Antidepressants, autonomic function and mortality in patients with coronary heart disease: data from the Heart and Soul Study

Psychol Med. 2014 Oct;44(14):2975-84. doi: 10.1017/S003329171400066X. Epub 2014 Mar 25.


Background: Antidepressants reduce depressive symptoms in patients with coronary heart disease, but they may be associated with increased mortality. This study aimed to examine whether the use of tricyclic antidepressants (TCA) or selective serotonin reuptake inhibitors (SSRI) is associated with mortality in patients with coronary heart disease, and to determine whether this association is mediated by autonomic function.

Method: A total of 956 patients with coronary heart disease were followed for a mean duration of 7.2 years. Autonomic function was assessed as heart rate variability, and plasma and 24-h urinary norepinephrine.

Results: Of 956 patients, 44 (4.6%) used TCA, 89 (9.3%) used SSRI, and 823 (86.1%) did not use antidepressants. At baseline, TCA users exhibited lower heart rate variability and higher norepinephrine levels compared with SSRI users and antidepressant non-users. At the end of the observational period, 52.3% of the TCA users had died compared with 38.2% in the SSRI group and 37.3% in the control group. The adjusted hazard ratio (HR) for TCA use compared with non-use was 1.74 [95% confidence interval (CI) 1.12-2.69, p = 0.01]. Further adjustment for measures of autonomic function reduced the association between TCA use and mortality (HR = 1.27, 95% CI 0.67-2.43, p = 0.47). SSRI use was not associated with mortality (HR = 1.15, 95% CI 0.81-1.64, p = 0.44).

Conclusions: The 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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Aged
  • Antidepressive Agents, Tricyclic / adverse effects*
  • Autonomic Nervous System / drug effects*
  • Coronary Disease / mortality*
  • Coronary Disease / psychology
  • Female
  • Heart Rate / drug effects
  • Humans
  • Male
  • Middle Aged
  • Norepinephrine / urine
  • Selective Serotonin Reuptake Inhibitors / adverse effects*
  • Treatment Outcome


  • Antidepressive Agents, Tricyclic
  • Serotonin Uptake Inhibitors
  • Norepinephrine