Pyridostigmine Relieves Orthostatic Hypotension Without Causing Supine Hypertension

Paula Moyer, MA

October 06, 2004

Oct. 6, 2004 (Toronto) — Patients with orthostatic hypotension can be effectively treated with pyridostigmine without experiencing supine hypertension as a trade-off, according Phillip A. Low, MD, who presented the findings here at the 129th annual meeting of the American Neurological Association. The findings suggest that pyridostigmine should be considered as a first-line therapy for the condition.

"It's important to have a treatment option for orthostatic hypotension that does not worsen supine hypertension," Dr. Low, the study's senior investigator, told Medscape. "The drug is easy to use and the drug is well-known to physicians." Pyridostigmine is commonly used to treat myasthenia gravis.

Dr. Low, a professor of neurology at the Mayo Clinic College of Medicine in Rochester, Minnesota, added that the findings suggest that pyridostigmine should be considered as a first-line therapy for orthostatic hypotension. The current standard treatment for orthostatic hypotension, midodrine (ProAmatine), is associated with supine hypertension. In order to have a response to pyridostigmine, Dr. Low stressed, the autonomic nerve fibers must be at least partially intact. Some patients have autonomic neuropathies as complications of diabetes, while others have central disorders such as multiple system atrophy, and still others have conditions that affect the autonomic nerves alone, such as pure autonomic failure.

The investigators recruited 58 patients to participate in an inpatient double-blind, randomized trial that also had a four-way crossover component. The patients had neurogenic orthostatic hypotension due to preganglionic and postganglionic autonomic disorders.

During the study, the patients received 60 mg of pyridostigmine either as monotherapy or in combination with midodrine at doses of either 2.5 mg or 5 mg. Patients also received midodrine or placebo on different days.

The investigators measured patients' supine and standing blood pressures immediately before and hourly after they received treatment. The investigators primarily wanted to assess patients' blood pressure changes from before treatment to one hour after treatment.

Patients showed no significant differences in either their systolic or diastolic supine blood pressure values ( P = .36 and P = .85, respectively). The diastolic blood pressure decline was significantly reduced with pyridostigmine monotherapy ( P = .023) and with both combination therapies ( P = .04 for 2.5 midodrine; P = .002 for 5 mg midodrine).

The combination using 5 mg of midodrine had the greatest effect compared with placebo ( P = .002). However, the combination with the 2.5-mg dose of midrodrine and the monotherapy treatment also produced statistically significant effects compared with placebo ( P = .026 and P = .051, respectively). Because these low doses of midodrine do not cause supine hypertension, either can be used in combination to augment the effect of pyridostigmine, Dr. Low reported.

The study was supported by grants from the National Institutes of Health and by internal funding from the Mayo Clinic.

ANA 129th Annual Meeting: Abstract PL3. Presented Oct. 5, 2004.

Reviewed by Gary D. Vogin, MD