Trial By Error: Trio of Trials Shows Limits of CBT for Medically Unexplained Symptoms

Lancet Psychiatry recently published the results of a high-profile trial of cognitive behavior therapy as a treatment for so-called dissociative seizures, also known as psychogenic non-epileptic seizures. The trial, nicknamed CODES, found that CBT had no impact on seizure frequency–the primary outcome. The average number of seizures per month dropped in both the treatment and comparison groups, with no statistically significant difference between them.

With this study, British investigators from the so-called biopsychosocial (BPS) camp have completed an impressive trifecta of major, presumably definitive trials of CBT as a treatment for so-called “medically unexplained symptoms” (MUS). The others include the PACE trial for chronic fatigue syndrome, with key results published in 2011 and 2013, and a trial for irritable bowel syndrome, with results published last year.

As a group, this trio of trials demonstrates the ineffectiveness of cognitive behavior therapy as a treatment for the kinds of MUS targeted by the UK National Health Service’s Improving Access to Psychological Therapies (IAPT) program. The metastasizing IAPT program began a decade ago to boost mental health care for those suffering from depression and anxiety. It has since expanded to offer psychological treatment to patients with long-term conditions, such as cancer and multiple sclerosis, and those diagnosed with MUS.

In implementation guidelines, IAPT splits MUS into sub-categories, including chronic fatigue syndrome, irritable bowel syndrome, and “not otherwise specified.” The latter would presumably include functional neurological disorders (FNDs), of which dissociative seizures are an example. The implementation guidelines recommend specialized variations of CBT as treatments for MUS.

Northwestern University law professor Steven Lubet and I have recently published a commentary on the need for humility in making categorical statements regarding conditions of unknown etiology. And a recent series of articles on the advocacy site Opposing MEGA has highlighted estimates of high misdiagnosis rates for various subgroups of MUS, although proponents of the construct tend to downplay or ignore these data.

In any event, the concerns raised would matter less if the evidence indicated that an intervention like CBT were an effective treatment for the conditions in question. So let’s review.

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As is well-known, the PACE trial reported benefits from CBT that turned out to be largely illusory, according to reanalyses of the study’s main findings. (I was a minor co-author on the main paper debunking the findings.) The lead investigators weakened their outcome measures for improvement and recovery, providing inadequate and even laughable reasons for having abandoned their own protocol methodology.

In any event, the international community has spoken on PACE. An open letter to The Lancet, signed by more than 100 scientists, clinicians and other experts, denounced the study’s “unacceptable methodological lapses,” and the US Centers for Disease and Control and Prevention has removed recommendations based on the trial.

Last year, a team from King’s College London published two papers from the largest trial of CBT for irritable bowel syndrome, with 558 participants. Specifically, the trial tested a web-based CBT program that the investigators had spent many years developing and piloting. The first paper, in a BMJ journal called Gut, featured the 12-months results. The second, in Lancet Gastroenterology & Hepatology, included the 24-month results.

As I have reported at length, the web-based CBT program produced statistically significant but clinically insignificant benefits over treatment-as-usual in reducing IBS symptom severity at 12 months. At 24 months, any benefits were neither statistically nor clinically significant. Yet a start-up company based in San Francisco licensed the product from King’s College London and has falsely promoted it as effective in reducing IBS symptom severity. (A course of telephone-based CBT produced slightly better results at 12 months, although by 24 months these results were also clinically insignificant. In any event, the web-based version is what King’s College London licensed as a commercial product.)

The web-based program produced modest improvements in scales measuring more generic domains, such as work and social adjustment. It is not surprising that a course of CBT, whether in person or online, might lead to an improvement in reported ability to adapt to or cope with an illness, especially in an open-label trial relying on subjective outcomes. But that does not mean it is accurate or ethical to present or market this intervention as a treatment for the illness itself—especially given, in this case, the poor results for the core outcome of symptom severity.

Finally, we have CODES. While the primary outcome yielded null results, the investigators reported positive findings in nine out of 16 secondary outcomes. Most of these secondary outcomes assessed subjective generic domains, such as social adjustment, emotional states, quality of life, and attitudes toward treatment; subjective outcomes in open-label trials are highly susceptible to bias. After correcting for multiple comparisons, only five of the 16 secondary outcomes were statistically significant. (More on these secondary outcomes in another post.) And yet, on the basis of these secondary outcomes, King’s College London issued a deceptive press release touting the success of the trial.

A commentary published alongside the trial report, written by another expert in the FND field, adopted the convenient position that seizure frequency wasn’t the best primary outcome for dissociative seizures anyway. The author did not mention that CODES investigators had been promoting seizure frequency as the best primary outcome since at least 2010, when they published a pilot study of their CBT program.

For what must be a range of reasons, MUS experts maintain a persistent faith in CBT’s healing powers as a treatment rather than as helpful but limited adjunct support. Their own research demonstrates that this faith is not warranted. The body of evidence from these three studies is consistent: CBT is not an effective treatment for chronic fatigue syndrome, irritable bowel syndrome, or dissociative seizures, although it might help some patients feel a bit better in some ways.

Comments on this entry are closed.

  • Barbara McMullen 17 June 2020, 1:12 am

    Very well said. You would think that after all this time, they would start to feel embarrassed by themselves.

  • @MECFSNews 17 June 2020, 2:57 am

    The true results of these studies show that this brand of psychosomatic medicine is a failure. It’s extremely unethical to misrepresent the facts to create the illusion that these illnesses belong to psychosomatic medicine. Are these researchers delusional or just lying deliberately?

  • CT 17 June 2020, 3:29 am

    Excellent – this is so important. Time after time the theories and models of this BPS camp fall apart. CBT is clearly not effective for patients with medically unexplained symptoms, whether it’s for ME, IBS or any other condition they’ve labelled ‘MUS’ and thrown in the mix, like FND. The most it does is to make some patients feel mentally a little bit better, but we know that a lot of patients will be physically worse as a result, will be harmed by wasting precious time and energy on this treatment. And it’s wasting NHS resources that could be used far more effectively elsewhere, preferably on good biomedical research into those MUS conditions. The NHS has been sold a very expensive pup.

    But it’s a cheap way to get rid of patients when they slash outpatient care post-covid. Don’t think that the NHS will return to its old way of working, I understand that plans are being made for the majority of outpatient consultations to continue by phone or via computer, and they’ll likely expect a large percentage of them to be ‘MUS’ that can be dealt with via a computerized CBT app. How many doctors will find that their workload disappears in a similar way to how non-covid patients disappeared when infection rates were high? Patients can easily be put off visiting their doctors, especially if they feel that they’re not being listened to or believed. So doctors lose their jobs while their patients get sicker? What a fantastic model for future UK healthcare!

  • CT 17 June 2020, 4:53 am

    My local NHS trust aims to have 70% of its outpatient appointments and follow-up appointments either by telephone or video consultation by the end of this year. I had a telephone outpatient appointment the other day. I was pleased that it was much shorter and much less bother than a face-to-face appointment would have been but I forgot to mention things that I might not have forgotten in a face-to-face scenario. I suspect this is all part of Matt Hancock’s technology-driven plan for the NHS, (for ‘technology’ read ‘CBT apps’). If this was any other industry the workers would be seriously worried for their futures.

  • Random reader 17 June 2020, 8:51 am

    A 2017 review https://pubmed.ncbi.nlm.nih.gov/28808618/ pointed out that structural and functional abnormalities were apparent in pseudoseizures.
    CBT or some other psychotherapy may be able to help with things like grey matter changes or functional changes it certainly won’t be able to fix the kind of structural issues found:
    ” Indeed, several researchers have identified brain abnormalities such as tumours, cysts, aneurysms, evidence of stroke, white matter lesions, hippocampal sclerosis, venous angioma, and general atrophy in PNES patients with or without epilepsy.”

    This is another case of “psychologization” – rather than admitting that medical science doesn’t have the answers yet, patients are told (not asked) that they have dysfunctional illness beliefs which are “perpetuating a viscous cycle” and thus responsible for their illness (at least to a degree). CBT pushes onto the patient a responsibility to identify these supposed “dysfunctional beliefs” because without those CBT can’t be completed.

    This is psychological harm and the UK really must develop a yellow card scheme for reporting dangerous non-drug therapies immediately.

  • CT 17 June 2020, 10:34 am

    When they do find structural or ‘hardware’ changes, it seems that the BPS mob try to re-interpret their findings as being psych-related -https://www.sciencedirect.com/science/article/pii/S2213158219301482 . Can’t they just admit that they got it wrong? And why hasn’t Jon Stone updated his neurosymptoms.org website -https://www.neurosymptoms.org/causes/4594358020 – yet to inform people that ‘hardware’ problems have been found? IMO this is pretty poor considering the time he’s had to do it and that neurologists all over the UK will be directing their patients to his site.

  • Alicia Butcher Ehrhardt, PhD 18 June 2020, 11:51 am

    These examples of trying to save money for the NHS are scary. And are not helping the US advocates of universal health care.

    The problem is succinct: put the cost for medical care into a single line item in the budget – and then reduce that number by fiat.

    It is the wrong way to economize, but very hard to fight.

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