Pilot study of pyridostigmine in constipated patients with autonomic neuropathy

Clin Auton Res. 2008 Aug;18(4):194-202. doi: 10.1007/s10286-008-0476-x. Epub 2008 Jul 11.

Abstract

Background: The effects of cholinesterase inhibitors, which increase colonic motility in health, on chronic constipation are unknown. Our aims were to evaluate the efficacy of cholinesterase inhibitors for dysautonomia and chronic constipation and to assess whether acute effects could predict the long term response.

Methods: In this single-blind study, 10 patients with autonomic neuropathy and constipation were treated with placebo (2 weeks), followed by an escalating dose of pyridostigmine to the maximum tolerated dose (i.e., 180-540 mg daily) for 6 weeks. Symptoms and gastrointestinal transit were assessed at 2 and 8 weeks. The acute effects of neostigmine on colonic transit and motility were also assessed.

Results: At baseline, 4, 6, and 3 patients had delayed gastric, small intestinal, and colonic transit respectively. Pyridostigmine was well tolerated in most patients, improved symptoms in 4 patients, and accelerated the geometric center for colonic transit at 24 h by > or =0.7 unit in 3 patients. The effects of i.v. neostigmine on colonic transit and compliance predicted (P < 0.05) the effects of pyridostigmine on colonic transit.

Conclusions: Pyridostigmine improves colonic transit and symptoms in some patients with autonomic neuropathy and constipation. The motor response to neostigmine predicted the response to oral pyridostigmine.

Publication types

  • Controlled Clinical Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Autonomic Nervous System / drug effects
  • Autonomic Nervous System Diseases / complications
  • Autonomic Nervous System Diseases / drug therapy*
  • Autonomic Nervous System Diseases / physiopathology
  • Cholinesterase Inhibitors / administration & dosage
  • Cholinesterase Inhibitors / therapeutic use*
  • Constipation / drug therapy*
  • Constipation / etiology
  • Constipation / physiopathology
  • Female
  • Gastrointestinal Transit / drug effects*
  • Humans
  • Male
  • Middle Aged
  • Neostigmine / administration & dosage
  • Neostigmine / therapeutic use
  • Pilot Projects
  • Pyridostigmine Bromide / administration & dosage
  • Pyridostigmine Bromide / adverse effects
  • Pyridostigmine Bromide / therapeutic use*
  • Single-Blind Method

Substances

  • Cholinesterase Inhibitors
  • Neostigmine
  • Pyridostigmine Bromide