For over two decades, the standard of care for myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) has been cognitive behavior therapy (CBT) and graded exercise therapy (GET). Both interventions had been recommended by the US Centers for Disease Control and the UK NICE guidelines.1
Behavioral intervention as the clinical standard was given a considerable boost by the 5 million–pound PACE trial, a large multi-arm randomized trial of CBT and GET launched in 2007.2 This British government–funded trial was intended to definitively answer whether such interventions were beneficial in ME/CFS. In their 2011 and 2013 publications, the PACE trial authors announced with widespread publicity that 22% of their patients had “recovered” and 59–61% had clinically improved across the CBT and GET interventions.2, 3
More generally, multiple literature reviews have reported that these therapies are not only effective at improving fatigue and, to a lesser extent, physical function in ME/CFS but also safe.4, 5, 6 It would seem obvious then that good clinical care of these patients would include these behavioral interventions. But, a closer look at these trials has generated many concerns about their applicability to these patients. This perspective critically examines their findings and more generally discusses the behavioral intervention literature in ME/CFS. Finally, we briefly describe a pragmatic clinical approach for these often-marginalized patients.
CARING FOR ME/CFS PATIENTS
In clinical practice, many individuals presenting with the common symptom of persistent fatigue may benefit from activity-based behavioral interventions, e.g., Friedberg et al.26 However, persistent fatigue is not equivalent to the multi-symptom debilitating illness of ME/CFS. Despite the lack of approved treatments or a fully articulated standard of medical care, there are still many actions physicians can take to help these underserved patients. First, practitioners can acknowledge the biomedical reality of the illness and their belief that the patient is genuinely ill. Next, clinicians can help patients to better manage a major illness challenge: how to minimize debilitating post-exertional malaise by learning to stay within their energy envelope.36
The energy envelope delineates the amount of energy that a ME/CFS patient has available to perform all activities.37 The size of this energy envelope can vary from day to day and between patients with some patients lacking energy for basic activities of daily living. When patients exceed their limited energy levels, they experience post-exertional worsening of symptoms and functioning. Medical providers can teach patients how to recognize their own personal energy limits and use pacing (dividing symptom-producing activities into smaller parts with interspersed rest intervals) to stay within those limits.34, 37 Once pacing is effectively used, some patients may be able to use an individualized exercise plan to increase available energy and functioning while avoiding post-exertional worsening.34, 36
Practitioners can also help patients with appropriate pharmacological and non-pharmacological treatments.38, 39 This includes treatments for unrefreshing sleep, e.g., trazodone and low-dose tricyclic antidepressants, and sleep hygiene measures.
In addition, pain can be addressed with low-dose naltrexone40 and anti-epileptics, e.g., gabapentin, and orthostatic intolerance can be treated with fludrocortisone and salt loading. Comorbidities can be managed using standard of care. Drugs should usually be started at low doses because patients can be sensitive to medications. If needed, patients can be referred to counseling to improve coping with the severe impacts of ME/CFS on quality of life.
For optimal patient care, we recommend a ME/CFS specialist or a specialist center supported by a multi-disciplinary team. Unfortunately, few of these practitioners or centers are available, which highlights the need for provider education and training regarding this illness. Realistically, when specialists are not available, care is best provided by the generalist (internal medicine or family doctor) working as part of a multidisciplinary team including expertise (as available) in immunology, infectious disease, cardiology or neurology, psychology, occupational therapy, and social work. With this interprofessional approach, practitioners can lessen harms while helping patients improve their health, function, and quality of life to the extent possible.
Further information on clinical management may be found in the following sources: a free practitioner’s guide to ME/CFS,34 a clinically focused review, 41 and a pragmatic clinical paper.36