Neurogenic orthostatic hypotension: a double-blind, placebo-controlled study with midodrine.
OBJECTIVE
To investigate the efficacy and safety of midodrine for treatment of patients with orthostatic hypotension due to autonomic failure.


METHODS
Ninety-seven patients with orthostatic hypotension were randomized in a 4-week, double-blinded, placebo-controlled study with a 1-week placebo run-in period. Patients ranged in age from 22 to 86 years (mean: 61 years).


METHODS
After a 1-week run-in phase, either placebo or midodrine at a dose of 2.5 mg, 5 mg, or 10 mg was administered three times a day for 4 weeks. Both the placebo group and the 2.5-mg midodrine group received constant doses throughout the double-blind phase. The patients receiving 5 mg or 10 mg of midodrine were given doses that were increased at weekly intervals by 2.5-mg increments until the designated dose was reached. Efficacy evaluations were based on an improvement at 1-hour postdose in standing systolic blood pressure and in symptoms of orthostatic hypotension (syncope, dizziness/lightheadedness, weakness/fatigue, and low energy level).


RESULTS
Midodrine (10 mg) increased standing systolic blood pressure by 22 mm Hg (28%, p < 0.001 versus placebo). Midodrine improved (p < 0.05) the following symptoms of orthostatic hypotension compared to placebo: dizziness/lightheadedness, weakness/fatigue, syncope, low energy level, impaired ability to stand, and feelings of depression. The overall side effects were mainly mild to moderate. One or more side effects were reported by 22% of the placebo group compared with 27% of the midodrine-treated group. Scalp pruritus/tingling, which was reported by 10 of 74 (13.5%) of the midodrine-treated patients, was most frequent. Other reported side effects included supine hypertension (8%) and feelings of urinary urgency (4%).


CONCLUSIONS
We conclude that midodrine is an effective and well-tolerated treatment for moderate-to-severe orthostatic hypotension associated with autonomic failure.
Jankovic
J
J
Department of Neurology, Baylor College of Medicine, Houston, Texas 77030.
Gilden
J L
JL
Hiner
B C
BC
Kaufmann
H
H
Brown
D C
DC
Coghlan
C H
CH
Rubin
M
M
Fouad-Tarazi
F M
FM
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001342:Autonomic Nervous System Diseases / Q000150:complications*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007024:Hypotension, Orthostatic / Q000188:drug therapy* / Q000209:etiology; D008297:Male; D008875:Middle Aged; D008879:Midodrine / Q000009:adverse effects / Q000627:therapeutic use*
D008879:Midodrine