Depression, antidepressants and the risk of cardiovascular events and death in older men

Introduction: It is uncertain whether depression and exposure to antidepressants increase the risk of cardiovascular events in later life. This study attempts to clarify whether the risk of cardiovascular events associated with exposure to antidepressant medications varies according to history of depression. Methods: Cohort study of 5522 Australian men aged 70-89 years living in the metropolitan region of Perth, Western Australia, who were followed for novel cardiovascular events over 12 years. Clinical diagnoses followed the International Classification of Diseases (ICD) codes for ischaemic heart disease, cerebrovascular events and depressive disorders. Participants self-reported their use of medications. Other study measures included age, schooling, smoking history and the following concurrent morbidities: diabetes, hypertension, cancer, dementia, and respiratory diseases, gastrointestinal and renal diseases. Results: 374 men (6.8%) had a recorded or current diagnosis of depression and 365 (6.6%) were using an antidepressant. Prevalent depression and antidepressant use were associated with increased mortality hazard, but not the interaction between them (hazard ratio, HR = 0.46, 95%CI = 0.33, 0.65). Depression (HR = 1.50, 95%CI = 1.21, 1.86) and antidepressants (HR = 1.52, 95%CI = 1.20, 1.93) were associated with an increased risk of cardiovascular events, but the interaction term was associated with decreased risk (HR = 0.51, 95%CI = 0.30, 0.87). All analyses were adjusted for other study measures. Discussion: Depression and antidepressant use were associated with an increase in the 12-year risk of cardiovascular events, while antidepressants were associated with a decrease in the risk of cardiovascular events among older men with depression, but not among those without. This suggests that the effect of this interaction on the risk of cardiovascular events may be driven by the ability of antidepressants to lead to clinical improvements in mood.