OBJECTIVE: The purpose of this paper is to review the literature on the impact of antidepressants on depressive symptom severity, quality of life (QoL), morbidity, and mortality in patients with heart failure (HF). METHODS: Following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) Reporting Items for Systematic Reviews and Meta-Analyses guidelines, studies published from December 1969 to December 2019 that pertain to depression and HF were identified through the use of the PubMed and PsycINFO databases, using the keywords: antidepressant* and heart failure. Two authors independently conducted a focused analysis and reached a final consensus on 17 studies that met the specific selection criteria and passed the study quality checks. RESULTS: Studies varied in types of antidepressants used as well as in study designs. Ten studies were analyzed for the impact of antidepressant medications on depressive symptom severity. Five of these were randomized controlled trials (RCTs), out of which sertraline and paroxetine showed a significant reduction in depressive symptoms despite the small samples utilized. Four of the 17 studies addressed QoL as part of their outcomes showing no difference for escitalopram (RCT), significantly greater improvements for paroxetine controlled release (RCT), statistical significance for sertraline compared to control (pilot study), and showing significant improvement before and after treatment (open-label trial) for nefazodone. Thirteen of the 17 studies included measures of morbidity and mortality. Although early analyses have pointed to an association of antidepressant use and mortality particularly with fluoxetine, the reviewed studies showed no increase in mortality for antidepressants, and secondary analyses showed improved mortality in patients who achieved remission of depressive symptoms. CONCLUSION: Out of the various antidepressants studied, which included sertraline, paroxetine, escitalopram, citalopram, bupropion, nefazodone, and nortriptyline, selective serotonin reuptake inhibitors seem to be a safe treatment option for patients with depression and HF. However, due to the variety of study designs as well as the mixed results for each antidepressant, more information for reducing depression severity, morbidity, and mortality and improving quality of life in patients with HF should be examined using robust large sample RCTs
