ANTIPSYCHOTIC AGENTS IN ANXIETY DISORDERS: AN UMBRELLA REVIEW

Abstract Background Although not approved for the treatment of anxiety (except trifluoperazine) there is ongoing off-label, unapproved use of first-generation antipsychotics (FGAs) and second-generation antipsychotics (SGAs) for anxiety. There have been systematic reviews and meta-analyses on the use of antipsychotics in anxiety disorders, most of which focused on SGAs. Aims and objectives The specific aims of this umbrella review are to: (1) Evaluate the evidence of efficacy of FGAs and SGAs in anxiety disorders as an adjunctive treatment to traditional antidepressant treatments and other non- antipsychotic medications; (2) Compare monotherapy with antipsychotics to first-line treatments for anxiety disorders in terms of effectiveness, risks, and side effects. The review protocol is registered on PROSPERO. (CRD42021237436). Methods: An initial search was undertaken to identify systematic reviews and meta-analyses from inception until 2020, with an updated search completed August 2021 and January 2023. The searches were conducted in PubMed, MEDLINE (Ovid), EMBASE (Ovid), APA PsycInfo (Ovid), CINAHL Complete (EBSCOhost), and the Cochrane Library through hand searches of references of included articles. Review quality was measured using the AMSTAR-2 (A MeaSurement Tool to Assess Systematic Reviews) scale. Results The original and updated searches yielded 1796 and 3744 articles respectively, of which 45 were eligible. After final review, 25 systematic reviews and meta- analyses were included in the analysis. Most of the systematic reviews and meta-analyses were deemed low-quality through AMSTAR-2 with only one review being deemed high-quality. In evaluating the monotherapies with antipsychotics compared to first-line treatments for anxiety disorder there was insufficient evidence due to experimental designs. There was limited evidence suggesting efficacy of antipsychotic agents in anxiety disorders other than quetiapine in generalized anxiety disorder (GAD) and monotherapy or augmentation with olanzapine in meta-analyses. Discussion and conclusions This umbrella review indicates a lack of high-quality studies of antipsychotics in anxiety disorders outside of the use of quetiapine in GAD. Although potentially effective for anxiety, FGAs and SGAs may have risks and side effects that outweigh their efficacy. Further long-term and larger-scale studies of antipsychotics in anxiety are needed. References Katzman MA, Bleau P, Blier P, Chokka P, Kjernisted K, Van Ameringen M, et al. Canadian clinical practice guidelines for the management of anxiety, posttraumatic stress and obsessive-compulsive disorders. BMC Psychiatry. 2014;14 Suppl 1:S1. Nardi AE, Quagliato LA. Benzodiazepines Are Efficacious and Safe for Long-Term Use: Clinical Research Data and More than Sixty Years in the Market. Psychother Psychosom. 2022;91(5):300-303. doi:10.1159/000524730 Patterson B, Van Ameringen M. Augmentation strategies for treatment-resistant anxiety disorders: a systematic review and meta-analysis. Depress Anxiety. 2016;33(8):728-736. doi:10.1002/da.22525 Bystritsky A. Treatment-resistant anxiety disorders. Mol Psychiatry. 2006;11(9):805-14. Saha S, Lim CCW, Cannon DL, Burton L, Bremner M, Cosgrove P, et al. Co-morbidity between mood and anxiety disorders: A systematic review and meta-analysis. Depress Anxiety. 2021;38(3):286-306. Pollack MH. Comorbid anxiety and depression. J Clin Psychiatry 2005;66: 22-29. Pies R. Should psychiatrists use atypical antipsychotics to treat nonpsychotic anxiety? Psychiatry (Edgmont). 2009;6(6): 29-37. Mendels J, Krajewski TF, Huffer V, Taylor RJ, Secunda S, Schless A, et al. Effective short-term treatment of generalized anxiety disorder with trifluoperazine. J Clin Psychiatry. 1986;47(4): 170-174.Citrome L, Kalsekar I, Guo Z, Laubmeier K, Hebden T. Diagnoses associated with use of atypical antipsychotics in a commercial health plan: a claims database analysis. Clin Ther. 2013;35(12): 1867-1875.