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(Hypertension. 2007;50:47.)
© 2007 American Heart Association, Inc.

Original Articles

Norepinephrine Transporter Blockade With Atomoxetine Induces Hypertension in Patients With Impaired Autonomic Function

Cyndya Shibao; Satish R. Raj; Alfredo Gamboa; André Diedrich; Leena Choi; Bonnie K. Black; David Robertson; Italo Biaggioni

From the Department of Medicine, Division of Clinical Pharmacology, and the Autonomic Dysfunction Center (C.S., S.R.R., A.G., A.D., B.K.B., D.R., I.B.), and the Department of Biostatistics (L.C.) Vanderbilt University School of Medicine, Nashville, Tenn.

Correspondence Italo Biaggioni, MD, 1500 21st Avenue South, Suite 3500, Clinical Trials Center, Vanderbilt University, Nashville, TN 37212. E-mail Italo.biaggioni{at}vanderbilt.edu

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.

Key Words: atomoxetine • norepinephrine transporter protein • hypertension • autonomic nervous system diseases • multiple system atrophy