title: Effect of Escitalopram on All-Cause Mortality and Hospitalization in Patients With Heart Failure and Depression: The MOOD-HF Randomized Clinical Trial.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  METHODS
  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.
  
  
  METHODS
  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
  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.
  
  
  BACKGROUND
  isrctn.com Identifier: ISRCTN33128015.
authors.affiliation: Comprehensive Heart Failure Center and Department of Medicine I, University Hospital Würzburg, Wurzburg, Germany.
authors.forename: Christiane E
authors.initials: CE
authors.lastname: Angermann
authors.affiliation: Institute of Clinical Epidemiology and Biometry, University of Würzburg and Clinical Trial Center Würzburg, University Hospital Würzburg, Wurzburg, Germany.
authors.forename: Götz
authors.initials: G
authors.lastname: Gelbrich
authors.affiliation: Comprehensive Heart Failure Center and Department of Medicine I, University Hospital Würzburg, Wurzburg, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Störk
authors.affiliation: Department of Medicine and Cardiology and Heart Center, University Hospital Leipzig, Leipzig, Germany.
authors.forename: Hilka
authors.initials: H
authors.lastname: Gunold
authors.affiliation: Department of Cardiology, University Hospital Göttingen, Gottingen, Germany5Department of Internal Medicine, Cardiology, Charité-Campus Virchow-Klinikum, Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Frank
authors.initials: F
authors.lastname: Edelmann
authors.affiliation: Department of Cardiology, University Hospital Göttingen, Gottingen, Germany.
authors.forename: Rolf
authors.initials: R
authors.lastname: Wachter
authors.affiliation: German Heart Center Munich, Technical University München, Munich.
authors.forename: Heribert
authors.initials: H
authors.lastname: Schunkert
authors.affiliation: Department of Medicine II, University Hospital Lübeck, Lubeck, Germany.
authors.forename: Tobias
authors.initials: T
authors.lastname: Graf
authors.affiliation: Department of Medicine III, Saarland University Hospital, Homburg (Saar), Germany.
authors.forename: Ingrid
authors.initials: I
authors.lastname: Kindermann
authors.affiliation: Department of Cardiology, Theresienkrankenhaus (Academic Teaching Hospital of the University of Heidelberg), Heidelberg, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Haass
authors.affiliation: University Heart Center Hamburg, Hamburg, Germany.
authors.forename: Stephan
authors.initials: S
authors.lastname: Blankenberg
authors.affiliation: Department of Cardiology, University Hospital Marburg, Marburg, Germany.
authors.forename: Sabine
authors.initials: S
authors.lastname: Pankuweit
authors.affiliation: Clinical Trial Center Leipzig, University of Leipzig, Leipzig, Germany.
authors.forename: Christiane
authors.initials: C
authors.lastname: Prettin
authors.affiliation: Department of Cardiology, University Hospital Nürnberg, Klinikum Nürnberg, Nurnberg, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Gottwik
authors.affiliation: Department of Medicine III, Saarland University Hospital, Homburg (Saar), Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Böhm
authors.affiliation: Department of Medical Psychology, Medical Sociology and Rehabilitation Sciences, Center of Mental Health, University of Würzburg, Wurzburg, Germany.
authors.forename: Hermann
authors.initials: H
authors.lastname: Faller
authors.affiliation: Department of Psychiatry, Psychosomatic Medicine and Psychotherapy, Center of Mental Health, University Hospital Würzburg, Wurzburg, Germany.
authors.forename: Jürgen
authors.initials: J
authors.lastname: Deckert
authors.affiliation: Comprehensive Heart Failure Center and Department of Medicine I, University Hospital Würzburg, Wurzburg, Germany.
authors.forename: Georg
authors.initials: G
authors.lastname: Ertl
mesh_terms: D000339:Affect; D000368:Aged; D018687:Antidepressive Agents, Second-Generation / Q000627:therapeutic use*; D002908:Chronic Disease; D015283:Citalopram / Q000627:therapeutic use*; D003863:Depression / Q000150:complications / Q000188:drug therapy*; D004334:Drug Administration Schedule; D005260:Female; D006333:Heart Failure / Q000150:complications / Q000523:psychology*; D006760:Hospitalization; D006801:Humans; D008297:Male; D008875:Middle Aged; D009017:Morbidity; D011569:Psychiatric Status Rating Scales; D013318:Stroke Volume; D016896:Treatment Outcome
chemical_list: D018687:Antidepressive Agents, Second-Generation; D015283:Citalopram