Sertraline Treatment of Major Depression in Patients With Acute MI or Unstable Angina

Abstract

Context Major depressive disorder (MDD) occurs in 15% to 23% of patients with acute coronary syndromes and constitutes an independent risk factor for morbidity and mortality. However, no published evidence exists that antidepressant drugs are safe or efficacious in patients with unstable ischemic heart disease. Objective To evaluate the safety and efficacy of sertraline treatment of MDD in patients hospitalized for acute myocardial infarction (MI) or unstable angina and free of other life-threatening medical conditions. Design and Setting Randomized, double-blind, placebo-controlled trial conducted in 40 outpatient cardiology centers and psychiatry clinics in the United States, Europe, Canada, and Australia. Enrollment began in April 1997 and follow-up ended in April 2001. Patients A total of 369 patients with MDD (64% male; mean age, 57.1 years; mean 17-item Hamilton Depression [HAM-D] score, 19.6; MI, 74%; unstable angina, 26%). Intervention After a 2-week single-blind placebo run-in, patients were randomly assigned to receive sertraline in flexible dosages of 50 to 200 mg/d (n=186) or placebo (n=183) for 24 weeks. Main Outcome Measures The primary (safety) outcome measure was change from baseline in left ventricular ejection fraction (LVEF); secondary measures included surrogate cardiac measures and cardiovascular adverse events, as well as scores on the HAM-D scale and Clinical Global Impression Improvement scale (CGI-I) in the total randomized sample, in a group with any prior history of MDD, and in a more severe MDD subgroup defined a priori by a HAM-D score of at least 18 and history of 2 or more prior episodes of MDD. Results Sertraline had no significant effect on mean (SD) LVEF (sertraline: baseline, 54% [10%]; week 16, 54% [11%]; placebo: baseline, 52% [13%]; week 16, 53% [13%]), treatment-emergent increase in ventricular premature complex (VPC) runs (sertraline: 13.1%; placebo: 12.9%), QTc interval greater than 450 milliseconds at end point (sertraline: 12%; placebo: 13%), or other cardiac measures. All comparisons were statistically nonsignificant (PՆ.05). The incidence of severe cardiovascular adverse events was 14.5% with sertraline and 22.4% with placebo. In the total randomized sample, the CGI-I (P=.049), but not the HAM-D (P=.14), favored sertraline. The CGI-I responder rates for sertraline were significantly higher than for placebo in the total sample (67% vs 53%; P=.01), in the group with at least 1 prior episode of depression (72% vs 51%; P=.003), and in the more severe MDD group (78% vs 45%; P=.001). In the latter 2 groups, both CGI-I and HAM-D measures were significantly better in those assigned to sertraline. Conclusion Our results suggest that sertraline is a safe and effective treatment for recurrent depression in patients with recent MI or unstable angina and without other life-threatening medical conditions.

Postmyocardial Infarction Mortality in Relation to Depression: A Systematic Critical Review

“…In 4 of the 7 studies accepted to be of good quality, non-significant results regarding depression and post-MI mortality were reported [13, 17, 23, 31; ]Appendix 1], whereas in the three other studies a positive relation was reported [[5, 21, 26]; Appendix1]. In 10 of the 20 studies of medium quality, a positive relation was reported [1, 2, 8,14,15,16, 19, 20, 24, 25; ]Appendix 1], whereas in the remaining ten studies a non-significant relation was reported [3, 6, 10, 12, 18, 22,27,28,29,30]; Appendix 1].…”

“…In 4 of the 8 studies, where depression was assessed based on interviews, a positive relation between depression and post-MI mortality was found [5, 16, 21, 26; ]Appendix 1], whereas a non-significant relation was reported in the other four studies [[13, 22, 23, 31; ]Appendix 1]. In 5 of the 9 studies, where the BDI was applied, a positive relation was reported [1, 8, 14, 15, 26; ]Appendix 1], whereas a non-significant relation was reported in three studies [18, 27, 30; ]Appendix 1], and the sixth and last study [7]; Appendix 1] failed to report on this.…”

“…In 5 of the 9 studies, where the BDI was applied, a positive relation was reported [1, 8, 14, 15, 26; ]Appendix 1], whereas a non-significant relation was reported in three studies [18, 27, 30; ]Appendix 1], and the sixth and last study [7]; Appendix 1] failed to report on this. Fifteen studies applied other questionnaires than the BDI.…”

“…Articles that fitted these criteria were given an identification number [1,2,3,4,5,6,7,8,9,10,11,12,13,14,15,16,17,18,19,20,21,22,23,24,25,26,27,28,29,30,31] Appendix 1]. They were then systematically reviewed for descriptive information for quality issues.…”

Depression and anxiety in cardiovascular disease

“…A study showing a decrease in the severity of the disease during treatment with antidepressants was carried out in India on a group of 50 patients. The remaining studies were carried out in the United States, Canada, and Holland [27][28][29][30].…”