| Summary: | Rationale/statement of the problem: Although tricyclic antidepressants (TCAs) are not recommended as first line therapy for depression in patients with coronary heart disease (CHD), they are still occasionally prescribed. Rationales may include resistance to other classes of antidepressants, previous response to TCAs, or treatment continuation after onset of a CHD. Despite their antidepressive effectiveness, TCAs may worsen cardiovascular prognosis because of autonomic side effects. Here, we examined potential adverse effects of TCAs on autonomic function as marked by heart rate variability (HRV) and norepinephrine (NE) levels. Methods: A total of 956 outpatients with stable CHD, 44 used TCAs. All patients were prospectively followed for 7.2±2.6 years. Standard deviation of all normal RR intervals (SDNN) as a measure of HRV was calculated from 24 h-electrocardiographic recordings. NE levels were measured in plasma and 24 h-urinary samples. We also calculated hazard ratios for all-cause mortality. Results: Users of TCAs had an increased risk of mortality compared to non-users (p=0.02 in an unadjusted model, p=0.01 in a model adjusted for age, sex, smoking, diabetes, congestive heart failure and depressive symptoms). When additionally adjusted for HRV and plasma NE, there was no significant association of TCA use and mortality. TCA users had an increased risk of being in the lowest tertile of HRV (p<0.01) and in the highest tertile of urinary NE (p<0.01) and plasma NE (p<0.01). Adjustment for age, sex, smoking, diabetes, congestive heart failure and depressive symptoms did not significantly change the results. Conclusion: Use of TCAs was associated with increased mortality in patients with CHD. Unfavourable changes in autonomic function as marked by low HRV and high NE levels might be a potential mechanism.
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