Evidence-based treatment approaches for generalized anxiety disorder (GAD) comprise psychotherapy, pharmacotherapy, or a combination of the two. First-line pharmacotherapy agents include selective serotonin reuptake inhibitors, selective serotonin-norepinephrine reuptake inhibitors, and, in certain European guidelines, pregabalin, which gained European Commission approval. Although short- and long-term efficacy have been established for these agents in controlled trials, response rates of 60–70 % are insufficient, remission rates are relatively modest, and relapse rates considerable. Moreover, questions increasingly arise regarding tolerability and side-effect profiles. As an alternative, antipsychotics have long been of interest for the treatment of anxiety disorders, but investigation had been tempered by their potential for irreversible side effects. With the improved side-effect profiles of atypical antipsychotics, these agents are increasingly being investigated across Axis I disorders. Atypical antipsychotics such as quetiapine, aripiprazole, olanzapine, and risperidone have been shown to be helpful in addressing a range of anxiety and depressive symptoms in individuals with schizophrenia and schizoaffective disorders, and have since been used in the treatment of a range of mood and anxiety disorders. In this article, we review the efficacy and tolerability of atypical antipsychotics as adjunctive therapy and/or monotherapy for individuals with GAD, a currently off-label indication. The most evidence has accumulated for quetiapine. Findings suggest that approximately 50 % of participants tolerate the side effects, most commonly sedation and fatigue. Among this subset, those who continue treatment demonstrate significant reductions in anxiety when used as adjunctive therapy or monotherapy. The appropriateness of the use of antipsychotics in the treatment of GAD is discussed.
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This material is the result of work supported with resources and the use of facilities of the VISN 4 Mental Illness Research, Education, and Clinical Center, Philadelphia Veterans Affairs Medical Center, Philadelphia, PA, USA, and the Ralph H. Johnson Veterans Affairs Medical Center. The views expressed in this article are those of the authors and do not necessarily reflect the position or policy of the Department of Veterans Affairs or the US government. There were no conflicts of interest in the preparation of this manuscript for Drs. Rachel Hershenberg or Daniel F. Gros. Dr. Olga Brawman-Mintzer received grant support from Forest Laboratories.
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Hershenberg, R., Gros, D.F. & Brawman-Mintzer, O. Role of Atypical Antipsychotics in the Treatment of Generalized Anxiety Disorder. CNS Drugs 28, 519–533 (2014). https://doi.org/10.1007/s40263-014-0162-6