No, It Isn't All in Your Head

Is Chronic Fatigue Syndrome an organic disease that should be addressed by biomedical research, or is it only a psychological condition best treated by some form of psychotherapy? Until recently, the answer to that question was in dispute, with immunologists and microbiologists tending to take one side, and a group of psychiatrists on the other. The latest research, however, has come down decisively in favor of the physiological explanation, to the embarrassment of the doubters and the relief of many long suffering patients.

 Chronic Fatigue Syndrome (also known as Myalgic Encephalomyelitis, or ME/CFS) is an incurable disease with devastating symptoms that include blinding headaches, profound exhaustion, muscle weakness verging on immobility, exertion intolerance, extreme sensitivity to light and sound, and the inability to stand or sit upright. Most patients will tell you, however, that by far the worst part has been the scorn they once had to endure from physicians, employers, and even friends and family, who frequently refused to believe that they were truly sick. 

 Fortunately, the situation has improved significantly in the United States, where there is now widespread recognition that Chronic Fatigue Syndrome is a biomedical illness with physiological causes. Regrettably, other countries have not all gotten the news – most notably the United Kingdom, where prominent psychiatrists have successfully argued that it should be treated primarily as a cognitive and behavioral disorder. That may also be about to change, however, because a new investigation – just published on the website of a Columbia University virology expert -- has thoroughly debunked the underpinnings of the British psychiatrists’ approach (more on that after the jump).

There has seldom been good news for ME/CFS patients, many of whom have been housebound or bedridden for years.  Fortunately, 2015 has turned out to be a very encouraging year for ME/CFS sufferers in the United States. In early February, the Institute of Medicine released a long-awaited report titled “Beyond Myalgic Encephalomyelitis/ Chronic Fatigue Syndrome: Redefining an Illness,” stating that “ME/CFS is a serious, chronic, complex, systemic disease that often can profoundly affect the lives” of as many as 2.5 million Americans. In addition to criticizing the many physicians who “mistake it for a mental health condition,” the IOM committee proposed new diagnostic criteria and called for greatly increased research funding for ME/CFS.  In the words of the committee chair, Dr. Ellen Clayton, a professor of both medicine and law at Vanderbilt University, "It's time to stop saying that this is a just figment of people's imagination. This is a real disease, with real physical manifestations that need to be identified and cared for." The IOM report broke the barrier of indifference, but of course it could not do anything to solve the intractable nature of the disease.

 Even better news arrived later the same month when Drs. Ian Lipkin and Mady Hornig, of Columbia University’s Center for Infection and Immunity, announced the results of their multi-center cohort studies of ME/CFS patients. The study revealed altered plasma immune signatures among ME/CFS patients, thus providing a possible first step toward identifying a biomarker, which in turn could be a crucial step toward effective clinical diagnosis and treatment. The Columbia results left no doubt that ME/CFS “is a physical disorder that may be kick-started by an infection.” In the words of Dr. Hornig, “We now have evidence confirming what millions of people with this disease already know, that ME/CFS isn't psychological.”

 The era of enlightenment has not yet dawned in the United Kingdom, however, where medical research has been sidelined while psychiatrists continue to insist that ME/CFS is best addressed by Cognitive Behavior Therapy and an increase in activity known as Graded Exercise Therapy.  The founder of the group is Dr. Simon Wessely, whose theory is that ME/CFS is “perpetuated predominantly by dysfunctional illness beliefs and coping behaviours [that] interact with the patient's emotional and physiological state and interpersonal situation to form self-perpetuating vicious circles of fatigue and disability.”

 Patients, and many U.S. researchers, have for years rejected the idea that ME/CFS is caused by nothing more than a “dysfunctional illness belief,” but Wessely and his followers have been adamant. Writing in the journal of the American Psychosomatic Society, for example, that ME/CFS “represents one of a cluster of functional somatic syndromes, which all share similar psychosocial etiological and maintaining factors,” including childhood abuse.

 A multi-year study called the PACE trial, financed by the British government at a cost of nearly $8 million (at current exchange rates), was designed to definitively establish the validity of the Wessely theory. The results – first published in 2011 in The Lancet, with later updates in other papers – seemed to confirm that ME/CFS patients showed significant improvement and even “recovery” after treatment with Cognitive Behavior Therapy (CBT) and graded exercise therapy (GET). If valid, the PACE trial would indicate that the persistence of ME/CFS indeed has a powerful psychological component. Dr. Peter White, one of the leaders of the PACE trial, makes just that claim, arguing that the apparent success of CBT and GET demonstrated a “reduction in fear avoidance” among subjects, meaning that the disabling symptoms of ME/CFS had previously been due not to some organic cause, but rather to patients’ ungrounded fear of exercise.

 The soundness of the PACE study, however, has been questioned from its inception, not least because it required participants to make regular trips to medical offices for therapy. That excluded all bedridden or housebound patients, the extreme severity of whose symptoms could least be attributed to “physical deconditioning” from exercise avoidance. Thus, the PACE study has gotten mixed reviews in the U.S.  The CDC has obliquely referenced it on several occasions, and once recommended CBT and GET in its “CFS Toolkit.” On the other hand, the PACE results were not even mentioned in either the IOM report or the Lipkin/Hornig study. Even so, the PACE trial has remained the gold standard for ME/CFS research in Britain with Dr. Wessley calling it “a thing of beauty.” That characterization, however, has now been firmly discredited by the medical journalist David Tuller.

 Writing last week on Virology Blog – an internet site hosted by  Dr. Vincent Racaniello, a microbiologist at Columbia University – Tuller has exposed such deep flaws in the PACE trial as to make it highly unreliable at best. Most significantly, it turns out that some of the PACE results were essentially predetermined to support the effectiveness of CBT and GET. As Tuller learned, the baseline criteria for inclusion in the study actually indicated better health – in terms of fatigue and physical function – than the benchmark for “recovery” at the end. In other words, a patient could be simultaneously sick enough to be included in the PACE study, and healthy enough to be counted among the positive outcomes. In fact, 13 % of the study participants were actually “recovered” on at least one of the two key measures before the trial even began.

 Tuller, who runs the journalism and public health program at the University of California - Berkeley, also discovered that the PACE team had potentially skewed the outcome by publishing a “participants newsletter” in the middle of the study that touted the effectiveness of CBT and GET – the very therapies for which they were supposed to be gathering unbiased results. The newsletter included testimonials from earlier participants about how much better they felt after the treatment and therapy they received during the trial, which could well have primed later subjects to report similar improvement.

 Tuller’s findings have been commended by many American experts on medical research. For example, Dr. Ronald Davis of Stanford University expressed surprise that the PACE study had ever survived peer review at The Lancet, and Columbia’s Dr. Bruce Levin called it “the height of clinical trial amateurism.”

Meanwhile, there is still no cure for ME/CFS, and patients would be facing a grim outlook if their future were solely in the hands of benighted British psychiatrists. Fortunately, promising biomedical research is proceeding at an unprecedented pace in the U.S., so there is finally cause for hope. “I think the microbiome is going to be where the action is in ME/CFS,” said Columbia’s Dr. Lipkin. “I am really eager to pursue that work.” 

 (Tuller’s investigation was posted in three parts:  Installment one is here; installment two is here; installment three is here.)

Comments

[Mark Vink, MD, Family Physician/GPwSI]

As a doctor who has been bedridden with severe ME/CFS for more than a decade I would like Thank You for your exquisite analysis of the situation for people with this debilitating neuro immune disease.

I recently published an article in which I combined my own abnormal blood results with my symptoms to demonstrate why I do not have the power to sit, stand to walk anymore.

Or as Cort said:
Severely ill patients rarely, if ever, show up in studies, let alone exercise studies - so Mark Vink, a doctor, marathoner and a former Dutch national field hockey champion - and now a very severely ill patient - did one on his own. His exercise test - a six yard walk from his bed to the bathroom.

His results were astonishing.

You can read the full article, which is open access, in the Journal of Neurology and Neurobiology, here at:

https://sciforschenonline.org/journals/neurology/JNNB-1-112.php

[Peter Kemp]

Thank you.
IMO the most extraordinary thing about the PACE Trial and the data it produced is that it conclusively proved by any objective analysis; that the theories of the principal investigators are wrong and their preferred 'treatments' are useless. Treating deconditioning, phobia or aversion could not be more straightforward. If the researchers theories had been correct, participants should have been bouncing back to their former busy lives.

Had they been correct, then treating participants should have been simple and effective and should have resulted in significant improvements compared to the Control Group. Yet the results show that 85% of those that received GET or CBT did not benefit over and above the Control Group. Furthermore, the 15% that were claimed to have improved could remain so ill that they would be no more able-bodied than a typical 75 to 84 year old, though the average age of PACE volunteers was only 38 years.

The only impressive thing about the PACE Trial was the extraordinary spin put on the results, with the assistance of the Science Media Centre, which had the Trial reported in the media as a resounding success. It just goes to prove, it's not what you know, it's who you know.

[Chris Welton]

Indeed an invigorating piece for the completion of the ultimate jigsaw.

One of the benighted British psychiatrists is actually 'beknighted', dontchaknow !!

[SL]

The pun was intentional.

[cathy hannon]

Research is needed so badly for the thousands who suffer&are not believed...more research is the way forward

[Mary Schweitzer]

Thank you for posting this. To me the most frightening aspect of the long-term neglect of this illness is that, by CDC's own admission, at least 850,000 adult Americans with the disease don't even have a diagnosis. Yet in looking for a places to cut costs in the upcoming budget, the US Senate budget committee initially reduced the CDC's CFS spending to zero (so far we do not know how that will eventually turn out).

NIH spends less than $6 million per year on research on this disease - compared to $145 million for malaria and $41 million on smallpox. NIH has allocated $122 million for multiple sclerosis, which is a comparable illness in severity but only half as prevalent. It is URGENT that this disease be recognized as a critical national threat that must be faced now. New patients come down with it all the time - without diagnosis or treatment, they are doomed to a lifetime of illness. We must do better. This disease is not going to go away by itself.

[ME]

"A thing of beauty is a ploy forever."

[MB]

Excellent piece. Thank you for this.

[elizabeth Corran]

Thank you so much for this

[judy wickert]

Genetic testing and subsequent supplements put me on the right road to recovery: thru Dr.Amy Yasko,ND,PhD holistichealth.com. I also take Healthy Aging, a supplement dealing with the mitochondria. And I use VieLight 810 re my dementia, ME issues. Viral Pneumonia started me off on this path...probably EBV..

Judy Wickert

[A Hefferon]

Excellent piece, we are sick and tired of all the lies and corrupt information written about this coniditon. It is a national scandal allowed to happen for too long. The psychiatrists should be prosecuted.

[Amy Stamey]

I take issue with the opening statement that ME/CFS is an incurable disease. I recovered after nine years of CFS, and have remained sans CFS for 14 years. I can't point to anyone treatment or therapy, rather just becoming extremely health conscious and doing all I could to support my health. Eating healthy, had my amalgam fillings removed which cleared up candida, getting 8+ hours sleep a night, reducing stress, exercising, and taking supplements. It was a lot of baby steps.

[jimells]

I keep hoping that a hungry young lawyer, maybe even one of your own graduates, will see a potentially profitable opportunity to help a few million patients achieve justice.

If a class-action compliant is ever filed against the "Wessely School" and its corporate sponsors (the disability insurers) I will be standing (well, laying down) in line to sign up.

We are looking at 30 years of fraud, collusion, and corruption between the CDC, NIH, UK health and pension agencies, the insurers, and the "Wessely School". In fact, the record shows that Simon Wessely is thread that ties it all together.

We know it can be done. The tobacco industry lawsuits show us that.

Any takers?

[Anonymouse]

Yesterday brought us a companion piece to David Tuller's writing, this time by James Coyne:

http://blogs.plos.org/mindthebrain/2015/10/29/uninterpretable-fatal-flaws-in-pace-chronic-fatigue-syndrome-follow-up-study/

Today we saw two more, very different installments on Virology Blog: the first is the PACE trial researchers offering a response to David's criticisms; the second is David's rebuttal of their response.

http://www.virology.ws/2015/10/30/pace-trial-investigators-respond-to-david-tuller/

http://www.virology.ws/2015/10/30/david-tuller-responds-to-the-pace-investigators/

Which is, if anything, so eviscerating that one wonders if the PACE folks don't wish they'd have left well enough alone. It's certainly not as driven by the data and the problems with it (and beyond), but it's clear, concise, and very, very cutting. James Coyne's Twitter feed over the past week or so has been fairly incendiary towards PACE, as well.

https://twitter.com/CoyneoftheRealm