The antidepressant escitalopram (Lexapro) did not prevent hospitalization, reduce mortality, or improve mood in heart failure patients with depression, a double-blind, placebo-controlled German trial showed.
During a median of about 18 months, 63% of the 185 patients in the escitalopram group and 64% of the 187 patients in the placebo group died or were hospitalized (HR 0.99, 95% CI 0.76-1.27), the MOOD-HF study showed.
The mean Montgomery-Åsberg Depression Rating Scale (MADRS) sum score decreased in both groups, with a between-group difference of just -0.9 on the 60-point scale (P=0.26), Christiane E. Angermann, MD, of Germany's University Hospital Würzburg, and colleagues reported online in the Journal of the American Medical Association.
"These findings do not support the use of escitalopram in patients with chronic systolic heart failure and depression," they concluded.
Although the SADHEART and ENRICHD trials both previously failed to find a benefit of 6 months of antidepressant treatment for patients with coronary disease, Angermann said in an interview that MOOD-HF's findings with an antidepressant considered one of the more effective in primary depression came as a surprise.
"Since it is well established that depression increases the risk of death proportionally to the severity of the depression, we hypothesized that escitalopram, which has proven efficacious in primary depression, might also improve comorbid depression in our patients and thus reduce mortality and morbidity," she said in an email. "It was particularly surprising that, given escitalopram serum levels in the therapeutic range, our results seem to indicate an absence of any relevant therapeutic efficacy in this patient population."
Angermann noted that more and more primary care physicians and internists are prescribing antidepressants to patients with cardiovascular disease and depression and recommended involving a specialist. "To me, it seems very important now that physicians always get a reliable depression diagnosis by a psychiatrist or psychologist before introducing any specific antidepressant therapy in an individual patient," she said. An attitude of 'Just prescribe an antidepressant and see what happens' is not justifiable, she told MedPage Today.
The MOOD-HF trial was carried out at 16 tertiary medical centers where patients who presented to an outpatient clinic with New York Heart Association class II-IV heart failure and left ventricular ejection fraction under 45% were screened for depression. The participants were diagnosed as having a major depressive disorder according to the DSM-IV but had baseline MADRS scores indicative of only mild to moderate depression.
Study participants were randomized to escitalopram (10-20 mg) or matching placebo as well as enhanced care for heart failure. Mean age was 62 years, and three-quarters of the participants were male. A decision to stop the trial early was made during the regular data review process, the researchers said.
The only difference in serious adverse event rates between the groups was worsening depression in the placebo group, the researchers noted.
"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," Angermann and colleagues said.
The study is limited by its lack of generalizability, and the results can't be extended beyond its study population, which was mostly white and of a higher risk category, the researchers noted.
The study did not assess the impact of escitalopram alone or in various sub-groups, including women, black adults and people 65 years of age and older, who have been identified as particularly resistant to antidepressant therapy. It also excluded patients with suicidal ideation as well as those suffering from bipolar disorder.
"One needs to keep in mind that depression is a very heterogeneous condition, and that MOOD-HF does not prove that antidepressants are useless in all patients with cardiovascular disease and depression," Angermann said. On the other hand, she added, study participants in both groups "likely benefited from the enhanced heart failure care provided."
A combination of "classical" collaborative disease management strategies to optimize heart failure pharmacotherapy, self-supervision, and drug adherence with cognitive behavioral therapy components and physical exercise may be the best approach to managing this patient population, Angermann said.
Ultimately, she added, "results such as ours raise doubts on the causal status of depression in heart failure." Future research, she said, needs to focus on the mechanisms that may account for the adverse prognostic importance of depressive symptoms in heart failure. "This type of mechanistic research might eventually lead us to novel treatment options not only for the comorbid depressive symptoms but also for heart failure itself," she told MedPage Today.
The study was funded by the German Ministry of Education and Research and Lundbeck AS Denmark.
Angermann reported receiving grants, personal fees, nonfinancial support, and other from ResMed; grants, personal fees, and other from Novartis; personal fees and other from Servier; grants and personal fees from Thermo Fisher, Boehringer Ingelheim, and Vifor; personal fees, grants, and nonfinancial support from Lundbeck AS; nonfinancial support from the University Hospital Würzburg and the Comprehensive Heart Failure CenterWürzburg; and grants from the German Ministry for Education and Research.
Co-authors disclosed a number of relationships with industry.
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