Joanna M Biernacka1, Susan L McElroy2, Scott Crow3, Alexis Sharp4, Joachim Benitez5, Marin Veldic4, Simon Kung4, Julie M Cunningham6, Robert M Post7, David Mrazek4, Mark A Frye8. 1. Department of Psychiatry and Psychology, Mayo Clinic, Rochester, MN, United States; Department of Health Sciences Research, Mayo Clinic, Rochester, MN, United States. Electronic address: biernacka.joanna@mayo.edu. 2. Lindner Center of HOPE, Mason, OH, United States; University of Cincinnati College of Medicine, Cincinnati, OH, United States; The Bipolar Collaborative Network, Bethesda, MD, United States. 3. Department of Psychiatry, University of Minnesota, Minneapolis, MN, United States. 4. Department of Psychiatry and Psychology, Mayo Clinic, Rochester, MN, United States. 5. Department of Psychiatry, Austin Medical Center, Mayo Health System, Austin, MN, United States. 6. Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, United States. 7. The Bipolar Collaborative Network, Bethesda, MD, United States. 8. Department of Psychiatry and Psychology, Mayo Clinic, Rochester, MN, United States; The Bipolar Collaborative Network, Bethesda, MD, United States.
Abstract
BACKGROUND: Antidepressants can trigger a rapid mood switch from depression to mania. Identifying genetic risk factors associated with antidepressant induced mania (AIM) may enable individualized treatment strategies for bipolar depression. This review and meta-analysis evaluates the evidence for association between the serotonin transporter gene promoter polymorphism (5HTTLPR) and AIM. METHODS: Medline up to November 2009 was searched for key words bipolar, antidepressant, serotonin transporter, SLC6A4, switch, and mania. RESULTS: Five studies have evaluated the SLC6A4 promoter polymorphism and AIM in adults (total N=340 AIM+ cases, N=543 AIM- controls). Although a random effects meta-analysis showed weak evidence of association of the S allele with AIM+ status, a test of heterogeneity indicated significant differences in estimated genetic effects between studies. A similar weak association was observed in a meta-analysis based on a subset of three studies that excluded patients on mood stabilizers; however the result was again not statistically significant. LIMITATIONS: Few pharmacogenomic studies of antidepressant treatment of bipolar disorder have been published. The completed studies were underpowered and often lacked important phenotypic information regarding potential confounders such as concurrent use of mood stabilizers or rapid cycling. CONCLUSIONS: There is insufficient published data to confirm an association between 5HTTLPR and antidepressant induced mania. Pharmacogenomic studies of antidepressant induced mania have high potential clinical impact provided future studies are of adequate sample size and include rigorously assessed patient characteristics (e.g. ancestry, rapid cycling, concurrent mood stabilization, and length of antidepressant exposure).
BACKGROUND: Antidepressants can trigger a rapid mood switch from depression to mania. Identifying genetic risk factors associated with antidepressant induced mania (AIM) may enable individualized treatment strategies for bipolar depression. This review and meta-analysis evaluates the evidence for association between the serotonin transporter gene promoter polymorphism (5HTTLPR) and AIM. METHODS: Medline up to November 2009 was searched for key words bipolar, antidepressant, serotonin transporter, SLC6A4, switch, and mania. RESULTS: Five studies have evaluated the SLC6A4 promoter polymorphism and AIM in adults (total N=340 AIM+ cases, N=543 AIM- controls). Although a random effects meta-analysis showed weak evidence of association of the S allele with AIM+ status, a test of heterogeneity indicated significant differences in estimated genetic effects between studies. A similar weak association was observed in a meta-analysis based on a subset of three studies that excluded patients on mood stabilizers; however the result was again not statistically significant. LIMITATIONS: Few pharmacogenomic studies of antidepressant treatment of bipolar disorder have been published. The completed studies were underpowered and often lacked important phenotypic information regarding potential confounders such as concurrent use of mood stabilizers or rapid cycling. CONCLUSIONS: There is insufficient published data to confirm an association between 5HTTLPR and antidepressant induced mania. Pharmacogenomic studies of antidepressant induced mania have high potential clinical impact provided future studies are of adequate sample size and include rigorously assessed patient characteristics (e.g. ancestry, rapid cycling, concurrent mood stabilization, and length of antidepressant exposure).
Authors: Mark A Frye; Allen Doederlein; Barbara Koenig; Susan L McElroy; Malik Nassan; Lisa R Seymour; Joanna M Biernacka; Allen S Daniels Journal: Bipolar Disord Date: 2015-08-20 Impact factor: 6.744
Authors: Isabella Pacchiarotti; David J Bond; Ross J Baldessarini; Willem A Nolen; Heinz Grunze; Rasmus W Licht; Robert M Post; Michael Berk; Guy M Goodwin; Gary S Sachs; Leonardo Tondo; Robert L Findling; Eric A Youngstrom; Mauricio Tohen; Juan Undurraga; Ana González-Pinto; Joseph F Goldberg; Ayşegül Yildiz; Lori L Altshuler; Joseph R Calabrese; Philip B Mitchell; Michael E Thase; Athanasios Koukopoulos; Francesc Colom; Mark A Frye; Gin S Malhi; Konstantinos N Fountoulakis; Gustavo Vázquez; Roy H Perlis; Terence A Ketter; Frederick Cassidy; Hagop Akiskal; Jean-Michel Azorin; Marc Valentí; Diego Hidalgo Mazzei; Beny Lafer; Tadafumi Kato; Lorenzo Mazzarini; Anabel Martínez-Aran; Gordon Parker; Daniel Souery; Ayşegül Ozerdem; Susan L McElroy; Paolo Girardi; Michael Bauer; Lakshmi N Yatham; Carlos A Zarate; Andrew A Nierenberg; Boris Birmaher; Shigenobu Kanba; Rif S El-Mallakh; Alessandro Serretti; Zoltan Rihmer; Allan H Young; Georgios D Kotzalidis; Glenda M MacQueen; Charles L Bowden; S Nassir Ghaemi; Carlos Lopez-Jaramillo; Janusz Rybakowski; Kyooseob Ha; Giulio Perugi; Siegfried Kasper; Jay D Amsterdam; Robert M Hirschfeld; Flávio Kapczinski; Eduard Vieta Journal: Am J Psychiatry Date: 2013-11 Impact factor: 18.112
Authors: Eva Lindholm Carlström; Peter Saetre; Anders Rosengren; Johan H Thygesen; Srdjan Djurovic; Ingrid Melle; Ole A Andreassen; Thomas Werge; Ingrid Agartz; Håkan Hall; Lars Terenius; Erik G Jönsson Journal: Behav Brain Funct Date: 2012-05-17 Impact factor: 3.759
Authors: Mark A Frye; Susan L McElroy; Manuel Fuentes; Bruce Sutor; Kathryn M Schak; Christine W Galardy; Brian A Palmer; Miguel L Prieto; Simon Kung; Christopher L Sola; Euijung Ryu; Marin Veldic; Jennifer Geske; Alfredo Cuellar-Barboza; Lisa R Seymour; Nicole Mori; Scott Crowe; Teresa A Rummans; Joanna M Biernacka Journal: Int J Bipolar Disord Date: 2015-06-24
Authors: Alfredo B Cuéllar-Barboza; Susan L McElroy; Marin Veldic; Balwinder Singh; Simon Kung; Francisco Romo-Nava; Nicolas A Nunez; Alejandra Cabello-Arreola; Brandon J Coombes; Miguel Prieto; Hannah K Betcher; Katherine M Moore; Stacey J Winham; Joanna M Biernacka; Mark A Frye Journal: Int J Bipolar Disord Date: 2020-07-04