Sympathetic activity in major depressive disorder: identifying those at increased cardiac risk?

Abstract

We have identified a subset of patients with MDD in whom sympathetic nervous activity is extraordinarily high, including in the sympathetic outflow to the heart. Treatment with an SSRI may reduce sympathetic activity in a manner likely to reduce cardiac risk.

Effects of Antidepressants, but not Psychopathology, on Cardiac Sympathetic Control: A Longitudinal Study

“…Differential effects of SNRI and SSRI were also seen by Koschke et al (2009) and findings are consistent with most previous studies on the effects of these drugs (Howell et al, 2007;Barton et al, 2007;Shores et al, 2001;Roth et al, 1988;Veith et al, 1983;Vincent et al, 2004;Dawood et al, 2009;Licht et al, 2009a;Koschke et al, 2009). TCAs and SNRIs both work through inhibition of NE in the synaptic cleft or by blocking its clearance.…”

“…Esler et al (1982) detected greater SNS activity by whole body NE spillover in 11 depressed outpatients compared with 17 healthy controls, arguing in favor of a true increase in sympathetic activity in the nerves in depressed patients. This was partly replicated by later spillover studies that only detected high sympathetic nervous activity, including in the sympathetic outflow to the heart, in the subset of MDD patients comorbid for panic disorder (Barton et al, 2007). It is important to note that an increase in cardiac sympathetic nerve activity is not incompatible with the absence of effects on cardiac contractility as reported here.…”

“…Various studies reported increased sympathetic activity in depressed and anxious subjects compared with healthy controls, measured by different indices like spillover of norepinephrine (NE) and epinephrine (EPI), skin conductance responses, QT interval variability (QTvi), or the pre-ejection period (PEP) (Light et al, 1998;Esler et al, 1982;Guinjoan et al, 1995;Gold et al, 2005;Koschke et al, 2009;Barton et al, 2007). However, other studies reported no association between psychopathology and SNS activity or reported decreased SNS activity in subjects with depressive or anxiety disorders (Wilkinson et al, 1998;Esler et al, 2004;Roth et al, 2008;Ahrens et al, 2008), so findings remain inconclusive.…”

“…Similar results were found by other research groups: Roth et al (1988) and Koschke et al (2009) reported increases in HR after administration of imipramine (a TCA) and venlafaxine and duloxetine (SNRIs). Shores et al (2001) and Barton et al (2007) found decreases in plasma NE, after SSRI use. These patterns of findings suggest differential effects of different antidepressants (Dawood et al, 2009;Licht et al, 2009a;Koschke et al, 2009).…”

“…Throughout the text, we therefore refer to PEP as a measure of cardiac sympathetic control, rather than activity. In contrast to cardiac NE spillover (Barton et al, 2007;Esler et al, 1982Esler et al, , 2004, PEP is a measure that can be obtained in large samples of patients and controls.…”