How the UNSW chronic fatigue syndrome studies use ‘potentially harmful’ guidelines

by Sasha Nimmo

Interviewing Prof Andrew Lloyd last year for this story, he explained he was working on an online program of graded exercise therapy (GET) and cognitive behavior therapy (CBT) program at the University of NSW’s Fatigue Clinic.

Prof Lloyd described the PACE trial, which evaluated these therapies, as having “reasonably solid data”.

The University of NSW has now registered a trial to ‘investigate the efficacy of online continuing education for health professionals to improve the management of chronic fatigue syndrome’.

The study is designed to educate medical professionals. Prof Lloyd said it would ‘protocolise the intervention’ and that he had a grant to turn into an online module and evaluate it.

The study isn’t evaluating CBT and GET, it already accepts those as “widely acknowledged as best-practice interventions for CFS”, it is training health professionals in:

  1. Psychoeducation;
  2. Activity pacing and graded exercise therapy;
  3. Interventions for sleep-wake cycle disturbance;
  4. Interventions of neurocognitive functioning in CFS;
  5. Interventions for mood disturbance;
  6. Interventions for anxiety;
  7. Interventions for coping.

This study is funded by the Mason Foundation.

Modifinil study
The second study he mentioned was the trial for a brain stimulant called Modafinil. Prof Lloyd received a grant for this work and is accessing the drug directly from the manufacturer, he said.

“It changes the perception of fatigue and lengthens time to exhaustion”, Prof Lloyd said.

Modafinil is used to treat idiopathic somnolence (excessive sleepiness) and the US National Library of Medicine warns “Modafinil may be habit-forming. Modafinil may decrease your sleepiness, but it will not cure your sleep disorder. Modafinil should not be used in place of getting enough sleep.”

What needs to be done
Prof Lloyd is one of the authors of the 2002 Australian criteria and also sits on NHMRC grant review committees.

The Australian set of criteria states chronic fatigue syndrome overlaps with the psychiatric condition, neurasthenia, that it is on the spectrum of fatigue so it is not its own ‘entity’ and apart from minor, non-specific signs of illness, the physical examination in people with CFS is normal.  Prof Lloyd doesn’t believe these criteria need updating.

Here are extracts:

“Graded exercise programs have been shown to be beneficial for some people with CFS, and can improve functional status.

[Patients] may have been led to believe that any physical activity at all could be harmful. Unwarranted concerns of this kind may lead to maladaptive attitudes and behaviours that may increase disability and retard recovery.

Doctors should avoid simplistic attributions of CFS to “chronic infection”, “immune dysfunction”, “malingering”, or “mere depression”. Instead, it should be recognised that the illness is likely to be multifactorial in origin. A broad perspective that encompasses medical, psychological, and social aspects is more appropriate.

“Concurrent psychological disorder, somatic symptoms, high levels of fatigue and a low sense of control over symptoms are associated with poorer outcomes.

Neurasthenia (literally meaning “nervous exhaustion”) is a diagnosis included in the International classification of diseases (ICD-10) to describe a syndrome of mental and physical fatigue of at least three months’ duration. The term has a long tradition of use in psychiatric classification, but the extent of its overlap with CFS, and with common psychological disorders such as anxiety and depression, remains to be determined.

Perhaps the most difficult diagnostic uncertainty between CFS and psychological illness is in relation to “somatoform” disorders (DSM-IV107). In these disorders, people present with medically inexplicable physical symptoms that are hypothesised to be the result of underlying psychological processes. As the causes of CFS are “unexplained”, there is an obvious overlap between the diagnostic criteria for the somatoform disorders and CFS.

The mental state examination of people with prolonged fatigue should focus on the observed behavioural features rather than simply those reported by the person. These include psychomotor slowing (which may suggest a serious depressive disorder), demonstrable cognitive impairment (suggesting intoxication, delirium or a dementia syndrome), odd or bizarre interpersonal behaviour (suggesting a psychosis), and hostile, angry or excessively irritable responses (suggesting a personality disorder).

Diagnostic labelling of patients with fatigue

In the general population, fatigue states form a continuum in terms of severity and duration, and it is only in those with the most severe and persistent symptoms that a diagnosis of ‘CFS’ may be appropriate. Although the internationally accepted CFS case definition remains the “gold standard” for diagnosis, it is necessarily arbitrary, having been developed for the purpose of making valid comparisons between research studies carried out in different settings. As such, it creates an artificial boundary within the clinical continuum of fatigue states, giving the false impression that a specific clinical “entity” has thereby been delineated.

In the absence of a clear understanding of aetiology and pathogenesis, the term CFS should be regarded as a descriptive label only. Diagnostic boundaries are further blurred by the clinical overlap with other conditions such as fibromyalgia, irritable bowel syndrome, neurasthenia, anxiety and depression, in each of which fatigue can occur as a major symptom. In each person with chronic fatigue the doctor must exercise clinical judgement in deciding whether CFS is an appropriate diagnostic label.

And this…

Apart from minor, non-specific signs of illness, the physical examination in people with CFS is normal.

2002 Australian chronic fatigue syndrome criteria

What you can do
The 2002 Australian criteria need replacing, for the purposes of the NHMRC and other bodies evaluating grants, as well as for the Australian Medical Association (AMA) and the Royal Australian College of General Practitioners (RACGP) to distribute to their members, who are our GPs.

In research, Griffith University already uses the International Consensus Criteria (ICC) and they are the some of the authors of this Primer for Medical Practitioners.

Other reputable researchers, such as the Murdoch Childrens’ Research Institute, the Australian National University and the CFS Discovery Clinic use an earlier version of the ICC, the Canadian Consensus Criteria.

The majority of the Australian patient organisations endorse the ICC; Emerge Australia (who represent Victoria, Tasmania, NT and others), ME/CFS Australia (South Australia), the ACT ME/chronic fatigue syndrome society (Canberra) and ME/CFS NSW (NSW).

Western Australia’s society endorse the earlier version, the Canadian Consensus Criteria and Queensland doesn’t make mention on their website. (to be updated with information from them once provided)

The Australian ME/CFS society’s former chairman, Simon R. Molesworth AM, QC, has issued two written complaints to the AMA’s Dr Martin Van Der Weyden about the 2002 Australian criteria, here and here, which are worth reading. The letters say the guidelines will result in misdiagnosis, inappropriate and inadequate medical care and the promotion of widespread misconceptions about the illness.

“Evidence is not good enough for the Guidelines to be called ‘evidence-based,’ the assessment and presentation of the evidence has not been objective, the Working Group was not truly representative and so the end product is unreliable. The document provides potentially harmful management suggestions with insufficient supporting evidence.”

Simon R. Molesworth AM, QC, Chairman, ME/CFS Australia 

Emerge Australia has made it’s views on CBT and GET quite clear: “There is no good evidence to support the use of graded exercise therapy or cognitive behaviour therapy and there is important emerging evidence on genetic and immune markers for the condition, so we ask the Department of Health not to waste precious research dollars on those studies”.

In an interview, Senator Ludlam said  “Australia shouldn’t be funding research into totally inappropriate exercise regimes or therapy, “these remedies are actually counter-productive and dangerous”.

Australia needs to adopt the International Consensus Criteria for Myalgic Encephalomyelitis, which does not recommend these therapies and has a much higher standard, providing much more evidence of the biological processes of a disease.

As well as writing to the UNSW and Mason Foundation, we should urge our representatives at the state and territory societies to endorse the International Consensus Criteria and commend the ICC Medical Primer to the National Medical Health Research Council (NHMRC), the AMA and the RACGP. Write to them, call them and let them know this is the time to act.

As authors of the Canadian and International Consensus Criteria, the National Centre for Neuroimmunology (NCNED) at Griffith University should also be commending this criteria to the NHMRC, ask NCNED to recommend it formally.

If the NHMRC has the International Consensus Criteria, we can point to it as an authoritative source and say “this is not how the government recognises this disease should be treated.”

It has become urgent, now is the time to act. Our representative bodies are already supportive – now is the time to ask them, the NHMRC, the AMA and the RACGP to make the change from the potentially dangerous 2002 Australian criteria to the 2012 International Consensus Criteria.
ICP-front-cover

19 thoughts on “How the UNSW chronic fatigue syndrome studies use ‘potentially harmful’ guidelines

  1. Nice article, Sasha. Good to see someone is looking closely at the Australian situation.

    Lloyd is a long term problem for ME and CFS patients in Australia, since he has the govt’s ear. He has the potential to be Australia’s Wessely. At least the landscape is a little less complex than in the US and UK and we have a clear idea about who is pulling the strings.

  2. “The study isn’t evaluating CBT and GET, it already accepts those as “widely acknowledged as best-practice interventions for CFS”, it is training health professionals in:

    [..]

    Activity pacing and graded exercise therapy”

    Given that the PACE Trial is mentioned, this may not be to recommend pacing but in fact contrast pacing with graded exercise and say that graded exercise is better.

  3. I’m an American PWME who was prescribed Modafanil by an expert psychopharmacologist, now retired, and has continued to use it (generic provigil) very occasionally for many years now, for the single use it is good for in M.E., (see below) and I can say authoritatively that Prof. Lloyd, as indicated by his quotation above, is not properly explaining how the drug works or what it is good for. Modafanil was targeted first and foremost at narcolepsy, and unlike “speedy” type drugs like Ritalin or the methedrine family, it aims at orexins — peptides in the brain that directly act on sleepyness/wakefulness. By interfering with the orexins it can stop narcoleptics from nodding off. It also has found widespread use in helping shift workers stay awake at work. Through various means Modafanil also affects a gamut of complementary substances in the brain — dopamine, histamine, norepinephrine, glutamate, serotin and gaba. Only the gaba, which inclines one to relaxation and sleepiness, is down-regulated by the drug. The others are mainly pepper-ups or cheerer-ups in the brain and therefore would tend to augment wakefulness.
    As to the use in M.E., If one is properly rested and not over-exerting, and if it is taken only for a specific purpose, it can help extend the amount of time one can spend at a dinner party or during an afternoon at the library before one feels like total crap. It does not, as Lloyd claims, “change the perception of fatigue.” Rather, it delays and offsets the arrival of “sleepiness” biochemical signaling in the brain. Equally, it does not “lengthen time to exhaustion.” Rather, it delays and offsets the biochemical signaling that causes our brain to register a feeling of exhaustion.
    Meanwhile Modafanil has acquired thousands of fans in high-powered professions such as computer programming and business management, where wakefulness and concentration are valued. Many say it enhances brain power. This and other “noocepts” now have a large and growing market wherein helpful substances may be “stacked” together to supposed greater focus and concentration. It would be great to see some testing take place and learn more. Meanwhile, Dr. Cheney once expressed some reservations about possible long term harm to the brain. I have no further detail on that.

  4. Sure glad I don’t live in Australia. GET is harmful for people with severe ME/CFS the PACE trial conclusions are based on bad statistics! (And now the authors and the publisher are trying to cover it up.) Too bad that not all Doctors around the world obide by the DO NO HARM rule. May be in a few years we will see a documentary like “Voices from the Shadows” coming out of Australia. You should learn from the British experience. GET does not allow people to return to their former lives. I provides false hope and often causes detrimental effects that show up month after the studies are published. This is bad science and bad medicine.

  5. Very good article Sasha, much appreciated. Just one little thing: Simon R. Molesworth was formerly the chair of ME/CFS Australia. He was never the chair of the SA Association.

  6. The USA has rejected the assertion that GET and CBT are helpful to patients with ME/CFS.
    The PACE trial itself published a graph, figure 2, in the appendix of its one year follow up to trial, which clearly showed that GET and CBT are harmful not helpful.
    The USA Centre for Disease Comtrol has guidelines for this disease, and recognises the devastating severity and incapacity caused by the disease.
    The NCNED, has diagnostic biomarkers for the disease and its scientists understand the pathophysiology of the disease- any drug trials need to be initiated by people that understand the disease. Stimulants may be harmful and do not address the fundamental core disease process- something causes people’s symptoms to exacerbate after exertion, this is not “fatigue” as found in people without ME/CFS.

    1. Hello Rob,
      That PACE trial graph tells the story, you are right.
      As scientists who do know the disease publish more of their work, I hope it increases understanding.
      Thank you for reading and commenting.
      Sasha

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