Midrodine: how long did it take you to ramp up the dose?

[Sasha]

I've been prescribed midrodine for NMH and started off at 2.5mg plus sodium tablets, 3 times a day.

That dose had no effect on my BP or symptoms after ten days so yesterday I was told to increase the midrodine to 5mg, 3 times a day.

It didn't do much for my BP but it did seem to improve my symptoms slightly but noticeably, particularly by the evening. I was looking forward to the effect building, but this morning I had a migraine (not unusual for me) with loss of visual field and an arc of sparkling lights (once a decade) and the on-call GP has advised me to drop my dose back down until I can speak to the prescribing doctor at the hospital.

Anybody have problems ramping up?

Or no problems ramping up?

How fast did you up your dose?

 

[SOC]

I'm going by ME memory here, so don't take this as a certainty...

IIRC, my daughter was told the following: Midodrine is a vasoconstrictor. It works for some cases of OI where vasoconstriction is impaired. It may not work well if the OI is caused by other factors. In fact, if vasoconstriction is not faulty, midodrine can cause headaches and/or migraines from too much vasoconstriction. She was told to try Florinef first (desmopressin might also work in this regard) to make sure there is enough blood volume before assuming vasoconstriction will help. Since low blood volume is thought by expert ME clinicians to be a common problem in ME, it makes sense to work on that first.

Are you aware that it is not safe to lie down within 3-4 hours of taking midodrine? It can cause dangerous supine hypertension. I'm surprised you're being told to take it 3 times a day since that means you can't lie down at all during the day, which seems a difficult proposition for a PWME.

My daughter took midodrine for a while, only once a day at mid-day. She said it didn't do her much good and was too much trouble to manage since she'd have to decide before every dose whether she was confident she could remain upright for the next 4 hours. Florinef along with lots of potassium and fluids worked well enough.

Midodrine is a good med if you really need it, but a PITA if it's not really the best med for your particular case.

 

[Sasha]

IIRC, my daughter was told the following: Midodrine is a vasoconstrictor. It works for some cases of OI where vasoconstriction is impaired. It may not work well if the OI is caused by other factors. In fact, if vasoconstriction is not faulty, midodrine can cause headaches and/or migraines from too much vasoconstriction.

That's interesting - I asked before I started taking it if it might make my migraines worse and the doctor said it wouldn't. This is a specialist syncope unit in a major city hospital.

She was told to try Florinef first (desmopressin might also work in this regard) to make sure there is enough blood volume before assuming vasoconstriction will help. Since low blood volume is thought by expert ME clinicians to be a common problem in ME, it makes sense to work on that first.

Also interesting. I'm scared of Florinef (it being a steroid) but didn't know about desmopressin. I haven't been tested for low blood volume. Was your daughter tested or did they just start her on Florinef?

Are you aware that it is not safe to lie down within 3-4 hours of taking midodrine? It can cause dangerous supine hypertension. I'm surprised you're being told to take it 3 times a day since that means you can't lie down at all during the day, which seems a difficult proposition for a PWME.

Yes, I was told this and I explained that I would really struggle to do that but the doc thought I'd be able to remain upright because the drug would work. The lower dose didn't shift my sitting BP at all. I've been having to compromise by lying on the sofa with my upper body propped up with pillows when ordinarily I'd lie down but I'm finding it pretty stressful, worrying in case I'm going to stroke out! I told him I wasn't managing and we increased the dose. It did help yesterday but I'm still not remotely at the point where I can even have my feet on the floor much.

My daughter took midodrine for a while, only once a day at mid-day. She said it didn't do her much good and was too much trouble to manage since she'd have to decide before every dose whether she was confident she could remain upright for the next 4 hours. Florinef along with lots of potassium and fluids worked well enough.

I'm kind of regretting taking my most recent dose (half an hour ago!). I think I'll come off it and phone the hospital tomorrow.

Midodrine is a good med if you really need it, but a PITA if it's not really the best med for your particular case.

I'm finding it extremely stressful, TBH.

 

[SOC]

That's interesting - I asked before I started taking it if it might make my migraines worse and the doctor said it wouldn't. This is a specialist syncope unit in a major city hospital.

Perhaps that's true if you actually have vasoconstriction problems. OTOH, if your vasoconstriction is normal, it seems quite possible that excessive vasoconstriction could exacerbate migraines. Maybe he was working with some incorrect assumptions...?

Also interesting. I'm scared of Florinef (it being a steroid) but didn't know about desmopressin. I haven't been tested for low blood volume. Was your daughter tested or did they just start her on Florinef?

My daughter was given a TTT which she failed. After that, they didn't even bother to test me. They just assumed same illness, same symptoms, probably same OI and gave me florinef too. It has helped both of us a lot.

I think something to consider is that not all steroids are created equal. They have differing effects and different dosages have different risk factors. It might be worth looking into further. ME/CFS specialists with extensive knowledge of immune impairment in ME/CFS use florinef quite a bit, so I don't think they're worried about immune suppression at the doses they are using.

Yes, I was told this and I explained that I would really struggle to do that but the doc thought I'd be able to remain upright because the drug would work. The lower dose didn't shift my sitting BP at all. I've been having to compromise by lying on the sofa with my upper body propped up with pillows when ordinarily I'd lie down but I'm finding it pretty stressful, worrying in case I'm going to stroke out! I told him I wasn't managing and we increased the dose. It did help yesterday but I'm still not remotely at the point where I can even have my feet on the floor much.

I'm kind of regretting taking my most recent dose (half an hour ago!). I think I'll come off it and phone the hospital tomorrow.

I'm finding it extremely stressful, TBH.

If all we had was the kind of OI that develops in elderly people with poor vasoconstriction and blood pooling in the extremities, then the idea that midodrine alone could keep us upright all day might have some validity. With ME added in, that assumption seems off.

My daughter finally gave up on it, mostly because she found she wasn't taking it much since she often needed a bit of horizontal time in the afternoon even when taking midodrine. She didn't really feel any benefit and found it far too stressful to manage.

Can you get aldosterone or vasopressin tested to see if you are deficient in either? That would (hopefully) justify the use of fludrocortisone or desmopressin. Have you checked your pulse pressure (systolic minus diastolic) first thing in the morning or when you feel rotten? A low PP suggests low blood volume and so might get a doctor to investigate further.

 

[Sasha]

Perhaps that's true if you actually have vasoconstriction problems. OTOH, if your vasoconstriction is normal, it seems quite possible that excessive vasoconstriction could exacerbate migraines. Maybe he was working with some incorrect assumptions...?

I don't know how we'd know if it was normal. Is there a test?

My daughter was given a TTT which she failed. After that, they didn't even bother to test me. They just assumed same illness, same symptoms, probably same OI and gave me florinef too. It has helped both of us a lot.

I think something to consider is that not all steroids are created equal. They have differing effects and different dosages have difference risk factors. It might be worth looking into further. ME/CFS specialists with extensive knowledge of immune impairment in ME/CFS use florinef quite a bit, so I don't think they're worried about immune suppression at the doses they are using.

I'm glad you've been helped so much by florinef. You're reassuring me somewhat about it! I have osteopenia after years of being immobile and housebound and it worries me that a steroid could make it worse but maybe on balance it would allow me to be active and to build up more bone.

If all we had was the kind of OI that develops in elderly people with poor vasoconstriction and blood pooling in the extremities, then the idea that midodrine alone could keep us upright all day might have some validity. With ME added in, that assumption seems off.

I don't get blood pooling (that I'm aware of). I wonder if that's a sign I don't have poor vasoconstriction?

Can you get aldosterone or vasopressin tested to see if you are deficient in either? That would (hopefully) justify the use of fludrocortisone or desmopressin. Have you checked your pulse pressure (systolic minus diastolic) first thing in the morning or when you feel rotten? A low PP suggests low blood volume and so might get a doctor to investigate further.

I could ask, for sure. That's a good idea to test my PP. I had a TTT and I would have thought that a low PP would have shown up if it was a problem throughout the day but maybe it varies with hydration.

 

[SOC]

@Sasha, perhaps this is of some help to you...?

INDICATIONS AND USAGE
Midodrine hydrochloride tablets are indicated for the treatment of symptomatic orthostatic hypotension (OH). Because Midodrine HCl can cause marked elevation of supine blood pressure (BP >200 mmHg systolic), it should be used in patients whose lives are considerably impaired despite standard clinical care, including non-pharmacologic treatment (such as support stockings), fluid expansion, and lifestyle alterations. The indication is based on Midodrine HCl's effect on increases in 1-minute standing systolic blood pressure, a surrogate marker considered likely to correspond to a clinical benefit. At present, however, clinical benefits of Midodrine HCl, principally improved ability to perform life activities, have not been established. Further clinical trials are underway to verify and describe the clinical benefits of Midodrine HCl.

After initiation of treatment, Midodrine HCl tablets should be continued only for patients who report significant symptomatic improvement.

from Drugs.com
[my bolding]
It seems that midodrine should be a second- or third-line treatment because the benefits are limited and the risks larger than other treatments. That isn't to say that it isn't very helpful for the right patients, just that it isn't a one-size-fits-all first line treatment.

I don't get blood pooling (that I'm aware of). I wonder if that's a sign I don't have poor vasoconstriction?

I think so, but I'm really not sure. I'm fairly certain that if you have blood pooling you have poor vasoconstriction, but I'm not sure if that transfers to the negative -- that no blood pooling means sufficient vasoconstriction.

I had a TTT and I would have thought that a low PP would have shown up if it was a problem throughout the day but maybe it varies with hydration.

Do you have the results of your TTT? You could check and see if your PP was low. They may or may not have looked at that since low blood volume is not the most common cause of syncope in the general population, I think. I assume you failed the TTT, which is why they prescribed midodrine in the first place...?

I suppose the bottom line here is that it might be worth asking your doctor why s/he didn't try support garments (which are probably only helpful if blood pooling exists) or fluid expansion via fludrocortisone or desmopressin before prescribing midodrine. Perhaps s/he had good reason for skipping over the usual first line treatments. Or maybe they're so used to seeing only one type of syncope (perhaps mostly in the elderly?) that they jump right to the treatment that is most effective in that demographic.

 

[Sasha]

Midodrine hydrochloride tablets are indicated for the treatment of symptomatic orthostatic hypotension (OH). Because Midodrine HCl can cause marked elevation of supine blood pressure (BP >200 mmHg systolic), it should be used in patients whose lives are considerably impaired despite standard clinical care, including non-pharmacologic treatment (such as support stockings), fluid expansion, and lifestyle alterations. The indication is based on Midodrine HCl's effect on increases in 1-minute standing systolic blood pressure, a surrogate marker considered likely to correspond to a clinical benefit. At present, however, clinical benefits of Midodrine HCl, principally improved ability to perform life activities, have not been established. Further clinical trials are underway to verify and describe the clinical benefits of Midodrine HCl.

After initiation of treatment, Midodrine HCl tablets should be continued only for patients who report significant symptomatic improvement.

It seems that midodrine should be a second- or third-line treatment because the benefits are limited and the risks larger than other treatments. That isn't to say that it isn't very helpful for the right patients, just that it isn't a one-size-fits-all first line treatment.

200mmHg!!!

My life certainly is considerably impaired by this. I wonder what they mean by "standard clinical care". I've tried bespoke support stockings (no use), an abdominal binder (not enough use to be worth it), I drink shedloads of water and pee it all straight out again, salt makes no difference...

I wasn't given a 1-minute standing test with midrodine.

They didn't give me the results of my TTT - I can't remember if I asked about PP at the time (I nearly passed out so might not have had the wits). I failed the TTT but only after a GTN spray.

I suppose the bottom line here is that it might be worth asking your doctor why s/he didn't try support garments (which are probably only helpful if blood pooling exists) or fluid expansion via fludrocortisone or desmopressin before prescribing midodrine. Perhaps s/he had good reason for skipping over the usual first line treatments. Or maybe they're so used to seeing only one type of syncope (perhaps mostly in the elderly?) that they jump right to the treatment that is most effective in that demographic.

That's a good point. I may have been wittering on about being scared of fludro but I would rather have had a sensible discussion of risks/benefits. In fact, I had no such conversation at all - I was told to take salt tablets and only got put on midrodine because I phoned back to say they were useless. I couldn't even get a straight answer on the phone about whether they were going to bring me in again. I can hardly hear the guy talking and I need to see them face to face.

Thanks so much for this info, SOC. There are no books about this for patients and it's ridiculous that we have to mug up the entire subject in order to try to get to the right treatment. This is so incredibly frustrating. I'm sure I'd function a great deal better if I could get on top of this symptom.

 

[SOC]

I drink shedloads of water and pee it all straight out again, salt makes no difference...

That's a pretty good sign you're either aldosterone or vasopressin deficient, or both . It might be worth asking to have that followed up. I was in the same boat as you pre-florinef. All the extra water and electrolytes did nothing because I just peed it all out as fast as it went in. I needed the appropriate med to control how much water my kidneys were taking out of my blood. My daughter was prescribed midodrine in addition the florinef in an effort to get more improvement in her OI, but for her it didn't help. Paying more attention to increasing her fluid and electrolyte intake had a bigger effect (in addition to the florinef) than the midodrine.

FYI, there are higher-strength prescription support garments which work much better in serious cases than the bespoke ones. You could ask for that, I suppose. My guess is, though, that if you don't have blood pooling, they're not likely to help. My daughter had some, but found them to be more trouble than they were worth for her. But then, she didn't have noticeable blood pooling, either.

If you do decide to try florinef, be aware that it's potassium wasting, so you'll probably need to supplement potassium while you're taking it. There are prescription potassium supps you can get if your doc is willing to prescribe it.

Yeah, it drives me nuts that we can't rely on the supposed experts to handle these things properly. What are we paying these doctors for, anyway, if it's not their expertise? The information here a PR is generally better than we get at the doctors' offices. I suppose that's because we can focus on one particular illness, while they have to try to be informed on hundreds of them. Still, it's frustrating.

@Sushi is quite well-informed where dysautonomia is concerned -- much more so than I am. Perhaps she can chime in here with better information.

 

[Sasha]

That's a pretty good sign you're either aldosterone or vasopressin deficient, or both .

Argh! I told them about the peeing!

FYI, there are higher-strength prescription support garments which work much better in serious cases than the bespoke ones. You could ask for that, I suppose. My guess is, though, that if you don't have blood pooling, they're not likely to help. My daughter had some, but found them to be more trouble than they were worth for her. But then, she didn't have noticeable blood pooling, either.

I got mine on prescription, made to my specific measurements, but they didn't include an abdo binder (I used a pull-on corset). They were so incredibly difficult to get on and off that I hurt my back. They were incredibly hot and my temperature is all over the shop anyway. I think I'd find higher-strength ones impossible to get into and intolerable to wear.

If you do decide to try florinef, be aware that it's potassium wasting, so you'll probably need to supplement potassium while you're taking it. There are prescription potassium supps you can get if your doc is prescribe it.

Starting to wish you were my doctor!

Yeah, it drives me nuts that we can't rely on the supposed experts to handle these things properly. What are we paying these doctors for, anyway, if it's not their expertise? The information here a PR is generally better than we get at the doctors' offices. I suppose that's because we can focus on one particular illness, while they have to try to be informed on hundreds of them. Still, it's frustrating.

But this is a sodding syncope unit!

How did you find out all this great info, SOC?

 

[SOC]

I got mine on prescription, made to my specific measurements, but they didn't include an abdo binder (I used a pull-on corset). They were so incredibly difficult to get on and off that I hurt my back. They were incredibly hot and my temperature is all over the shop anyway. I think I'd find higher-strength ones impossible to get into and intolerable to wear.

That was pretty much my daughter's experience as well. It's my impression that if they're going to work for you, they're worth the effort because you feel a lot better. If you don't have major blood pooling, though, they're way more trouble than they're worth for the miniscule benefit you get.

How did you find out all this great info, SOC?

1) @Sushi
2) our ME/CFS specialist
3) other sources here at PR
4) internet research once the above sources got me going on the right track

 

[Sushi]

FYI, there are higher-strength prescription support garments which work much better in serious cases than the bespoke ones.

My guess is, though, that if you don't have blood pooling, they're not likely to help.

I don't have any noticeable blood pooling or swelling and I found the full support hose too much of a pain in the ass, but I do very well with medium compression knee socks--they make a huge difference for me.

@Sushi is quite well-informed where dysautonomia is concerned -- much more so than I am. Perhaps she can chime in here with better information.

I used to see a very good autonomic specialist and ran a dys support group so learned some of the tricks of the trade.

I got mine on prescription, made to my specific measurements, but they didn't include an abdo binder (I used a pull-on corset). They were so incredibly difficult to get on and off that I hurt my back. They were incredibly hot and my temperature is all over the shop anyway.

Sounds like they were too high compression. Though having used both, I much prefer the cotton based knee socks--25 - 30 whatever the calibration number is.

But this is a sodding syncope unit!

 

[Sasha]

I hadn't thought about knee socks - I assumed that since the tights were pretty useless, so would the socks be. Did you find the tights effective but just not worth the agony, @Sushi?

 

[Sushi]

Did you find the tights effective but just not worth the agony, @Sushi?

When I found the right compression they were helpful, but never very comfortable and so much of a pain to put on that I switched to knee socks.

 

[Sasha]

When I found the right compression they were helpful, but never very comfortable and so much of a pain to put on that I switched to knee socks.

Sounds like they were too high compression. Though having used both, I much prefer the cotton based knee socks--25 - 30 whatever the calibration number is.

I didn't realise that you could have too much compression. Maybe I should try a pair anyway. I suspect that the main problem for me might be abdominal pooling but every little might help.

Did you buy off the shelf, or made to measure? If the former, what brand?

Is there a good summary of all this stuff somewhere? The general philosophy behind the different drug treatments (because that's the stage I'm at now), some sort of decision map about what to test, rather than just picking stuff on the basis of "the usual patient" vs a PWME?

 

[halcyon]

Is there a good summary of all this stuff somewhere?

You might find this useful. It's about POTS not NMH but the drugs being discussed are the same. You'll note that they don't recommend long term use of midrodine because it can actually lead to lower blood volume over time.

 

[Sasha]

You might find this useful. It's about POTS not NMH but the drugs being discussed are the same.

Thank you!

You'll note that they don't recommend long term use of midrodine because it can actually lead to lower blood volume over time.

 

[Sushi]

I didn't realise that you could have too much compression. Maybe I should try a pair anyway. I suspect that the main problem for me might be abdominal pooling but every little might help.

Yes, you can have too much compression! It can cause pressure points, cut off circulation in some places and raise your BP too much. Mostly, it is just uncomfortable.

Did you buy off the shelf, or made to measure? If the former, what brand?

Off the shelf but they helped me measure by phone. It is a US company but I'll give a link cause I like them so much. http://www.brightlifedirect.com/allegro-samba-cotton-socks-20-25mmhg.asp They come in 5 colors and I don't even know I am wearing them. I am tall and for me, I needed to order one size up from their sizing chart.

Is there a good summary of all this stuff somewhere?

You might explore http://www.dinet.org/ . They used to be called POTSplace!

 

[ahimsa]

You might find this useful. It's about POTS not NMH but the drugs being discussed are the same. You'll note that they don't recommend long term use of midrodine because it can actually lead to lower blood volume over time.

Thanks for posting that link.

This is the first time that I've seen (that I remember!) that long term midodrine can lead to lower blood volume.

I think direct testing for blood volume, while possible, is rarely done for ME patients. Mostly not done because of cost, I think? But also because ME patients have a hard time getting doctors to do ANY tests. So, I think a lot of patients won't even know their baseline value, let alone whether it is changing.

There are indirect methods for measuring blood volume but I'm not sure how accurate they are. Probably not useful for telling whether midodrine has caused a change?

Anyway, thanks for passing on that information.

Edit: I'm sure a lot of you have seen this info on blood volume by Dr. David Bell but I'm posting the link here since it's relevant and so I can find it again!

http://www.cortjohnson.org/forums/r...blood-volume-in-chronic-fatigue-syndrome.234/

 

[ahimsa]

@Sasha, if you search my posts I've talked about midodrine use before. Sorry that I'm not up for finding any of those posts but they might help you.

Everyone is different. Many patients have posted about bad side effects from midodrine and/or it not working for them. I've been lucky in that it seems to help and has minimal side effects.

 

[Sasha]

Thanks, @ahimsa - I've come off it for now until I can have a proper consultation with my doctor. I've printed off the Bell article - looks very interesting!