Medical Matters > Treatments: Mestinon (Pyridostigmine)

ME Essential Winter 2022


I’ve read about a drug called Mestinon being helpful for some people with ME, especially if you also have postural orthostatic tachycardia syndrome (PoTS), and I would really like to try using it. I know it can cause unpleasant side-effects but I’m willing to take a risk. Do you have any advice on how I might be able to convince my GP to prescribe it? Or do you know of any private doctors that might be willing to prescribe it?


Mestinon (pyridostigmine) is a drug that prevents the breakdown of a chemical called acetylcholine that enables messages to be passed between nerves and muscles. So, it is mainly used in the treatment of the muscle disease Myasthenia Gravis – where nerve to muscle transmission is defective. However, it has also been shown to help with Postural Orthostatic Tachycardia Syndrome (PoTS) and there is some preliminary research evidence to indicate that it could be helpful for ME/CFS.


Background: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is characterized by intractable fatigue, postexertional malaise, and orthostatic intolerance, but its pathophysiology is poorly understood. Pharmacologic cholinergic stimulation was used to test the hypothesis that neurovascular dysregulation underlies exercise intolerance in ME/CFS.

Research question: Does neurovascular dysregulation contribute to exercise intolerance in ME/CFS, and can its treatment improve exercise capacity?

Study design:

Forty-five subjects with ME/CFS were enrolled in a single-center, randomized, double-blind, placebo-controlled trial. Subjects were assigned in a 1:1 ratio to receive a 60-mg dose of oral pyridostigmine or placebo after an invasive cardiopulmonary exercise test (iCPET). A second iCPET was performed 50 min later. The primary end point was the difference in peak exercise oxygen uptake (Vo2). Secondary end points included exercise pulmonary and systemic hemodynamics and gas exchange.


Twenty-three subjects were assigned to receive pyridostigmine and 22 to receive placebo. The peak Vo2 increased after pyridostigmine but decreased after placebo, Interpretation: Pyridostigmine improves peak Vo2 in ME/CFS by increasing cardiac output and right ventricular filling pressures. Worsening peak exercise Vo2, cardiac output, and right atrial pressure following placebo may signal the onset of postexertional malaise. We suggest that treatable neurovascular dysregulation underlies acute exercise intolerance in ME/CFS.

This is clearly an interesting approach to the possible treatment of ME/CFS that requires further investigation. However, in our current state of knowledge, the use of this drug has to be regarded as a speculative and research-based treatment for ME/CFS. So this is not a drug that has been recommended by NICE in the new ME/CFS Guideline. And it’s very unlikely that a GP would be willing to experiment with it. But if you also have PoTS, and are under the care of a specialist who has experience in using this drug, it is possible that they might consider it.

More information


Information provided by The ME Association should not be construed as medical advice. Don't assume any new or worsened symptoms are simply the result of having ME/CFS or Long Covid. We recommend that any information you deem relevant is discussed with your NHS GP as soon as possible. It is important that you seek personalised medical advice from the GP who is in charge of your care and who knows you well.

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