An open-label study of nefazodone treatment of major depression in patients with congestive heart failure.

OBJECTIVES To evaluate the feasibility of screening and recruiting patients with major depression and congestive heart failure (CHF) in a tertiary care cardiology hospital and to obtain preliminary efficacy, tolerability, and safety data for nefazodone treatment of a major depressive episode in CHF patients. METHOD We conducted a 12-week, open-label trial of nefazodone given in dosages up to 600 mg daily. We assessed patients at baseline, 1, 2, 4, 8, and 12 weeks. Measures used were the 17-item Hamilton Depression Rating Scale (HDRS), the Clinical Global Impression Scale, the Beck Depression Inventory, Spielberger's State-Trait Anxiety Inventory, and the Minnesota Living with Heart Failure Questionnaire. We also obtained pre- and poststudy ECGs, 24-hour Holter monitor recordings, and plasma levels of norepinephrine. RESULTS After screening 443 CHF patients, 28 patients with major depression met study eligibility criteria. The 23 patients who completed 4 or more weeks of medication showed significant improvement on all depression scales and in quality of life. Of 19 subjects who completed the full 12-week trial, 74% experienced a decline of 50% or more on HDRS scores. The completers also showed a significant reduction in heart rate, an increase in QT intervals (but not in the QTc), and a marginally significant decrease in plasma norepinephrine. There were no changes in heart rate variability. CONCLUSIONS It is feasible to screen and recruit CHF patients with major depression for an anti-depressant trial. Nefazodone seems sufficiently safe, tolerable, and efficacious to justify a larger, placebo-controlled trial.