A Systematic Review of Drug Therapies for Chronic Fatigue Syndrome/Myalgic Encephalomyelitis

[Gingergrrl]

Low dose Cortef allows me to eat food without allergic reactions so is crucial for me.

Did the study look at POTS, autonomic dysfunction, dyspnea, or allergic reactions or autoimmune stuff? Don't have FB to see it currently.

It seems very general vs. subgroups? Was glad to see IVIG and RTX in there as these are what I hope/plan to try as soon as humanly possible.

 

[Hip]

I take low-dose Hydrocortisone. I don't think I'd still be here without it. I never had a synacthen test before taking the hydrocortisone but my serum (9am) cortisol was very low - below the range.

The synacthen test determines whether your adrenal gland is working properly. I had the test, and mine is, but whenever I cut the dose down much below 10mg I get intense sinus-type headaches and have more fatigue.

Do you guys take hydrocortisone at any particular time? The natural peak in the 24 hour cortisol cycle is the hours just before and just after you wake up, so I wonder if that would be the best time to take hydrocortisone.

Also, what constitutes low dose hydrocortisone? Are we talking doses around 10 mg?

 

[Gingergrrl]

I take 15 mg per day (10 mg AM and 5 mg afternoon or late afternoon.)

 

[Hip]

Hydrocortisone, rituximab, NAD, Nefazodone, Moclobemide, IVIG, ALCAR, Dextroamphetamine, Rintatolimod, and lisdexamfetamine.

I guess out of that list, the accessible and affordable ones are:

Hydrocortisone — threads here and here.
Nefazodone — thread here.
NADH (nicotinamide adenine dinucleotide) — thread here.
Moclobemide — thread here.
ALCAR (acetyl-L-carnitine) — lots of threads here.


Dextroamphetamine and lisdexamfetamine (Vyvanse) may be hard to get a prescription for (perhaps less so in the US, but unfortunately it is hard to get an adult prescription for these ADHD drugs in the UK).

 

[Izola]

The synacthen test determines whether your adrenal gland is working properly. I had the test, and mine is, but whenever I cut the dose down much below 10mg I get intense sinus-type headaches and have more fatigue. My ME erupted after a sinus operation. I have this belief (which causes that "look" from doctors) that the inherent infection is still lying there dormant somewhere, and the steroids keep the inflammation down.

Bob: I feel the same way, that my original (inherent) infection is hibernating somewhere in me and occasionally it awakens and raises holy hell in me. In addition to the multitude of sustaining symptoms getting amped up high, I get the original sore throat, swollen glands, an additional 1 or 2 extra type head aches, fevers, chills, night sweats, body slams, and it feels like my brain is infected plus all the general feelings of having a bad viral infection.
iz

 

[Kati]

Personally I would not rely too much on the study findings, because
- you can't even be sure that te patients really have ME
- clinical trials in general have used small sample size
- we do not have biomarkers of the disease.
- i am questioning the fact that Valcyte and other antivirals are proving ineffective when many ME experts keep on using them.

I think this paper stands as systematic review, and is definitely better than a graded exercise therapy systematic review, but plenty of work needs to be done in the science side of thing, and I would suggest that in a couple of years time, things will look very different.

Disclaimer: I did not read the full paper

 

[charles shepherd]

This is the summary on Hormonal Treatments from the MEA purple booklet (2016 edition) in the section covering pharmacological interventions drugs aimed at the underlying disease process:

7.4.9 Hormonal treatments
Research studies have confirmed a number of hormonal abnormalities in ME/CFS (in particular low levels of cortisol) that may be contributing to symptoms and, consequently, could be amenable to treatment.

· Clinical trials involving low doses of hydrocortisone have produced conflicting results. An American RCT (McKenzie et al 1998) found there was “some improvement” but there was also evidence of adrenal suppression in some patients. A UK RCT (Cleare et al 1999), which used a slightly lower dose of hydrocortisone (i.e. 5mg or 10mg daily), produced short-term benefits in some patients with no evidence of suppression of the adrenal gland’s natural output of cortisol. Combination therapy with hydrocortisone and fludrocortisone did not improve symptoms (Blockmans et al 2003).

· Raised levels of dehydroepiandrosterone (DHEA) correlating with a degree of self-reported disability have been reported (Cleare et al 2004) – a finding which suggests that DHEA supplementation is unnecessary and possibly even harmful.

· Estradiol patch and cyclical progestagen supplementation may be of value in women who have a premenstrual exacerbation of symptoms (Studd and Panay 1996). These two obstetricians from Chelsea and Westminster Hospital in London suggested that there may be a sub-population of females with ME/CFS where there is a chronic oestrogen deficiency state that improves during pregnancy when oestrogen levels are high. Around 80% of patients in this group improved with 200 microgram estradiol patches and cyclical progestagens.

· Use of a thyroxine supplement in patients who have normal thyroid function is a controversial form of treatment that carries a number of risks, including the potential complication of precipitating an Addisonian crisis in patients with hypocortisolaemia (Shepherd 1997). We do not recommend it.

A patient information sheet covering the menopause and research into female hormone disturbances in ME/CFS is available from The ME Association.

 

[charles shepherd]

It's very disappointing to note that we haven't really moved on in any significant way regarding pharmacological treatments aimed at the underlying disease process in ME/CFS (with the exception of rituximab - where the jury is still out) since the York University Systematic Review was carried out as part of supporting information for the (2007) NICE guideline on ME/CFS

The York Review did, of course, also include behavioural interventions (i.e. CBT and GET) - which is why we are stuck with a NICE recommendation that the only effective treatments for mild or moderate ME/CFS are CBT and GET…..

Updated York Review of treatment interventions for ME/CFS:

https://www.york.ac.uk/media/crd/crdreport35_summ.pdf

 

[Graham]

Do you guys take hydrocortisone at any particular time? The natural peak in the 24 hour cortisol cycle is the hours just before and just after you wake up, so I wonder if that would be the best time to take hydrocortisone.

Prednisolone is slow-release in comparison. I take 10mg each morning. I don't have any knowledge or experience with other forms. There's no reason for me to think that my natural cortisol levels are low, which is why I think it is suppressing low-level inflammation.

I went down with ME after a sinus operation. I had had severe sinus head pain for 18 months which normal painkillers didn't touch, but my GP wouldn't prescribe anything stronger. When I finally got him to refer me to an ENT specialist, she decided I needed the full rebore, decoke and straightening job. The trouble is that during the op I lost a lot of blood, and afterwards it wouldn't heal: I went back into hospital twice for 5 days stays. Eventually they succeeded in stopping the bleeding, sent me home, I developed a high temperature and my legs went weird - ME struck. That's what makes me think there is an infection still skulking around. I didn't get the steroids for the ME though - that would be weird, actually getting something from a GP for ME. I went down with PMR (poly-myalgic rheumatica) 4 years later. The initial higher dose of 25mg for 6 days made me feel really good.

 

[Hip]

Prednisolone is slow-release in comparison. I take 10mg each morning.

It says here that: "prednisolone 5mg is approximately equivalent to hydrocortisone 20mg in terms of equivalent anti-inflammatory dose".

So I guess that means you are taking the equivalent of 40 mg of hydrocortisone daily, although spread out across the day if prednisolone acts as slow release.

The trouble is that during the op I lost a lot of blood

If you lost a lot of blood, do you know if you were given a blood transfusion during the operation? When ME/CFS appears after surgery, if there has been a transfusion, I always wonder whether an ME/CFS-associated virus may have been picked up from the transfusion, such as an enterovirus or EBV.

Blood transfusion products are screened for viruses such as HIV and hep B and C, but not for enteroviruses or EBV.

Although there have been cases on these forums of ME/CFS relapse being triggered by minor surgery with no transfusion and only a local anesthetic, so I don't think transfusion-transmitted infections will explain every case of post-surgery ME/CFS.

Have you been tested for active infections with the usual range of ME/CFS-associated viruses?

Is there any feeling of inflammation or mucus congestion in your sinuses nowadays, by the way?

 

[Graham]

Have you been tested for active infections with the usual range of ME/CFS-associated viruses?

Tested? Hmmm?? Well I had a number of tests 16 years ago when I went down with it, but only the usual blood stuff. Then the diagnosis appeared 3 years later, and that was the end of any interest. Normal story in other words.

No, I didn't get a blood transfusion. It was borderline, but they decided not to. It was pretty obvious that I had infected sinuses when they operated.

I don't get a lot of trouble with my sinuses these days: it's hard to pin down whether headaches are sinus related or not. I get pain over and under the eyes, along above my teeth to my ear and behind my neck. I keep getting told it can't be sinus related if there is pain in the neck, but it very much feels like sinus pain to me.

Thanks Hip!

 

[JamBob]

Do you guys take hydrocortisone at any particular time? The natural peak in the 24 hour cortisol cycle is the hours just before and just after you wake up, so I wonder if that would be the best time to take hydrocortisone.

Also, what constitutes low dose hydrocortisone? Are we talking doses around 10 mg?

Hi Hip

Sorry I only just saw this post. I take 25mg daily which is more than I'd like but I had some absorption issues. I take mine 4 times a day in the following way: first get up (10mg), after lunch (5mg) 4pm (5mg) and 6:30 (5mg). I double or sometimes treble up for illness depending on the severity. I also take fludrocortisone.

Doctors will often put people on two or three doses of HC per day (that's what they are told in the textbooks) but that doesn't mimic physiological production. In reality we have a pulsatile release of cortisol that follows ultradian rhythms. I went to a really great talk by Stafford Lightman (neuroendocrinologist) whose uni is trialling the use of insulin pumps filled with cortisol and delivered in a pulsatile way with a goal to better replicate physiological cortisol production.

Last time I had my morning cortisol taken it was around 12 (range was 167-550) which was so bad that the hospital called my GP as a matter or urgency, so I know in the morning I make next to no cortisol and I definitely feel like rubbish every morning before the HC kicks in. I take mine more as a replacement rather than "low dose" as I had low cortisol to start with. When I tried taking "low dose" early on to start with (10mg) I went into crisis so the doctor told me to increase and I've been on higher amounts every since.

I would really like not to have to take it as it really isn't like the real thing but I am also grateful that it stopped my terrible deterioration and I was bedbound before and getting worse week by week whereas now I am up every day and able to do some things so it's a trade off.

Also the thing about HC is that it has a short half life so when you don't have enough in your body - you really, really feel it badly. For comparison I am dependent on various other hormones (insulin) and I always have some long acting insulin in my body like a safety net which lessens the peaks and troughs, whereas with the HC you can go from feeling okay to feeling really bad very quickly. I don't go anywhere without an emergency injection in my bag as I can deteriorate really rapidly.

The kind Graham takes is long lasting so could explain why he feels better than me but I'm not keen on pred, particularly as a diabetic I know it would impact badly on my insulin sensitivity. I take pred sometimes when I get a really bad chest infection.

 

[Hip]

In reality we have a pulsatile release of cortisol that follows ultradian rhythms.

So you are saying that even within the 24 hour circadian cortisol cycle, there are even shorter duration cycles taking place? And that's why it is best to take hydrocortisone in 4 divided doses each day, in the way you do it.

I was bedbound before and getting worse week by week whereas now I am up every day and able to do some things so it's a trade off.

That is quite a major improvement in symptoms, and all from a total of 25 mg of hydrocortisone? Impressive. I tried up to 10 mg of hydrocortisone in the morning, but never went higher than that.

 

[JamBob]

There's a few papers on the ultradian rhythms

http://press.endocrine.org/doi/full/10.1210/en.2012-1484
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0015766

I think that even taking HC 4 times a day doesn't come close to replicating the normal release of cortisol - it just works better for me than 2/3 times a day. Doctors won't recommend anything they haven't tested though the Prof did say in his lecture that more smaller doses might theoretically be better. Ideally the pump would be better able to deliver pulsatile release of cortisol - there is a study at Bristol underway at the moment.

I'd imagine that 10mgs probably wouldn't make too much difference if you are producing enough already - if you aren't producing enough then you definitely would need more than 10mg. I'm not sure that HC would help people unless they have a cortisol deficiency to begin with. Eg. the symptoms that improved for me and that left me bed bound (substantial unexplained weight loss, postural hypotension, hypoglycaemia in spite of stopping my insulin and severe muscle weakness) are all symptoms relating to glucocorticoid/mineralcorticoid deficiency.

HC does nothing for my PEM, my weird immune problems, dysautonomia, sleep issues and whatever it is that is causing me to lack the ability to normally produce energy and completely crash after not much physical exertion.

 

[Hip]

Very interesting, @JamBob. I wonder if there are any studies demonstrating advantages to pulsing hydrocortisone. From this diagram (found in this article), it looks like the body creates a cortisol pulse approx every 90 minutes.


What's you view on the idea that hydrocortisone may be good initially for ME/CFS for a few months, but bad in the long term (probably because it reduces the immune attack against viruses, so viral infection may slowly grow)?

I have heard some ME/CFS patients say low dose hydrocortisone was good for a few months, but then after they started to feel worse.