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Antidepressant use and risk of cardiovascular outcomes in people aged 20 to 64: Cohort study using primary care database

Coupland, Carol; Hill, Trevor; Morriss, Richard K.; Moore, Michael; Arthur, Antony; Hippisley-Cox, Julia

Authors

CAROL COUPLAND carol.coupland@nottingham.ac.uk
Professor of Medical Statistics

RICHARD MORRISS richard.morriss@nottingham.ac.uk
Professor of Psychiatry and Community Mental Health

Michael Moore

Antony Arthur

Julia Hippisley-Cox



Abstract

© BMJ Publishing Group Ltd 2016. Objective To assess associations between different antidepressant treatments and rates of three cardiovascular outcomes (myocardial infarction, stroke or transient ischaemic attack, and arrhythmia) in people with depression. Design Cohort study. Setting UK general practices contributing to the QResearch primary care database. Participants 238 963 patients aged 20 to 64 years with a first diagnosis of depression between 1 January 2000 and 31 July 2011. Exposures Antidepressant class (tricyclic and related antidepressants, selective serotonin reuptake inhibitors, other antidepressants), dose, duration of use, and commonly prescribed individual antidepressant drugs. Main outcome measures First diagnoses of myocardial infarction, stroke or transient ischaemic attack, and arrhythmia during five years' follow-up. Cox proportional hazards models were used to estimate hazard ratios, adjusting for potential confounding variables. Results During five years of follow-up, 772 patients had a myocardial infarction, 1106 had a stroke or transient ischaemic attack, and 1452 were diagnosed as having arrhythmia. No significant associations were found between antidepressant class and myocardial infarction over five years' follow-up. In the first year of follow-up, patients treated with selective serotonin reuptake inhibitors had a significantly reduced risk of myocardial infarction (adjusted hazard ratio 0.58, 95% confidence interval 0.42 to 0.79) compared with no use of antidepressants; among individual drugs, fluoxetine was associated with a significantly reduced risk (0.44, 0.27 to 0.72) and lofepramine with a significantly increased risk (3.07, 1.50 to 6.26). No significant associations were found between antidepressant class or individual drugs and risk of stroke or transient ischaemic attack. Antidepressant class was not significantly associated with arrhythmia over five years' follow-up, although the risk was significantly increased during the first 28 days of treatment with tricyclic and related antidepressants (adjusted hazard ratio 1.99, 1.27 to 3.13). Fluoxetine was associated with a significantly reduced risk of arrhythmia (0.74, 0.59 to 0.92) over five years, but citalopram was not significantly associated with risk of arrhythmia even at high doses (1.11, 0.72 to 1.71 for doses ≥40 mg/day). Conclusions This study found no evidence that selective serotonin reuptake inhibitors are associated with an increased risk of arrhythmia or stroke/transient ischaemic attack in people diagnosed as having depression between the ages of 20 to 64 or that citalopram is associated with a significantly increased risk of arrhythmia. It found some indication of a reduced risk of myocardial infarction with selective serotonin reuptake inhibitors, particularly fluoxetine, and of an increased risk with lofepramine.

Citation

Coupland, C., Hill, T., Morriss, R. K., Moore, M., Arthur, A., & Hippisley-Cox, J. (2016). Antidepressant use and risk of cardiovascular outcomes in people aged 20 to 64: Cohort study using primary care database. BMJ, 2016(352), Article i1350. https://doi.org/10.1136/bmj.i1350

Journal Article Type Article
Acceptance Date Feb 20, 2016
Online Publication Date Mar 22, 2016
Publication Date Mar 22, 2016
Deposit Date Mar 24, 2016
Publicly Available Date Mar 28, 2024
Journal BMJ (Online)
Print ISSN 0959-8138
Electronic ISSN 1756-1833
Publisher BMJ Publishing Group
Peer Reviewed Peer Reviewed
Volume 2016
Issue 352
Article Number i1350
DOI https://doi.org/10.1136/bmj.i1350
Public URL https://nottingham-repository.worktribe.com/output/779367
Publisher URL https://www.bmj.com/content/352/bmj.i1350