Paroxetine-induced increase in metabolic end products of nitric oxide.

Decreased production of endothelium-derived nitric oxide (NO) has been implicated in the pathogenesis of cardiovascular diseases. Metabolic end products of nitric oxide (NOx) are often used as markers for endothelial NO production in humans. Decreased endothelium-derived NO has been suggested to mediate some of the deleterious effects of conventional cardiovascular risk factors such as hypercholesterolemia, smoking, and physical inactivity because they induce a decrease in plasma NOx. A substantial number of patients with cardiovascular diseases suffer from comorbid major depressive disorder, which is a predictor of a poorer cardiovascular outcome. Paroxetine is a first-line antidepressant and has been reported to decrease plasma NOx, theoretically suggesting a potential deleterious effect on the cardiovascular system. We assessed the hypothesis that paroxetine would induce a decrease in plasma NOx in healthy volunteers. Plasma NOx levels were measured by chemiluminescence at baseline, after 8 weeks of paroxetine administration, and at postdiscontinuation. Contrary to our hypothesis, we found that paroxetine administration induced a significant increase in plasma NOx that normalized after paroxetine discontinuation. It remains to be demonstrated that the paroxetine-induced increase in plasma NOx is associated with a modification of the cardiovascular risk in patients with major depressive disorder.