Onset of major depression associated with acute coronary syndromes - Relationship of onset, major depressive disorder history, and episode severity to sertraline benefit

Context: Depression observed following acute coronary syndrome (ACS) is common and associated with an increased risk of death. The Sertraline Antidepressant Heart Attack Trial (SADHART) tested the safety and efficacy of a selective serotonin reuptake inhibitor in this population. No evidence of harm was seen, and sertraline hydrochloride had an overall beneficial effect on mood that occurred primarily in patients with a history of episodes of major depressive disorder (MDD). Objectives: To determine how frequently the MDD began before ACS and whether onset of the current MDD episode before or after the ACS event influenced response to sertraline. Design, Settings, and Participants: A randomized, double-blind, placebo-controlled treatment of 369 patients with ACS and MDD was conducted in 40 outpatient clinics in 10 countries between April 1, 1997, and April 30, 2001. Main Outcome Measures: Diagnosis of MDD, number of previous episodes of depression, and episode onset before or after hospitalization were established using the Diagnostic Interview Schedule. Treatment response was measured with the Clinical Global Impression Improvement scale. Results: Fifty-three percent of MDD episodes began before hospitalization for the index episode of ACS (for 197 of 369 patients), and 94% of the MDD episodes began more than 30 days before the index ACS episode. Episodes of MDD that began prior to ACS responded more frequently to sertraline than to placebo (63% vs 46%, respectively; odds ratio, 2.0; 95% confidence interval, 1.13-3.55) whereas depression with onset beginning after hospitalization showed a high placebo response rate (69% vs 60%, respectively) and low sertraline-placebo response ratio (1.15). Multivariate analysis indicated that time of onset of the current episode, history of MDD, and baseline severity independently predicted the sertralinep-lacebo response ratio. Conclusions: Half of the episodes of major depression associated with ACS began long before ACS and therefore were not caused by ACS. Patients whose current episodes of MDD begin before ACS, those with a history of MDD, and those whose episodes are severe should be treated because they will benefit considerably from sertraline. Since these 3 predictors of sertraline response are independent, having more than 1 of them substantially increases the benefit of sertraline while reducing the chance of spontaneous recovery.