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

Abstract

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.

Fig 1 Adjusted hazard ratios (compared with periods of non-use of antidepressants) for arrhythmia for individual antidepressant drugs over 5 years’ follow-up. SSRI=selective serotonin reuptake inhibitor; TCA=tricyclic and related antidepressant

Fig 2 Adjusted hazard ratios (compared with periods of non-use of antidepressants) for myocardial infarction for individual antidepressant drugs over 5 years’ follow-up. SSRI=selective serotonin reuptake inhibitor; TCA=tricyclic and related antidepressant

Fig 3 Adjusted hazard ratios (compared with periods of non-use of antidepressants) for stroke or transient ischaemic attack for individual antidepressant drugs over 5 years’ follow-up. SSRI=selective serotonin reuptake inhibitor; TCA=tricyclic and related antidepressant