• Horacio Kaufmann, Roy Freeman, Italo Biaggioni, Phillip Low, Simon Pedder, L Arthur Hewitt, Joe Mauney, Michael Feirtag, Christopher J Mathias, and NOH301 Investigators.
• From the Department of Neurology (H.K.), NYU Medical Center, New York; Department of Neurology (R.F.), Beth Israel Deaconess Medical Center, Boston, MA; Department of Medicine (I.B.), Vanderbilt University Medical Center, Nashville, TN; Department of Neurology (P.L.), Mayo Clinic, Rochester, MN; Chelsea Therapeutics, Inc. (S.P., L.A.H.), Charlotte, NC; Chiltern (J.M.), Wilmington, NC; The Curry Rockefeller Group, LLC (M.F.), Tarrytown, NY; Autonomic and Neurovascular Medicine Departments (C.J.M.), Imperial College London; and Institute of Neurology (C.J.M.), University College London, UK. horacio.kaufmann@nyumc.org.
• Neurology. 2014 Jul 22; 83 (4): 328-35.

ObjectiveTo determine whether droxidopa, an oral norepinephrine precursor, improves symptomatic neurogenic orthostatic hypotension (nOH).MethodsPatients with symptomatic nOH due to Parkinson disease, multiple system atrophy, pure autonomic failure, or nondiabetic autonomic neuropathy underwent open-label droxidopa dose optimization (100-600 mg 3 times daily), followed, in responders, by 7-day washout and then a 7-day double-blind trial of droxidopa vs placebo. Outcome measures included patient self-ratings on the Orthostatic Hypotension Questionnaire (OHQ), a validated, nOH-specific tool that assesses symptom severity and symptom impact on daily activities.ResultsFrom randomization to endpoint (n = 162), improvement in mean OHQ composite score favored droxidopa over placebo by 0.90 units (p = 0.003). Improvement in OHQ symptom subscore favored droxidopa by 0.73 units (p = 0.010), with maximum change in "dizziness/lightheadedness." Improvement in symptom-impact subscore favored droxidopa by 1.06 units (p = 0.003), with maximum change for "standing a long time." Mean standing systolic blood pressure (BP) increased by 11.2 vs 3.9 mm Hg (p < 0.001), and mean supine systolic BP by 7.6 vs 0.8 mm Hg (p < 0.001). At endpoint, supine systolic BP >180 mm Hg was observed in 4.9% of droxidopa and 2.5% of placebo recipients. Adverse events reported in ≥ 3% of double-blind droxidopa recipients were headache (7.4%) and dizziness (3.7%). No patients discontinued double-blind treatment because of adverse events.ConclusionsIn patients with symptomatic nOH, droxidopa improved symptoms and symptom impact on daily activities, with an associated increase in standing systolic BP, and was generally well tolerated.Classification Of EvidenceThis study provides Class I evidence that in patients with symptomatic nOH who respond to open-label droxidopa, droxidopa improves subjective and objective manifestation of nOH at 7 days.© 2014 American Academy of Neurology.

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