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Supplements Understanding the Diagnosis, Management, and Treatment Options for Neurogenic Orthostatic Hypoten

Managed Care Approach to the Treatment of Neurogenic Orthostatic Hypotension

Stuart H. Isaacson, MD
In 1996, Shire received fast-track approval from the FDA to market midodrine for symptomatic OH, with 7 years of marketing exclusivity as an orphan drug. Approval was based on studies that demonstrated improvement in a surrogate outcome, 1-minute standing systolic blood pressure. The company agreed to complete additional studies to establish symptomatic efficacy.

In 2003, when marketing exclusivity ended, Shire discontinued the brand name product, leaving only generic products available. In 2010, the FDA proposed withdrawing approval of midodrine because Shire had failed to submit adequate postmarketing studies to establish symptomatic benefit. In 2012, Shire agreed to conduct 2 studies to establish the efficacy of midodrine for relieving OH symptoms.64

These studies have been completed, but not published. Preliminary results have been posted on www.clinicaltrials.gov.65,66 In a placebo-controlled tilt table test, the time to onset of syncope or near-syncope was significantly lon-ger with midodrine (1105.6 vs 1626.6 sec; mean difference 521 sec; 95% CI, 124.2-917.7; P = .0131).65 In a midodrine withdrawal study, 98 patients with severe OH were treat-ed with the midodrine regimen they had taken before the study. Patients were randomized to receive midodrine for 16 days or midodrine for 15 days followed by placebo on the last day. The primary outcome of the study was the percentage of patients who failed to maintain a response 30 minutes after the dose on day 16, with failure defined as either a 4-point increase on OHSA item 1 or an increase in syncopal or near-syncopal events within 15 minutes after standing. The percentage of patients who failed to maintain a response was 30.3% for midodrine and 44.1% for placebo (mean difference of 13.8%; 95% CI, −37.6 to 9.8; P = .3145).66 Patients and clinicians maintain that midodrine may have QOL and symptomatic benefits that the clinical trials have failed to identify.67 An independent systematic review evaluated symp-tom improvement and adverse effects of midodrine in clinical trials of symptomatic OH. There was high het-erogeneity (I2 = 73%) among 5 studies that were included in the analysis. The odds ratio for symptom improvement with midodrine was 3.9 (95% CI, 1.8-8.3), providing an NNT of 3 (95% CI, 2-7).68

Adverse Effects

Adverse effects reported with midodrine are related to its alpha-agonist activity. These include pilo-erection, pruritus (especially on the scalp), paresthesia, urinary reten-tion, and SH.48,69 The previously cited systematic review evaluated adverse effects with midodrine in clinical trials of symptomatic OH.63 The relative risk of a minor adverse event (primarily piloerection, paresthesias, chills, and GI discomfort) was 4.58 (95% CI, 2.03-10.37), providing an NNH of 8 (95% CI, 3-27). Based on data from 3 studies, midodrine increased the risk of SH (relative risk 5.31; 95% CI, 1.39-20.27), with an NNH of 14 (95% CI, 9-50).68 Drug Interactions Because midodrine is a direct alpha1-agonist, its effects are opposed by alpha1-antagonists.45 There is concern that co-administration of midodrine and digoxin or beta-blockers may cause bradycardia. Fludrocortisone Fludrocortisone is a mineralocorticoid that causes volume expansion by increasing renal sodium reabsorption.10 These effects normalize over time, so other mechanisms may be responsible for its effects in NOH. Unlike the sympathomimetic drugs, it has a long duration of action (biologic half-life of 18 to 36 hours).46 In addition, it had equivalent effects on standing and supine blood pressure in a study of patients with OH due to diabetic autonomic neuropathy.70 These properties raise concern about exacerbation of SH.10 Doses of 0.1 to 0.2 mg are suggested, but some patients can respond with up to 0.6 mg daily. Clinical Efficacy Clinical trials provide little evidence for the efficacy of fludrocortisone in NOH. In a double-blind crossover trial, fludrocortisone 0.1 mg twice daily improved orthostatic blood pressure measurements in 5 patients with NOH due to diabetic neuropathy.70,71 Increases in stand-ing blood pressure were reported with fludrocortisone plus head-up sleeping in an observational study of 8 patients with NOH.72 A Movement Disorder Society Task Force found insufficient evidence to evaluate the safety and efficacy of fludrocortisone for OH in PD.73 Adverse Effects Fludrocortisone can cause hypokalemia, pedal edema, SH, and glucocorticoid effects.45 In order to minimize the risk of these adverse effects, the lowest effective dose of fludrocortisone should be used. Weight gain is expected due to fluid retention; therefore, heart failure is a relative contraindication.7 To prevent hypokalemia, potassium levels should be monitored and potassium supplementa-tion provided if needed.

Additional Pharmacotherapy Options

Other drugs have been evaluated for treatment of NOH, but they do not have a well-defined role in management. These include non-steroidal anti-inflamma-tory drugs (primarily indomethacin), erythropoietin in patients with anemia, and desmopressin in patients with nocturnal polyuria.74-76 Octreotide and acarbose have been evaluated for postprandial hypotension.77,78

Atomoxetine inhibits norepinephrine reuptake by inhibiting the pre-synaptic norepinephrine transporter. In patients with NOH due to autonomic failure who have residual sympathetic activity, this has the potential to raise blood pressure by increasing synaptic nor-epinephrine levels.7 Atomoxetine displayed a pressor effect only in patients with central autonomic failure in a study that compared its effects in patients with central and peripheral autonomic failure.79 A placebo-controlled crossover study compared single doses of atomoxetine and midodrine in 65 patients with severe autonomic failure and NOH.80

At 1 minute, upright systolic blood pressure was significantly higher with atomoxetine than midodrine (means difference 7.5 mm Hg; 95% CI, 0.6-15; P = .03). Change in the OHQ total score was significantly greater with atomoxetine than placebo (0.4 points; 95% CI, −0.1 to −0.8; P = .02). The OHQ total score with midodrine was not significantly different from placebo (0.5 points; 95% CI, −0.1 to 1.0; P = .08). Further study is necessary to define the role of atomoxetine in NOH. The cholinesterase inhibitor pyridostigmine may increase standing blood pressure by increasing choliner-gic transmission in the autonomic ganglia.10 A potential advantage of pyridostigmine is that it has demonstrated little potential to cause SH. A randomized controlled trial evaluated a single dose of pyridostigmine alone or in combination with midodrine in 60 patients with NOH.81 It caused a modest increase in standing blood pressure that was associated with symptom improvement. A sur-vey reported moderate to marked symptom improvement in 17 of 20 patients who continued long-term treatment with pyridostigmine after the single-dose study.82 In a sec-ond study of patients with NOH and autonomic failure, pyridostigmine did not improve standing blood pressure or symptoms.83 Cholinergic adverse effects can limit the use of pyridostigmine in NOH.10

Author affiliation: Parkinson’s Disease and Movement Disorders Center of Boca Raton, Florida International University Herbert Wertheim College of Medicine.

Funding source: This activity is supported by an educational grant from Lundbeck, LLC.

Author disclosure: Dr. Isaacson has the following relevant commer-cial financial relationships or affiliations to disclose:

Grant/Research Support: Abbvie, Acadia, Acorda, Adamas, Addex, Amarantus, Auspex, Biotie, Cynapsus, Eisai, GE Healthcare, Ipsen, Kyowa, Lundbeck, Merz, Novartis, Neurocrine, Pfizer, Pharma2B, Roche, Santhera, Serono, Shire, Teva, UCB, US World Meds,

Xenoport Consultant: Acadia, Acorda, Allergan, Amarantus, Auspex, Biotie, Britannia, Cynapsus, Eisai, GE Healthcare, Impax, Ipsen, Kyowa, Lundbeck, Teva, UCB, US World Meds, Xenoport

Speaker’s Bureau: Abbvie, Acadia, Allergan, GE Healthcare, Impax, Lundbeck, Teva, UCB, US World Meds, Xenoport

Authorship information: Concept and design, acquisition of data, analysis and interpretation of data, drafting of the manuscript, and critical revision of the manuscript for important intellectual content.

Address correspondence to: isaacson@ParkinsonsCenter.org.
1. Goldstein DS, Sharabi Y. Neurogenic orthostatic hypotension: a pathophysiological approach. Circulation. 2009;119(1):139-146.

2. Arnold AC, Shibao C. Current concepts in orthostatic hypoten-sion management. Curr Hypertens Rep. 2013;15(4):304-312.

3. Freeman R. Clinical practice. Neurogenic orthostatic hypoten-sion. N Engl J Med. 2008;358(6):615-624.

4. Low PA, Opfer-Gehrking TL, McPhee BR, et al. Prospective evaluation of clinical characteristics of orthostatic hypotension. Mayo Clin Proc. 1995;70(7):617-622.

5. Poon IO, Braun U. High prevalence of orthostatic hypotension and its correlation with potentially causative medications among elderly veterans. J Clin Pharm Ther. 2005;30(2):173-178.

6. Perez-Lloret S, Rey MV, Fabre N, et al. Factors related to orthostatic hypotension in Parkinson’s disease. Parkinsonism Relat Disord. 2012;18(5):501-505.

7. Shibao C, Lipsitz LA, Biaggioni I. Evaluation and treatment of orthostatic hypotension. J Am Soc Hypertens. 2013;7(4):317-324.

8. Maule S, Milazzo V, Maule MM, Di Stefano C, Milan A, Veglio F. Mortality and prognosis in patients with neurogenic orthostatic hypotension. Funct Neurol. 2012;27(2):101-106.

9. Biaggioni I. Treatment: special conditions: orthostatic hypoten-sion. J Am Soc Hypertens. 2015;9(1):67-69; quiz 70. 

10. Schroeder C, Jordan J, Kaufmann H. Management of neuro-genic orthostatic hypotension in patients with autonomic failure. Drugs. 2013;73(12):1267-1279.

11. Jordan J, Shannon JR, Biaggioni I, Norman R, Black BK, Robertson D. Contrasting actions of pressor agents in severe autonomic failure. Am J Med. 1998;105(2):116–24.

12. Kamaruzzaman S, Watt H, Carson C, Ebrahim S. The asso-ciation between orthostatic hypotension and medication use in the British Women’s Heart and Health Study. Age Aging. 2010;39(1):51-56.

13. Milazzo V, Stefano CD, Servo S, et al. Drugs and orthostatic hypotension: evidence from literature. J Hypertens. 2012;1(2):1-8.

14. Gugger JJ. Antipsychotic pharmacotherapy and orthostatic hypotension: identification and management. CNS Drugs. 2011;25(8):659-671.

15. American Geriatrics Society updated Beers Criteria for poten-tially inappropriate medication use in older adults. J Am Geriatr Soc. 2012;60(4):616-631.

16. Sica DA. Alpha1-adrenergic blockers: current usage consider-ations. J Clin Hypertens (Greenwich). 2005;7(12):757-762.

17. American Psychiatric Association practice guidelines. American Psychiatric Association website. http://www.psychiatry-online.org/guidelines. Accessed June 19, 2015.

18. Noack C, Schroeder C, Heusser K, Lipp A. Cardiovascular effects of levodopa in Parkinson’s disease. Parkinsonism Relat Disord. 2014;20(8):815-818.

19. Pahwa R, Factor SA, Lyons KE, et al. Practice parameter: treat-ment of Parkinson disease with motor fluctuations and dyskinesia (an evidence-based review): report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology. 2006;66(7):983-995.

20. Milazzo V, Di Stefano C, Servo S, et al. Drugs and orthostatic hypotension: evidence from literature. J Hypertens. 2012;1(2):1-8.

21. Seo GH, Lee YK, Ha YC. Risk of hip fractures in men with alpha-blockers: a nationwide study base on claim registry. J Bone Metab. 2015;22(1):29-32.

22. Bird ST, Delaney JA, Brophy JM, Etminan M, Skeldon SC,Hartzema AG. Tamsulosin treatment for benign prostatic hyper-plasia and risk of severe hypotension in men aged 40-85 years in the United States: risk window analyses using between and within patient methodology. BMJ. 2013;347:f6320.

23. Yoshimura K, Kadoyama K, Sakaeda T, Sugino Y, Ogawa O, Okuno Y. A survey of the FAERS database concerning the adverse event profiles of alpha1-adrenoreceptor blockers for lower urinary tract symptoms. Int J Med Sci. 2013;10(7):864-869.

24. Baker WL, Smyth LR, Riche DM, Bourret EM, Chamberlin KW, White WB. Effects of sodium-glucose co-transporter 2 inhibitors on blood pressure: a systematic review and meta-analysis. J Am Soc Hypertens. 2014;8(4):262-275.e269.

25. Invokana [package insert]. Titusville, NJ: Janssen Pharmaceuticals, Inc; 2015.

26. Rascol O, Perez-Lloret S, Damier P, et al. Falls in ambula-tory non-demented patients with Parkinson’s disease. J Neural Transm. 2015.

27. Gangavati A, Hajjar I, Quach L, et al. Hypertension, orthostatic hypotension, and the risk of falls in a community-dwelling elderly population: the maintenance of balance, independent living, intellect, and zest in the elderly of Boston study. J Am Geriatr Soc. 2011;59(3):383-389.

28. Krediet CT, Go-Schon IK, van Lieshout JJ, Wieling W. Optimizing squatting as a physical maneuver to prevent vasova-gal syncope. Clin Auton Res. 2008;18(4):179-186.

29. Krediet CT, van Dijk N, Linzer M, van Lieshout JJ, Wieling W. Management of vasovagal syncope: controlling or abort-ing faints by leg crossing and muscle tensing. Circulation. 2002;106(13):1684-1689.

30. Wieling W, van Dijk N, Thijs RD, de Lange FJ, Krediet CT, Halliwill JR. Physical countermeasures to increase orthostatic tol-erance. J Intern Med. 2015;277(1):69-82.

31. de Lang FJ, de Jong J, Wieling W. SYNCOpedia.org website. http://syncopedia.org/wiki/Main_Page. Accessed July 22, 2015.

32. Syncope trust and reflex anoxic seizures (STARS). STARS website. http://www.stars.org.uk/. Accessed July 22, 2015

33. Smit AA, Wieling W, Opfer-Gehrking TL, van Emmerik-Levelt HM, Low PA. Patients’ choice of portable folding chairs to reduce symptoms of orthostatic hypotension. Clin Auton Res. 1999;9(6):341-344.

34. Figueroa JJ, Singer W, Sandroni P, et al. Effects of patient-controlled abdominal compression on standing systolic blood pressure in adults with orthostatic hypotension. Arch Phys Med Rehabil. 2015;96(3):505-510.

35. Mills PB, Fung CK, Travlos A, Krassioukov A. Nonpharmacologic management of orthostatic hypotension: a systematic review. Arch Phys Med Rehabil. 2015;96(2):366-375.e366.

36. Raj SR, Coffin ST. Medical therapy and physical maneuvers in the treatment of the vasovagal syncope and orthostatic hypoten-sion. Prog Cardiovasc Dis. 2013;55(4):425-433.

37. Isaacson SH, Skettini J. Neurogenic orthostatic hypotension in Parkinson’s disease: evaluation, management, and emerging role of droxidopa. Vasc Health Risk Manag. 2014;10:169-176.

38. Lahrmann H, Cortelli P, Hilz M, et al. Orthostatic hypotension. In: European Handbook of Neurological Management. Oxford, England: Wiley-Blackwell; 2010:469-475.

39. Mathias CJ, Young TM. Water drinking in the management of orthostatic intolerance due to orthostatic hypotension, vasovagal syncope and the postural tachycardia syndrome. Eur J Neurol. 2004;11(9):613-619.

40. Ooi WL, Hossain M, Lipsitz LA. The association between ortho-static hypotension and recurrent falls in nursing home residents. Am J Med. 2000;108(2):106-111.

41. Pathak A, Lapeyre-Mestre M, Montastruc JL, Senard JM. Heat-related morbidity in patients with orthostatic hypotension and pri-mary autonomic failure. Mov Disord. 2005;20(9):1213-1219.

42. STEADI - Older Adult Fall Prevention: make STEADI part of your medical practice. CDC website. http://www.cdc.gov/steadi/ index.html. Accessed June 19, 2015.

43. Panel on Prevention of Falls in Older Persons, American Geriatrics Society and British Geriatrics Society. Summary of the Updated American Geriatrics Society/British Geriatrics Society clinical practice guideline for prevention of falls in older persons. J Am Geriatr Soc. 2011;59(1):148-157.

44. Northera [package insert]. Charlotte, NC: Chelsea Therapeutics, Inc. 2014.

45. Midodrine hydrochloride tablets [package insert]. Weston, FL: Apotex Corp. 2011.

46. Fludrocortisone acetate tablets [package insert]. Summerville, PA: Teva Pharmaceuticals. 2011.

47. Kaufmann H, Saadia D, Voustianiouk A, et al. Norepinephrine precursor therapy in neurogenic orthostatic hypotension. Circulation. 2003;108(6):724-728.

48. Wright RA, Kaufmann HC, Perera R, et al. A double-blind, dose-response study of midodrine in neurogenic orthostatic hypo-tension. Neurology. 1998;51(1):120-124.

49. Droxidopa (Northera) for neurogenic orthostatic hypotension. Med Lett Drugs Ther. 2015;57(1471):92-93.

50. Micromedex 2.0 (electronic version). Truven Health Analytics, Grewwnwood Village, Colorado, USA. http://www.micromedexso-lutions.pacificlib.idm.oclc.org/. Accessed Sepember 29, 2015.

51. Freeman R, Wieling W, Axelrod FB, et al. Consensus statement on the definition of orthostatic hypotension, neurally mediated syncope and the postural tachycardia syndrome. Clin Auton Res. 2011;21(2):69-72.

52. Adis Medical Writers. Consider pharmacotherapy for neuro-genic orthostatic hypotension only if non-pharmacological mea-sures fail. Drugs & Therapy Perspectives. 2014;30(4):135-140.

53. Kaufmann H, Malamut R, Norcliffe-Kaufmann L, Rosa K, Freeman R. The Orthostatic Hypotension Questionnaire (OHQ): validation of a novel symptom assessment scale. Clin Auton Res. 2012;22(2):79-90.

54. Brillman S, Husain S, Isaacson SH. Long-term evaluation of 24 hour ambulatory blood pressure monitoring in patients with Parkinson’s disease and symptomatic neurogenic orthostatic hypotension treated with droxidopa [abstract 188]. Mov Disord. 2015;30(suppl 1):S72-S73.

55. Kaufmann H, Freeman R, Biaggioni I, et al; NOH301 Investigators. Droxidopa for neurogenic orthostatic hypoten-sion: a randomized, placebo-controlled, phase 3 trial. Neurology. 2014;83(4):328-335.

56. Biaggioni I, Freeman R, Mathias CJ, Low P, Hewitt LA, Kaufmann H. Randomized withdrawal study of patients with symptomatic neurogenic orthostatic hypotension responsive to droxidopa. Hypertension. 2015;65(1):101-107.

57. Hauser RA, Hewitt LA, Isaacson S. Droxidopa in patients with neurogenic orthostatic hypotension associated with Parkinson’s disease (NOH306A). J Parkinsons Dis. 2014;4(1):57-65.

58. Hauser RA, Isaacson S, Lisk JP, Hewitt LA, Rowse G. Droxidopa for the short-term treatment of symptomatic neuro-genic orthostatic hypotension in Parkinson’s disease (nOH306B). Mov Disord. 2015;30(5):646-654.

59. Keating GM. Droxidopa: a review of its use in symptomatic neurogenic orthostatic hypotension. Drugs. 2015;75(2):197-206.

60. Francois C, Rowse GJ, Hauser RA, Hewitt LA. Number-needed-to-treat analysis of droxidopa in patients with symptomatic neu-rogenic hypertension [abstract 222]. Mov Disord. 2015;30(suppl 1):S86.

61. Isaacson S, Liang G, Lisk JP, Rowse GJ. Durability of effect with long-term droxidopa treatment in patients with symptomatic NOH [abstract 239]. Mov Disord. 2015;30(suppl 1):S93.

62. Isaacson S, Shill H, Vernino S, Cioffi C, Hutchman R. Durability of effect with longterm, open-label droxidopa treatment in patients with symptomatic neurogenic orthostatic hypoten-sion (NOH 303) [abstract 1291]. Mov Disord. 2012;27(suppl 1):S424-S425.

63. Lundbeck NA Ltd. NORTHERA Support Center website. https:// www.northera.com/support-center. Accessed June 22, 2015.

64. Mitka M. Trials to address efficacy of midodrine 18 years after it gains FDA approval. JAMA. 2012;307(11):1124, 1127.

65. Shire Pharmaceuticals. Tilt-table study of the clinical efficacy of midodrine in symptomatic orthostatic hypotension. Clinicaltrials.gov website. https://clinicaltrials.gov/ct2/show/NCT01518946. Updated October 10, 2014. Accessed June 17, 2015.

66. Shire Pharmaceuticals. Clinical efficacy of midodrine in symptomatic orthostatic hypotension. Clinicaltrials.gov website. https:// www.clinicaltrials.gov/ct2/show/results/NCT01515865?sect=X701 56&term=midodrine&rank=12#outcome1. Updated November 10, 2014. Accessed June 17, 2015.

67. Dysautonomia International. RE: Docket ID: FDA-2012-N-0967-0595. http://www.dysautonomiainternational.org/pdf/ Dysautonomia_International_Comment_12.3.14.pdf. Published December 3, 2014. Accessed June 17, 2015.

68. Izcovich A, Gonzalez Malla C, Manzotti M, Catalano HN, Guyatt G. Midodrine for orthostatic hypotension and recurrent reflex syncope: a systematic review. Neurology. 2014;83(13):1170-1177.

69. Low PA, Gilden JL, Freeman R, Sheng KN, McElligott MA. Efficacy of midodrine vs placebo in neurogenic orthostatic hypo-tension. A randomized, double-blind multicenter study. Midodrine Study Group. JAMA. 1997;277(13):1046-1051.

70. Campbell IW, Ewing DJ, Clarke BF. 9-Alpha-fluorohydrocortisone in the treatment of postural hypotension in diabetic autonomic neuropathy. Diabetes. 1975;24(4):381-384.

71. Ong AC, Myint PK, Shepstone L, Potter JF. A systematic review of the pharmacological management of orthostatic hypo-tension. Int J Clin Pract. 2013;67(7):633-646.

72. van Lieshout JJ, ten Harkel AD, Wieling W. Fludrocortisone and sleeping in the head-up position limit the postural decrease in car-diac output in autonomic failure. Clin Auton Res. 2000;10(1):35-42.

73. Seppi K, Weintraub D, Coelho M, et al. The Movement Disorder Society Evidence-Based Medicine Review Update: treat-ments for the non-motor symptoms of Parkinson’s disease. Mov Disord. 2011;26(suppl 3):S42-S80.

74. Abate G, Polimeni RM, Cuccurullo F, Puddu P, Lenzi S. Effects of indomethacin on postural hypotension in Parkinsonism. Br Med J. 1979;2(6203):1466-1468.

75. Winkler AS, Landau S, Watkins PJ. Erythropoietin treatment of postural hypotension in anemic type 1 diabetic patients with auto-nomic neuropathy: a case study of four patients. Diabetes Care. 2001;24(6):1121-1123.

76. Mathias CJ, Fosbraey P, da Costa DF, Thornley A, Bannister R. The effect of desmopressin on nocturnal polyuria, overnight weight loss, and morning postural hypotension in patients with autonomic failure. Br Med J (Clin Res Ed). 1986;293(6543):353-354.

77. Bordet R, Benhadjali J, Destee A, Belabbas A, Libersa C. Octreotide effects on orthostatic hypotension in patients with mul-tiple system atrophy: a controlled study of acute administration. Clin Neuropharmacol. 1995;18(1):83-89.

78. Shibao C, Gamboa A, Diedrich A, et al. Acarbose, an alpha-glucosidase inhibitor, attenuates postprandial hypotension in autonomic failure. Hypertension. 2007;50(1):54-61.

79. Shibao C, Raj SR, Gamboa A, et al. Norepinephrine transporter blockade with atomoxetine induces hypertension in patients with impaired autonomic function. Hypertension. 2007;50(1):47-53.

80. Ramirez CE, Okamoto LE, Arnold AC, et al. Efficacy of atomox-etine versus midodrine for the treatment of orthostatic hypoten-sion in autonomic failure. Hypertension. 2014;64(6):1235-1240.

81. Singer W, Sandroni P, Opfer-Gehrking TL, et al. Pyridostigmine treatment trial in neurogenic orthostatic hypoten-sion. Arch Neurol. 2006;63(4):513-518.

82. Sandroni P, Opfer-Gehrking TL, Singer W, Low PA. Pyridostigmine for treatment of neurogenic orthostatic hypoten-sion [correction of hypertension]--a follow-up survey study. Clin Auton Res. 2005;15(1):51-53.

83. Shibao C, Okamoto LE, Gamboa A, et al. Comparative effi-cacy of yohimbine against pyridostigmine for the treatment of orthostatic hypotension in autonomic failure. Hypertension. 2010;56(5):847-851.
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