title: Efficacy of atomoxetine versus midodrine for the treatment of orthostatic hypotension in autonomic failure.
abstract: The 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.
authors.affiliation: 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.).
authors.forename: Claudia E
authors.initials: CE
authors.lastname: Ramirez
authors.affiliation: 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.).
authors.forename: Luis E
authors.initials: LE
authors.lastname: Okamoto
authors.affiliation: 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.).
authors.forename: Amy C
authors.initials: AC
authors.lastname: Arnold
authors.affiliation: 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.).
authors.forename: Alfredo
authors.initials: A
authors.lastname: Gamboa
authors.affiliation: 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.).
authors.forename: André
authors.initials: A
authors.lastname: Diedrich
authors.affiliation: 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.).
authors.forename: Leena
authors.initials: L
authors.lastname: Choi
authors.affiliation: 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.).
authors.forename: Satish R
authors.initials: SR
authors.lastname: Raj
authors.affiliation: 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.).
authors.forename: David
authors.initials: D
authors.lastname: Robertson
authors.affiliation: 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.).
authors.forename: Italo
authors.initials: I
authors.lastname: Biaggioni
authors.affiliation: 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.). cyndya.shibao@vanderbilt.edu.
authors.forename: Cyndya A
authors.initials: CA
authors.lastname: Shibao
mesh_terms: D000284:Administration, Oral; D018759:Adrenergic Uptake Inhibitors / Q000008:administration & dosage; D058646:Adrenergic alpha-1 Receptor Agonists / Q000008:administration & dosage; D000368:Aged; D000069445:Atomoxetine Hydrochloride; D001794:Blood Pressure / Q000187:drug effects*; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007024:Hypotension, Orthostatic / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D008879:Midodrine / Q000008:administration & dosage*; D011187:Posture / Q000502:physiology*; D011437:Propylamines / Q000008:administration & dosage*; D054970:Pure Autonomic Failure / Q000150:complications* / Q000188:drug therapy / Q000503:physiopathology; D016037:Single-Blind Method; D016896:Treatment Outcome
chemical_list: D018759:Adrenergic Uptake Inhibitors; D058646:Adrenergic alpha-1 Receptor Agonists; D011437:Propylamines; D000069445:Atomoxetine Hydrochloride; D008879:Midodrine
keywords: atomoxetine; autonomic failure; midodrine; orthostatic hypotension