Neurogenic orthostatic hypotension: A double-blind, placebo-controlled study with midodrine

https://doi.org/10.1016/0002-9343(93)90230-MGet rights and content

Abstract

purpose: To investigate the efficacy and safety of midodrine for treatment of patients with orthostatic hypotension due to autonomic failure.

patients: 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 midodrinetreated patients, was most frequent. Other reported side effects included supine hypertension (8%) and feelings of urinary urgency (4%).

conclusion: We conclude that midodrine is an effective and well-tolerated treatment for moderate-to-severe orthostatic hypotension associated with autonomic failure.

References (50)

  • AV Chobanian et al.

    Mineralocorticoid-induced hypotension in patients with orthostatic hypotension

    N Engl J Med

    (1979)
  • RJ Polinsky

    Pharmacological responses and biochemical changes in progressive autonomic failure

  • AV Chobanian et al.

    Treatment of chronic orthostatic hypotension with ergotamine

    Circulation

    (1983)
  • G Jennings et al.

    Treatment of orthostatic hypotension with dihydroergotamine

    BMJ

    (1979)
  • FM Fouad et al.

    Dihydroergotamine in idiopathic orthostatic hypotension: short-term intramuscular and long-term oral therapy

    Clin Pharmacol Ther

    (1981)
  • MA Diamond et al.

    Idiopathic postural hypotension: physiological observations and reports of a new mode of therapy

    J Clin Invest

    (1970)
  • RJ Polinsky et al.

    Effect of indomethacin inhibition of prostaglandin synthesis on blood pressure and plasma norepinephrine levels in patients with orthostatic hypotension

    Neurology

    (1981)
  • O Kuchel et al.

    Treatment of severe orthostatic hypotension by metoclopropamide

    Ann Intern Med

    (1980)
  • D Robertson et al.

    Clonidine raises blood pressure in idiopathic orthostatic hypotension

    Am J Med

    (1983)
  • AJ Moss et al.

    Atrial tachypacing in the treatment of a patient with primary orthostatic hypotension

    N Engl J Med

    (1980)
  • IJ Schatz

    Orthostatic hypotension: II. Clinical diagnosis, testing, and treatment

    Arch Intern Med

    (1984)
  • O Thulesius et al.

    Vasoconstrictor effect of midodrine, ST 1059, noradrenaline, etilefrine and dihydroergotamine on isolated human veins

    Eur J Clin Pharmacol

    (1979)
  • R Yamazaki et al.

    Effects of a-adrenoceptor agonists on cardiac output and blood pressure in spinally anesthetized ganglion-blocked dogs

    Arch Int Pharmacodyn Ther

    (1988)
  • H Pittner et al.

    Pharmacodynamic actions of midodrine, a new alpha-adrenergic stimulating agent, and its main metabolite, ST 1059

    Arzneimittelforschung

    (1976)
  • PK Zachariah et al.

    Pharmacodynamics of midodrine, an antihypotensive agent

    Clin Pharmacol Ther

    (1986)
  • Cited by (342)

    • New approaches to treatments for sleep, pain and autonomic failure in Parkinson's disease - Pharmacological therapies

      2022, Neuropharmacology
      Citation Excerpt :

      No ransomised, double-blind, placebo-controlled trials have evaluated the efficacy of midodrine, a short-acting α1-adrenoreceptor agonist, on OH in a homogenous cohort of patients with PD. However, a series of high-quality trials have confirmed its efficacy in heterogenous groups of patients with n-OH, including subjects with PD (Jankovic et al., 1993; Low et al., 1997; Smith et al., 2016). The long-acting synthetic mineralocorticoid, fludrocortisone, is commonly used in clinical practice for treating OH in PD, based on outcomes from two small double-blind RCTs with a cross-over design comparing the efficacy of fludrocortisone with domperidone or pyridostigmine bromide, respectively, in patients with PD and OH (Schoffer et al., 2007; Schreglmann et al., 2017).

    • Midodrine

      2022, Primer on the Autonomic Nervous System, Fourth Edition
    • Principles and Practice of Movement Disorders

      2021, Principles and Practice of Movement Disorders
    View all citing articles on Scopus

    This study was supported by a grant-in-aid from Roberts Pharmaceutical Corporation, Eatontown, New Jersey. This work was presented as an abstract at the 43rd Annual Meeting of the American Academy of Neurology, Boston, Massachusetts, April 21–27, 1991.

    View full text