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Antidepressant use and risk of cardiovascular outcomes in people aged 20 to 64: cohort study using primary care
Carol Coupland1, Trevor Hill1, Richard Morriss2
1Division of Primary Care, School of Medicine, University of Nottingham, Nottingham NG7 2RD, UK.
Insights
Selective serotonin reuptake inhibitors (SSRIs) may reduce myocardial infarction risk in depression patients, particularly fluoxetine. Tricyclic antidepressants showed increased arrhythmia risk initially, while lofepramine was linked to higher heart attack risk.
Area of Science:
- Cardiovascular Medicine
- Psychiatry
- Pharmacology
Background:
- Depression is a prevalent mental health condition associated with increased cardiovascular risk.
- Antidepressant medications are widely prescribed, necessitating an understanding of their cardiovascular safety profiles.
- Previous research has yielded conflicting results regarding the cardiovascular effects of different antidepressant classes.
Purpose of the Study:
- To investigate the associations between various antidepressant treatments and the incidence of myocardial infarction, stroke/transient ischemic attack, and arrhythmia in individuals diagnosed with depression.
- To compare the cardiovascular risks associated with different classes of antidepressants, including tricyclic and related antidepressants (TCAs), selective serotonin reuptake inhibitors (SSRIs), and other antidepressants.
- To examine the impact of specific antidepressant drugs on cardiovascular outcomes.
Main Methods:
- A large-scale cohort study utilizing data from UK general practices within the QResearch primary care database.
- Inclusion of 238,963 patients aged 20-64 with a first-time depression diagnosis between 2000 and 2011.
- Analysis of antidepressant class, dose, duration, and individual drug exposure, with cardiovascular outcomes (myocardial infarction, stroke/TIA, arrhythmia) assessed over five years using Cox proportional hazards models.
Main Results:
- Over five years, no significant association was found between antidepressant class and myocardial infarction. However, SSRIs were linked to a reduced risk of myocardial infarction in the first year, with fluoxetine showing a protective effect and lofepramine an increased risk.
- No significant associations were observed between antidepressant use and the risk of stroke or transient ischemic attack.
- While antidepressant class was not significantly associated with arrhythmia over five years, TCAs showed an increased risk in the first 28 days. Fluoxetine was associated with a reduced arrhythmia risk, whereas citalopram did not show a significant association, even at high doses.
Conclusions:
- The study found no evidence that SSRIs increase the risk of arrhythmia or stroke/transient ischemic attack in depressed patients aged 20-64.
- There is some indication of a reduced risk of myocardial infarction with SSRIs, particularly fluoxetine, and an increased risk with lofepramine.
- Citalopram was not found to be significantly associated with an increased risk of arrhythmia, even at high doses.
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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