MedicalResearch.com Interview with:
Prof. Dr. med. Christiane E. Angermann, FESC, HFA
Deutsches Zentrum für Herzinsuffizienz Würzburg
Comprehensive Heart Failure Center (CHFC)
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: Previous meta-analysis indicates that depression prevalence in patients with heart failure is much higher than in the general population, 10 percent to 40 percent, depending on disease severity. Depression has been shown to be an independent predictor of mortality and rehospitalization in patients with heart failure, with incidence rates increasing in parallel with depression severity. Furthermore, it is associated with poor quality of life and increased healthcare costs.
It would, against this background, seem desirable to treat the depression, and when planning the study we hypothesized that by doing so we might be able to improve depression and thus reduce mortality and morbidity of this population. Long-term efficacy and safety of selective serotonin reuptake inhibitors (SSRIs), which are widely used to treat depression and have proven efficacious in individuals with primary depression, is unknown for patients with heart failure and (comorbid) depression.
MedicalResearch.com: What should readers take away from your report?
Response: Our findings do not support the use of escitalopram for patients with chronic heart failure and depression. They seem of particular relevance since more and more general practitioners and internists who are increasingly becoming aware of depression as an important comorbidity in heart failure are prescribing these drugs to cardiac patients. According to our results escitalopram has in patients with heart failure no significant beneficial effect, but could possibly even have adverse longer-term side effects, in particular if heart failure and depression are more severe. The study does not prove that this is a class effect, but this possiblity exists.
One needs also to consider, on the other hand, that depression is a very heterogenous condition, and several subtypes, as e.g. bipolar disorders or patients with suicidal ideation, were excluded from participation in MOOD-HF. The MOOD-HF does therefore not prove that antidepressants are useless in all patients with cardiovascular diseases and depression. To me, it seems of utmost importance now that physicians always get first for their individual patients a reliable depression diagnosis by a specialist, i.e. a psychiatrist or psychologist, before introducing any specific antidepressant therapy. ‚Just prescribe an antidepressent and see what happens‘ is not justifiable.
MedicalResearch.com: What recommendations do you have for future research as a result of this study?
Response: Also against the background of previous SSRI trials in coronary disease and the SADHART-CHF short-term study using sertralin in a heart failure population our observations support the concept of alternative pathophysiological mechanisms for mood disorders in somatic illnesses, with depressive symptoms less responsive or, as in SADHART-CHF and MOOD-HF, unresponsive to sertraline or escitalopram.
We believe that results as ours should rise doubts on the causal status of depression in heart failure. The lack of response to antidepressant therapy despite adaequate drug levels of the antidepressant in the serum may indicate that although depression is a recognized independent risk marker in heart failure, it is perhaps not itself a causal risk factor. Future research must focus more on the mechanisms that may account for the adverse prognostic importance of the 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.
MedicalResearch.com: Is there anything else you would like to add?
Response: Placebo-controlled trials for marketing authorization of antidepressants have in the past tended to exclude patients with severe somatic illnesses. Our observations suggest that the efficacy results of these studies may not necessarily be transferable to all individuals in whom antidepressants are then prescribed in clinical practice. Strictly speaking there was no previous evidence available supporting antidepressant treatment with sertralin or escitalopram in patients with heart failure, and our study indicates lack of benefit from these drugs in this population. So caution on the side of the physicians is necessary. Manufacturers should adjust their future research regarding new psychotropic agents, and include in their trials also populations with somatic comordidities. Furthermore, studies of sufficient duration are required to identify possible longer-term side effects in such more vulnerable patients.
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Christiane E. Angermann, MD et al. Effect of Escitalopram on All-Cause Mortality and Hospitalization in Patients With Heart Failure and Depression: The MOOD-HF Randomized Clinical Trial. JAMA, June 2016 DOI:10.1001/jama.2016.7207
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