Prednisone against myalgic encephalomyelitis / chronic fatigue syndrome?

[deleder2k]

Published in Journal of the Norwegian Medical Association: http://tidsskriftet.no/article/3449081

First online (18th of February 2016)

Prednisone against myalgic encephalomyelitis / chronic fatigue syndrome?
F Hilpüsch
In recent months there has been a great debate about the treatment of chronic fatigue.

Myalgic encephalomyelitis / chronic fatigue syndrome (ME / CFS) has been heavily debated since Egeland et al article was published in the journal No.. 19/2015 ( 1 ).

I wish to make a contribution. I suffered from aprolonged fatigue from in 2013 and 2014. 30 mg of prednisone made a striking effect on the symptoms. Therefore, I decided to search for studies that have examined the effect of prednisolone / cortisone on chronic fatigue and myalgic encephalomyelitis.

three studies
After searching in two different databases (PubMed, Cochrane library) with the keywords "hydrocortisone", "prednisolone" and "myalgic encephalomylitis / Chronic Fatigue Syndrome" I found two articles - McKenzie et al ( 2 ) and Block Mans and colleagues ( 3 ) - where treatment with low-dose hydrocortisone alone or in combination with fludrokortison described. In the study by McKenzie and employees received 70 patients 20 to 30 mg hydrocortisone daily for three months or placebo.Block Mans and colleagues included 80 patients in a crossover study in which participants were treated for three months with 5 mg hydrocortisone and 50 micrograms fludrokortison (a mineralokortikoid) and for three months with placebo. In McKenzie and collaborators participants had improvement of individual symptom scores for daily well-being, while Block Mans and collaborators failed to show any effect.

I also found a third study to evaluate the efficacy of low-dose cortisone versus placebo. Cleare et treated 32 patients with 5 to 10 mg of hydrocortisone in four weeks in a cross-study ( 4 ).Hydrocortisone gave statistically significantly better outcomes than placebo. The authors called for follow-up studies to determine if low-dose hydrocortisone treatment can be useful in chronic fatigue syndrome.

In the Norwegian debate about the subject Vegard Bruun Wyller and colleagues ( 5 ) wrote that cortisone has not proven effective. As reference he used a survey article by Smith et al ( 6 ), which refers to McKenzie et al ( 2 ) and Block Mans et al ( 3 ). Smith et al article is based on systematic searches in different databases, which resulted in 6175 identified abstracts, 35 treatment studies and 45 articles.In only nine studies were effects of drug therapy studied. Two of these were the above studies where low-dose hydrocortisone was used ( 2 , 3 ). The conclusion of Smith et al article was that drug therapy had a positive effect, but that the study population was too small.

In The Norwegian Knowledge Centre for the Health Serivices recommendations from 2008 on the treatment of myalgic encephalomyelitis / chronic fatigue syndrome are discussed briefly that drug treatment with cortisone is attempted, without providing appreciable effect ( 7 ). Again using two of the above articles as references ( 3 , 4 ).

In a review on chronic fatigue syndrome by Erlend Hem journal from 2001, he writes that cognitive therapy and moderate exercise seems to have the best effect on chronic fatigue ( 8 ). It is mentioned also that treatment with low-dose hydrocortisone positive effects of chronic fatigue syndrome. The reference Hem used was an article by Whiting et al ( 9 ). The conclusion of this was that low-dose hydrocortisone seems to have effect, but the results are considered inconclusive because few studies. Whiting and co-workers used the studies to McKenzie et al ( 2 ) and Clears and colleagues ( 4 ) as the basis for its conclusion, while Smith and colleagues built their conclusions on studies of McKenzie et al ( 2 ) and Block Mans et al ( 3 ). In the period 2001-15 is thus the same three articles have been assumed that cortisone does not have effect in myalgic encephalomyelitis / chronic fatigue syndrome, even if one of these three studies have only investigated treatment with low-dose hydrocortisone and results deemed inconclusive due to too few studies and small study population.

In all these three primary studies, published in prestigious journals and well also well-designed, patients were treated with a low dose hydrocortisone, 5-25 mg. The aim of this low dose was to correct any real hypocortisolism, caused by a disorder of the hypothalamus-pituitary-adrenal axis (HPA axis).

The effect of cortisone should be examined
I know little about myalgic encephalomyelitis / chronic fatigue syndrome, but I understand that the discussion on the pathogenesis also greatly concerns autoimmune reactions and non-specific inflammatory conditions. This is well illustrated in the articles of Egeland and colleagues and Bruun Wyller and employees. The anti-inflammatory effect of cortisone in adequate dose is, after that I can sign, not been investigated so far. I left with the impression that the potential effect of cortisone on myalgic encephalomyelitis / chronic fatigue syndrome has been rejected on the basis of three studies where one only has studied low-dose hydrocortisone treatment of an estimated hypokortisolisme and are expected to have little power to conclude with something.

Could it be an idea to investigate steroid anti-inflammatory effect in a double-blind study which employs adequate doses prednisolone?

Literature
1.

Egeland T, Angelsen A, Haug R et al. What exactly is myalgic encephalopathy? Tidsskr Nor Legeforen 2015; 135: 1756 - 98. [ PubMed ] [ CrossRef ]

2.

McKenzie R, O'Fallon A, Dale J et al. Low-dose hydrocortisone for treatment of chronic fatigue syndrome: a randomized controlled trial. JAMA 1998; 280: 1061 - 6. [ PubMed ] [ CrossRef ]

3.

Block Mans D, Persoons P, Van Houdenhove B et al. Combination therapy with hydrocortisone and fludrocortisone does not improve Symptoms in chronic fatigue syndrome: a randomized, placebo-controlled, double-blind, crossover study. Am J Med 2003; 114: 736 - 41. [ PubMed ] [ CrossRef ]

4.

Clears AJ, Heap E, Malhi GS et al. Low-dose hydrocortisone in chronic fatigue syndrome: a randomized crossover trial. Lancet 1999; 353: 455 - 8. [ PubMed ] [ CrossRef ]

5.

Wyller VB, Reme SE, Mollnes TE. Chronic fatigue syndrome / myalgic encephalomyelitis - pathophysiology, diagnosis and treatment. Tidsskr Nor Legeforen 2015; 135: 2172 - 5. [ PubMed]

6.

Smith ME, Haney E, McDonagh M et al. Treatment of myalgic encephalomyelitis / chronic fatigue syndrome: a systematic review of a National Institutes of Health pathways to prevention workshop. Ann Intern Med 2015; 162: 841 - 50. [ PubMed ] [ CrossRef ]

7.

Wyller VB, Bjorn Klett A, Brubakk Q et al. Diagnosis and treatment of chronic fatigue syndrome / myalgic encephalomyelitis (CFS/ME). www.kunnskapssenteret.no/publikasjoner/diagnostisering-og-behandling-av-kronisk-utmattelsessyndrom-myalgisk-encefalopati-cfs-me (5.2.2016).

8.

Hem E. Treatment of Chronic Fatigue Syndrome. JNMA 2001; 121: 3125.

9.

Whiting P, Bagnall AM, Sowden AJ et al. Interventions for the treatment and management of chronic fatigue syndrome: a systematic review. JAMA 2001; 286: 1360 - 8. [ PubMed ] [ CrossRef ]

Translation mainly by Google Translate (a subsidiary of Google, California, USA)

 

[Woolie]

Thank you, @deleder2k, very interesting. I did pretty much the same search as this author when considering to take prednisone. The doses that have been tested are very low (they're formulated on the basis that we have hypocortolism). They're not used in the right doses in these studies to be immune suppressants.

I decided to give prednisone a try because I was severely ill at the time - had been for months - and was facing losing my job. I had to take a huge dose to get any effect - 40mg to start with. But its effect was nothing short of miraculous, I was out of bed the next day picking fruit in my garden!

The major problem I found was that when I tried to drop the dose (which you need need to pretty quickly, because 40mg is pretty dangerous), the illness episodes started recurring (I have a very relapsing-remitting form of ME). Also, it felt to me as if the effects were just "wearing off" after a few months. There are a lot of downsides - weight gain, puffy face, risk of osteoporosis, feeling hot, slightly "jumpy", cataracts. I'd happily accept all of these for an effective drug, but it just didn't seem to be doing much after a while.

I would still recommend you talk about pred with your doc if you're going through a truly awful crash that just won't let up. Might be well worth the risks if it gets you out of bed. But at the moment, I'm thinking maybe prednisone is better used by us in "quick bursts" at key times, so it remains effective, rather than as a long-term med.