 150 mg of quetiapine was more likely to lead to a clinical response (RR = 1.31; 95% CI, 1.20-1.44), remission (RR = 1.44; 95% CI, 1.23-1.68), and a greater decrease in the Hamilton Anxiety Rating Scale score (−3.66; 95% CI, −5.13 to −2.19) than placebo. However, an increased risk of all-cause discontinuation (RR = 1.30; 95% CI, 1.09-1.54) and weight gain (2.2 lb; 95% CI, 1.16-3.24) was observed. Existing data suggest that SGAs are not superior to placebo as augmentation for refractory GAD. Quetiapine monotherapy is more efficacious than placebo for uncomplicated GAD, but issues with adverse effects and tolerability may limit its use. Supplemental Digital Content is available in the text. © 2011 Lippincott Williams & Wilkins, Inc.