Any Dr. Systrom patients here? - Mestinon (Pyridostigmine bromide) and safety profile

[marcjf]

Decided to come back to give an update, as I got to try Mestinon, Huperzine and other stuff since this was posted.

I did see Dr Systrom, and he unsurprisingly recommended Mestinon. I asked about the safety profile, and he did not seem concerned. According to him, It is a FDA approved drug with decades of experience. Maybe this GWI-link is a bit flimsy.

My response to Mestinon was OK, but a bit underwhelming. It has helped with my blood pooling issues, much better than those crappy compression socks ever did. But as exercise goes, it is not really this miracle it is painted to be. I used Mestinon for at least two months (maybe more). The only side-effect was that my gut was running at "turbo" speed, at least for the first few weeks, but that normalized afterwards. Sounds like a great drug for whoever is dealing with constipation.

Then I took a bit of a break, and switched to Huperzine A, taken in the morning. I did not get the gut side-effects, but much worse. My sleep quality decreased considerably. I could go to sleep fine, but I would wake up maybe 4-5 hours later, and could not go back to sleep. It made the next day terrible. The good thing is that I was able to notice this coinciding with Huperzine A intake. My sleep went back to normal once I stopped it. Now I am sleeping like a baby again.

I also trialed Midodrine, which I am currently taking. It was positive. It has a very direct effect on the blood pooling, same as Mestinon. But no side effects at all, it feels like a very clean vasocompressor. I wish I had asked Systrom why he prefers Mestinon to Midodrine. I feel both of them would increase the cardiac preload.

And lastly, I also tried Butcher's Broom, but that is just garbage, compared to Midodrine. Would not waste my time again with that.

Just judging by the symptoms, I would stick with Midrodrine. I would not mind switching back to Mestinon though. Not a bad drug, just disappointed, based on what it promises.

 

[Learner1]

Decided to come back to give an update, as I got to try Mestinon, Huperzine and other stuff since this was posted.

I did see Dr Systrom, and he unsurprisingly recommended Mestinon. I asked about the safety profile, and he did not seem concerned. According to him, It is a FDA approved drug with decades of experience. Maybe this GWI-link is a bit flimsy.

My response to Mestinon was OK, but a bit underwhelming. It has helped with my blood pooling issues, much better than those crappy compression socks ever did. But as exercise goes, it is not really this miracle it is painted to be. I used Mestinon for at least two months (maybe more). The only side-effect was that my gut was running at "turbo" speed, at least for the first few weeks, but that normalized afterwards. Sounds like a great drug for whoever is dealing with constipation.

Then I took a bit of a break, and switched to Huperzine A, taken in the morning. I did not get the gut side-effects, but much worse. My sleep quality decreased considerably. I could go to sleep fine, but I would wake up maybe 4-5 hours later, and could not go back to sleep. It made the next day terrible. The good thing is that I was able to notice this coinciding with Huperzine A intake. My sleep went back to normal once I stopped it. Now I am sleeping like a baby again.

I also trialed Midodrine, which I am currently taking. It was positive. It has a very direct effect on the blood pooling, same as Mestinon. But no side effects at all, it feels like a very clean vasocompressor. I wish I had asked Systrom why he prefers Mestinon to Midodrine. I feel both of them would increase the cardiac preload.

And lastly, I also tried Butcher's Broom, but that is just garbage, compared to Midodrine. Would not waste my time again with that.

Just judging by the symptoms, I would stick with Midrodrine. I would not mind switching back to Mestinon though. Not a bad drug, just disappointed, based on what it promises.

Maybe you don't need more acetylcholine, which is what Mestinon and Huperzine A increase.

 

[RYO]

I have taken pyridostigmine for over 2 years. I slowly titrated my dose over 2-4 weeks. I currently take 60 mg three times daily with meals and 1/2 tablet at bedtime. Slow release pyridostigmine is cost prohibitive. Through trial and error I received the most benefit from taking DHEA 10 mg in the morning along with pyridostigmine. For me the two medications had a synergistic effect. This regimen along with daily acetaminophen 500 mg has made my existence less miserable. DHEA causes hair thinning but it is a side effect I am willing to live with. Higher doses of DHEA can cause palpitations and acne. I still can’t escape PEM but half dose of Zofran helps with “concussion” symptoms. Lastly, I found a Chinese herbal medication called Joints Joy which helps with body aches and brain fog and I use it when I crash. I always monitor my liver and kidney function while I take herbal supplements. Perhaps Jared Younger can add this supplement to his list of anti inflammatory supplements to test its effects on CNS glial cells. My experience is that MECFS patients have highly variable responses to medications and supplements. What works for one person may make another patient worse. There is also a widely reported phenomenon where a supplement helps for a period of time but loses its efficacy long term. The main components of my current regimen which includes melatonin, generic Pepcid and half dose xyzal seems to be helpful.

 

[minimus]

My response to Mestinon was OK, but a bit underwhelming. It has helped with my blood pooling issues, much better than those crappy compression socks ever did. But as exercise goes, it is not really this miracle it is painted to be. I used Mestinon for at least two months (maybe more).

I also trialed Midodrine, which I am currently taking. It was positive. It has a very direct effect on the blood pooling, same as Mestinon. But no side effects at all, it feels like a very clean vasocompressor. I wish I had asked Systrom why he prefers Mestinon to Midodrine. I feel both of them would increase the cardiac preload.

Systrom prefers mestinon to midodrine and florinef because the latter two drugs increase blood pressure. He will prescribe midodrine and florinef if mestinon doesn't work, but he is cautious about using them for that reason. Midodrine and florinef are fine if you are hypotensive, but if you have normal BP or are slightly hypertensive, chronic use of either medication can result in hypertension. At least when I saw him about 4 years ago, he wanted patients on midodrine and florinef to check their BP daily and would either lower the dosage or take patients off these meds if BP rose above 140/100 or so.

As far as mestinon is concerned, Systrom recently published a double-blind study in which ME/CFS patients underwent an iCPET, were then given a single dose of either mestinon or placebo and underwent a second iCPET about an hour later. Cardiac preload failure improved in the patients who received mestinon. Previously, he would have patients do an iCPET, prescribe mestinon as his first-line treatment and have patients return for a CPET roughly six months later, observing an improvement in cardiac preload failure among those returning patients.

His findings make mestinon seem like an effective first-line treatment for ME/CFS. Yet among the patient population, mestinon doesn't seem to be regarded as all that effective a drug. This makes me wonder if some element of selection bias is affecting his findings.

In my case, I went to Systrom for an iCPET, was prescribed mestinon, and got much worse on it -- muscle cramps and twitching galore as well as increased muscle fatigabilty/weakness from which I never fully recovered. (Around that time, I was referred by my PCP to a Weill-Cornell neurologist who thought I had a motor neuron disease after hearing my symptoms and noting severe muscle twitching during my physical exam. Fortunately, I decided to halt mestinon temporarily before I returned to the neurologist for an EMG, by which point the twitching had stopped. My EMG was normal and the neurologist thanked me for stopping mestinon prior to the EMG, saying it would probably have been abnormal if I had remained on mestinon.)

Systrom's physician's assistant told me to cancel my 6-month follow-up appointment with Systrom because he told me there's no point in seeing him if I was too sick to withstand a follow-up CPET. If patients who get worse despite mestinon are told not to come back for follow-up, that introduces obvious selection bias in his qualitative assessments of the drug's efficacy.

Even in his recent double-blind study, I suspect there is selection bias towards mildly ill ME/CFS patients. Those patients are the only ones who would have the stamina to undergo two back-to-back CPETs one hour apart. Moderate and severe patients often can't do a single CPET, let alone two in a row. Maybe mild patients respond fairly well to mestinon, but moderate and severe patients don't.

 

[marcjf]

Systrom prefers mestinon to midodrine and florinef because the latter two drugs increase blood pressure. He will prescribe midodrine and florinef if mestinon doesn't work, but he is cautious about using them for that reason. Midodrine and florinef are fine if you are hypotensive, but if you have normal BP or are slightly hypertensive, chronic use of either medication can result in hypertension. At least when I saw him about 4 years ago, he wanted patients on midodrine and florinef to check their BP daily and would either lower the dosage or take patients off these meds if BP rose above 140/100 or so.

As far as mestinon is concerned, Systrom recently published a double-blind study in which ME/CFS patients underwent an iCPET, were then given a single dose of either mestinon or placebo and underwent a second iCPET about an hour later. Cardiac preload failure improved in the patients who received mestinon. Previously, he would have patients do an iCPET, prescribe mestinon as his first-line treatment and have patients return for a CPET roughly six months later, observing an improvement in cardiac preload failure among those returning patients.

His findings make mestinon seem like an effective first-line treatment for ME/CFS. Yet among the patient population, mestinon doesn't seem to be regarded as all that effective a drug. This makes me wonder if some element of selection bias is affecting his findings.

In my case, I went to Systrom for an iCPET, was prescribed mestinon, and got much worse on it -- muscle cramps and twitching galore as well as increased muscle fatigabilty/weakness from which I never fully recovered. (Around that time, I was referred by my PCP to a Weill-Cornell neurologist who thought I had a motor neuron disease after hearing my symptoms and noting severe muscle twitching during my physical exam. Fortunately, I decided to halt mestinon temporarily before I returned to the neurologist for an EMG, by which point the twitching had stopped. My EMG was normal and the neurologist thanked me for stopping mestinon prior to the EMG, saying it would probably have been abnormal if I had remained on mestinon.)

Systrom's physician's assistant told me to cancel my 6-month follow-up appointment with Systrom because he told me there's no point in seeing him if I was too sick to withstand a follow-up CPET. If patients who get worse despite mestinon are told not to come back for follow-up, that introduces obvious selection bias in his qualitative assessments of the drug's efficacy.

Even in his recent double-blind study, I suspect there is selection bias towards mildly ill ME/CFS patients. Those patients are the only ones who would have the stamina to undergo two back-to-back CPETs one hour apart. Moderate and severe patients often can't do a single CPET, let alone two in a row. Maybe mild patients respond fairly well to mestinon, but moderate and severe patients don't.

Thanks for the response. It makes a lot of sense what you said about the BP. When another dysautonomia doctor first recommended Midodrine to me, I asked her about the risk of BP being raised, but she did not seem alarmed, given my readings at the time. I am on 2.5mg every 8 hours, so not sure if it is considered a low or high dose.

I have normal BP, and I have been measuring it, although less often these days. It is hard for me to determine how much midodrine is raising it though. I am currently taking a mitochondrial cocktail containing a couple of things that tend to lower BP (e.g. Taurine, Magnesium, PLCAR, etc.). Overall, my BP has been trending lower, although within a healthy range. They may be cancelling each other out.

Not sure if I am missing out on anything by not taking Mestinon. Following Systrom's advice, I am trying to work on incremental exercise. I think the Mestinon is just one of the means to get there. Even though this can be frustrating at times, my experience has been positive. I have been able to re-gain most of the weight I lost because of the illness, in muscle mass. Still miles away from the fitness level from my previous healthy life, and I do not know if I can bridge that can just with incremental exercise.

 

[Learner1]

I was allergic to ingredients in all commercial forms of Mestinon. I used compounded til the active ingredient was no longer available to compounding pharmacies. I hated the intentional side effects of Mestinon. My neurologist and I found Huperzine A which has the same mechanism of action.

 

[pattismith]

interestingly, Valaciclovir, an AntiHerpetic Drug often used with some success for ME/CFS patients, seems to be an Acetylcholinesterase inhibitor. (and also improves insulin activity)

This is a very new study (sept 2022):

Insights of Valacyclovir in Treatment of Alzheimer's Disease: Computational Docking Studies and Scopolamine Rat Model. - Abstract - Europe PMC

Genetic Optimisation for Ligand Docking scores and fitness scores of acyclovir were comparable to donepezil. Valacyclovir improved neurobehavioral markers.

It inhibited AChE and BuChE (p<0.001) enzymes.

It also possessed disease-modifying efficacy as it decreased the levels of BACE-1 (p<0.001), amyloid beta 1-42 (p<0.001), amyloid beta 1-40 (p<0.001), phosphorylated-tau (p<0.001), neprilysin (p<0.01), and insulin-degrading enzyme.

It ameliorated neuroinflammation through decreased levels of tumour necrosis factor α (p<0.001), nuclear factor-kappa B (p<0.001), interleukin 6 (p<0.001), interleukin 1 beta (p<0.001), and interferon-gamma (p<0.001). It also maintained synaptic plasticity and consolidated memory. Histopathology showed that valacyclovir could restore cellular density and also preserve the dentate gyrus.

 

[Jenc]

I was allergic to ingredients in all commercial forms of Mestinon. I used compounded til the active ingredient was no longer available to compounding pharmacies. I hated the intentional side effects of Mestinon. My neurologist and I found Huperzine A which has the same mechanism of action.

@Learner1 , could you let me know what pharmacy you got your Mestinon compounded at? TIA