Antidepressants, autonomic function, and mortality in patients with coronary heart disease: Data from the heart & soul study

The use of antidepressants in patients with coronary heart disease is a current topic of debate. The aim of this study was to examine whether the use of tricyclic antidepressants (TCA) or selective serotonin reuptake inhibitors (SSRI) is associated with mortality in these patients, and whether the association is mediated by autonomic function. 956 patients (44 TCA users, 89 SSRI users, 823 antidepressant non-users) with stable coronary heart disease were followed for a mean of 7.2 years. Proportional hazard models were used to determine the association of TCA or SSRI use and mortality. Autonomic function was assessed as heart rate variability, plasma and 24-hour urinary norepinephrine. At baseline, TCA users showed lower heart rate variability and higher norepinephrine levels compared to SSRI users and antidepressant non-users. TCA use was associated with increased mortality compared to non-use (adjusted hazard ratio 1.74, 95 confidence interval, 1.12 – 2.69, p = 0.01). Further adjustment for measures of autonomic function reduced the association between TCA use and mortality (hazard ratio 1.27, 95% confidence interval 0.67 – 2.43, p = 0.47). SSRI use was not associated with mortality (hazard ratio 1.15, 95 confidence interval 0.81 – 1.64, p = 0.44). In summary, use of TCA was associated with increased mortality. This association was at least partially mediated by differences in autonomic function. Our findings suggest that TCA should be avoided in patients with coronary heart disease.