Efficacy of atomoxetine versus midodrine for the treatment of orthostatic hypotension in autonomic failure

Claudia E. Ramirez, Luis E. Okamoto, Amy C. Arnold, Alfredo Gamboa, André Diedrich, Leena Choi, Satish R. Raj, David Robertson, Italo Biaggioni, Cyndya A. Shibao

Research output: Contribution to journalArticle

42 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)1235-1240
Number of pages6
JournalHypertension
Volume64
Issue number6
DOIs
StatePublished - Jan 1 2014

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Midodrine
Orthostatic Hypotension
Blood Pressure
Therapeutics
Placebos
Norepinephrine Plasma Membrane Transport Proteins
Atomoxetine Hydrochloride
Sympathetic Nervous System
Syncope
Vasoconstrictor Agents
Pharmacology
Pediatrics

All Science Journal Classification (ASJC) codes

  • Internal Medicine

Cite this

Ramirez, Claudia E. ; Okamoto, Luis E. ; Arnold, Amy C. ; Gamboa, Alfredo ; Diedrich, André ; Choi, Leena ; Raj, Satish R. ; Robertson, David ; Biaggioni, Italo ; Shibao, Cyndya A. / Efficacy of atomoxetine versus midodrine for the treatment of orthostatic hypotension in autonomic failure. In: Hypertension. 2014 ; Vol. 64, No. 6. pp. 1235-1240.
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Ramirez, CE, Okamoto, LE, Arnold, AC, Gamboa, A, Diedrich, A, Choi, L, Raj, SR, Robertson, D, Biaggioni, I & Shibao, CA 2014, 'Efficacy of atomoxetine versus midodrine for the treatment of orthostatic hypotension in autonomic failure', Hypertension, vol. 64, no. 6, pp. 1235-1240. https://doi.org/10.1161/HYPERTENSIONAHA.114.04225

Efficacy of atomoxetine versus midodrine for the treatment of orthostatic hypotension in autonomic failure. / Ramirez, Claudia E.; Okamoto, Luis E.; Arnold, Amy C.; Gamboa, Alfredo; Diedrich, André; Choi, Leena; Raj, Satish R.; Robertson, David; Biaggioni, Italo; Shibao, Cyndya A.

In: Hypertension, Vol. 64, No. 6, 01.01.2014, p. 1235-1240.

Research output: Contribution to journalArticle

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T1 - Efficacy of atomoxetine versus midodrine for the treatment of orthostatic hypotension in autonomic failure

AU - Ramirez, Claudia E.

AU - Okamoto, Luis E.

AU - Arnold, Amy C.

AU - Gamboa, Alfredo

AU - Diedrich, André

AU - Choi, Leena

AU - Raj, Satish R.

AU - Robertson, David

AU - Biaggioni, Italo

AU - Shibao, Cyndya A.

PY - 2014/1/1

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N2 - 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.

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