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Adjunctive Use of Atypical Antipsychotics for Treatment‐Resistant Generalized Anxiety Disorder

Generalized anxiety disorder (GAD) is a common, chronic mental illness that has a significant burden on the patient's quality of life. Treatment for GAD routinely consists of monotherapy with a proven anxiolytic such as an antidepressant or benzodiazepine, but many patients do not respond fully to these drugs, and additional treatment may be needed. Therefore, we reviewed the safety and efficacy of atypical antipsychotics as adjunct therapy to standard GAD pharmacotherapy in patients deemed treatment resistant. We performed a literature search of the MEDLINE database for English‐language articles published from January 1966‐May 2009. Identified articles were evaluated, and only open‐label trials and randomized controlled trials (RCTs) were included in the review. Relevant references from the articles were also evaluated. Only a few reports of large‐scale RCTs that assessed an atypical antipsychotic for treatment‐resistant GAD have been published. Articles were found for five of the eight currently available atypical antipsychotics, but not for asenapine, clozapine, and paliperidone. Several open‐label trials and smaller RCTs support the need for further evaluation of aripiprazole and quetiapine for treatment‐refractory GAD, although one quetiapine trial demonstrated negative results. There is disparate data for risperidone, with one open‐label trial and one small RCT showing positive results and one large RCT showing negative results. One open‐label trial of ziprasidone and one RCT of olanzapine both showed beneficial effects of the drugs. Adverse effects were specific to each agent, with weight gain being the most common, but many studies did not monitor systematically for lipid level, weight, or glucose level changes. Although data suggest efficacy regarding the use of atypical antipsychotics for augmentation of treatment‐refractory GAD, more rigorous studies (large, double‐blind, placebo‐controlled trials) on the safety and efficacy of these agents are needed in order to recommend their use in patients with GAD.