SERTRALINE SUPPRESSES SYMPATHETIC NERVOUS SYSTEM ACTIVITY

Abstract

The purpose of this study was to determine if short-term treatment with sertraline in healthy volunteers effects sympathetic nervous system (SNS) activity. SNS activity is increased in patients with major depression and in normal aging. This increase in SNS activity in depression and in aging may exacerbate comorbid medical conditions, such as cardiac disease, in which depression is a significant risk factor for mortality. Thirteen healthy volunteers were given either placebo or sertraline 50–100 mg for 2 days and then 1 week later underwent the same protocol with the other drug. The sequence of drug or placebo was randomized. After an overnight fast, intravenous lines were placed in the antecubital vein for infusion of tritiated norepinephrine (3H-NE) and in the dorsal vein of the hand, which was then placed in a heated box (60° C), to obtain arterialized plasma samples. After a 30-minute stabilization period, baseline samples were obtained for plasma norepinephrine (NE) and epinephrine. 3H-NE was administered in a 15 μCi/m2 bolus followed immediately by a constant infusion at the rate of 0.35 μCi/m2/min for a period of 30 minutes. Three sets of blood samples were obtained at 5-minute intervals to determine steady state NE and 3H-NE. Plasma NE concentrations were slightly lower in the sertraline compared to the placebo condition (212 + 77 vs. 254 + 102 pg/ml; P=0.10). By single compartmental analysis, plasma NE appearance rates were significantly lower in the sertraline compared to the placebo condition (0.26 + 0.10 vs. 0.39 + 0.23 μCi/m2/min; P=0.03). A decrease in plasma NE clearance in the sertraline condition also occurred (1.20 + 0.16 vs. 1.45 + 0.34 L/m2/min; P=0.007), which would be expected to increase rather than decrease plasma NE. These preliminary findings that short-term sertraline significantly decreases the plasma NE appearance rate demonstrate that sertraline suppresses systemic SNS activity in healthy control subjects. These results could have significant therapeutic relevance for treating elderly patients with depression and cardiac disease, in which elevated SNS activity could significantly exacerbate underlying cardiac illness. P27