Christiane E Angermann1, Götz Gelbrich2, Stefan Störk1, Hilka Gunold3, Frank Edelmann4, Rolf Wachter5, Heribert Schunkert6, Tobias Graf7, Ingrid Kindermann8, Markus Haass9, Stephan Blankenberg10, Sabine Pankuweit11, Christiane Prettin12, Martin Gottwik13, Michael Böhm8, Hermann Faller14, Jürgen Deckert15, Georg Ertl1. 1. Comprehensive Heart Failure Center and Department of Medicine I, University Hospital Würzburg, Wurzburg, Germany. 2. Institute of Clinical Epidemiology and Biometry, University of Würzburg and Clinical Trial Center Würzburg, University Hospital Würzburg, Wurzburg, Germany. 3. Department of Medicine and Cardiology and Heart Center, University Hospital Leipzig, Leipzig, Germany. 4. Department of Cardiology, University Hospital Göttingen, Gottingen, Germany5Department of Internal Medicine, Cardiology, Charité-Campus Virchow-Klinikum, Universitätsmedizin Berlin, Berlin, Germany. 5. Department of Cardiology, University Hospital Göttingen, Gottingen, Germany. 6. German Heart Center Munich, Technical University München, Munich. 7. Department of Medicine II, University Hospital Lübeck, Lubeck, Germany. 8. Department of Medicine III, Saarland University Hospital, Homburg (Saar), Germany. 9. Department of Cardiology, Theresienkrankenhaus (Academic Teaching Hospital of the University of Heidelberg), Heidelberg, Germany. 10. University Heart Center Hamburg, Hamburg, Germany. 11. Department of Cardiology, University Hospital Marburg, Marburg, Germany. 12. Clinical Trial Center Leipzig, University of Leipzig, Leipzig, Germany. 13. Department of Cardiology, University Hospital Nürnberg, Klinikum Nürnberg, Nurnberg, Germany. 14. Department of Medical Psychology, Medical Sociology and Rehabilitation Sciences, Center of Mental Health, University of Würzburg, Wurzburg, Germany. 15. Department of Psychiatry, Psychosomatic Medicine and Psychotherapy, Center of Mental Health, University Hospital Würzburg, Wurzburg, Germany.
Abstract
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 withplacebo 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.
RCT Entities:
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 FailurePatients (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.
Authors: Christopher M Celano; Ana C Villegas; Ariana M Albanese; Hanna K Gaggin; Jeff C Huffman Journal: Harv Rev Psychiatry Date: 2018 Jul/Aug Impact factor: 3.732
Authors: Emily C Gathright; Mary A Dolansky; John Gunstad; Joseph D Redle; Richard A Josephson; Shirley M Moore; Joel W Hughes Journal: Health Psychol Date: 2017-07-20 Impact factor: 4.267