Should SSRIs Be Prescribed for Depression in Heart Failure Patients?

Depression affects 10% to 40% of patients with heart failure (HF), depending on disease severity.

Aside from the obvious concerns related to depression in the general population, the condition is considered an independent predictor of mortality and readmission among HF patients, and it has also been linked to poor quality of life, increased health care costs, and low treatment adherence.

Selective serotonin reuptake inhibitors (SSRIs) are the most commonly used agents to treat depression in the general population. In patients with coronary disease, results of randomized studies have shown SSRIs are safe and may improve depression symptoms, but have no benefit for prognosis.

Previously, the only trial to explore SSRIs’ benefit in HF patients (SADHART-CHF) determined sertraline didn’t improve depression or cardiovascular status. However, it was limited by a relatively short treatment duration of 12 weeks.¹

Recently, researchers behind the MOOD-HF trial investigated escitalopram’s long-term efficacy and safety in chronic HF patients with a reduced ejection fraction and depression.² They hypothesized the antidepressant would curb the increased mortality and morbidity risk associated with comorbid depression in HF patients.

Eligible patients were randomized 1:1 to receive either escitalopram (10-20 mg once-daily) or matching placebo for up to 24 months, in addition to optimal HF care. Starting December 5, 2011, the maximum dose was limited to 10 mg/day in participants 65 years or older based on the manufacturer’s recommendation.

Up-titration of HF pharmacotherapy and patient counseling and empowerment (with modules addressing HF signs and symptoms, lifestyle modifications, drug adherence, self-care, and self-supervision skills) occurred in parallel during telephone contacts and personal visits.

Follow-up was conducted used the 10-item Montgomery-Åsberg Depression Rating Scale (MADRS) to assess depression. Each item of the 10-item MADRS yields a score of 0 to 6, resulting in an overall score from 0 to 60, with higher values indicating more severe depression. Commonly used cutoff ranges are 0 to 6 (normal), 7 to 19 (mild depression), 20 to 34 (moderate depression), and >34 (severe depression).

On February 28, 2014, when 372 patients were included, the steering committee stopped enrollment based on futility following a recommendation from the data and safety monitoring committee.

Overall, the results showed escitalopram was well tolerated in HF patients with depression, but failed to demonstrate an impact on the elevated mortality and morbidity risk associated with this comorbidity. The changes in MADRS scores observed in MOOD-HF were in line with those seen in SADHART-CHF, but they were contrary to evidence from patients with coronary disease, in whom SSRIs were associated with significantly greater improvement in depressive symptoms.

Interestingly, these observations support the concept of alternative pathophysiological mechanisms for mood disorders in somatic illnesses, with depressive symptoms unresponsive to conventional SSRI therapy. This notion is supported by the fact that placebo-controlled trials of antidepressants tended to exclude patients with severe somatic illnesses.

Taken together, these observations suggest SSRIs’ efficacy may not necessarily be transferable to all patients for whom antidepressants are prescribed.

The researchers also observed some disturbing trends in several interesting subgroup analyses. N-terminal pro-B-type natriuretic peptide levels decreased more slowly while patients were taking escitalopram, left ventricular cavity size didn’t decrease like it did in the placebo group, and there was a trend toward lower health-related quality of life (HRQOL). Interpretation of these secondary and exploratory findings requires great caution, but the possibility of unfavorable effects with longer-term escitalopram therapy on cardiac status and HRQOL can’t be ruled out.

Clearly, more research is needed to identify effective means of combating the deleterious impact of depression in HF patients. Still, based on the results of MOOD-HF and previous trials, SSRIs shouldn’t be recommended as first-line therapy. A better approach may be combining the optimization of HF pharmacotherapy while emphasizing drug adherence, physical training, and cognitive behavior therapy.

References

• O’Connor CM, Jiang W, Kuchibhatla M, et al. Safety and efficacy of sertraline for depression in patients with heart failure: results of the SADHART-CHF (Sertraline Against Depression and Heart Disease in Chronic Heart Failure) trial. J Am Coll Cardiol. 2010;56:692-699.
• Angermann CE, Gelbrich G, Störk S, 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. 2016;315(24):2683-2693.