Comment on the planned study of Interferon-alpha induced Fatigue

UPDATE 13.4.12
The MRC have now posted more information on their website and the study is a little different than first described - and possibly more interesting.

Instead of focusing on the fatigue that comes with IFN-alpha treatment, they are instead looking at fatigue and other CFS-like symptoms that continues in up to half of all patients for 6-12months after the IFN-alpha treatment has finished. In this way they have a model that is closer to that for CFS after a triggering infection; the Dubbo studies found that the pro-inflammatory cytokine response of patients to an infection was important in determining which patients went on to develop CFS. And IFN-alpha is a pro-inflammatory cytokine.

more of the new information
on this study.
Taken from the thread: Carmine Pariante's MRC research award-Persistent fatigue induced by interferon-alpha

oceanblue;230862 said:
When the MRC grants were announced last week there was a lot of scepticism about the Pariente study of fatigue in Interferon-alpha treated Hepatitis C patients. First, it isn't actually studying CFS and second, Carmine Pariente is a psychiatrist from the Institute of Pschiatry, Kings College London, making him a stablemate of Simon Wessely, which understandably causes some suspicion.

Points in favour of the study
However, looking at some of the literature, I can see the case for using IFN-alpha treatment as a model of how fatigue is generated. IFN-alpha treatment rapidly induces fatigue in most patients, and quite often causes sleep disturbances, pain and cognitive dysfunction too, which are also common in CFS. While IFN-alpha often causes depression as well, this usually takes much longer to develop than the fatigue and can be blocked (unlike the fatigue) by pre-treating patients with anti-depressants - suggesting depression is caused by a mechanism independent of fatigue.

The brain imaging findings are intriguing too. The PET study found the basal ganglia of fatigued IFN-alpha-treated patients were more active than untreated patients, and another study found a correlation between fatigue and errors in another part of the brain during a demanding visuo-spatial task.

And of course, cytokines have long been suspects in CFS research, though no one has really pinned down their role. The most interesting finding to date has come from the Dubbo studies of Post Viral Fatigue, which found a strong correlation between acute illness cytokines and illness severity, and later development of fatigue. The authors suggested that the intial high levels of cytokines in the body led to long-term cytokine production in the brain, causing fatigue and other symptoms of CFS.

Unfortunately most of the work on biological changes associated with IFN-alpha treatment have been focused on the link with depression - in fact, it's widely used as a model of inflammation-linked depression. The link with fatigue has received surprisingly little attention.

Issues for the study
A confounding factor with this study is that IFN-alpha treatment can trigger depression and sleep problems, both of which can contribute to fatigue. Around 30% of IFN-alpha patients develop a Major Depressive Disorder, but more have lesser levels of depression. The study will need to control for this so will need to be quite big. As with CFS research, many of the findings in this field to date have been based on small samples with no attempts to replicate them. An MRC grant should provide the funds for a substantive study likely to yield more reliable findings.

Of course, whatever the findings about the nature of fatigue in IFN-alpha-treated Hepatitis C patients, they won't automatically apply to CFS patients. But should the study make significant findings about the nature of fatigue in IFN-alpha-treated patients, it will provide a clear target for investigating fatigue in CFS. And there aren't too many of those currently.

Whether or not Carmine Pariente will share Simon Wessely's preference for psychological explanations of fatigue remains to be seen. However, unlike Wessely, Pariente is a Biological Pyschiatrist and biological psychiatrists tend to prefer biological explanations for things.

Comments

Oceanblue,

Good to see you've started a blog. You've posted lots of intelligent and informative messages to the forums since you joined. I've just subscribed to your blog so I don't miss anything (i.e. hint to others! note: oceanblue didn't suggest I post or anything)
 
Thanks, Dolphin :D First time I've tried blogging a post and was surprised to see it got a lot more views than the thread I originally posted on!
 
oceanblue;bt6383 said:
Thanks, Dolphin :D First time I've tried blogging a post and was surprised to see it got a lot more views than the thread I originally posted on!
Wow, that is a huge amount of views alright. If those are individual people who generally read what you wrote, it's a lot of people. Your name caught my eye - I usually don't see blog entries. Maybe I should check them out more.
 
Well this is a new experience for me. Embarrassing but true! I have just subscribed also Ocean. Got the link from Cort's latest Ottawa coverage and your comment there.

Interesting stuff above. Thanks. Now I can understand where my Live Bookmarks are found on this darn machine I should be able to stay tuned!

Look forward to reading more.
 
Regarding the problem of depression symptoms getting greatly ramped up during alpha interferon treatment:

The French drug amisulpride (an atypical anti-psychotic) has been shown to mitigate the depression symptoms that can arise with interferon treatment.

This may be of considerable benefit during interferon treatment

A paper by Chantal H, Castra L, Demotes-Mainard J, "Hepatitis C and interferon: Watch for hostility, impulsivity," says:

"Pegylated interferon-alpha with ribavirin is the most effective therapy for chronic hepatitis C infection, but psychiatric patients often discontinue IFN-alpha because of its mood side effects."

"IFN-induced mood disorders improved rapidly on low dosages of amisulpride, and antiviral therapy discontinuation rates were low (4%). By comparison, other studies have reported antiviral treatment discontinuation rates of 30% to 40% in patients taking antidepressants."

So low doses of amisulpride may be of use during interferon therapy.

Low dose amisulpride is also of general benefit in ME/CFS, a preliminary study showed. Ref: here.

Interestingly, when I tried 12.5 mg of amisulpride daily for my own ME/CFS symptoms, amisulpride more-or-less eliminated my chronic sore throat symptoms while I was taking this drug.

Amisulpride is not licensed in the US at present (though can of course be obtained legally from overseas suppliers).
 
Firestormm;bt6859 said:
Well this is a new experience for me. Embarrassing but true! I have just subscribed also Ocean. Got the link from Cort's latest Ottawa coverage and your comment there.

Interesting stuff above. Thanks. Now I can understand where my Live Bookmarks are found on this darn machine I should be able to stay tuned!

Look forward to reading more.
Wow, thanks, I'll have to write some more blogs now! I've only just found your comment as I don't seem to have subscribed to my own blog...

nb blog now updated, see above.
 
Hip;bt6903 said:
A paper by Chantal H, Castra L, Demotes-Mainard J, "Hepatitis C and interferon: Watch for hostility, impulsivity," says:

"Pegylated interferon-alpha with ribavirin is the most effective therapy for chronic hepatitis C infection, but psychiatric patients often discontinue IFN-alpha because of its mood side effects."

"IFN-induced mood disorders improved rapidly on low dosages of amisulpride, and antiviral therapy discontinuation rates were low (4%). By comparison, other studies have reported antiviral treatment discontinuation rates of 30% to 40% in patients taking antidepressants."

So low doses of amisulpride may be of use during interferon therapy.

Low dose amisulpride is also of general benefit in ME/CFS, a preliminary study showed. Ref: here.

Interestingly, when I tried 12.5 mg of amisulpride daily for my own ME/CFS symptoms, amisulpride more-or-less eliminated my chronic sore throat symptoms while I was taking this drug.

Amisulpride is not licensed in the US at present (though can of course be obtained legally from overseas suppliers).
Thanks very much for that.
 

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