SAN DIEGO, CA — In what its investigators call "the first larger-scale" randomized controlled trial to assess long-term efficacy and safety of a selective serotonin reuptake inhibitor (SSRI) in patients with chronic heart failure (CHF), there were no significant differences in clinical outcomes between escitalopram and placebo.
The Mortality, Morbidity and Mood in Depressed Heart Failure Patients (MOOD-HF) study of more than 300 patients showed that 60% of those who received the SSRI escitalopram and 61% of those receiving matching placebo had an unplanned hospitalization for any reason or all-cause death over the following 24 months (the primary outcome).
Although patients receiving the SSRI did have significant decreases in depression symptom scores after 12 weeks of treatment, the reduction was similar in the placebo group. The findings were presented last week at a featured clinical-research session at the American College of Cardiology (ACC) 2015 Scientific Sessions.
"MOOD-HF does not provide a rationale for the use of escitalopram in these patients," said lead investigator Dr Christiane E Angermann (University of Würzburg Comprehensive Heart Failure Center, Germany) during her presentation.
It does suggest, however, "that optimal heart-failure management resulting in improved signs and symptoms might possibly also be a means to ameliorate comorbid depression," added Angermann.
No Significant Differences
The investigators enrolled 372 adult patients (mean age 62 years) with stable symptomatic CHF (LV ejection fraction <45%) and clinically diagnosed depression, based on scores of at least 12 on the Patient Health Questionnaire 9 (PHQ-9; mean baseline score 15) and later confirmed by a psychiatrist using the Structured Clinical Interview (SCID).
Within 2 weeks of undergoing the SCID, all were randomly assigned to receive, along with heart-failure pharmacotherapy, up to 20 mg of escitalopram once daily (n=185, 76% men; mean daily dose at 12 weeks 13.7 mg) or matching placebo (n=187, 75% men).
None of the participants had taken an SSRI or other antidepressant previously or had a history of suicide or severe depressive episodes. Follow-ups were scheduled for 24 months after baseline (actual mean participation was 18.4 months for the escitalopram group vs 18.8 months for the placebo group).
The primary end point was a composite of unplanned hospitalizations for any cause or deaths; the major secondary end point was reduced score on the Montgomery-Åsberg Depression Rating Scale (MADRS). Prespecified secondary outcomes included individual components of the primary end point, CV deaths, and HF-related hospitalizations, and safety issues.
Results showed no significant differences between the treatment groups for the primary outcome measure, with events happening to 116 of those receiving the study drug vs 119 of those receiving placebo (hazard ratio [HR] 0.99). There were no differences for the individual components of the primary end point.
Depression score decreases at 12 weeks on the MADRS were significant but similar between groups (change from 20.3 to 11.1 and from 21.4 to 12.6, respectively; both, P<0.001).
In addition, 46% of those receiving the active medication vs 48% of those receiving placebo had a treatment-related adverse event not including hospitalization and death; 86% vs 80% of these patients reported that the event was severe.
Overall, "escitalopram neither improved the composite primary outcome nor depression in this population compared with placebo," said Angermann.
Different Types of Depression?
Session moderator Dr Robert J Siegel (Cedars-Sinai Medical Center, Los Angeles, CA) told heartwire from Medscape that the reason there were no significant differences between the two treatment groups could be due to the way the depression was classified.
"Post–myocardial-infarction depression, situation depression, might be very different from endogenous depression or other types of depression, where SSRIs have been shown to have benefit," said Siegel. "Also, the effect of depression on mortality is very complex.
"In addition, depression in men and women is very different, and there are different types of antidepressant medication," he noted, adding that the author also mentioned that neither group was receiving additional psychotherapy. "I think there are still a lot of questions."
Siegel reported that he has seen many patients develop depression after undergoing open-heart surgery, especially middle-aged men.
"I don't know if it's posttraumatic stress related to coronary bypass surgery, but it's something that should be addressed. I'll often give my patients short-term SSRI therapy for their depression, and it works out well. The key is letting them know before surgery that this happens and should be treated. Then, short-term therapy is usually efficient," he concluded.
The study was funded by a grant from the German Ministry of Education and Research. The study drug and cofunding of patient recruitment was provided by Lundbeck. Angermann reports receiving consultant fees and honoraria from Novartis Pharma, Resmed, and Vifor and receiving research grants from Alere, Boehringer Ingelheim Pharmaceuticals, and Lundbeck. Disclosures for the coauthors are linked to the abstract. Siegel reports being on the speaker's bureau for Philips Ultrasound.
Heartwire from Medscape © 2015 Medscape, LLC
Cite this: MOOD-HF: SSRI No Better Than Placebo in Depressed CHF Patients - Medscape - Mar 25, 2015.