Effect of escitalopramonall-Cause mortality and hospitalization in patients with heart failure and depression the mood-hf randomized clinical trial

IMPORTANCE Depression is frequent in patients with heart failure and is associated with adverse clinical outcomes. Long-term efficacy and safety of selective serotonin reuptake inhibitors in these patients are unknown. OBJECTIVE To determine whether 24 months of treatment with escitalopram improves mortality, morbidity, and mood in patients with chronic systolic heart failure and depression. DESIGN, SETTING, AND PARTICIPANTS The Effects of Selective Serotonin Re-Uptake Inhibition on Morbidity, Mortality, andMoodin Depressed Heart Failure Patients (MOOD-HF) studywas a double-blind, placebo-controlled randomized clinical trial conducted at 16 tertiary medical centers inGermany.BetweenMarch2009andFebruary2014, patients at outpatient clinics withNewYork Heart Association class II-IV heart failureandreduced leftventricular ejection fraction (<45%)were screened for depression using the 9-item Patient Health Questionnaire. Patients with suspected depressionwere then invited to undergo a Structured Clinical Interview based on the Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition) to establish the diagnosis. INTERVENTIONS Patients were randomized 1:1 to receive escitalopram (10-20mg) or matching placebo in addition to optimal heart failure therapy. Study duration was 24 months. MAIN OUTCOMES AND MEASURES The composite primary outcomewas time to all-cause death or hospitalization. Prespecified secondary outcomes included safety and depression severity at 12 weeks of treatment (including the titration period), which were determined using the 10-item Montgomery-Åsberg Depression Rating Scale (total possible score, 0 to 60; higher scores indicate more severe depression). RESULTS Atotal of 372 patients (mean age, 62 years; 24%female)were randomized and had taken at least 1 dose of study medication when the data and safety monitoring committee recommended the trial be stopped early. During a median participation time of 18.4 months (n = 185) for the escitalopramgroup and 18.7 months (n = 187) for the placebo group, the primary outcome of death or hospitalization occurred in 116 (63%) patients and 119 (64%) patients, respectively (hazard ratio,0.99 [95%CI,0.76 to 1.27]; P = .92). The mean MontgomeryÅsberg Depression Rating Scale sum score changed from 20.2 at baseline to 11.2 at 12weeks in the escitalopramgroup and from 21.4 to 12.5 in the placebo group (between-group difference, -0.9 [95%CI,-2.6 to0.7]; P = .26). Safety parameterswere comparable between groups. CONCLUSIONS AND RELEVANCE In patients with chronic heart failure with reduced ejection fraction and depression, 18 months of treatment with escitalopram compared with placebo did not significantly reduce all-cause mortality or hospitalization, and there was no significant improvement in depression. These findings do not support the use of escitalopram in patients with chronic systolic heart failure and depression.