COMPARISON OF PAROXETINE AND NORTRIPTYLINE IN DEPRESSED-PATIENTS WITHISCHEMIC-HEART-DISEASE

Context.-Depression and ischemic heart disease often are comorbid cond itions and, in patients who have had a myocardial infarction, the pres ence of depression is associated with increased mortality. Patients wi th heart disease need a safe and effective treatment for depression. O bjective.-To compare the efficacy, cardiovascular effects, and safety of a specific serotonin reuptake inhibitor, paroxetine, with a tricycl ic antidepressant, nortriptyline hydrochloride, in depressed patients with ischemic heart disease. Design.-Two-week placebo lead-in followed by a double-blind randomized 6-week medication trial. Setting.-Resear ch clinics in 4 university centers. Patients.-Eighty-one outpatients m eeting Diagnostic and Statistical Manual of Mental Disorders, Fourth E dition criteria for major depressive disorder and with documented isch emic heart disease. Interventions.-Treatment with either paroxetine, 2 0 to 30 mg/d, or nortriptyline targeted to a therapeutic plasma level, 190 to 570 nmol/L (50-150 ng/mL), for 6 weeks. Main Outcome Measures. -For effectiveness of treatment, a decline in the score of the Hamilto n Rating Scale for Depression by 50% and final score of 8 or less; for cardiovascular safety, heart rate and rhythm, supine and standing sys tolic and diastolic blood pressures, electrocardiogram conduction inte rvals, indexes of heart rate variability, and rate of adverse events. Results.-By intent-to-treat analysis, 25 (61%) of 41 patients improved during treatment with paroxetine and 22 (55%) of 40 improved with nor triptyline. Neither drug significantly affected blood pressure or cond uction intervals. Paroxetine had no sustained effects on heart rate or rhythm or indexes of heart rate variability, whereas patients treated with nortriptyline had a sustained 11% increase in heart rate from a mean of 75 to 83 beats per minute (P<.001) and a reduction in heart ra te variability, as measured by the SD of all normal R-R intervals over a 24-hour period, from 112 to 96 (P<.01). Adverse cardiac events occu rred in 1 (2%) of 41 patients treated with paroxetine and 7 (18%) of 4 0 patients treated with nortriptyline (P<.03). Conclusions.-Paroxetine and nortriptyline are effective treatments for depressed patients wit h ischemic heart disease. Nortriptyline treatment was associated with a significantly higher rate of serious adverse cardiac events compared with paroxetine.