• Claudia E Ramirez, Luis E Okamoto, Amy C Arnold, Alfredo Gamboa, André Diedrich, Leena Choi, Satish R Raj, David Robertson, Italo Biaggioni, and Cyndya A Shibao.
• From the Department of Medicine, Division of Clinical Pharmacology and the Autonomic Dysfunction Center, Vanderbilt University School of Medicine, Nashville, Tennessee (C.E.R., L.E.O., A.C.A., A.G., A.D., S.R.R., D.R., I.B., C.A.S.); and Department of Biostatistics, Vanderbilt University School of Medicine, Nashville, Tennessee (L.C.).
• Hypertension. 2014 Dec 1; 64 (6): 1235-40.

AbstractThe clinical presentation of autonomic failure is orthostatic hypotension. Severely affected patients require pharmacological treatment to prevent presyncopal symptoms or frank syncope. We previously reported in a proof of concept study that pediatric doses of the norepinephrine transporter blockade, atomoxetine, increases blood pressure in autonomic failure patients with residual sympathetic activity compared with placebo. Given that the sympathetic nervous system is maximally activated in the upright position, we hypothesized that atomoxetine would be superior to midodrine, a direct vasoconstrictor, in improving upright blood pressure and orthostatic hypotension-related symptoms. To test this hypothesis, we compared the effect of acute atomoxetine versus midodrine on upright systolic blood pressure and orthostatic symptom scores in 65 patients with severe autonomic failure. There were no differences in seated systolic blood pressure (means difference=0.3 mm Hg; 95% confidence [CI], -7.3 to 7.9; P=0.94). In contrast, atomoxetine produced a greater pressor response in upright systolic blood pressure (means difference=7.5 mm Hg; 95% CI, 0.6 to 15; P=0.03) compared with midodrine. Furthermore, atomoxetine (means difference=0.4; 95% CI, 0.1 to 0.8; P=0.02), but not midodrine (means difference=0.5; 95% CI, -0.1 to 1.0; P=0.08), improved orthostatic hypotension-related symptoms as compared with placebo. The results of our study suggest that atomoxetine could be a superior therapeutic option than midodrine for the treatment of orthostatic hypotension in autonomic failure.© 2014 American Heart Association, Inc.

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