Bottom line: Overall the data on use of pyridostigmine for treating chronic orthostatic hypotension is limited but suggest mild improvement in clinical symptoms. More data is needed.
Summary: Singer W, et al. Pyridostigmine Treatment Trial in Neurogenic Orthostatic Hypotension. Arch Neurol 2006 Apr;63(4):513
RCT (n=58 patients with neurogenic orthostatic hypotension) Patients randomized to each of 4 single-session treatments in crossover trial
pyridostigmine bromide only; pyridostigmine bromide plus subthreshold dose of midodrine hydrochloride; pyridostigmine bromide plus above threshold dose of midodrine hydrochloride;
placebo. Measured supine and standing blood pressure measured hourly for 6 hours after treatment
RESULTS: No significant differences between groups in supine systolic or diastolic blood pressures. The mean fall in standing diastolic blood pressure for placebo was 34 mm Hg. Difference in mean fall comparing placebo v. pyridostigmine (27.6 mm Hg) had p = 0.04.
Difference in mean fall comparing placebo v. pyridostigmine plus midodrine hydrochloride suprathreshold (27.2 mm Hg) had p = 0.002. The effect was statistically significant, but the difference in the drop in diastolic pressure on standing was only 7 mmHg between the placebo and the pyridostigmine groups.
There is an observational study documenting effect of pyridostigmine on orthostatic hypotension:
Kanjwal K, et al. Pyridostigmine in the treatment of postural orthostatic tachycardia: a single-center experience. Pacing Clin Electrophysiol. 2011 Jun;34(6):750-5. doi: 10.1111/j.1540-8159.2011.03047.x. Epub 2011 Mar 16. In 202 patients with POTS followed 9-15 months, use of pyridostigmine was associated with improved symptoms (fatigue, palpitations, presyncope and syncope) in 43% of the patients. Improvement in symptoms correlated with heart rate and blood pressure measures.