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Clinical Autonomic Research

, Volume 11, Issue 4, pp 235–242 | Cite as

l-threo-dihydroxyphenylserine (l-threo-DOPS; droxidopa) in the management of neurogenic orthostatic hypotension: A multi-national, multi-center, dose-ranging study in multiple system atrophy and pure autonomic failure

  • Christopher J. Mathias
  • Jean-Michel Senard
  • Stefan Braune
  • Laura Watson
  • Atsushi Aragishi
  • Joelle E. A. Keeling
  • Michael D. Taylor
Research Article

Abstract

This study was designed to determine the efficacy and tolerability of increasing doses ofl-threo-dihydroxyphenylserine (l-threo-DOPS) in treating symptomatic orthostatic hypotension associated with multiple system atrophy (MSA) and pure autonomic failure (PAF). Following a one-week run-in, patients (26 MSA; 6 PAF) with symptomatic orthostatic hypotension received increasing doses ofl-threo-DOPS (100, 200 and 300 mg, twice daily) in an open, dose-ranging study. Incremental dose adjustment (after weeks two and four of outpatient treatment) was based on clinical need until blood pressure (BP), and symptoms improved. Final dosage was maintained for six weeks. Withl-threo-DOPS, systolic BP decrease was reduced during orthostatic challenge (−22±28 mm Hg reduction from a baseline decrease of 54.3±27.7 mm Hg, p=0.0001, n=32; supine systolic BP at final visit was 118.9±28.2 mm Hg). By the end of the study, 25 patients (78%) improved, and in 14 patients (44%) orthostatic hypotension was no longer observed. Decreased orthostatic systolic BP decrease occurred in 22% (7/32), 24% (6/25) and 61% (11/18) of patients treated with 100, 200, and 300 mgl-threo-DOPS twice daily, respectively. An improvement occurred in symptoms associated with orthostatic hypotension, such as light-headedness, dizziness (p=0.0125), and blurred vision (p=0.0290).l-threo-DOPS was well tolerated, with the 2 serious adverse events reported being a possible complication of the disease under study, and with no reports of supine hypertension. I conclusion,l-threo-DOPS (100, 200, and 300 mg, twice daily) was well tolerated. The dosage of 300 mg twice dailyl-threo-DOPS seemed to offer the most effective control of symptomatic orthostatic hypotension in MSA and PAF.

Key words

l-threo-DOPS neurogenic orthostatic hypotension multiple system atrophy (MSA, Shy-Drager syndrome) pure autonomic failure (PAF) 

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Copyright information

© Lippincott Williams & Wilkins 2001

Authors and Affiliations

  • Christopher J. Mathias
    • 1
    • 5
  • Jean-Michel Senard
    • 3
  • Stefan Braune
    • 4
  • Laura Watson
    • 1
  • Atsushi Aragishi
    • 2
  • Joelle E. A. Keeling
    • 2
  • Michael D. Taylor
    • 2
  1. 1.Neurovascular Medicine Unit, Division of NeuroScience and Psychological MedicineImperial College of Science, Technology and Medicine at St Mary'sLondonU.K.
  2. 2.Autonomic Unit National Hospital of Neurology and Neurosurgery, Institute of NeurologyUniversity CollegeLondonU.K.
  3. 3.Laboratoire de Pharmacologie Medicale et Clinique, INSERM U 317Faculté de MédecineToulouseFrance
  4. 4.Department of NeurologyUniversity of FreiburgFreiburgGermany
  5. 5.(Clinical Research) Sumitomo Pharmaceuticals UKLondonU.K.

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