Comparison of Paroxetine and Nortriptyline in Depressed Patients With Ischemic Heart Disease

Abstract

Context.-Depression and ischemic heart disease often are comorbid conditions and, in patients who have had a myocardial infarction, the presence of depression is associated with increased mortality. Patients with heart disease need a safe and effective treatment for depression. Objective.-To compare the efficacy, cardiovascular effects, and safety of a specific serotonin reuptake inhibitor, paroxetine, with a tricyclic antidepressant, nortriptyline hydrochloride, in depressed patients with ischemic heart disease. Design.-Two-week placebo lead-in followed by a double-blind randomized 6week medication trial. Setting.-Research clinics in 4 university centers. Patients.-Eighty-one outpatients meeting Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria for major depressive disorder and with documented ischemic heart disease. Interventions.-Treatment with either paroxetine, 20 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 Hamilton Rating Scale for Depression by 50% and final score of 8 or less; for cardiovascular safety, heart rate and rhythm, supine and standing systolic and diastolic blood pressures, electrocardiogram conduction intervals, 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 nortriptyline. Neither drug significantly affected blood pressure or conduction 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 (PϽ.001) and a reduction in heart rate variability, as measured by the SD of all normal R-R intervals over a 24-hour period, from 112 to 96 (PϽ.01). Adverse cardiac events occurred in 1 (2%) of 41 patients treated with paroxetine and 7 (18%) of 40 patients treated with nortriptyline (PϽ.03). Conclusions.-Paroxetine and nortriptyline are effective treatments for depressed patients with ischemic heart disease. Nortriptyline treatment was associated with a significantly higher rate of serious adverse cardiac events compared with paroxetine.

Platelet/Endothelial Biomarkers in Depressed Patients Treated With the Selective Serotonin Reuptake Inhibitor Sertraline After Acute Coronary Events

“…6 The selective serotonin reuptake inhibitors (SSRIs) are well-established antidepressant drugs that have shown little evidence of cardiac toxicity, even in patients with stable heart disease. [7][8][9] However, no data on the safety or efficacy of SSRIs in either post-acute myocardial infarction (AMI) or unstable angina patients were available until the recent Sertraline AntiDepressant Heart Attack Randomized Trial (SADHART) of 364 depressed patients with ACSs. 10 The results of SADHART documented no evidence of harm with sertraline treatment.…”

Levels of three distinct p75 neurotrophin receptor forms found in human plasma are altered in type 2 diabetic patients

“…All participants in this study had normal renal function. Type 2 diabetic patients taking tricyclic antidepressants were excluded as these medications are known to affect heart rate [7]. All routine blood parameters shown in this study were detected in the clinical laboratory of the University of Heidelberg using standardised and certified methods.…”

Effect of Antidepressants and Their Relative Affinity for the Serotonin Transporter on the Risk of Myocardial Infarction

“…4 All of the high-affinity SSRIs represented in the present study have been shown to reduce platelet aggregation. 5,[13][14][15] We know of no studies that have suggested altered platelet activity attributed to the other antidepressants with low or moderate serotonin transporter affinity; however, one study demonstrated no effect of nortriptyline on platelet activity. 14 If the mechanism of reducing MI is related to the effect of antidepressants on platelet serotonin, and if antidepressants in the higher-affinity groups have a greater antiplatelet effect than lower-affinity ones, then these drugs might be expected to have the greatest effect on MI risk.…”

“…5,[13][14][15] We know of no studies that have suggested altered platelet activity attributed to the other antidepressants with low or moderate serotonin transporter affinity; however, one study demonstrated no effect of nortriptyline on platelet activity. 14 If the mechanism of reducing MI is related to the effect of antidepressants on platelet serotonin, and if antidepressants in the higher-affinity groups have a greater antiplatelet effect than lower-affinity ones, then these drugs might be expected to have the greatest effect on MI risk. The potential effects of high serotonin transporter affinity antidepressants on platelet biology therefore form the basis for the a priori hypothesis that the extent of serotonin reuptake inhibition correlates with reduction in serotonin-mediated platelet aggregation and thus reduced risk of MI in users of these agents.…”

“…However, unlike the tricyclic agents, SSRIs are not arrhythmogenic and did not change ECG parameters in randomized trials. 14,17 …”