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

This study was designed to determine the efficacy and tolerability of incre asing doses of L-threo-dihydroxyphenylserine (L-threo-DOPS) in treating sym ptomatic orthostatic hypotension associated with multiple system atrophy (M SA) and pure autonomic failure (PAF). Following a one-week run-in, patients (26 MSA; 6 PAF) with symptomatic orth ostatic hypotension received increasing doses of L-threo-DOPS (100, 200 and 300 mg, twice daily) in an open, dose-ranging study. Incremental dose adju stment (after weeks two and four of outpatient treatment) was based on clin ical need until blood pressure (BP), and symptoms improved. Final dosage wa s maintained for six weeks. With L-threo-DOPS, systolic BP decrease was reduced during orthostatic chal lenge (-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 turn Hg). By the end of the study, 25 patients (78%) improved, and i n 14 patients (44%) orthostatic hypotension was no longer observed. Decreas ed 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 twic e 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 dise ase under study, and with no reports of supine hypertension. In conclusion, L-threo-DOPS (100, 200, and 300 mg, twice daily) was well to lerated. The dosage of 300 mg twice daily L-threo-DOPS seemed to offer the most effective control of symptomatic orthostatic hypotension in MSA and PA F.