Sertraline treatment of major depression in patients with acute MI or unstable angina.
BACKGROUND
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.


METHODS
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.


METHODS
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%).


METHODS
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.


METHODS
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 (P> or = .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.


CONCLUSIONS
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.
Glassman
Alexander H
AH
Department of Clinical Psychopharmacology, New York State Psychiatric Institute, 1051 Riverside Dr, Unit 116, New York, NY 10032, USA. ahg1@columbia.edu
O'Connor
Christopher M
CM
Califf
Robert M
RM
Swedberg
Karl
K
Schwartz
Peter
P
Bigger
J Thomas
JT
Krishnan
K Ranga Rama
KR
van Zyl
Louis T
LT
Swenson
J Robert
JR
Finkel
Mitchell S
MS
Landau
Charles
C
Shapiro
Peter A
PA
Pepine
Carl J
CJ
Mardekian
Jack
J
Harrison
Wilma M
WM
Barton
David
D
Mclvor
Michael
M
D000789:Angina, Unstable / Q000523:psychology*; D003865:Major Depressive Disorder / Q000188:drug therapy* / Q000209:etiology; D004311:Double-Blind Method; D005260:Female; D006760:Hospitalization; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000523:psychology*; D017367:Selective Serotonin Reuptake Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D020280:Sertraline / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome
D017367:Selective Serotonin Reuptake Inhibitors; D020280:Sertraline