Atomoxetine, a selective
norepinephrine transporter blocker, could increase blood pressure by elevating
norepinephrine concentration in peripheral sympathetic neurons. This effect may be masked in healthy subjects by central
sympatholytic mechanisms. To test this hypothesis we studied the pressor effect of 18 mg of
atomoxetine (pediatric dose) in 21 patients with damage of the central (10 subjects) and peripheral (11 subjects) autonomic nervous system.
Atomoxetine was administered in a randomized, crossover, placebo-controlled fashion, and blood pressure and heart rate were measured at baseline and for 60 minutes after
drug intake.
Atomoxetine acutely increased seated and standing systolic blood pressure in patients with central autonomic failure by 54+/-26 (mean+/-standard deviation; P=0.004) and 45+/-23 mm Hg (P=0.016), respectively, as compared with placebo. At the end of the observation period the mean seated systolic blood pressure in the
atomoxetine group was in the hypertensive range (149+/-26, range 113 to 209 mm Hg). However, in patients with peripheral autonomic failure,
atomoxetine did not elicit a pressor response; seated and standing systolic blood pressure increased by 4+/-18 mm Hg (P=0.695) and 0.6+/-8 mm Hg (P=0.546) with
atomoxetine as compared with placebo. In conclusion,
atomoxetine induces a dramatic increase in blood pressure in patients with central autonomic failure even at very low doses. These findings suggest that a functional central
sympatholytic pathway is essential to avoid
hypertension in patients treated with this
drug. Caution should be exercised when this medication is used in patients with milder form of autonomic impairment.