Mestinon: A glimmer of hope for POTs patients


Medical care for patients who have a diagnosis of POTS remains hugely unsatisfactory.

POTS or rather dysautonomia is a very heterogenous condition. No two people are exactly the same. There is no one single aetiology that can even sometimes be identified. Often the patient who is really suffering looks alright from the outside. Many doctors, largely out of ignorance or perhaps arrogance, don’t even believe in the condition. Many don’t know enough about it to start treatment.

Research into this hugely debilitating condition is only being driven by a handful of institutions with limited funding and a limited number of patients to recruit. Given the lack of big robust evidence, doctors tend to be unwilling to try out new medications which may through small studies have been shown to possibly benefit some patients. Because doctors are reluctant to try out new meds, we don’t develop any experience and the treatment of the patient remains stagnant. It therefore become imperative for patients with POTS to become as informed as possible and become their own advocates.

In view of this today I wanted to talk about a medication which has been shown through small research studies to help some patients with POTS but one which is not being prescribed much because many people don’t know about it.

This medication is called Pyridostigmine. It is also known as Mestinon.

Pyridostigmine: The science:

In POTS/dysautonomia, there is an imbalance between our flight and fright response which is largely mediated by adrenaline and noradrenaline and the contrasting rest and digest system which is medicated by a neurotransmitter called Acetylcholine. Much of the medications we use are designed to blunt or damp down the flight or fright response. However it is possible that if we exaggerate the rest and digest response we could achieve the same result in a different way and in so doing it offers us another therapeutic target. Acetylcholine which increases the rest and digest responses is broken down by an enzyme called acetylcholynesterase. If we had something which could stop the breakdown of acetylcholine by stopping the acetylcholinesterase enzyme from functioning, we could increase the rest and digest responses. This is where pyridostigmine comes in. Pyridostigmine is an acetylcholinesterase inhibitor and therefore should increase our rest and digest responses.

Does it work in POTS?

There was a paper published by Raj et al. in 2005 in Circulation journal called ‘Acetylcholinesterase inhibition improves tachycardia in postural tachycardia syndrome’ where the authors compared the effects of giving 17 patients with POTS, pyridostigmine at a dose of 30 mg daily compared to placebo in a randomised cross over study. They were interested in finding out what happened to the blood pressure, heart rate and symptoms when the patient was seated, and then when the patient had been standing for 10 minutes 2 and 4 hours after being given the drug.

In terms of symptoms, researchers were interested in the following 9 symptoms:

Mental clouding

Blurred vision

Shortness of breath

Rapid heart beat


Chest discomfort




At baseline the average heart rate was 75/min and blood pressure 112/70 mmhg. These patients also had normal adrenaline and noradrenaline levels at rest.

When they stood up, the heart rate went up excessively to an average of 124 (almost by 50 beats/min!) and the blood pressure went up to 127/77 and adrenaline and noradrenaline levels went up significantly too.

2 hours after the study drug, the heart rate in patients who had taken the pyridostigmine had fallen to 100/min compared to placebo which had fallen to 110/min. At 4 hours, the patients on pryridostigmine had an average heart rate of 104/min compared to the placebo patients who had an average of 109/min

2 hours after the study drug, the blood pressure had fallen very slightly from 119 to 117mmHg in patients on pyridostigmine compared to 117mmhg to 122mmhg on patients on placebo

In terms of symptoms, patients reported a significant improvement in symptoms compared to placebo

So the conclusion of this very small study was that pyridostigmine could benefit some patients with POTS.

I have started using pyridostigmine in may of my patients and a lot of them seem to tolerate it well and actually feel a bit better on it.  I tend to use it in doses of 30mg twice a day initially but then if the patient is able to tolerate it I increase the dose to 30mg TDS and upto 60mg po TDS.

I tend to avoid using it in asthma and I have also found that it can increase gastric motility. Some patients with POTS are always constipated due to gastroparesis and in those patientsit is helpful. However in those patients who have predominantly diarrhoea, I don’t use it as often because it can cause abdominal cramps.

Other side effects include nausea, muscle twitching, headaches and shortness of breath but as I say, in my experience most people tolerate it reasonably well. Obviously before trying out any medication, it is important to seek the advice of your local doctor who will undoubtedly know you a lot better than me.

Here is a link to a video I have done on the subject of Mestinon

About the Author:

I'm Dr Sanjay Gupta, a Consultant Cardiologist with specialist interest in Cardiac Imaging at York Teaching Hospital in York, UK. I believe that high quality reliable jargon-free information about health should be available at no cost to everyone in the world.


  1. Theda Wilson 24th May 2019 at 5:17 pm - Reply

    I have been using Mestinon for about 5 years using daily and nightly pills and have noticed a significant difference in morning symptoms and also in fatigue and muscle weakness. I was suspected of having myasthenia gravis and started it and realized what a big difference it created for my POTs symptoms.

  2. Nicole Miranda 24th May 2019 at 11:37 pm - Reply

    My daughter has taken Mestinon for POTS for 2-3 years. She started on a lower dose recommended by Dr. Grubb with BID 30 mg. and titrated up. She got profoundly better once we changed to the 180 mg extended release because it was challenging to time the doses of the shorter acting form in a school day and with meals to prevent nausea. Interestingly, I am a neurological physical therapist and I notice that off Mestinon my daughter appears to have poor muscle tone. If she misses a morning dose before school she is guaranteed 2 days absences following due to a ‘crash’. Prior to POTS she was an athlete and violinist but once she acquired POTS she could no longer do sustained aerobic activity or hold her violin. Mestinon allows her to have more typical neuromuscular tone to do limited exercise and attend school and participate in social activities with her friends. She has the typical comorbid MCAS and thus it can be challenging to know how mestinon is affecting her GI motility and other symptoms when there appears to be mast cell flares, but anti-histamine therapy and mestinon appear to be our management plan until science offers better understanding and options for management. Thank you for making this video!!!

    • Robin Kaufman 18th March 2021 at 9:58 pm - Reply

      How old was your daughter when diagnosed? I have a friend just diagnosed at 12

    • Jackie 28th March 2021 at 4:48 pm - Reply

      I take other meds so I’m curious if she started the mestinon first thing in the morning and right before bed? Also the er she takes only 1x a day?

  3. Rebecca 25th May 2019 at 12:53 am - Reply

    I have POTS – but I also have Myasthenia Gravis. It’s actually fairly common to see dysautonomia in MG patients, and in those with autoimmune issues in general.
    Obviously, I am on Mestinon for the MG – 90mg every 3 hours. As you said, every patient is unique – true of both POTS and MG, especially. Mestinon does nada for my POTS. Fludrocortisone controls my POTS very well for the most part. If I go off of it, even with the Mestinon, I have a heart rate of 170 and I’m fainting 2-3 times a day.
    The only time florinef fails me is if I get very dehydrated, don’t get enough sodium (IE in the hospital for a while…low sodium hospital food, ugh), or when I have plasma exchange treatments, I flare severely and need an immediate 1L saline bolus, lest I have up to a 190 hr while sitting and will faint while sitting even, forget standing. POTS is a weird thing. And a scary thing. Many doctors know little of it. Many ignore you, won’t take it seriously at all. Then, paradoxically, some take it too seriously – my POTS flaring after PLEX while I was in the hospital made them put me in the ICU and keep me there for 6 days, despite me repeatedly telling them that it’s just POTS and, while it is unpleasant, it is beniegn. I had a code called when I passed out from it. Rapid response another time. Other times, I had to beg the nurse to NOT call rapid response (I did not even faint, but severe pre-syncope).

    It’s weird. Very weird.

  4. Cindy Parker 25th May 2019 at 2:36 am - Reply

    My son has Dysautonomia. Mestonin was a game changer for him. Florinef and propranolol were taking care of his feeling dizzy upon standing and racing heartbeat. He was still plagued with abdominal belly pain and constipation.He started Mestonin low and slow, when he reached 60 mg 2x day his motility was good and his belly pain subsided. He also had a rash on the inside elbow area that the dermatologist treated as eczema but wouldn’t go away… it did after Mestonin.
    Thank you, Dr. Gupta for your research and caring for Dysautonomia patients!

    • Lynne Keenan 13th September 2019 at 5:07 pm - Reply

      Does anyone that has posted have Dysautonomia related to Ehlers Danlos syndrome? I’m trying to figure out if it will work the same for my son who has hEDS and Dysautonomia.

    • Loretta Vialpando 9th October 2019 at 5:53 pm - Reply

      To Lynne Keenan, I have dysautonomia and EDS, and generic Mestinon helps me a lot with many symptoms. Less dizziness upon standing. Help with very lax, nearly always constipated bowels. An unexpected bonus is that it thins mucous. I also have Sjogren’s syndrome, which causes dry eyes, mouth and intestines, allowing mucus to get too thick and sticky. Mestinon eases the dryness, which sometimes results in very watery eyes and nose. But that’s better than mucous wrapped around my eyeballs and constant sinus pain.

  5. Laurie Rocke 26th March 2020 at 10:07 pm - Reply

    Very, very interesting. I have been trying to get a diagnosis of Myasthenia Gravis, because I have debilitating shortness of breath with any activity but I’ve had difficulty because I have a diagnosis of COPD from a pneumonia I had in the late teens. I tried Mestinon and had extreme, explosive diarrhea, which I could not manage given my shortness of breath and I had to go to the ER for dehydration. I’ve suffered from a condition which doctors apparently do not recognize: I cannot stay awake after eating. Doesn’t matter how much I eat OR what I eat. If I have so much as a cup of coffee with cream and sugar, I fall asleep. And the disturbing part of the sleepiness is that I cannot be awakened by conventional alarms. It takes someone speaking to me, or a very loud noise to awaken me. I also have extreme sweating, and cannot breath in the summer without air conditioning set at 67 degrees. I take hydrocortisone for adrenal insufficiency and have a rescue inhaler (Levalbuterol tartrate HFA). I take each every six hours round the clock. And I have hypothyroidism and have had surgery for a parathyroid adenoma. I had ball bladder surgery at age 25. One of the oddities I’ve encountered is that I have difficulty breathing long after a meal. My stomach is distended and it interferes with filling my lungs. I am currently being treated for MG by a doctor who practices integrative medicine and he believes I have MG (I’ve been with his practice for 20 years), but I can’t seem to convince any other doctor that I have anything besides COPD and therefore cannot get expert treatment.

  6. 17th August 2020 at 4:21 pm - Reply

    Often in early phase of POTS patients don t like how their bodies feel and look. Be careful of fad diets or diet supplements for weight loss.

  7. Jennifer Struk 12th January 2021 at 9:16 pm - Reply

    Thanks for this article, my doctor just prescribed this for Dysautonomia. I have hEDS, Mast Cell Disease and Dysautonomia. Hoping this will ease some of the symptoms.

    • Loretta Eubanks 23rd March 2021 at 2:28 am - Reply

      How is the mestinon working for you? I just started it

  8. Khadija 26th May 2021 at 5:02 am - Reply

    My son was diagnosed with POTS IN 2016. He was under the care of an excellent doctor and followed a treatment until he was weened of the medicine in 2018. Now, late 2020 and early 2021, he started to notice that the symptoms are returning. After numerous tests, his doctor is recommending Mestinon 180 mg. Of course, with any medication there are side effects. I am wondering if there are natural ways to try out and see if they improve the situation. Perhaps, taking Mestinon can be taken as a last option. Thoughts?

  9. Goldie McAlexander 22nd August 2021 at 11:27 pm - Reply

    So if I suffer constiption this could help me.

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