Ole Köhler-Forsberg1, Erik Roj Larsen2, Henriette N Buttenschøn3, Marcella Rietschel4, Joanna Hauser5, Daniel Souery6, Wolfgang Maier7, Anne Farmer8, Peter McGuffin8, Katherine J Aitchison9, Rudolf Uher10, Ole Mors11. 1. Psychosis Research Unit,Aarhus University Hospital - Psychiatry;Department of Clinical Medicine,Aarhus University;and iPSYCH, The Lundbeck Foundation Initiative for Integrative Psychiatric Research,Denmark. 2. Chief Physician,Department of Psychiatry,Psychiatry in the Region of Southern Denmark,Institute of Clinical Research,Research Unit of Psychiatry,University of Southern Denmark,Denmark. 3. Associate Professor,iPSYCH, The Lundbeck Foundation Initiative for Integrative Psychiatric Research;and Translational Neuropsychiatry Unit,Department of Clinical Medicine,Aarhus University,Denmark. 4. Professor,Central Institute of Mental Health,Department of Genetic Epidemiology in Psychiatry,Medical Faculty Mannheim/Heidelberg University,Germany. 5. Professor,Laboratory of Psychiatric Genetics,Department of Psychiatry,Poznan University of Medical Sciences,Poland. 6. Professor,Laboratoire de Psychologie Médicale,Université Libre de Bruxelles;Psy Pluriel - Centre Européen de Psychologie Médicale,Belgium. 7. Professor,Department of Psychiatry,University of Bonn,Germany. 8. Professor,Social, Genetic and Developmental Psychiatry Centre,Institute of Psychiatry, Psychology and Neuroscience,King's College London,UK. 9. Professor,University of Alberta,Canada. 10. Professor,Social, Genetic and Developmental Psychiatry Centre,Institute of Psychiatry,Psychology and Neuroscience,King's College London,UK;and Department of Psychiatry,Dalhousie University,Canada. 11. Professor,Psychosis Research Unit,Aarhus University Hospital - Psychiatry;Department of Clinical Medicine,Aarhus University;and iPSYCH, The Lundbeck Foundation Initiative for Integrative Psychiatric Research,Denmark.
Abstract
BACKGROUND: For patients with major depressive disorder (MDD) experiencing side-effects or non-response to their first antidepressant, little is known regarding the effect of switching between a tricyclic antidepressant (TCA) and a selective serotonin reuptake inhibitor (SSRI).AimsTo compare the switch between the TCA nortriptyline and the SSRI escitalopram. METHOD: Among 811 adults with MDD treated with nortriptyline or escitalopram for up to 12 weeks, 108 individuals switched from nortriptyline to escitalopram or vice versa because of side-effects or non-response (trial registration: EudraCT No.2004-001723-38 (https://eudract.ema.europa.eu/) and ISRCTN No.03693000 (http://www.controlled-trials.com)). Patients were followed for up to 26 weeks after switching and response was measured with the Montgomery-Åsberg Depression Rating scale (MADRS). We performed adjusted mixed-effects linear regression models with full information maximum likelihood estimation reporting β-coefficients with 95% CIs. RESULTS: Switching antidepressants resulted in a significant decrease in MADRS scores. This was present for switchers from escitalopram to nortriptyline (n = 36, β = -0.38, 95% CI -0.51 to -0.25, P<0.001) and from nortriptyline to escitalopram (n = 72, β = -0.34, 95% CI -0.41 to -0.26, P<0.001). Both switching options resulted in significant improvement among individuals who switched because of non-response or side-effects. The results were supported by analyses on other rating scales and symptom dimensions. CONCLUSIONS: These results suggest that switching from a TCA to an SSRI or vice versa after non-response or side-effects to the first antidepressant may be a viable approach to achieve response among patients with MDD.Declarations of interestK.J.A. holds an Alberta Centennial Addiction and Mental Health Research Chair, funded by the Government of Alberta. K.J.A. has been a member of various advisory boards, received consultancy fees and honoraria, and has received research grants from various companies including Johnson and Johnson Pharmaceuticals Research and Development and Bristol-Myers Squibb Pharmaceuticals Limited. D.S. has served on advisory boards for, and received unrestricted grants from, Lundbeck and AstraZeneca. A.F. and P.M. have received honoraria for participating in expert panels for Lundbeck and GlaxoSmithKline.
BACKGROUND: For patients with major depressive disorder (MDD) experiencing side-effects or non-response to their first antidepressant, little is known regarding the effect of switching between a tricyclic antidepressant (TCA) and a selective serotonin reuptake inhibitor (SSRI).AimsTo compare the switch between the TCA nortriptyline and the SSRI escitalopram. METHOD: Among 811 adults with MDD treated with nortriptyline or escitalopram for up to 12 weeks, 108 individuals switched from nortriptyline to escitalopram or vice versa because of side-effects or non-response (trial registration: EudraCT No.2004-001723-38 (https://eudract.ema.europa.eu/) and ISRCTN No.03693000 (http://www.controlled-trials.com)). Patients were followed for up to 26 weeks after switching and response was measured with the Montgomery-Åsberg Depression Rating scale (MADRS). We performed adjusted mixed-effects linear regression models with full information maximum likelihood estimation reporting β-coefficients with 95% CIs. RESULTS: Switching antidepressants resulted in a significant decrease in MADRS scores. This was present for switchers from escitalopram to nortriptyline (n = 36, β = -0.38, 95% CI -0.51 to -0.25, P<0.001) and from nortriptyline to escitalopram (n = 72, β = -0.34, 95% CI -0.41 to -0.26, P<0.001). Both switching options resulted in significant improvement among individuals who switched because of non-response or side-effects. The results were supported by analyses on other rating scales and symptom dimensions. CONCLUSIONS: These results suggest that switching from a TCA to an SSRI or vice versa after non-response or side-effects to the first antidepressant may be a viable approach to achieve response among patients with MDD.Declarations of interestK.J.A. holds an Alberta Centennial Addiction and Mental Health Research Chair, funded by the Government of Alberta. K.J.A. has been a member of various advisory boards, received consultancy fees and honoraria, and has received research grants from various companies including Johnson and Johnson Pharmaceuticals Research and Development and Bristol-Myers Squibb Pharmaceuticals Limited. D.S. has served on advisory boards for, and received unrestricted grants from, Lundbeck and AstraZeneca. A.F. and P.M. have received honoraria for participating in expert panels for Lundbeck and GlaxoSmithKline.
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