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.”