Treating depression in patients with heart failure: what is (not) recommended?

This editorial refers to ‘Commentary concerning treatment of depression in patients with heart failure according to 2021 ESC guidelines on cardiovascular disease prevention in clinical practice’ by A. Wilkowska et al. , https: //doi. org/10. 1093/eurjpc/zwac077. Depression is a frequent comorbidity in patients with heart failure (HF), adversely affecting both, quality of life (QoL), and prognosis. Recognition and treatment of depression is therefore recommended by current guidelines. However, treatment trials have so far not yielded fully convincing results, and it is often unclear how depression should be treated in individual patients with HF. Depression treatments that have proven useful in patients without heart disease (and to some extent also in patients with coronary heart disease) have shown only small or even no effects in the limited number of studies specifically testing their efficacy in depressed HF patients. Current European Society of Cardiology (ESC) guidelines are therefore careful in recommending specific depression treatments, especially antidepressant drugs, for HF patients. The ESC HF guideline1 avoids to make any clear recommendation on antidepressant medication use. It mentions that the two largest antidepressant trials in HF patients found the selective serotonin reuptake inhibitors (SSRIs) sertraline and escitalopram safe for HF patients but not superior to placebo in improving either depression or medical disease outcomes. On the other hand, the ESC cardiovascular prevention guideline2 even issued a class III recommendation against any use of antidepressant drugs in HF patients. This recommendation is based on both, their unproven efficacy and a recent meta-analysis suggesting a possibly increased mortality risk associated with the use of antidepressants, including SSRIs, in this patient group. 3 This slight inconsistency is addressed by Wilkowska et al. 4 in their commentary. The authors argue that the meta-analytic findings of adverse prognostic effects of antidepressants are largely based on retrospective data with insufficient control of depression severity and have to be interpreted with caution. They raise the concern that discouraging antidepressant use may lead to patients remaining untreated for their depression, if alternative, e. g. psychosocial, treatments are either not available or not acceptable for patients. This might lead to an increased risk associated with untreated depression and to general doubts in the relevance of recognizing and treating depression, when physicians assume that no appropriate treatment be available. The limited availability of non-pharmacological treatments may indeed be a problem in several regions of Europe and beyond. The idea to simply prescribe a drug that has been proven helpful in other contexts may therefore appear attractive. However, in a world of evidence-based medicine, it is at least questionable if a treatment should really be recommended to patients ‘ut aliquid fiat’, although it has explicitly not been found superior to placebo in the two largest independent randomized controlled trials (RCTs) on this specific indication, 5, 6 regardless of whether or not it even increases mortality. One lesson from both, the two antidepressant trials cited by the guidelines and a number of studies testing telemonitoring7 or nurse-based interventions (e. g. 8) is that substantial improvements in depressive symptoms can be achieved in HF patients who receive regular monitoring and personal support, even in the absence of a specific depression treatment. An additional focus on self-help support for coping with depression may increase the effect of such non-specific support. 8 The EU-funded ESCAPE (Evaluation of a patient-centred biopsychoSocial blended collaborative CAre Pathway for the treatment of multi-morbid Elderly Patients) consortium is currently testing the effectiveness of a blended collaborative care intervention on the QoL and numerous secondary outcomes in multimorbid elderly patients with HF and mental distress or comorbidity (such as depression) in six European countries (https: //www. drks. de/drksweb/navigate. do? navigationId=trial. HTML&TRIALID=DRKS00025120). Here, as in the Hopeful Heart trial, 8 trained non-physician care managers, regularly supervised by a multidisciplinary specialist team, offer remote support to patients and their general practitioners and informal carers in dealing with both medical and mental health conditions. While the results of that study have to be awaited, more specific depression treatments are already available. Although still based on limited numbers of studies and patients, meta-analyses (e. g. 9) have shown that cognitive behavioural therapy (CBT) improves not only depressive symptoms but also QoL in HF patients. Where no sufficient local CBT infrastructure is available, it might be an option to offer CBT over the phone, via General Data Protection Regulation-compliant video-conferencing tools or even through one of several existing web applications. The effectiveness of such remote interventions in general is comparable with face-to-face interventions, and while it must be admitted that remote CBT has not sufficiently been tested in depressed HF patients, the proven benefits of telemonitoring and telephone-based collaborative care in these patients and the low risk of adverse side effects of such treatments are encouraging. The meta-analysis mentioned above9 found even slightly larger antidepressant effects of exercise training, while it again detected no significant effect of antidepressants. However, neither exercise nor CBT alone showed satisfactory effect sizes to ‘cure’ depression. A small study combing CBT with exercise training—as often found in cardiac rehabilitation—suggests that this combination may yield synergistic effects10 and could be a viable option. So, there is no need to fear that discouraging the use of antidepressant drugs in treatment of depressed HF patients might open the door to therapeutic nihilism. Quite to the contrary, the criticized ESC prevention guideline2 recommends intensified attention, adherence support, evidence-based healthcare, and interdisciplinary cooperation for cardiac patients with mental disorders, especially those with a need for psychotropic medication. This is probably more effective and more acceptable to patients than a pretended ‘quick fix’ of easily prescribing a drug with no proven efficacy but a considerable risk of serious adverse effects. And, it is a genuine medical task for general practitioners and treating cardiologists to counsel patients in dealing with their illness. Cardiological societies in some European countries nowadays offer regular trainings for physicians and nurses to enable them to support cardiac patients in coping with their heart disease and overcoming mild to moderate mental health problems. Networks of cardiologists and mental health specialists can be established and facilitate the interdisciplinary cooperation recommended by the guideline. In certain situations, especially in severe depressive episodes, there is still a place for the individual use of antidepressant drugs (except the clearly contraindicated tricyclics). However, the prescription must be accompanied by close monitoring of the electrocardiogram, lab values, and bleeding complications and embedded in an interdisciplinary treatment concept, thoroughly taking into account the medical and mental status of the patient and possible drug–drug interactions. In this context, Wilkowska et al. 4 mention a current position paper issued by the European Association of Preventive Cardiology (EAPC) 11 and the importance it ascribes to weighing the improvements in QoL against the increased mortality risk associated with both depression and possibly also antidepressant medications. That position paper recommends thorough risk estimation, balancing the cardiac risk of untreated depression against the risk due to adverse cardiac events of psychopharmacological treatment. It presents evidence and gaps in evidence for both pharmacological and non-pharmacological treatments and shows the way to go from here: Clinically, treatment should be individualized, based on the best available evidence, availability of treatment options, and open discussions between physicians and their depressed HF patients. Here, pharmacological and non-pharmacological treatment options for mental health conditions with all their potential (dis) advantages should be explained, and the best-fitting treatment should be agreed upon in a shared decision-making process. In terms of research, the position paper agrees with the suggestion by Wilkowska et al. 4 that more RCTs are needed to obtain valid information on whether antidepressants are safe and effective for HF patients. This certainly also applies to non-SSRI antidepressants with favourable safety profiles but still insufficient efficacy data in HF patient samples. Equally, non-pharmacological and combined treatments—not just for depression or HF but for whole patients who suffer from both conditions at the same time and may need multimodal interventions—need to be developed further and tested in sufficiently large trials. This requires sufficient public funding for research. Equally, viable reimbursement from health insurers for non-pharmacological interventions of proven efficacy is needed. Only then will it be possible to offer them to all patients who need—and often prefer—them. None declared.