Midodrine hydrochloride in symptomatic orthostatic hypotension: a double-blind, placebo-controlled, randomized, tilt-table study

Kyla

ᴀɴɴɪᴇ ɢꜱᴀᴍᴩᴇʟ
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https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4951503/
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Clinical benefit of midodrine hydrochloride in symptomatic orthostatic hypotension: a phase 4, double-blind, placebo-controlled, randomized, tilt-table study
William Smith, Hong Wan, David Much, Antoine G. Robinson, and Patrick Martin

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Abstract
Objective
Midodrine hydrochloride is a short-acting pressor agent that raises blood pressure in the upright position in patients with orthostatic hypotension. The US Food and Drug Administration’s Subpart H approval, under which midodrine was initially approved, requires post-marketing studies to confirm midodrine’s clinical benefit in this indication. The purpose of this study was to evaluate the clinical benefit of midodrine with regard to symptom response.

Methods
This was a double-blind, placebo-controlled, randomized, crossover, multicenter study (NCT01518946). Following screening, patients aged ≥18 years with severe symptomatic orthostatic hypotension and on a stable dose of midodrine for at least 3 months were randomized to treatment with either their previous midodrine dose or placebo on day 1 and the respective alternate treatment on day 2. The primary endpoint measured time to syncopal symptoms or near-syncope using a 45-min tilt-table test at 1 h post-dose.

Results
Thirty-three patients were screened for inclusion: 19 received at least one dose of midodrine and had at least one post-dose measurement of the primary endpoint. The least-squares mean time to syncopal symptoms or near-syncope after tilt-table initiation (mean ± standard error) was 1626.6 ± 186.8 s for midodrine and 1105.6 ± 186.8 s for placebo (difference, 521.0 s; 95 % confidence interval 124.2–971.7 s;p = 0.0131). There were 15 adverse events in 10 patients; all of these were mild or moderate in severity, with none considered by the investigators to be related to midodrine.

Interpretation
Midodrine is a well-tolerated and clinically effective treatment for symptomatic orthostatic hypotension.
 
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I got a referral to a blood pressure doctor and had an appointment last week. He has prescribed me midodrine. I expect to get the prescription in the mail soon and will let you all know if it has any effect.

I have been diagnosed with POTS. I struggle with standing for an extended period , being out in the sun, and working with my arms raised, although my blood pressure rarely registers as low. I drink enormous quantities of water and consume heroic volumes of salt. I have previously tried florinef but it had little impact other than giving me anxiety. The doc says midodrine is different. If it works, you know it is working right away.
 
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I got a referral to a blood pressure doctor and had an appointment last week. He has prescribed me midodrine. I expect to get the prescription in the mail soon and will let you all know if it has any effect.

I have been diagnosed with POTS. I struggle with standing for an extended period , being out in the sun, and working with my arms raised, although my blood pressure rarely registers as low. I drink enormous quantities of water and consume heroic volumes of salt. I have previously tried florinef but it had little impact other than giving me anxiety. The doc says midodrine is different. If it works, you know it is working right away.

Early signs are that, for me, midodrine reduces the chance of PEM and also reduces the feeling of PEM even after I've got it. It feels pretty miraculous at this stage! Have got away with some things I didn't expect to get away with. Will keep you updated.
 
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Two more weeks of evidence and I'm increasingly convinced Midodrine is great. I've never taken a pill that I could actually feel working on me before. The effect it has at preventing PEM seems to be amazing. I dug a hole in my backyard yesterday and felt afterwards like nothing had happened at all.

I may even be able to do more exercise than that - I'm not sure I've found my new limits yet! It is a challenge to shake the habits of a decade or two of being careful to ration out my efforts.

The only downside I'm finding is that it is so effective that I can forget to drink a lot of water to maintain my blood volume. Then when it wears off - because it only lasts four hours in the body - I will feel thirsty and tired and cross.

I'd probably recommend investigating it for anyone who matches my symptoms - POTS diagnosis and can generate PEM from alcohol, exercise or working with your arms.
 
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Two more weeks of evidence and I'm increasingly convinced Midodrine is great. I've never taken a pill that I could actually feel working on me before. The effect it has at preventing PEM seems to be amazing. I dug a hole in my backyard yesterday and felt afterwards like nothing had happened at all.

I may even be able to do more exercise than that - I'm not sure I've found my new limits yet! It is a challenge to shake the habits of a decade or two of being careful to ration out my efforts.

The only downside I'm finding is that it is so effective that I can forget to drink a lot of water to maintain my blood volume. Then when it wears off - because it only lasts four hours in the body - I will feel thirsty and tired and cross.

I'd probably recommend investigating it for anyone who matches my symptoms - POTS diagnosis and can generate PEM from alcohol, exercise or working with your arms.
This sounds great! Does it increase your blood pressure in general or just help with maintaining a normal response to being upright?

What is your daily dose?
 
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This sounds great! Does it increase your blood pressure in general or just help with maintaining a normal response to being upright?

What is your daily dose?
I actually haven't done blood pressure measurements siince I started taking it. I probably should.

Although I'm not sure what I'd be comparing it to, as my old blood pressure readings were usually fine, even though I have a clear POTS marker (hr rises 30bp on standing) and classic dysautonomia symptoms. I was lucky to find a doctor who said "what matters is the symptoms more than the BP reading."

dose is 10mg morning and again in the early afternoon.
 
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I actually haven't done blood pressure measurements siince I started taking it. I probably should.

Although I'm not sure what I'd be comparing it to, as my old blood pressure readings were usually fine, even though I have a clear POTS marker (hr rises 30bp on standing) and classic dysautonomia symptoms. I was lucky to find a doctor who said "what matters is the symptoms more than the BP reading."

dose is 10mg morning and again in the early afternoon.
Oh ok cool, what does your HR rise by now? It would be helpful to know what your BP is now, if you have the means and effort to check. :)
 
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Well, it happened. I used midodrine to really push myself way beyond my limits and felt amazing at the time. But the payback!! Reader, I still got PEM. :(

Now, did the PEM feel the same? It did not. it was hard to identify, actually, because the midodrine masks so many symptoms. But *something* was badly disordered. Took me about a week to get back on an even keel.

I still believe in midodrine might be a way for me to push my boundaries a *little*. but not a lot.
 

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Hi @Murph thanks for posting about your midodrine experience. I'm glad that you found something that seems to help you, at least as long as you are staying within your energy envelop. I don't have POTS, but do have excessive thirst/urination and very low BP. I always have the sense that I'm not getting enough blood flow to the brain. I did try midodrine, but my very sensitive system didn't react well to it. Desmopressin, on the other hand, has been helping significantly with brain fog and mental fatigue. Desmopressin increases blood volume and also provides some peripheral vasoconstriction. Two different medications, but they are likely helping us with a similar issue.
 

Shanti1

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You can get these symptoms when you have central diabetes insipidus and is also treated with desmopressin.
https://my.clevelandclinic.org/health/diseases/16618-diabetes-insipidus
It is an important point to consider. I think I have more of a hypothalamic dysfunction, as described by Dr. Bateman and Dr. Shoemaker than frank diabetes inspidus. I think this because at some point if I don't drink, my body does start to concentrate urine, which I think would preclude me from the official diagnosis. I was also drinking about 7 liters of water per day (prior to taking desmopressin), as opposed to gallons.

Both times I have tested my ADH it has been below the detection limit with a normal or high-end osmolality, but I have never done the official "water deprivation test". An MRI showed no pituitary abnormalities.

At some point, I may do more of a workup. I would be interested in speaking with an experienced endocrinologist on the topic. My doc didn't seem to think undetectable ADH was connected to my BP of 85/55, excessive water intake, and feeling like no blood was getting to my brain, so I was left trying the medication on my own. Right now I am enjoying my newly recovered brain function:).
 

Pyrrhus

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Related discussions:

Midodrine and Lying Down
https://forums.phoenixrising.me/threads/midodrine-and-lying-down.48941/

How to take midodrine for POTS and still take a daily nap?
https://forums.phoenixrising.me/thr...ne-for-pots-and-still-take-a-daily-nap.45519/

Midrodine: how long did it take you to ramp up the dose?
https://forums.phoenixrising.me/thr...ng-did-it-take-you-to-ramp-up-the-dose.41260/

Has anyone had Midodrine make them sedated like a sleeping pill?
https://forums.phoenixrising.me/thr...make-them-sedated-like-a-sleeping-pill.33264/

Butcher's broom (Ruscus aculeatus) - herbal midodrine
https://forums.phoenixrising.me/threads/butchers-broom-ruscus-aculeatus-herbal-midodrine.14104/
 
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Another update since it's been a while. I've been on midodrine (aka vasodrine) for almost a year now and yes, it has worked really well. I am not *cured* but my symptoms are very very much less. The trigger for PEM is much harder to reach. I look back at how constrained I was and think wow, you were sick.

Now I can do a lot more. At one point there I even started jogging. I never once got PEM from it (although, after 2 decades of PEM I was careful to do only a little and build up slow, I never ran more than 500m in a row before dropping back to a walk). I visit the shops and walk the dog and work on cognitive things at night without drama. I sleep 7.5 hours instead of 9 or 10. it's pretty amazing.

Points to note:
  • I currently have a bad respiratory infection and with it my ability to get PEM has returned. So i'm not out of the woods.
  • This is not a pure experiment in midodrine. The same doctor also prescribed dexamphetamine and i've been taking that. I also went keto in the period where I took up jogging. that's well-described in these pages as a power-enhancer. So it could be the combination of the two drugs and the changed diet that gave me the big boost to capacity.
  • Midodrine is not a well-studied drug and the risks of takig it long-term aren't well-defined, so the doc wants me to come off it later this year.
Nevertheless, i've had mecfs for 20 years now (ages 20-40) and tried a lot of herbs and pills and stuff. Not much else has given me the same boost. Admittedly I'm a perennial optimist but I am actually hopeful that if I stop taking it I continue to feel relatively good.

My suggestion: if you think you have POTS but that it is a sideline, and ME/CFS is your main issue, getting proactive on POTS might do you more good than you think. Not every doc will prescribe midodrine (and pharmacies don't have it to hand they need to order it in, and it's not subsidised in Australia) but it could be worth trying. good luck!

nb. This experience is also definitely opening up my mind to theories of me/cfs that are circulation based, like this one from Fluge or the emerging crop of ideas about monocytes and endothelial function in long covid. 1, 2. It could explain why all the blood tests come back fine - the blood itself is okay, it's just not moving to where it needs to go.
 
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hapl808

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Nevertheless, i've had mecfs for 20 years now (ages 20-40) and tried a lot of herbs and pills and stuff. Not much else has given me the same boost. Admittedly I'm a perennial optimist but I am actually hopeful that if I stop taking it I continue to feel relatively good.
Very interesting. How'd you find a doctor to treat this? My problem is it seems that each doctor has their pet treatments, or they know nothing. It's too tough and expensive for me to go through the whole process of finding a new doctor just to randomly trial one or two treatments.
 
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Very interesting. How'd you find a doctor to treat this? My problem is it seems that each doctor has their pet treatments, or they know nothing. It's too tough and expensive for me to go through the whole process of finding a new doctor just to randomly trial one or two treatments.
I guess I found a doctor whose pet treatment works for me! It's this guy:
. I got a referral to him after seeing the video, and yes, I basically knew in advance what he would prescribe and yes, it was very expensive. I'd only recommend looking into it if your symptoms are akin to mine ( can trigger PEM from anything that creates vasodilation, such as hot water, exercise, or alcohol), and you can afford it.
 

hapl808

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I'd only recommend looking into it if your symptoms are akin to mine ( can trigger PEM from anything that creates vasodilation, such as hot water, exercise, or alcohol), and you can afford it.
Ah thanks. I don't think that's the case for me as alcohol is meh - not good for me but not awful. I don't usually drink because even one drink definitely worsens my HRV for the next day or two. I don't have the energy to shower often, but I don't get a crash I think from hot water. Haven't been able to exercise in years.

Definitely connective tissue issues, HR rises upon standing but only 20 usually since my baseline is around 90. All very confusing, of course. :)