Skip to main content
Top
Published in: Journal of General Internal Medicine 11/2013

01-11-2013 | Review Article

Midodrine for Orthostatic Hypotension: A Systematic Review and Meta-Analysis of Clinical Trials

Authors: Ajay K. Parsaik, MD, Balwinder Singh, MD, Osama Altayar, MD, Soniya S. Mascarenhas, RN, Shannon K. Singh, Patricia J. Erwin, M. Hassan Murad, MD, MPH

Published in: Journal of General Internal Medicine | Issue 11/2013

Login to get access

ABSTRACT

OBJECTIVE

To perform a systematic review and meta-analysis of clinical trials evaluating the efficacy and safety of midodrine in orthostatic hypotension (OH).

METHODS

We searched major databases and related conference proceedings through June 30, 2012. Two reviewers independently selected studies and extracted data. Random-effects meta-analysis was used to pool the outcome measures across studies.

RESULTS

Seven trials were included in the efficacy analysis (enrolling 325 patients, mean age 53 years) and two additional trials were included in the safety analysis. Compared to placebo, the mean change in systolic blood pressure was 4.9 mmHg (p = 0.65) and the mean change in mean arterial pressure from supine to standing was −1.7 mmHg (p = 0.45). The change in standing systolic blood pressure before and after giving midodrine was 21.5 mmHg (p < 0.001). A significant improvement was seen in patients’ and investigators’ global assessment symptoms scale (a mean difference of 0.70 [95 % CI 0.30–1.09; p < 0.001] and 0.80 [95 % CI 0.76–0.85; p < 0.001], respectively). There was a significant increase in risk of piloerection, scalp pruritis, urinary hesitancy/retention, supine hypertension and scalp paresthesia after giving midodrine. The quality of evidence was limited by imprecision, heterogeneity and increased risk of bias.

CONCLUSION

There is insufficient and low quality evidence to support the use of midodrine for OH.
Appendix
Available only for authorised users
Literature
1.
go back to reference Freeman R, Wieling W, Axelrod FB, et al. Consensus statement on the definition of orthostatic hypotension, neurally mediated syncope and the postural tachycardia syndrome. Auton Neurosci. 2011;161:46–8.PubMedCrossRef Freeman R, Wieling W, Axelrod FB, et al. Consensus statement on the definition of orthostatic hypotension, neurally mediated syncope and the postural tachycardia syndrome. Auton Neurosci. 2011;161:46–8.PubMedCrossRef
2.
go back to reference Low PA. Update on the evaluation, pathogenesis, and management of neurogenic orthostatic hypotension: introduction. Neurology. 1995;45:S4–5.PubMedCrossRef Low PA. Update on the evaluation, pathogenesis, and management of neurogenic orthostatic hypotension: introduction. Neurology. 1995;45:S4–5.PubMedCrossRef
3.
go back to reference Low PA, Singer W. Management of neurogenic orthostatic hypotension: an update. Lancet Neurol. 2008;7:451–8.PubMedCrossRef Low PA, Singer W. Management of neurogenic orthostatic hypotension: an update. Lancet Neurol. 2008;7:451–8.PubMedCrossRef
5.
go back to reference Dhruva SS, Redberg RF. Accelerated approval and possible withdrawal of midodrine. JAMA. 2010;304:2172–3.PubMedCrossRef Dhruva SS, Redberg RF. Accelerated approval and possible withdrawal of midodrine. JAMA. 2010;304:2172–3.PubMedCrossRef
6.
go back to reference Mitka M. FDA takes slow road toward withdrawal of drug approved with fast-track process. JAMA. 2011;305:982–4.PubMedCrossRef Mitka M. FDA takes slow road toward withdrawal of drug approved with fast-track process. JAMA. 2011;305:982–4.PubMedCrossRef
7.
go back to reference Mitka M. Trials to address efficacy of midodrine 18 years after it gains FDA approval. JAMA. 2012;307:1124–7.PubMedCrossRef Mitka M. Trials to address efficacy of midodrine 18 years after it gains FDA approval. JAMA. 2012;307:1124–7.PubMedCrossRef
9.
go back to reference Cohen J. A coefficient of agreement for nominal scales. Educ Psychol Meas. 1960;20:37–46. Cohen J. A coefficient of agreement for nominal scales. Educ Psychol Meas. 1960;20:37–46.
10.
go back to reference Higgins JP, Green S, Eds. Cochrane handbook for systematic reviews of interventions version 5.1.0 [updated March 2011]. The Cochrane Collaboration, 2011 Available from www.cochrane-handbook.org 2011. Higgins JP, Green S, Eds. Cochrane handbook for systematic reviews of interventions version 5.1.0 [updated March 2011]. The Cochrane Collaboration, 2011 Available from www.​cochrane-handbook.​org 2011.
11.
go back to reference Atkins D, Best D, Briss PA, et al. Grading quality of evidence and strength of recommendations. BMJ. 2004;328:1490.PubMedCrossRef Atkins D, Best D, Briss PA, et al. Grading quality of evidence and strength of recommendations. BMJ. 2004;328:1490.PubMedCrossRef
12.
go back to reference Guyatt GH, Oxman AD, Kunz R, Vist GE, Falck-Ytter Y, Schunemann HJ. What is “quality of evidence” and why is it important to clinicians? BMJ. 2008;336:995–8.PubMedCrossRef Guyatt GH, Oxman AD, Kunz R, Vist GE, Falck-Ytter Y, Schunemann HJ. What is “quality of evidence” and why is it important to clinicians? BMJ. 2008;336:995–8.PubMedCrossRef
13.
14.
go back to reference Higgins JP, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta-analyses. BMJ. 2003;327:557–60.PubMedCrossRef Higgins JP, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta-analyses. BMJ. 2003;327:557–60.PubMedCrossRef
15.
go back to reference Fouad-Tarazi FM, Okabe M, Goren H. Alpha sympathomimetic treatment of autonomic insufficiency with orthostatic hypotension. Am J Med. 1995;99:604–10.PubMedCrossRef Fouad-Tarazi FM, Okabe M, Goren H. Alpha sympathomimetic treatment of autonomic insufficiency with orthostatic hypotension. Am J Med. 1995;99:604–10.PubMedCrossRef
16.
go back to reference Jankovic J, Gilden JL, Hiner BC, et al. Neurogenic orthostatic hypotension: a double-blind, placebo-controlled study with midodrine. Am J Med. 1993;95:38–48.PubMedCrossRef Jankovic J, Gilden JL, Hiner BC, et al. Neurogenic orthostatic hypotension: a double-blind, placebo-controlled study with midodrine. Am J Med. 1993;95:38–48.PubMedCrossRef
17.
go back to reference Low PA, Gilden JL, Freeman R, Sheng KN, McElligott MA. Efficacy of midodrine vs. placebo in neurogenic orthostatic hypotension. A randomized, double-blind multicenter study. Midodrine Study Group. JAMA. 1997;277:1046–51.PubMedCrossRef Low PA, Gilden JL, Freeman R, Sheng KN, McElligott MA. Efficacy of midodrine vs. placebo in neurogenic orthostatic hypotension. A randomized, double-blind multicenter study. Midodrine Study Group. JAMA. 1997;277:1046–51.PubMedCrossRef
18.
go back to reference Schrage WG, Eisenach JH, Dinenno FA, et al. Effects of midodrine on exercise-induced hypotension and blood pressure recovery in autonomic failure. J Appl Physiol. 2004;97:1978–84.PubMedCrossRef Schrage WG, Eisenach JH, Dinenno FA, et al. Effects of midodrine on exercise-induced hypotension and blood pressure recovery in autonomic failure. J Appl Physiol. 2004;97:1978–84.PubMedCrossRef
19.
go back to reference Wecht JM, Rosado-Rivera D, Handrakis JP, Radulovic M, Bauman WA. Effects of midodrine hydrochloride on blood pressure and cerebral blood flow during orthostasis in persons with chronic tetraplegia. Arch Phys Med Rehabil. 2010;91:1429–35.PubMedCrossRef Wecht JM, Rosado-Rivera D, Handrakis JP, Radulovic M, Bauman WA. Effects of midodrine hydrochloride on blood pressure and cerebral blood flow during orthostasis in persons with chronic tetraplegia. Arch Phys Med Rehabil. 2010;91:1429–35.PubMedCrossRef
20.
go back to reference Wright RA, Kaufmann HC, Perera R, et al. A double-blind, dose-response study of midodrine in neurogenic orthostatic hypotension. Neurology. 1998;51:120–4.PubMedCrossRef Wright RA, Kaufmann HC, Perera R, et al. A double-blind, dose-response study of midodrine in neurogenic orthostatic hypotension. Neurology. 1998;51:120–4.PubMedCrossRef
21.
go back to reference Axelrod FB, Krey L, Glickstein JS, Weider Allison J, Friedman D. Preliminary observations on the use of midodrine in treating orthostatic hypotension in familial dysautonomia. J Auton Nerv Syst. 1995;55:29–35.PubMedCrossRef Axelrod FB, Krey L, Glickstein JS, Weider Allison J, Friedman D. Preliminary observations on the use of midodrine in treating orthostatic hypotension in familial dysautonomia. J Auton Nerv Syst. 1995;55:29–35.PubMedCrossRef
22.
go back to reference Hoeldtke RD, Horvath GG, Bryner KD, Hobbs GR. Treatment of orthostatic hypotension with midodrine and octreotide. J Clin Endocrinol Metab. 1998;83:339–43.PubMedCrossRef Hoeldtke RD, Horvath GG, Bryner KD, Hobbs GR. Treatment of orthostatic hypotension with midodrine and octreotide. J Clin Endocrinol Metab. 1998;83:339–43.PubMedCrossRef
23.
go back to reference Kaufmann H, Brannan T, Krakoff L, Yahr MD, Mandeli J. Treatment of orthostatic hypotension due to autonomic failure with a peripheral alpha-adrenergic agonist (midodrine). Neurology. 1988;38:951–6.PubMedCrossRef Kaufmann H, Brannan T, Krakoff L, Yahr MD, Mandeli J. Treatment of orthostatic hypotension due to autonomic failure with a peripheral alpha-adrenergic agonist (midodrine). Neurology. 1988;38:951–6.PubMedCrossRef
24.
go back to reference Logan IC, Witham MD. Efficacy of treatments for orthostatic hypotension: a systematic review. Age Ageing. 2012;41:587–94.PubMedCrossRef Logan IC, Witham MD. Efficacy of treatments for orthostatic hypotension: a systematic review. Age Ageing. 2012;41:587–94.PubMedCrossRef
25.
go back to reference Pathak A, Raoul V, Montastruc JL, Senard JM. Adverse drug reactions related to drugs used in orthostatic hypotension: a prospective and systematic pharmacovigilance study in France. Eur J Clin Pharmacol. 2005;61:471–4.PubMedCrossRef Pathak A, Raoul V, Montastruc JL, Senard JM. Adverse drug reactions related to drugs used in orthostatic hypotension: a prospective and systematic pharmacovigilance study in France. Eur J Clin Pharmacol. 2005;61:471–4.PubMedCrossRef
26.
go back to reference Sterne JA, Gavaghan D, Egger M. Publication and related bias in meta-analysis: power of statistical tests and prevalence in the literature. J Clin Epidemiol. 2000;53:1119–29.PubMedCrossRef Sterne JA, Gavaghan D, Egger M. Publication and related bias in meta-analysis: power of statistical tests and prevalence in the literature. J Clin Epidemiol. 2000;53:1119–29.PubMedCrossRef
Metadata
Title
Midodrine for Orthostatic Hypotension: A Systematic Review and Meta-Analysis of Clinical Trials
Authors
Ajay K. Parsaik, MD
Balwinder Singh, MD
Osama Altayar, MD
Soniya S. Mascarenhas, RN
Shannon K. Singh
Patricia J. Erwin
M. Hassan Murad, MD, MPH
Publication date
01-11-2013
Publisher
Springer US
Published in
Journal of General Internal Medicine / Issue 11/2013
Print ISSN: 0884-8734
Electronic ISSN: 1525-1497
DOI
https://doi.org/10.1007/s11606-013-2520-3

Other articles of this Issue 11/2013

Journal of General Internal Medicine 11/2013 Go to the issue