title: 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.
abstract: This study was designed to determine the efficacy and tolerability of increasing doses of L-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 of L-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. With L-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 mg L-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. In conclusion, L-threo-DOPS (100, 200, and 300 mg, twice daily) was well tolerated. The dosage of 300 mg twice daily L-threo-DOPS seemed to offer the most effective control of symptomatic orthostatic hypotension in MSA and PAF.
authors.affiliation: Neurovascular Medicine Unit, Division of NeuroScience and Psychological Medicine, Imperial College of Science, Technology, and Medicine at St Mary's, London, UK. c.mathias@ic.ac.uk
authors.forename: C J
authors.initials: CJ
authors.lastname: Mathias
authors.forename: J M
authors.initials: JM
authors.lastname: Senard
authors.forename: S
authors.initials: S
authors.lastname: Braune
authors.forename: L
authors.initials: L
authors.lastname: Watson
authors.forename: A
authors.initials: A
authors.lastname: Aragishi
authors.forename: J E
authors.initials: JE
authors.lastname: Keeling
authors.forename: M D
authors.initials: MD
authors.lastname: Taylor
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000978:Antiparkinson Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001342:Autonomic Nervous System Diseases / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D001794:Blood Pressure / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D015103:Droxidopa / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007024:Hypotension, Orthostatic / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D019578:Multiple System Atrophy / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D009638:Norepinephrine / Q000097:blood
chemical_list: D000978:Antiparkinson Agents; D015103:Droxidopa; D009638:Norepinephrine