Review ArticlesAntidepressant-Associated Mania in Bipolar Disorder: A Review and Meta-analysis of Potential Clinical and Genetic Risk FactorsMelhuish Beaupre, Lindsay M. BSc∗,†; Tiwari, Arun K. PhD†,‡; Gonçalves, Vanessa F. PhD†,‡; Lisoway, Amanda J. BSc∗,†; Harripaul, Ricardo S. MSc∗,§; Müller, Daniel J. MD∗,‡,∥; Zai, Clement C. PhD∗,†,‡,¶; Kennedy, James L. MD, FRSC∗,†,‡ Author Information From the ∗Institute of Medical Science, University of Toronto †Molecular Brain Science Research Department, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health ‡Department of Psychiatry, University of Toronto §Molecular Neuropsychiatry & Development (MiND) Lab, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health ∥Pharmacogenetics Research Clinic, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health ¶Laboratory of Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada. Received August 16, 2019; accepted after revision January 1, 2020. Reprints: James L. Kennedy, MD, FRSC, Neurogenetics Section, Tanenbaum Centre for Pharmacogenetics, Campbell Family Mental Health Research Institute, CAMH 250 College Street, M5T 1R8, Toronto, ON, Canada (e-mail: [email protected]); or Clement Zai, PhD, Neurogenetics Section, Tanenbaum Centre for Pharmacogenetics, Campbell Family Mental Health Research Institute, CAMH 250 College Street, M5T 1R8, Toronto, ON, Canada (e-mail: [email protected]). Supplemental digital content is available for this article. Direct URL citation appears in the printed text and is provided in the HTML and PDF versions of this article on the journal’s Web site (www.psychopharmacology.com). C.C.Z. and J.L.K. are co-senior authors. Journal of Clinical Psychopharmacology: 3/4 2020 - Volume 40 - Issue 2 - p 180-185 doi: 10.1097/JCP.0000000000001186 Buy SDC Metrics Abstract Purposes/Background Antidepressants (ADs) play a valuable role in treating the depressive episodes of bipolar disorder. However, 14% of these individuals taking ADs experience AD-associated mania (AAM) within a few weeks of starting treatment. Numerous studies have suggested potential clinical and genetic risk factors. We aimed to conduct a comprehensive systematic review and meta-analysis that integrates the past literature with the recent studies and identifies important predictors for AAM. Methods/Procedures The review was limited to experimentally designed studies that contain the relevant search terms in PubMed and PsychInfo. After removing studies that were in discordance with our criteria, the review included 24 reports examining clinical risk factors and 10 investigating genetic risk factors. Our meta-analysis was conducted on 5 clinical risk factors, each of which had at least 4 articles with extractable data. Findings/Results The only clinical factors in the literature that have been shown to be more indicative of AAM risk are AD monotherapy and tricyclic ADs. Among genetic factors, the serotonin transporter gene polymorphism may play a minor role in AAM. Our meta-analysis provided support for the number of prior depressive episodes. Implications/Conclusion Prevention of AAM may be served by early detection of recurrent depression episodes. Further large-scale longitudinal studies are required to determine the underpinnings of AAM. Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.