Anyone got benefit from Sildenafil (Viagra) for fatigue?

[Kenny Banya]

Specifically for fatigue

 

[dreampop]

Interesting, I hadn't heard of it being a candidate drug before. I did some digging. Apparently a researcher had tried a pilot, radomized, blinded, placebo controlled pilot study of it - for, believe it or not, chronic fatigue syndrome. Pfizer was a sponsor. But they never published the results - they registered the trial in 2002 but didn't complete it until 2010! Maybe they registed the idea for the study, but never got to it. They are still updating the trial.gov page as recently as this year. Results submitted in April, 2017.

6 controls, 6 viagra. Increasing dose of viagra until 6 weeks. 1 Viagra dropped out and could not be contacted. Trial for cerebral blood flow and fatigue in Chronic Fatigue Syndrome. Primary outcome self reported fatigue after 6 weeks (using a 42 question fatigue impact score 0-142). No info on fatigue score averages at baseline. Placebo outcome was -1.5, Viagra outcome was -33. p<.05. Possibly the variance is high though, because the SD is high.


https://clinicaltrials.gov/ct2/show/results/NCT00598585?sect=X4370156#othr

 

[Jesse2233]

From Dr Jay Goldstein in “Betrayal by the Brain”

Viagra: I don't have enough money to buy stock in anything, but buying Pfizer a few months ago would have been almost as good as buying Microsoft in 1985. This drug works by inhibiting type 5 phosphodiesterase, one of the six known enzymes to degrade cyclic GMP (as important as cyclic AMP, but maybe not covered in biology class). Type 5 is supposed to be specific for the corpus cavemosurn of the penis and probably the clitoris as well. It is not all that specific, though, at least in my patients, who frequently experience flushing and headache. When Viagra works in CFS/FMS, patients experience a reduction in all symptoms. One patient whom I have been treating for 10 years had not responded to one medication until she took Viagra, whereupon she felt almost normal. Nitroglycerin and hydralazine, which stimulate cyclic GMP by different mechanisms, had not helped her

 

[E.man]

Mmmm....come to think of it. ....maybe, but that would be well and truly countered by a cracking headache.

 

[lauluce]

no, not at all. I took it a lot of times before intercourse (not on a daily basis) and I felt no improvement over fatigue or any other symptoms.

 

[dreampop]

no, not at all. I took it a lot of times before intercourse (not on a daily basis) and I felt no improvement over fatigue or any other symptoms.

Well the study was for daily use (three times a day) over six weeks, so it may be if (big if) the drug had a positive impact, it would take more long term dosing. It may work seperate than just plain vasodilation as well by disrupting il-1b pathways.

 

[Murph]

6 controls, 6 viagra. Increasing dose of viagra until 6 weeks. 1 Viagra dropped out and could not be contacted. Trial for cerebral blood flow and fatigue in Chronic Fatigue Syndrome. Primary outcome self reported fatigue after 6 weeks (using a 42 question fatigue impact score 0-142). No info on fatigue score averages at baseline. Placebo outcome was -1.5, Viagra outcome was -33. p<.05. Possibly the variance is high though, because the SD is high.

So that's a positive effect?

Seems like it might be further evidence of a problem with vasodilation. I remain torn between a hypothesis where we try to vasodilate but can't, and a hypothesis where we vasodilate too easily and can't subsequently constrict. a positive effect from viagra might support the former.

Problems with vasodialtion would explain exercise intolerance, heat intolerance, alcohol intolerance and thinking/stress intolerance. Could even explain problems with light and noise.

Endothelial cells are supposed to work to maintain homeostasis in the blood vessel. Too much turbulence and they expand, too little and they contract. (one of the signals to expand is ATP release from red blood cells, when they are squeezed by going through a tight or turblent spot. It's a kind of purinergic signalling. it appears acutely caused when the region in question is hypoxic)

 

[dreampop]

A higher score indicates more severe fatigue impact. I'm gonna guess it's about at least 25% reduction in fatigue for the participants, given a fatigue score of 120/142 (very, very high). However, the drop out may have been a negative score.

I tend to not overthink the autonomic stuff. It's messed up, and it's a little different in everbody. Most seem to have problems with things that increase vasodilation (heat, standing, alcohol, stress, as you mentioned). Some benefit from mild vasodilation, and maybe this study only had those people. But there are a lot of drugs that vasodilate/vasocontrict many have tried and not many would say they truly treated their fatigue by 25%. Even in a small group of 6 that would be rare.

If it's published next year, it will be interesting if the author noted improvements or worsening of autonomic function irrespective of fatigue.

 

[drob31]

Doesn't nitric oxide feed virus'? So increasing it would be good if you had issues that vasoconstrict blood vessels and prevented O2 / nutrient delivery to peripheral tissues, however it would be bad for those with viral issues like EBV that feed on NO2.

 

[Seven7]

I take midodrine a vasso contriction drug. I swear by it. If I still hold a job and have at somewhat normal live is tx to the game of contriction / dilation of the vessels. Note: I have VERY bad POTs also. I really don’t understand how the contriction drugs are so overlook on CFS when it is so accepted we have dysautonomia.