This Article  • Full text  • PDF  • Reply to article  • Send to a friend  • Save in My Folder  • Save to citation manager  • Permissions  Citing Articles  • Citation map  • Citing articles on HighWire  • Citing articles on ISI (13)  • Contact me when this article is cited  Related Content  • Similar articles in this journal  Topic Collections  • Neurology, Other  • Alert me on articles by topic

Wolfgang Singer, MD; Paola Sandroni, MD, PhD; Tonette L. Opfer-Gehrking; Guillermo A. Suarez, MD; Caroline M. Klein, MD; Stacy Hines; Peter C. O’Brien, PhD; Jeffrey Slezak; Phillip A. Low, MD

Arch Neurol. 2006;63:513-518. Published online February 13, 2006 (doi:10.1001/archneur.63.4.noc50340).

Background  Midodrine hydrochloride is the only drug demonstrated in a placebo-controlled treatment trial to improve orthostatic hypotension (OH) but it significantly worsens supine hypertension. By enhancing ganglionic transmission, pyridostigmine bromide can potentially ameliorate OH without worsening supine hypertension.

Objective  To evaluate the efficacy of a single 60-mg dose of pyridostigmine bromide, alone or in combination with a subthreshold (2.5 mg) or suprathreshold (5 mg) dose of midodrine hydrochloride, compared with placebo.

Design  We report a double-blind, randomized, 4-way cross-over study of pyridostigmine in the treatment of neurogenic OH. A total of 58 patients with neurogenic OH were enrolled. After 1 day of baseline measurements, patients were given 4 treatments (3 active treatments [60 mg of pyridostigmine bromide; 60 mg of pyridostigmine bromide and 2.5 mg of midodrine hydrochloride; 60 mg of pyridostigmine bromide and 5 mg of midodrine hydrochloride] and a placebo) in random order on successive days. Blood pressure (BP) and heart rate were measured, both supine and standing, immediately before treatment and hourly for 6 hours after the treatment was given.

Results  No significant differences were seen in the supine BP, either systolic (P = .36) or diastolic (P = .85). In contrast, the primary end point of the fall in standing diastolic BP was significantly reduced (P = .02) with treatment. Pairwise comparison showed significant reduction by pyridostigmine alone (BP fall of 27.6 mm Hg vs 34.0 mm Hg with placebo; P = .04) and pyridostigmine and 5 mg of midodrine hydrochloride (BP fall of 27.2 mm Hg vs 34.0 mm Hg with placebo; P = .002). Standing BP improvement significantly regressed with improvement in OH symptoms.

Conclusions  Pyridostigmine significantly improves standing BP in patients with OH without worsening supine hypertension. The greatest effect is on diastolic BP, suggesting that the improvement is due to increased total peripheral resistance.

Author Affiliations: Department of Neurology, Mayo Medical Center, Rochester, Minn.

THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES

Invited Article: Autonomic ganglia: Target and novel therapeutic tool
Vernino et al.
Neurology 2008;70:1926-1932.
ABSTRACT | FULL TEXT  

Neurogenic Orthostatic Hypotension
Freeman
NEJM 2008;358:615-624.
FULL TEXT  

Neurogenic orthostatic hypotension: chasing "the fall"
Gupta and Nair
Postgrad. Med. J. 2008;84:6-14.
ABSTRACT | FULL TEXT  

Pyridostigmine in the Treatment of Orthostatic Intolerance
Gales and Gales
The Annals of Pharmacotherapy 2007;41:314-318.
ABSTRACT | FULL TEXT  

Pharmacokinetics of Pyridostigmine in a Child With Postural Tachycardia Syndrome
Filler et al.
Pediatrics 2006;118:e1563-e1568.
ABSTRACT | FULL TEXT  

Evidently...
Lehman
Evid. Based Med. 2006;11:102-102.
FULL TEXT  

Other articles noted
Evid. Based Med. 2006;11:127-128.
FULL TEXT