Major Depression with Ischemic Heart Disease: Effects of Paroxetine and Nortriptyline on Measures of Nonlinearity and Chaos of Heart Rate

Abstract

Depression is associated with increased cardiovascular mortality in patients with preexisting cardiac illness. A decrease in cardiac vagal function as suggested by a decrease in heart rate variability (HRV) or heart period variability has been linked to sudden death in patients with cardiac disease as well as in normal controls. Recent studies have shown decreased vagal function in cardiac patients with depression as well as in depressed patients without cardiac illness. In this study, we compared 20 h awake and sleep heart period nonlinear measures using quantification of nonlinearity and chaos in two groups of patients with major depression and ischemic heart disease (mean age 59–60 years) before and after 6 weeks of treatment with paroxetine or nortriptyline. Patients received paroxetine, 20–30 mg/day or nortriptyline targeted to 190–570 nmol/l for 6 weeks. For HRV analysis, 24 patients were included in the paroxetine treatment study and 20 patients in the nortriptyline study who had at least 20,000 s of awake data. The ages of these groups were 60.4 ± 10.5 years for paroxetine and 60.8 ± 13.4 years for nortriptyline. There was a significant decrease in the largest Lyapunov exponent (LLE) after treatment with nortriptyline but not paroxetine. There were also significant decreases in nonlinearity scores on S_netPR and S_netGS after nortriptyline, which may be due to a decrease in cardiac vagal modulation of HRV. S_netGS and awake LLE were the most significant variables that contributed to the discrimination of postparoxetine and postnortriptyline groups even with the inclusion of time and frequency domain measures. These findings suggest that nortriptyline decreases the measures of chaos probably through its stronger vagolytic effects on cardiac autonomic function compared with paroxetine, which is in agreement with previous clinical and preclinical reports. Nortriptyline was also associated with a significant decrease in nonlinearity scores, which may be due to anticholinergic and/or sympatholytic effects. As depression is associated with a strong risk factor for cardiovascular mortality, one should be careful about using any drug that adversely affects cardiac vagal function.

Effects of sertraline on autonomic and cognitive functions in healthy volunteers

“…This concept fits well with the observation that patients suffering from depression after myocardial infarction are at a significantly higher risk for sudden death than their non-depressed counterparts (Lown and Verrier 1976). It is also in line with previous studies describing a heart rate lowering effect of SSRIs such as fluoxetine, paroxetine and citalopram (Roose et al 1998;Rasmussen et al 1999;Yeragani et al 2002). Interestingly, it has been shown that sertraline treatment in patients suffering from major depression after acute myocardial infarction was associated with reduced ventricular ectopic activity and facilitation of recovery of cardiac autonomic function (Shapiro et al 1999;McFarlane et al 2001).…”

Inhibitory effects of desvenlafaxine on gastric slow waves, antral contractions, and gastric accommodation mediated via the sympathetic mechanism in dogs

“…A number of studies showed that antidepressant treatment impacted on HRV. Tricyclic antidepressants (TCAs) reduced parasympathetic tone and decreased HRV (22,24,56,58). Nortriptyline was reported to decrease sympathetic activity in patients under awake and sleeping conditions and decreased vagal activity in the awaking condition (58).…”

Effect of sertraline on ouabain-induced arrhythmia in isolated guinea-pig atria

“…Our findings are important especially in view of the reports of increased side effects of TCAs such as nortriptyline that has stronger vagolytic effects on cardiac autonomic function compared with paroxetine, a SSRI drug. [2] But sertraline may have some cardio-protective effects against arrhythmia due to ouabain toxicity.…”

“…[1,2] TCAs exert a significant increase in QT variability that is associated with ventricular arrhythmia. [3] The newer antidepressant compounds, selective serotonin reuptake inhibitor (SSRI) drugs are widely used as antidepressants in treating patients.…”