Clinical Correlates of Efficacy of Pyridostigmine in the Treatment of Orthostatic Hypotension

BACKGROUND: The cholinesterase inhibitor pyridostigmine is used to treat orthostatic hypotension by facilitating cholinergic neurotransmission in autonomic ganglia, thereby harnessing residual sympathetic tone to increase blood pressure (BP) preferentially in the upright posture. We hypothesized that less severe autonomic impairment was associated with greater pressor responses to pyridostigmine. METHODS: To identify predictors of pressor response, linear regression analyses between the effect of pyridostigmine on upright BP and markers of autonomic impairment were retrospectively conducted on 38 patients who had a medication trial with pyridostigmine (60 mg single dose). RESULTS: Pyridostigmine increased upright BP by 4±2/3±2 mm Hg but with a wide range of responses (-20/-15 to 29/27 mm Hg; interquartile range, -6/-4 to 11/8 mm Hg). No differences were found between multiple system atrophy (n=14) and patients with pure autonomic failure (n=24). The upright BP response to pyridostigmine was negatively correlated with supine BP and with the pressure recovery time of the Valsalva maneuver, an index of severity of autonomic impairment. In patients with multiple system atrophy, the systolic blood pressure pressor response to pyridostigmine was also positively correlated with the increase in upright heart rate divided by the fall in systolic blood pressure (∆ heart rate/∆ systolic blood pressure) and with upright plasma norepinephrine, both surrogates of residual autonomic function. CONCLUSIONS: Patients with less severe autonomic impairment are more likely to have a positive pressor response to pyridostigmine. Importantly, in this cohort of patients with severe autonomic failure, pyridostigmine was not effective in those with supine hypertension who would benefit the most from the preferential pressor effect of the drug on upright BP. REGISTRATION: URL: http://www.clinicaltrials.gov; Unique identifier: NCT00223691.