Pilot study of pyridostigmine in constipated patients with autonomic neuropathy

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 ≥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.