0
We're unable to sign you in at this time. Please try again in a few minutes.
Retry
We were able to sign you in, but your subscription(s) could not be found. Please try again in a few minutes.
Retry
There may be a problem with your account. Please contact the AMA Service Center to resolve this issue.
Contact the AMA Service Center:
Telephone: 1 (800) 262-2350 or 1 (312) 670-7827  *   Email: subscriptions@jamanetwork.com
Error Message ......
Original Investigation |

Effect of Escitalopram on All-Cause Mortality and Hospitalization in Patients With Heart Failure and Depression The MOOD-HF Randomized Clinical Trial

Christiane E. Angermann, MD1; Götz Gelbrich, PhD2; Stefan Störk, MD, PhD1; Hilka Gunold, MD3; Frank Edelmann, MD4,5; Rolf Wachter, MD6; Heribert Schunkert, MD7; Tobias Graf, MD8; Ingrid Kindermann, MD9; Markus Haass, MD10; Stephan Blankenberg, MD11; Sabine Pankuweit, MD12; Christiane Prettin, PhD13; Martin Gottwik, MD14; Michael Böhm, MD9; Hermann Faller, MD, PhD15; Jürgen Deckert, MD16; Georg Ertl, MD1 ; for the MOOD-HF Study Investigators and Committee Members
[+] Author Affiliations
1Comprehensive Heart Failure Center and Department of Medicine I, University Hospital Würzburg, Wurzburg, Germany
2Institute of Clinical Epidemiology and Biometry, University of Würzburg and Clinical Trial Center Würzburg, University Hospital Würzburg, Wurzburg, Germany
3Department of Medicine and Cardiology and Heart Center, University Hospital Leipzig, Leipzig, Germany
4Department of Cardiology, University Hospital Göttingen, Gottingen, Germany
5Department of Internal Medicine, Cardiology, Charité-Campus Virchow-Klinikum, Universitätsmedizin Berlin, Berlin, Germany
6Department of Cardiology, University Hospital Göttingen, Gottingen, Germany
7German Heart Center Munich, Technical University München, Munich
8Department of Medicine II, University Hospital Lübeck, Lubeck, Germany
9Department of Medicine III, Saarland University Hospital, Homburg (Saar), Germany
10Department of Cardiology, Theresienkrankenhaus (Academic Teaching Hospital of the University of Heidelberg), Heidelberg, Germany
11University Heart Center Hamburg, Hamburg, Germany
12Department of Cardiology, University Hospital Marburg, Marburg, Germany
13Clinical Trial Center Leipzig, University of Leipzig, Leipzig, Germany
14Department of Cardiology, University Hospital Nürnberg, Klinikum Nürnberg, Nurnberg, Germany
15Department of Medical Psychology, Medical Sociology and Rehabilitation Sciences, Center of Mental Health, University of Würzburg, Wurzburg, Germany
16Department of Psychiatry, Psychosomatic Medicine and Psychotherapy, Center of Mental Health, University Hospital Würzburg, Wurzburg, Germany
JAMA. 2016;315(24):2683-2693. doi:10.1001/jama.2016.7635.
Text Size: A A A
Published online

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, and Mood in Depressed Heart Failure Patients (MOOD-HF) study was a double-blind, placebo-controlled randomized clinical trial conducted at 16 tertiary medical centers in Germany. Between March 2009 and February 2014, patients at outpatient clinics with New York Heart Association class II-IV heart failure and reduced left ventricular ejection fraction (<45%) were screened for depression using the 9-item Patient Health Questionnaire. Patients with suspected depression were 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 (10-20 mg) or matching placebo in addition to optimal heart failure therapy. Study duration was 24 months.

Main Outcomes and Measures  The composite primary outcome was 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  A total 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 escitalopram group 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 Montgomery-Åsberg Depression Rating Scale sum score changed from 20.2 at baseline to 11.2 at 12 weeks in the escitalopram group and from 21.4 to 12.5 in the placebo group (between-group difference, −0.9 [95% CI,−2.6 to 0.7]; P = .26). Safety parameters were 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.

Trial Registration  isrctn.com Identifier: ISRCTN33128015

Figures in this Article

Sign in

Purchase Options

• Buy this article
• Subscribe to the journal
• Rent this article ?

Figures

Place holder to copy figure label and caption
Figure 1.
Consolidated Standards of Reporting Trials Diagram of the Effects of Selective Serotonin Reuptake Inhibition on Morbidity, Mortality, and Mood in Depressed Heart Failure Patients Study

aFulfilled criteria of DSM-IV diagnosis of depression.

bWithdrew informed consent immediately after randomization prior to receiving study medication.

Graphic Jump Location
Place holder to copy figure label and caption
Figure 2.
Kaplan-Meier Curves for the Incidence of All-Cause Death or Hospitalization

According to a modified intention-to-treat analysis (4 patients who were randomized but did not take at least 1 dose of study medication were excluded). Median follow-up times were 560 days (interquartile range, 201-747 days) in the escitalopram group and 573 days (interquartile range, 306-747 days) in the placebo group. The median times at risk for the primary end point (all-cause death or all-cause hospitalization) were 148 days (interquartile range, 46-386 days) in the escitalopram group and 162 days (interquartile range, 42-377 days) in the placebo group. There were 116 patients in the escitalopram group with an event and 119 in the placebo group.

Graphic Jump Location
Place holder to copy figure label and caption
Figure 3.
Serial Changes in the Montgomery-Åsberg Depression Rating Scale (MADRS) Sum Score

The error bars indicate 95% CIs. The group sizes at baseline refer to all patients who had at least 1 MADRS follow-up assessment. Each item of the 10-item MADRS questionnaire yields a score of 0 to 6 resulting in an overall score from 0 to 60, with higher values indicating more severe depression. The effect of escitalopram vs placebo at 12 weeks was –0.9 (95% CI, –2.6 to 0.7; P = .26). The overall effect of escitalopram vs placebo across all MADRAS assessments was –0.9 (95% CI, –2.3 to 0.4; P = .16). The cutoff points are 0 to 6, which indicates normal; 7 to 19, mild depression; 20 to 34, moderate depression; and greater than 34, severe depression.26 Regression of an elevated MADRS sum score to a value of 10 or less has previously been proposed as a reasonable indicator of depression remission.24,32

aAssessment at 12 weeks was the prespecified secondary outcome.

Graphic Jump Location

Tables

References

CME


You need to register in order to view this quiz.

Multimedia

Some tools below are only available to our subscribers or users with an online account.

7,418 Views
0 Citations
×

Sign in

Purchase Options

• Buy this article
• Subscribe to the journal
• Rent this article ?

Related Content

Customize your page view by dragging & repositioning the boxes below.

Articles Related By Topic
Related Collections
Jobs
JAMAevidence.com

Care at the Close of Life: Evidence and Experience
Palliative Care for Patients With Heart Failure

The Rational Clinical Examination: Evidence-Based Clinical Diagnosis
Heart Failure

brightcove.createExperiences();