Alexander Viktorin1, Eleonore Rydén1, Michael E Thase1, Zheng Chang1, Cecilia Lundholm1, Brian M D'Onofrio1, Catarina Almqvist1, Patrik K E Magnusson1, Paul Lichtenstein1, Henrik Larsson1, Mikael Landén1. 1. From the Department of Medical Epidemiology and Biostatistics and the Department of Clinical Neuroscience, Karolinska Institutet, Stockholm; the Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York; the Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia; the Department of Psychological and Brain Sciences, Indiana University, Bloomington; Astrid Lindgren Children's Hospital, Karolinska University Hospital, Stockholm; the Department of Medical Sciences, Örebro University, Örebro, Sweden; and the Institute of Neuroscience and Physiology, University of Gothenburg, Gothenburg, Sweden.
Abstract
OBJECTIVE: The authors sought to determine the risk of treatment-emergent mania associated with methylphenidate, used in monotherapy or with a concomitant mood-stabilizing medication, in patients with bipolar disorder. METHOD: Using linked Swedish national registries, the authors identified 2,307 adults with bipolar disorder who initiated therapy with methylphenidate between 2006 and 2014. The cohort was divided into two groups: those with and those without concomitant mood-stabilizing treatment. To adjust for individual-specific confounders, including disorder severity, genetic makeup, and early environmental factors, Cox regression analyses were used, conditioning on individual to compare the rate of mania (defined as hospitalization for mania or a new dispensation of stabilizing medication) 0-3 months and 3-6 months after medication start following nontreated periods. RESULTS: Patients on methylphenidate monotherapy displayed an increased rate of manic episodes within 3 months of medication initiation (hazard ratio=6.7, 95% CI=2.0-22.4), with similar results for the subsequent 3 months. By contrast, for patients taking mood stabilizers, the risk of mania was lower after starting methylphenidate (hazard ratio=0.6, 95% CI=0.4-0.9). Comparable results were observed when only hospitalizations for mania were counted. CONCLUSIONS: No evidence was found for a positive association between methylphenidate and treatment-emergent mania among patients with bipolar disorder who were concomitantly receiving a mood-stabilizing medication. This is clinically important given that up to 20% of people with bipolar disorder suffer from comorbid ADHD. Given the markedly increased hazard ratio of mania following methylphenidate initiation in bipolar patients not taking mood stabilizers, careful assessment to rule out bipolar disorder is indicated before initiating monotherapy with psychostimulants.
OBJECTIVE: The authors sought to determine the risk of treatment-emergent mania associated with methylphenidate, used in monotherapy or with a concomitant mood-stabilizing medication, in patients with bipolar disorder. METHOD: Using linked Swedish national registries, the authors identified 2,307 adults with bipolar disorder who initiated therapy with methylphenidate between 2006 and 2014. The cohort was divided into two groups: those with and those without concomitant mood-stabilizing treatment. To adjust for individual-specific confounders, including disorder severity, genetic makeup, and early environmental factors, Cox regression analyses were used, conditioning on individual to compare the rate of mania (defined as hospitalization for mania or a new dispensation of stabilizing medication) 0-3 months and 3-6 months after medication start following nontreated periods. RESULTS:Patients on methylphenidate monotherapy displayed an increased rate of manic episodes within 3 months of medication initiation (hazard ratio=6.7, 95% CI=2.0-22.4), with similar results for the subsequent 3 months. By contrast, for patients taking mood stabilizers, the risk of mania was lower after starting methylphenidate (hazard ratio=0.6, 95% CI=0.4-0.9). Comparable results were observed when only hospitalizations for mania were counted. CONCLUSIONS: No evidence was found for a positive association between methylphenidate and treatment-emergent mania among patients with bipolar disorder who were concomitantly receiving a mood-stabilizing medication. This is clinically important given that up to 20% of people with bipolar disorder suffer from comorbid ADHD. Given the markedly increased hazard ratio of mania following methylphenidate initiation in bipolarpatients not taking mood stabilizers, careful assessment to rule out bipolar disorder is indicated before initiating monotherapy with psychostimulants.
Authors: Guilherme Polanczyk; Maurício Silva de Lima; Bernardo Lessa Horta; Joseph Biederman; Luis Augusto Rohde Journal: Am J Psychiatry Date: 2007-06 Impact factor: 18.112
Authors: Björn Wettermark; Niklas Hammar; Carl Michael Fored; C MichaelFored; Andrejs Leimanis; Petra Otterblad Olausson; Ulf Bergman; Ingemar Persson; Anders Sundström; Barbro Westerholm; Måns Rosén Journal: Pharmacoepidemiol Drug Saf Date: 2007-07 Impact factor: 2.890
Authors: Andrew A Nierenberg; Sachiko Miyahara; Tom Spencer; Stephen R Wisniewski; Michael W Otto; Naomi Simon; Mark H Pollack; Michael J Ostacher; Leslie Yan; Rebecca Siegel; Gary S Sachs Journal: Biol Psychiatry Date: 2005-06-01 Impact factor: 13.382
Authors: Ronald C Kessler; Lenard Adler; Russell Barkley; Joseph Biederman; C Keith Conners; Olga Demler; Stephen V Faraone; Laurence L Greenhill; Mary J Howes; Kristina Secnik; Thomas Spencer; T Bedirhan Ustun; Ellen E Walters; Alan M Zaslavsky Journal: Am J Psychiatry Date: 2006-04 Impact factor: 18.112
Authors: Robert L Findling; Elizabeth J Short; Nora K McNamara; Christine A Demeter; Robert J Stansbrey; Barbara L Gracious; Resaca Whipkey; Michael J Manos; Joseph R Calabrese Journal: J Am Acad Child Adolesc Psychiatry Date: 2007-11 Impact factor: 8.829
Authors: Zheng Chang; Laura Ghirardi; Patrick D Quinn; Philip Asherson; Brian M D'Onofrio; Henrik Larsson Journal: Biol Psychiatry Date: 2019-04-17 Impact factor: 13.382
Authors: Lakshmi N Yatham; Sidney H Kennedy; Sagar V Parikh; Ayal Schaffer; David J Bond; Benicio N Frey; Verinder Sharma; Benjamin I Goldstein; Soham Rej; Serge Beaulieu; Martin Alda; Glenda MacQueen; Roumen V Milev; Arun Ravindran; Claire O'Donovan; Diane McIntosh; Raymond W Lam; Gustavo Vazquez; Flavio Kapczinski; Roger S McIntyre; Jan Kozicky; Shigenobu Kanba; Beny Lafer; Trisha Suppes; Joseph R Calabrese; Eduard Vieta; Gin Malhi; Robert M Post; Michael Berk Journal: Bipolar Disord Date: 2018-03-14 Impact factor: 6.744
Authors: Louise Öhlund; Michael Ott; Robert Lundqvist; Mikael Sandlund; Ellinor Salander Renberg; Ursula Werneke Journal: Ther Adv Psychopharmacol Date: 2020-08-06
Authors: Chris Hollis; Qi Chen; Zheng Chang; Patrick D Quinn; Alexander Viktorin; Paul Lichtenstein; Brian D'Onofrio; Mikael Landén; Henrik Larsson Journal: Lancet Psychiatry Date: 2019-06-17 Impact factor: 77.056