This post is also available in: हिन्दी (Hindi)
Introduction:
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
Tremulousness
Chest discomfort
Headache
Lightheadedness
Nausea
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)
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.
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!!!
How old was your daughter when diagnosed? I have a friend just diagnosed at 12
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?
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.
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!
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.
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.
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.
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.
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.
How is the mestinon working for you? I just started it
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?
Satusha Raj … is that the correct spelling? Thanks again for this video… I have EDS, POTS. McAS (“The Trio” lol), along with the many other common things that go along with EDS. I went into Pituitary & Adrenal Failure post Brain/Spine Surgery (Cranial Cervical Fusion & Chiari Decompression) in 2017… However, this was not discovered for 2 years & I was left extremely debilitated (once again) for 2 years because Endocrinologists were trying to ween me off the steroids without ever doing ANY labs or testing to see if it was even possible…Only random Cortisol labs that thankfully my Primary would thankfully do occasionally that always showed my cortisol being 0.3-0.6…I was SO sick & had no idea why…I was made to feel like I wasn’t “trying hard enough to ween (Despite being primarily home & bed bound during those 2 years…after suffering greatly 18 months prior due to the severe Cranial Instability & Brain herniation post car accident from 2015-2017 until finally diagnosed & operated on. 3 or 4 Endos in a row refused to run labs until “I Weaned off”, again, never checking if I even COULD & I didn’t know what questions to ask or how to convey just how extreme my suffering was. I Had 2 Adrenal Crisis in 2017 (the 1st week I left the hospital, in which I nearly died , twice…in & our of consciousness ) & another close call while trying to “Ween”…Technically, every day was a close call & I had an 3 children, all below school age at the time…. Finally upon gaining 20lbs in 3 weeks, more testing was done, primary pituitary dysfunction confirmed , some tumors found “incidentally” & my medication FINALLY changed/increased to a better dose… To clarify, the weight gain was NOT from the steroids, I was adrenal insufficient when i started swelling up/gaining weight with LOW cortisol …I continued to gain until put on spirolactone last year & had gained a total of around 60lbs that year….However, once the I erratic was started and I was put on a higher Siri dose that that allowed me to feel better and be more active again I started to lose some of the weight…The symptoms have become harder to control however I did lose about 30 of those pounds within a few months I’ve going on the diuretic… We lost our insurance When covid hit and so the needed treatment and testing & specialty appointment had to be put on hold until I recently got my insurance back… It’s been a long journey & if anyone sees this who prays 🙏…I would SO appreciate all the help & (God willing) , Healing from above that I can get 🙏… Removing the Pheo has already helped some symptoms… However I was also diagnosed with Conns Syndrome, due to having high aldosterone and weight gain & that, along with a recent, & severe setting in of an MG flare, is what I’m praying is figured out, resolved/healed next….I just want my life back & to be the mom needed for my kids…
Although a full body scan has not yet been been done, There were some other tumors in my endocrine glands that we know of and just really hoping and praying I can figure out and like I said get resolved and healed then healed these other symptoms…
The first real debilitating symptoms of what appears to be Sero Negative Myathenia Gravis, started Shortly after the surgery while my body was under a lot of stress and adrenal insufficient… This and once I was on a better dose of steroids I started regaining strength and both the muscle weakness & muscle heaviness resolved for much of that year (2019-2020) & so I This went off of the trial of mestinon that my Neuro had put me on and Apart from the hormone issues, (Pheo symptoms and conns syndrome), I did much better for a while & thought that maybe I didn’t have MG… Until this past year…It hit like a freight train…The Pheo symptoms increased with it And so it makes me wonder if that was and has been triggering the MG episode…
Just a few weeks ago, the Pheochromacytoma was removed with my right Adrenal Gland & over all, I started doing better…However, the past week or so Has been extremely rough and traumatic…I had myv1st (God willing last 🙏) MG Crisis Monday & once again, nearly died… Most days the past year have been It’s extremely difficult where my entire body feels like it’s been dipped in cement and it is difficult to breathe, swallow, talk, see etc… Just everything feeling hard even talking, texting, thinking clear etc. When I’m having good or better moments, I try to research…
Monday was the 1st time though that my medication (Pyridostigmine), suddenly wasn’t working & I quickly found myself unable to Even lift my arms to search for my phone that had dropped & got lost in a pile of blankets… By God’s Grace, my youngest was This homesick that day and heard me calling for him and quickly came and found my phone so I could call for emergency help… My neighbor whose husband is a physician quickly got me to the ER, But due to covid they would not let her in and I could hardly talk or stink clear and could not explain to them all the things needed… They left me in a room for over 4 hours before even ONE pill of just my standard medication(Pyridostigmine) was given & I was too weak to hold my head & eyes open, let alone Reach or walk over to get my purse or own medication… THANKFULLY, once I took the medicine, it quickly started working this time…However, it Would be another hour before a doctor came into the room and so by the time he saw me I was able to talk and pass a neurological exam… Basically in a nutshell they did nothing and had no knowledge of the condition or how to treat it and sent me home, still in a flare…
I Started writing this comment not meaning to make it this long but because I noticed multiple other people In the comments on this video, have not only pots but other conditions I have, such as hormonal tumors and MG…. So that was my initial reason for writing because I think it’s important for the don’t for those of us with seemingly unrelated conditions to know when other people have them also… It could be coincidence however I did find it interesting And wondering if anyone knows if there is a link between EDS or pots and MG or tumors…. Sorry this is so long 🤦♀️
I made my Neurology appt in September & they are booked out till end of March…I’m Is suffering greatly right now or no afraid of something happening again and not being able to get to help in time…. It’s a terrifying feeling when not only are you struggling to breathe but your body quits working… Literally feels like a nightmare within a horror movie & to have my symptoms dismissed because I was neglected & then The medication did its job before a doctor came in 5 hours after I was just left there (1hr after the medication was given), Is beyond upsetting Because reminder standing the treatment to help pull me out of this flair is very standard I believe it’s just ivy infusions that could help prevent me from this not only happening again but Could have possibly pulled me out of this flare in general but maybe even given me my life back…End of March is so far off when Every day feels Like It’s not only a significant struggle but a gamble…. Anyways I didn’t mean to start venting but I guess it sort of helps …. And also I just wanted to thank the doctor again for helping bring awareness to bring awareness to conditions such as pots that are often ignored, misunderstood and not well treated by the medical community…
So if I suffer constiption this could help me.
Also I appreciate you really explaining how mestinon works for POTS… I Would probably have stayed on it even when I went into what was probably a remissive type state for MG had I understood how it can help with pots (The “Mechanism of action” if that’s the right way to word it🤔)…Also, I Hope my comment is legible as I was mostly voice texting and now too tired to go back and re read it lol
I have had unbelievable nausea and headache for a few weeks now. Can’t tell if from my new birth control with progestin no estrogen or if from Mestinon since started not so long ago as well
Also hard to tell . I have dysautonomia from a severe b12 deficiency. I take mestinon 2 x a day 30 mg and I make sure to eat with it
I was switched to Mestinon from Midodrine and Propranolol for the duration of my pregnancy and breastfeeding. My POTS was well managed by those two; so I’m glad to have the option of another drug to manage my symptoms instead of just having to go without for my baby’s sake!
Is bradycardia a contraindication for trying Pyridostigmine? I read in the package insert warnings that transient bradycardia may occur. I have been diagnosed with hyperadrenergic POTS & my average resting heart rate is around 54. My sleeping heart rate is in the mid-40’s. Would it be safe to try pyridostigmine?