Efficacy of midodrine vs placebo in neurogenic orthostatic hypotension. A randomized, double-blind multicenter study. Midodrine Study Group.
OBJECTIVE
To evaluate the efficacy of a 10-mg dose of midodrine 3 times per day in improving blood pressure (BP) and ameliorating symptoms of orthostatic hypotension in patients with neurogenic orthostatic hypotension. Midodrine hydrochloride, an alpha-agonist, could improve orthostatic BP by increasing vasomotor and venomotor tone.


METHODS
A total of 171 patients with orthostatic hypotension participated in a multicenter, randomized, placebo-controlled study. They were randomized to a 10-mg dose of midodrine or placebo 3 times per day in a 6-week study, comprising single-blind run-in (at week 1) and washout at weeks 5 and 6, with an intervening double-blind period (weeks 2 to 4).


METHODS
Twenty-five centers, with most patients evaluated in referral centers.


METHODS
The primary end points were improvement in standing systolic BP, symptoms of lightheadedness, and a global symptom relief score (by the investigator and patient separately).


RESULTS
Nine patients were not evaluable because of noncompliance or taking concomitant vasoactive medications (3 in the midodrine group, 6 in the placebo group). In the evaluable patients, midodrine resulted in improvements in standing systolic BP at all time points (P<.001 at visits 2, 3, 4, and 5), in reported symptoms by the end of the second week of treatment (P=.001), and in the global symptom relief score rated by both the patient (P=.03) and the investigator (P<.001). There was no effect by center, severity of orthostatic hypotension, use of fludrocortisone or compression garments, or diagnosis. The main adverse effects were those of pilomotor reactions, urinary retention, and supine hypertension.


CONCLUSIONS
Midodrine is efficacious and safe in the treatment of neurogenic orthostatic hypotension.
Low
P A
PA
Department of Neurology, Mayo Clinic, Rochester, Minn 55905, USA. low.phillip@mayo.edu
Gilden
J L
JL
Freeman
R
R
Sheng
K N
KN
McElligott
M A
MA
D000203:Activities of Daily Living; D000316:Adrenergic alpha-Agonists / Q000009:adverse effects / Q000627:therapeutic use*; D000704:Analysis of Variance; D004244:Dizziness; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007024:Hypotension, Orthostatic / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D008879:Midodrine / Q000009:adverse effects / Q000627:therapeutic use*; D013566:Sympathomimetics / Q000009:adverse effects / Q000627:therapeutic use*; D013599:Systole; D014662:Vasoconstrictor Agents / Q000009:adverse effects / Q000627:therapeutic use*
D000316:Adrenergic alpha-Agonists; D013566:Sympathomimetics; D014662:Vasoconstrictor Agents; D008879:Midodrine