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

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...

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Main Authors: Coupland, Carol, Hill, Trevor, Morriss, Richard K., Moore, Michael, Arthur, Antony, Hippisley-Cox, Julia
Format: Article
Published: BMJ Publishing Group 2016
Online Access:https://eprints.nottingham.ac.uk/32510/
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author Coupland, Carol
Hill, Trevor
Morriss, Richard K.
Moore, Michael
Arthur, Antony
Hippisley-Cox, Julia
author_facet Coupland, Carol
Hill, Trevor
Morriss, Richard K.
Moore, Michael
Arthur, Antony
Hippisley-Cox, Julia
author_sort Coupland, Carol
building Nottingham Research Data Repository
collection Online Access
description 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.
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spelling nottingham-325102020-05-04T17:40:46Z https://eprints.nottingham.ac.uk/32510/ 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 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. BMJ Publishing Group 2016-03-23 Article PeerReviewed Coupland, Carol, Hill, Trevor, Morriss, Richard K., Moore, Michael, Arthur, Antony and Hippisley-Cox, Julia (2016) Antidepressant use and risk of cardiovascular outcomes in people aged 20 to 64: cohort study using primary care database. BMJ, 2016 (352). i1350. ISSN 1756-1833 http://dx.doi.org/10.1136/bmj.i1350 doi:10.1136/bmj.i1350 doi:10.1136/bmj.i1350
spellingShingle Coupland, Carol
Hill, Trevor
Morriss, Richard K.
Moore, Michael
Arthur, Antony
Hippisley-Cox, Julia
Antidepressant use and risk of cardiovascular outcomes in people aged 20 to 64: cohort study using primary care database
title Antidepressant use and risk of cardiovascular outcomes in people aged 20 to 64: cohort study using primary care database
title_full Antidepressant use and risk of cardiovascular outcomes in people aged 20 to 64: cohort study using primary care database
title_fullStr Antidepressant use and risk of cardiovascular outcomes in people aged 20 to 64: cohort study using primary care database
title_full_unstemmed Antidepressant use and risk of cardiovascular outcomes in people aged 20 to 64: cohort study using primary care database
title_short Antidepressant use and risk of cardiovascular outcomes in people aged 20 to 64: cohort study using primary care database
title_sort antidepressant use and risk of cardiovascular outcomes in people aged 20 to 64: cohort study using primary care database
url https://eprints.nottingham.ac.uk/32510/
https://eprints.nottingham.ac.uk/32510/
https://eprints.nottingham.ac.uk/32510/