By Marcello Cherchi, MD PhD
For patients
Midodrine is a pill that can help some people whose blood pressure changes too rapidly. It has the risk of raising blood pressure too much.
For clinicians
Overview
Midodrine is used in the management of orthostatic hypotension. Its main risk is supine hypertension.
Introduction
Midodrine is a prodrug of desglymidodrine, which functions as sympathomimetic through its activity as a peripherally acting alpha adrenergic agonist. It is used in the management of orthostatic hypotension, though literature regarding its efficacy is mixed. The main risk of midodrine is supine hypertension. Midodrine is sometimes used in conjunction with other drugs (such as fludrocortisone or pyridostigmine). Patients with cardiac or renal disease should consult their cardiologist or nephrologist before using midodrine.
Pharmacology
Midodrine is a prodrug that undergoes enzymatic hydrolysis to desglymidodrine (McClellan, Wiseman, Wilde 1998), which functions as sympathomimetic through its activity as a peripherally acting alpha adrenergic agonist (McTavish and Goa 1989).
Adverse effects
The main risk of midodrine is hypertension, particularly supine hypertension.
Cautions and contraindications
Patients with a history of cardiac disease should consult their cardiologist before starting midodrine. Patients with a history of renal disease should consult their nephrologist before starting midodrine.
Relevance in otoneurology
The main clinical application of midodrine in otoneurology is in the management of orthostatic hypotension.
Randomized, prospective, double-blinded, placebo-controlled studies of midodrine for orthostatic hypotension generally report encouraging results. Jankovic and colleagues (Jankovic et al. 1993) conducted a placebo-controlled study of 97 patients with orthostatic hypotension and “conclude[d] that midodrine is an effective and well-tolerated treatment for moderate-to-severe orthostatic hypotension associated with autonomic failure.” Low and colleagues (Low et al. 1997) conducted a placebo-controlled study of 171 patients with orthostatic hypotension and concluded that, “Midodrine is efficacious and safe in the treatment of neurogenic orthostatic hypotension.” Smith and colleagues (Smith et al. 2016) concluded that, “Midodrine is a well-tolerated and clinically effective treatment for symptomatic orthostatic hypotension.”
Not all of the literature is so encouraging, and meta-analyses reach discrepant conclusions. A meta-analysis of the literature concluded that, “There is insufficient and low quality evidence to support the use of midodrine” for orthostatic hypotension (Parsaik et al. 2013). In contrast, a comparative meta-analysis of midodrine and droxidopa concluded that, “In patients with NOH [neurogenic orthostatic hypotension], both droxidopa and midodrine significantly increase sSBP [standing systolic blood pressure], the latter to a greater extent. However, midodrine, but not droxidopa, significantly increases the risk of supine hypertension” (Chen et al. 2018).
Other notes
Midodrine has a relatively short half-life (3 – 4 hours), and thus is usually scheduled to be taken two or three times per day.
Midodrine is sometimes used in conjunction with other medications aimed at treating orthostatic hypotension, such as pyridostigmine (Byun et al. 2017) or fludrocortisone.
References
Byun JI, Moon J, Kim DY, Shin H, Sunwoo JS, Lim JA, Kim TJ, Lee WJ, Lee HS, Jun JS, Park KI, Lee ST, Jung KH, Jung KY, Lee SK, Chu K (2017) Efficacy of single or combined midodrine and pyridostigmine in orthostatic hypotension. Neurology 89: 1078-1086. doi: 10.1212/WNL.0000000000004340
Chen JJ, Han Y, Tang J, Portillo I, Hauser RA, Dashtipour K (2018) Standing and Supine Blood Pressure Outcomes Associated With Droxidopa and Midodrine in Patients With Neurogenic Orthostatic Hypotension: A Bayesian Meta-analysis and Mixed Treatment Comparison of Randomized Trials. Ann Pharmacother 52: 1182-1194. doi: 10.1177/1060028018786954
Jankovic J, Gilden JL, Hiner BC, Kaufmann H, Brown DC, Coghlan CH, Rubin M, Fouad-Tarazi FM (1993) Neurogenic orthostatic hypotension: a double-blind, placebo-controlled study with midodrine. Am J Med 95: 38-48. doi: 10.1016/0002-9343(93)90230-m
Low PA, Gilden JL, Freeman R, Sheng KN, McElligott MA (1997) Efficacy of midodrine vs placebo in neurogenic orthostatic hypotension. A randomized, double-blind multicenter study. Midodrine Study Group. JAMA 277: 1046-51.
McClellan KJ, Wiseman LR, Wilde MI (1998) Midodrine. A review of its therapeutic use in the management of orthostatic hypotension. Drugs Aging 12: 76-86. doi: 10.2165/00002512-199812010-00007
McTavish D, Goa KL (1989) Midodrine. A review of its pharmacological properties and therapeutic use in orthostatic hypotension and secondary hypotensive disorders. Drugs 38: 757-77. doi: 10.2165/00003495-198938050-00004
Parsaik AK, Singh B, Altayar O, Mascarenhas SS, Singh SK, Erwin PJ, Murad MH (2013) Midodrine for orthostatic hypotension: a systematic review and meta-analysis of clinical trials. J Gen Intern Med 28: 1496-503. doi: 10.1007/s11606-013-2520-3
Smith W, Wan H, Much D, Robinson AG, Martin P (2016) Clinical benefit of midodrine hydrochloride in symptomatic orthostatic hypotension: a phase 4, double-blind, placebo-controlled, randomized, tilt-table study. Clin Auton Res 26: 269-77. doi: 10.1007/s10286-016-0363-9
