A double-blind placebo-controlled pilot study of controlled-release paroxetine on depression and quality of life in chronic heart failure.

BACKGROUND: Depression is frequently observed in patients with heart failure and is associated with poor quality of life and adverse prognosis. However, the prevalence of depression in heart failure could be overestimated because symptoms of depression overlap with those of heart failure. Similarly, the importance of depression may be overestimated if depression merely reflects worse heart failure. Because the response to depression treatment has not been evaluated in this patient population, we evaluated the efficacy of controlled-release paroxetine (paroxetine CR), a selective serotonin reuptake inhibitor, on depression and quality of life in chronic heart failure. METHODS: A double-blind, randomized, placebo-controlled design was used to evaluate reductions in depression following 12 weeks of treatment with paroxetine CR (n = 14, age 62.1 +/- 12.3 years) or placebo (n = 14, age = 61.9 +/- 9.0 years). Patients with symptomatic congestive heart failure and a score of at least 10 on the Beck Depression Inventory (BDI) were eligible. Beck Depression Inventory was obtained at baseline and 4, 8, and 12 weeks of follow-up. Quality of life was assessed using the Medical Outcomes Study Short Form and the Minnesota Living with Heart Failure Questionnaire. RESULTS: Controlled-release paroxetine resulted in significantly more recovery from depression (BDI <10) than placebo (69% vs 23%, P = .018) and resulted in lower continuous BDI scores throughout the intervention (P = .024). Controlled-release paroxetine was associated with higher general health levels compared with placebo on the Medical Outcomes Study 36-Item Short Form survey (38 +/- 10 vs 30 +/- 6, P = .016) at 12 weeks of follow-up. Reductions in depression were correlated with improvements in psychological aspects of quality of life (P < .05) but not with physical quality of life measures (P > .10). CONCLUSION: Antidepressant therapy with paroxetine CR results in significant reductions in depression among patients with heart failure. The reductions in depression with paroxetine CR are accompanied by improvements in psychological aspects of quality of life. Larger controlled trials are needed to further document the effectiveness of paroxetine CR and other selective serotonin reuptake inhibitors in patients with heart failure and to determine patient subgroups that are most likely to benefit from antidepressive interventions.

Nesiritide does not improve renal function in patients with chronic heart failure and worsening serum creatinine.

BACKGROUND: Nesiritide (synthetic human brain natriuretic peptide) is approved for the treatment of symptomatic heart failure. However, studies of brain natriuretic peptide in patients with heart failure have come to conflicting conclusions about effects on glomerular filtration rate (GFR), effective renal plasma flow, natriuresis, and diuresis. METHODS AND RESULTS: To identify a population at high risk of renal dysfunction with conventional treatment, we selected patients with a creatinine level increased from baseline (within 6 months). We examined the effects of nesiritide on GFR (measured by iothalamate clearance), renal plasma flow (measured by para-amino hippurate clearance), urinary sodium excretion, and urine output in a double-blind, placebo-controlled, crossover study. Patients received nesiritide (2 microg/kg IV bolus followed by an infusion of 0.01 microg/kg per minute) or placebo for 24 hours on consecutive days. Nesiritide and placebo data were compared by repeated-measures analysis and Student t test. We studied 15 patients with a recent mean baseline creatinine of 1.5+/-0.4 mg/dL and serum creatinine of 1.8+/-0.8 mg/dL on admission to the study. There were no differences in GFR, effective renal plasma flow, urine output, or sodium excretion for any time interval or for the entire 24-hour period between the nesiritide and placebo study days. For 24 hours, urine output was 113+/-51 mL/h with placebo and 110+/-56 mL/h with nesiritide. GFR during placebo was 40.9+/-25.9 mL/min and with nesiritide was 40.9+/-25.8. CONCLUSIONS: Nesiritide did not improve renal function in patients with decompensated heart failure, mild chronic renal insufficiency, and renal function that had worsened compared with baseline. The lack of effect may be related to renal insufficiency, hemodynamic alterations, sodium balance, severity of heart failure, or drug dose. Understanding the importance of these issues will permit effective and appropriate use of nesiritide.

The influence of age, gender, and race on the prevalence of depression in heart failure patients.

OBJECTIVES: The goal of this study was to determine the prevalence of depression in an out-patient heart failure (HF) population; its relationship to quality of life (QOL); and the impact of gender, race, and age. BACKGROUND: Most studies of depression in HF have evaluated hospitalized patients (a small percentage of the population) and have ignored the influence of various patient characteristics. Although reported depression rates among hospitalized patients range from 13% to 77.5%, out-patient studies have been small, have reported rates of 13% to 42%, and have not adequately accounted for the impact of age, race, or gender. METHODS: A total of 155 patients with stable New York Heart Association functional class II, III, and IV HF and an ejection fraction <40% were given questionnaires to assess QOL and depression. These included the Medical Outcomes Study Short Form, the Minnesota Living with Heart Failure questionnaire, and the Beck Depression Inventory (BDI). Depression was defined as a score on the BDI of > or =10. RESULTS: A total of 48% of the patients scored as depressed. Depressed patients tended to be younger than non-depressed patients. Women were more likely (64%) to be depressed than men (44%). Among men, blacks (34%) tended to have less depression than whites (54%). Depressed patients scored significantly worse than non-depressed patients on all components of both the questionnaires measuring QOL. However, they did not differ in ejection fraction or treatment, except that depressed patients were significantly less likely to be receiving beta-blockers. CONCLUSIONS: Depression is common in patients with HF, with age, gender, and race influencing its prevalence in ways similar to those observed in the general population. These data suggest that pharmacologic or non-pharmacologic treatment of depression might improve the QOL of HF patients.