Another SSRI Fails to Improve Heart Failure Outcomes

The antidepressant escitalopram does not reduce hospitalization or death for heart failure patients with depression, according to a new study.

“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,” stated the authors, led by Christiane E. Angermann, MD, of the Comprehensive Heart Failure Center and Department of Medicine I, University Hospital Würzburg, Wurzburg, Germany.

Depression is common among heart failure patients and is associated with adverse clinical outcomes, the authors stated. A previous meta-analysis indicates that depression prevalence in patients with heart failure is 10-40%, depending on disease severity. Depression has been shown to be an independent predictor of mortality and re-hospitalization among heart failure patients, with incidence rising along with depression severity.

[[{"type":"media","view_mode":"media_crop","fid":"51108","attributes":{"alt":"","class":"media-image media-image-right","id":"media_crop_393980514800","media_crop_h":"0","media_crop_image_style":"-1","media_crop_instance":"6287","media_crop_rotate":"0","media_crop_scale_h":"0","media_crop_scale_w":"0","media_crop_w":"0","media_crop_x":"0","media_crop_y":"0","style":"height: 199px; width: 265px; float: right;","title":"","typeof":"foaf:Image"}}]]The long-term efficacy and safety of selective serotonin reuptake inhibitors (SSRIs) is unknown for patients with heart failure and depression. The authors set out to determine whether 24 months of treatment with the SSRI escitalopram improves mortality, morbidity, and mood in patients with chronic systolic heart failure and depression. They hypothesized that escitalopram, an effective therapy for primary depression, might also improve comorbid depression in heart failure patients and thereby reduce mortality and morbidity.

They conducted a double-blind, placebo-controlled randomized clinical trial at 16 tertiary medical centers in Germany. The participants were diagnosed as having a major depressive disorder according to the DSM-IV, but had baseline Montgomery-Åsberg Depression Rating Scale (MADRS) scores indicative of only mild to moderate depression. The 372 patients, mean age 62 years, were randomized to receive escitalopram 10-20 mg or matching placebo in addition to optimal heart failure therapy.

During a median participation time of 18.4 months for the 185 patients in the escitalopram group and 18.7 months for the 187 patients in the placebo group, the primary outcome of death or hospitalization occurred in 116 (63%) patients and 119 (64%) patients, respectively.

No significant improvement in depression was observed in the treatment group. The mean sum MADRS score decreased in both groups, with a between-group difference of just -0.9 on the 60-point scale. Safety parameters were comparable between groups.

The authors state that a decision to stop the trial early was made during the regular data review process.

Two previous trials of SSRIs, SADHEART and ENRICHD, had both failed to find a benefit of 6 months of antidepressant treatment for patients with coronary disease.

“These observations support the concept of alternative pathophysiological mechanisms for mood disorders in somatic illnesses, with depressive symptoms less responsive or, as in both SADHART-CHF and our study, unresponsive to sertraline or escitalopram," they stated.

The results seem to suggest the best approach to managing heart failure patients with depression is a combination of strategies to optimize heart failure pharmacotherapy, self-supervision, and drug adherence with cognitive behavioral therapy and physical exercise.

Source: Angermann CE, Gelbrich G, Störk S, et al; for the MOOD-HF Study Investigators and Committee Members. Effect of Escitalopram on All-Cause Mortality and Hospitalization in Patients With Heart Failure and DepressionThe MOOD-HF Randomized Clinical Trial. JAMA. 2016;315(24):2683-2693. doi:10.1001/jama.2016.7635