Commentary
Skip the antidepressant when the patient has chronic disease?
One can only speculate as to why this antidepressant was not effective in this population.
ILLUSTRATIVE CASE
A 60-year-old man comes to your office for a follow-up visit to talk about his congestive heart failure. He has New York Heart Association Class III heart failure with a left ventricular ejection fraction of 30%. You notice that he is downcast, and after evaluation, including a score of 17 on a self-administered 9-item Patient Health Questionnaire (PHQ-9), you determine that he is having a concomitant major depressive episode. Should you start him on a selective serotonin reuptake inhibitor (SSRI)?
Depression is widely recognized as an independent risk factor for both the development of cardiovascular disease (CVD), as well as adverse outcomes in patients with known CVD.2-5 Previous studies have identified poor health behaviors as the primary underlying mechanisms linking depression and the risk of CVD.2,6 Conversely, a recent systematic review suggests that positive constructs—mediated primarily through lifestyle behaviors—may have a protective effect on CVD outcomes.7
As a result, researchers have focused on the treatment of depression to improve CVD outcomes in recent years, including in patients with heart failure. While some randomized studies have shown that SSRIs are a safe and effective treatment for depression in patients with coronary disease, they have not demonstrated improvement in CVD outcomes.8,9 However, a post hoc analysis of the ENRICHD (Enhancing Recovery in Coronary Heart Disease) trial did suggest that SSRI treatment may improve mortality and morbidity post-myocardial infarction.10
The prevalence of depression among patients with heart failure ranges from 10% to 40%, depending on disease severity.11 Depression is associated with worse quality of life, poorer treatment adherence, and higher rates of rehospitalization among patients with heart failure, and is an independent predictor of mortality in this patient population.1 Until recently, only one randomized controlled trial (RCT), the SADHART-CHF (Sertraline Against Depression and Heart Disease in Chronic Heart Failure) study, looked at treatment with SSRIs in patients with heart failure and depression.12 In this trial, sertraline, when compared with placebo, did not improve depression or CVD outcomes over 12 weeks, but the study period may have been insufficiently long to capture the impact on long-term outcomes.
STUDY SUMMARY
SADHART-CHF, but better
In the MOOD-HF (The effects of selective serotonin re-uptake inhibition on morbidity, mortality, and mood in depressed heart failure patients) study, investigators sought to determine whether SSRI treatment for depression in patients with heart failure could improve CVD outcomes over a longer study period (up to 24 months).1 Specifically, this RCT assessed whether treatment with escitalopram vs placebo could reduce the increased morbidity and mortality risk in patients with comorbid chronic systolic heart failure and depression.
This double-blind, placebo-controlled trial was conducted at 16 tertiary medical centers in Germany between 2009 and 2014. Adult patients established at heart failure clinics with New York Heart Association class II to IV heart failure and left ventricular ejection fractions <45% were screened for depression using the PHQ-9. Individuals with PHQ-9 scores ≥12 underwent a structured psychiatric interview with a psychiatrist or psychosomatic specialist. Those who received a diagnosis of major depression were invited to participate in the trial. Patients with recent SSRI use and/or psychotherapy were excluded from participation.
Eligible participants were randomized to receive either escitalopram (10-20 mg/d) or placebo for up to 24 months in addition to standard heart failure care. The starting dose of 5 mg was increased to 10 to 20 mg as tolerated until week 12 of the study; the dose at 12 weeks was considered the maintenance dose. Psychiatric and medical assessments were performed every 6 months during the study period. Depression severity was assessed using the 10-item Montgomery-Åsberg Depression Rating Scale (MADRS).
Outcomes. The primary study outcome was time to a first event of the composite of all-cause death or hospitalization. Secondary outcomes included MADRS score at 12 weeks, anxiety as assessed by the Generalized Anxiety Disorder 7-item scale (GAD-7), and health-related quality of life (QoL) as assessed by the Kansas City Cardiomyopathy Questionnaire (KCCQ). The sample size was calculated to achieve 80% power for the primary outcome. Baseline characteristics between the intervention and placebo groups were balanced after randomization, and the modified intention-to-treat study population included participants who took at least one dose of the study medication.1
Results. Ultimately, 372 participants were included in the analysis (185 in the escitalopram group and 187 in the placebo group). A primary endpoint event occurred in 116 participants (63%) in the escitalopram group and in 119 participants (64%) in the placebo group (hazard ratio [HR]=0.99; 95% confidence interval [CI], 0.76 to 1.27]; P=.92).1 No differences were found between treatment groups for the primary endpoints in either adjusted or unadjusted analyses.
The mean (SD) MADRS score changed from 20.2 (8.6) at baseline to 11.2 (8.1) at 12 weeks with escitalopram and from 21.4 (8.8) to 12.5 (7.6) in the placebo group (between-group difference = -0.9; 95% CI, -2.6 to 0.7; P =.26).10 Overall, participants in the 2 treatment groups had comparable daily doses of study medications, as well as mean treatment duration (18 months), and both groups demonstrated partial remission of depression symptoms over the study period, as well as improved health status and QoL as measured by KCCQ.
Interestingly, QoL as assessed by the KCCQ symptom score was significantly improved in the placebo group at 12 months.1 There were no between-group differences in adverse events or safety measures.1 The trial was discontinued prematurely on February 28, 2014, based on futility after a recommendation from the data and safety monitoring committee.