Has anyone tried Indomethacin for Orthostatic Hypotension?

Shanti1

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Indomethacin is a prescription NSAID usually dosed between 60mg- 150mg daily, total dose is usually not more than 200 mg per day (mayo).

There are some small older studies indicating it may be useful for orthostatic hypotension at doses between 75-150mg in divided doses (see below).

I am currently using Droxidopa to manage my hypotension. Fludrocortisone, midodrine, pyridostigmine, desmopressin, and phenylephrine did not help in my case. I'm likely going to trial indomethacin to see if I can't get another increase in function.

Studies:
Abate G, et al. Effects of indomethacin on postural hypotension in Parkinsonism. Br Med J. 1979 Dec 8;2(6203):1466-8.
"Indomethacin significantly reduced the fall in blood pressure on standing (P less than 0:001) and lessened or reversed orthostatic symptoms."
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Kochar MS, Itskovitz HD. Treatment of idiopathic orthostatic hypotension (Shy-Drager syndrome) with indomethacin. Lancet. 1978 May 13;1(8072):1011-14.

"Treatment with indomethacin (75-150 mg/day) raised the upright blood-pressure (B.P.) by an average of 20-30 mm Hg diastolic and allowed the four patients with I.O.H. to walk about without orthostatic symptoms but it had no effect in the fifth patient.

When indomethacin was discontinued in one patient who had been taking it for 9 months with symptomatic relief, the B.P. fell to pretreatment levels within 48 h. When indomethacin was reinstituted the B.P. rose again. Indomethacin was more effective in these patients than either propranolol or fludrocortisone."
Imaizumi T, etal. Increase in reflex vasoconstriction with indomethacin in patients with orthostatic hypotension and central nervous system involvement. Br Heart J. 1984 Nov;52(5):581-4.

"Since indomethacin may be effective in the treatment of orthostatic hypotension, the ability of this drug to increase reflex vasoconstriction was studied in six patients with orthostatic hypotension and in five normal subjects. Reflex forearm vasoconstriction during lower body negative pressure at 20-40 mm Hg was measured before and after indomethacin 50 mg by mouth.

In patients with orthostatic hypotension and central nervous system involvement indomethacin increased recumbent blood pressure, resting forearm vascular resistance, and reflex forearm vasoconstriction during lower body negative pressure."
Davies IB, et al. The pressor actions of noradrenaline and angiotension II in chronic autonomic failure treated with indomethacin. Br J Clin Pharmacol. 1980 Sep;10(3):223-9.
"Indomethacin increased the sensitivity of our patients to noradrenaline, as shown by the shift to the left of the log dose-response curves after treatment with indomethacin. All these patients were supersensitive to noradrenaline before indomethacin and for each patient the degree of supersensitivity was identical to that in a previous study (Davies, Bannister, Sever & Wilcox, 1979).

Therefore, although no formal control for the administration of indomethacin was made, it is likely that the change in sensitivity was due to indomethacin. Indomethacin increases the pressor responsiveness to noradrenaline in normal subjects (Guthrie et al., 1976) and in patients with Bartter's Syndrome (Silverberg, Mennes & Cryer, 1978)."
Note on side effects from drugs.com:
Indomethacin relieves inflammation and pain associated with various types of arthritis. The risk of stomach-related and cardiovascular side effects may be higher with indomethacin than that seen with other NSAIDs such as ibuprofen.
 
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katabasis

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That's really interesting, I had no idea that indomethacetin had this effect.

One thing you really ought to keep in mind is the propensity for NSAIDs to cause gastritis and stomach ulcers. All NSAIDs are capable of causing these kinds of problems, but indomethacetin is actually considered particularly 'high risk' when compared to other NSAIDs. I bring this up because you also state you are taking fludrocortisone, and corticosteroids are also associated with gastritis and ulcers.

Now, combining the two is almost certainly more risky than either alone, though not an absolute contraindication if you're especially desperate to deal with your orthostatic hypotension. But you should at least know to keep an eye out for stomach pain, nausea, blood in stool, etc. It may also make sense to consider taking something gastroprotective - acid reducing drugs like PPIs are a common adjunct when someone takes NSAIDs, though this is not really sustainable in the long term, and of course PPIs can have their own impact on your gut health. Licorice is supposedly also very helpful for preventing or treating gastritis/ulcers.

In any case, be careful, and if you do try it, I hope it works out for you.
 

Shanti1

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@katabasis Thank you for your concern and your good points. I am actually not taking fluidocortisone. As mentioned above it does not work for me. The only thing that has helped so far is droxidopa (actually, strattera helped too but droxidopa does the job better).

I am aware of the gastritis/ulcer issue with NSAIDS, especially indomethacin. Thankfully I am not pron to gastritis, GERD, ulcers etc, however, if indomethacin helps me I will not use it continuously for that reason as well as other concerns with NSAIDS, including cardiovascular. If it helps I will probably reserve it for days or periods when I have to be more active only.