title: Role of atypical antipsychotics in the treatment of generalized anxiety disorder.
abstract: 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.
authors.affiliation: VISN 4 Mental Illness Research, Education and Clinical Center at Philadelphia VA Medical Center, 3900 Woodland Ave, Philadelphia, PA, 19104, USA, rhersh@mail.med.upenn.edu.
authors.forename: Rachel
authors.initials: R
authors.lastname: Hershenberg
authors.forename: Daniel F
authors.initials: DF
authors.lastname: Gros
authors.forename: Olga
authors.initials: O
authors.lastname: Brawman-Mintzer
mesh_terms: D014150:Antipsychotic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001008:Anxiety Disorders / Q000188:drug therapy* / Q000523:psychology; D000068180:Aripiprazole; D001569:Benzodiazepines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D002986:Clinical Trials as Topic; D003987:Dibenzothiazepines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D005793:Generalization, Psychological / Q000187:drug effects*; D006801:Humans; D000077152:Olanzapine; D010879:Piperazines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D000069348:Quetiapine Fumarate; D015363:Quinolones / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D018967:Risperidone / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D014150:Antipsychotic Agents; D003987:Dibenzothiazepines; D010879:Piperazines; D015363:Quinolones; D001569:Benzodiazepines; D000069348:Quetiapine Fumarate; D000068180:Aripiprazole; D018967:Risperidone; D000077152:Olanzapine