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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

This post is also available in: हिन्दी (Hindi)