Fatigue in Multiple Sclerosis: A Common and Debilitating Symptom

Abbey J. Hughes, PhD
Johns Hopkins University School of Medicine

Key Takeaways

  • Data suggest that up to 90% of patients with MS report experiencing fatigue.
  • Objective measurements of muscle fatigability do not always correlate with a subjective rating of fatigue.
  • Patients with sleep disturbance often report much greater levels of fatigue than do those without sleep disturbance.
  • Helping patients improve their relationship with fatigue can reduce its impact on daily functioning. 
  • A multidisciplinary approach to managing fatigue can have a profound effect on fatigue management.
  • Although access to equitable health care is among the strongest predictors of patient outcomes, significant disparity exists.

In her research and in clinical practice, Abbey J. Hughes, PhD, works with people with MS and their loved ones to optimize psychosocial wellness, self-management, and rehabilitation.
Fatigue is one of the most frequently reported symptoms in people with MS, but its etiology and presentation can vary from patient to patient. In this discussion, Dr Hughes describes her approach to identifying fatigue and her team-based strategy for minimizing its impact on patients’ lives.

Can you describe your approach to identifying fatigue in a patient with MS?

I take both a quantitative and a qualitative approach to identifying fatigue. In every interview, I ask people if they experience fatigue and, if so, how they would describe it.  The reason I start off with this open-ended question is because fatigue is one of the most frequently reported symptoms in people with MS. It is reported in as many as 90% of people with MS.1,2 It can be caused by many different factors, and each person experiences it differently. 
It is helpful for me to understand a patient’s experience of fatigue in their own words. It helps me when taking a mental health history, [as mental illness] can certainly contribute to fatigue, or in assessing sleep, because sleep disturbance that causes fatigue is also a huge part of MS.3 I then look at things like neurologic fatigue, as well as what kind of medications the patient is taking, as sometimes people will say that their medications make them tired.
Another way to go about it would be to divide fatigue into 2 main categories: fatigue severity and fatigue impact.4 I ask people how severe their fatigue is on a typical basis, similar to asking a patient to “rate your pain on a scale of 1 to 10.”  When assessing the impact of fatigue, I ask people how their fatigue interferes with their daily functioning.4 How does it interfere with what they would normally do in their daily life? Fatigue can interfere with their ability to participate in their home activities with partners, families, and friends. It could have a greater impact at work and it can differ among patients, depending on their job and their family situation.

Causes of fatigue in MS
Causes of fatigue in MS
Complications of MS that may also cause fatigue symptoms include chronic pain, anemia, reduced physical fitness, emotional disorders, reduced thyroid function, sleeping issues, and diabetes.

Are there objective measures clinicians can use to assess fatigue in patients with MS?

Fatigue is complicated, because it is entirely subjective and it is a symptom that only the person experiencing it can feel.  But, that doesn’t mean you can’t get at other things that are related to fatigue. 
We often refer to “fatigability,” which is how easily someone becomes fatigued when they are under a particular challenge or when they are completing a specific task. 5,6  There is research that tests fatigability in patients by having them repeat certain tasks like walking on a treadmill or a fine motor task until their muscles give out from the fatigue.5,6 So, you can measure the muscle fatigability, but the fatigability does not always correlate with someone’s subjective rating of fatigue. Fatigue, as we most commonly assess it and measure it, really falls within that subjective experience.

How can professionals in mental health specifically and in medicine broadly address fatigue in MS?

For management of fatigue in MS, 2 of the most robustly [studied] interventions are physical activity and health behavior interventions.  So, broadly speaking, that’s psychotherapy.5-8 There are a few specific kinds of psychotherapy that have been examined in fatigue: cognitive behavioral therapy, mindfulness-based therapy, and acceptance and commitment therapy.7,8 These are 3 examples of orientations to a behavioral or psychological intervention that helps people manage their fatigue more effectively.
[Other] behavioral interventions that help people manage their fatigue better include pacing, mindfulness, and changing thoughts and behaviors about their fatigue. So, although you may not be able to change someone’s fatigue intensity, you can help them have a different relationship with it, so that it is not as interfering with their daily functioning.
[Editor’s Note: Previously, fatigue medications were observed to be ineffective in MS.9 However, the recently completed phase 3 OPTIMUM study (ClinicalTrials.gov Identifier: NCT02425644), which compared oral ponesimod and teriflunomide in relapsing MS, demonstrated positive results. The study revealed superiority of ponesimod vs teriflunomide across the primary and secondary end points.10 The primary end point was annualized relapse rate from baseline to end-of-treatment, while secondary end points included the measurement of change from baseline to end-of treatment in fatigue-related symptoms. Based on results from the Fatigue Symptoms and Impacts Questionnaire – Relapsing Multiple Sclerosis (FSIQ-RMS), statistically significant effects on fatigue symptoms were observed with ponesimod compared with teriflunomide.10]

What are some of the other nonpharmacologic approaches to broadly managing fatigue in patients with MS?

If we take sleep as an example, knowing that it is a potential contributor to fatigue, managing sleep would help prevent fatigue.3 For example, having good sleep hygiene and making sure that the patient is not sleeping during the day can build up sleep pressure so the patient can fall asleep at night. From a pacing standpoint, we’d advise not packing too many activities into a single period of time to avoid burnout and taking frequent breaks. Allowing for those brain and physical breaks can be a potential disability accommodation in the workplace. 
Eating a moderate, healthy diet — where you’re eating frequently enough but not so much that you’re getting lassitude — is also an important component of fatigue management. In addition, physical activity is important. We are continuing to see in the literature how important regular physical activity is for managing fatigue, although this often seems counterintuitive to patients.5,6,11 They feel that because they are tired they should rest, but the data show that physical activity on a regular basis actually helps reduce fatigue. 
Other types of exercises, like with mindfulness, make us pause and pay more attention to what is happening in a given moment and thus avoid information overload and its associated exhaustion.12,13 Mindfulness allows people to be more deliberate in their attention and to limit their attempts to manage many things at a time.  Pacing and doing one thing at a time form a baseline approach to fatigue management.11,12

Multidimensional Tools for Measuring Fatigue in MS

What are some of the non-MS-related causes of fatigue that clinicians may want to rule out?

Although you say “non-MS,” I put depression, anxiety, and social isolation in a category that can be related to MS or can be separate from MS. We know that fatigue is one of the symptoms of depression.27 If I am screening for depression, I automatically ask about fatigue; there’s a lot of overlap there. Sometimes people experience depression as fatigue. They may not be experiencing worthlessness or suicidal ideation that sometimes accompanies depression, but they are feeling down, depressed, and maybe hopeless. When you feel hopeless every day on waking up, it is pretty exhausting. 
Similarly, anxiety is very fatiguing. If you are a person living with MS, there are many things that MS could trigger in terms of depression and anxiety.27, 28 Getting a new diagnosis can change the way that people view themselves, and they have to integrate that into their identity in different ways. Depression can be a reaction to that. Similarly, with anxiety, there are a lot of MS medications or treatments that have side effects, and patients may feel reactionary anxiety about that, which can be very fatiguing. A patient may also have anxiety or depression that pre-existed the MS; once they develop MS, they get a recurrence of the depression or anxiety, and that contributes to fatigue.27-29

Can you describe the healthcare team you work with and your collective approach to managing fatigue in patients with MS?

My role as a rehabilitation psychologist is dedicated to understanding and advocating for and with people with chronic health conditions and disabilities. Most of what I do is team based. The rehabilitation team with which I work closely includes a physiatrist who specializes in the musculoskeletal system and the way it interfaces with the nervous system in physical functioning. A physical therapist, an occupational therapist, and a speech therapist are also part of our MS treatment team for managing fatigue. The physical therapist can help someone build strength in their core, for example, and then in their legs, so that they can walk with less effort. An occupational therapist helps people manage their essential daily activities, like getting dressed, doing the dishes, and doing the laundry. Although these things do not sound like they are very energy consuming, if you have MS and you have fatigue, any one of those tasks can be exhausting. 
As speech therapy is also important, speech/language pathologists assist with cognitive rehabilitation.  Imagine how exhausting talking is, especially if you have dysarthria or aphasia or some of these symptoms that can come along with MS. Working with a speech therapist can help with managing cognitive fatigue and the fatigue that comes with laryngeal and pharyngeal activity.

Can you highlight some gaps in the research that you hope to see addressed in the coming years?

The National MS Society has established task forces that are focused on different aspects of wellness.30 There is a physical wellness group that studies physical activity, there’s a nutrition group, and there’s even a psychosocial wellness group.28 The reason I bring this up is that one of the major criticisms about research in physical activity and MS has been the significant heterogeneity of study design. Do you have a control group? Do patients exercise 5 days a week, 6 days a week, 3 days a week? What kind of exercise do you do? Do you do strength-based exercise? Do you do cardiovascular-based exercise? What is really important is that gaps in the literature are slowly being filled in our understanding of what kinds of exercises are most effective and, again, for whom they are most effective. 
We need to get away from the idea of one-size-fits-all or that an intervention is effective for everyone.  It’s more of, “Okay, you have this weakness. What intervention do we use to address that weakness?” That gets us to personalized medicine and what is called precision medicine. That is the wave of the future of all research, but especially in the self-management of chronic health conditions like MS.

What is a final piece of advice or take-home message that you would like to share with clinicians who might be caring for patients with MS?

One thing that is important to emphasize is that access to equitable health care and insurance continue to be among the strongest predictors of patient outcomes. With the coming of COVID, medicine has moved toward telehealth, which has increased accessibility for so many patients. Yet, insurance companies are not consistently paying for telehealth visits, as they would for in-person visits, even though the research suggests that they are equal in their efficacy, especially when it comes to behavioral interventions.31
When people ask what can I do, where should my efforts be placed, where should money go, I respond that there is an advocacy need at the legislation level for insurance to cover these treatments that we know are effective but that are not being disseminated to the patients who are most in need.  So, we see a divide in care, and we see a divide in patients who can benefit from these services.
I can talk about the research participants who agree to enroll in our studies, but it is a biased selection. Until we can really reach a fully representative sample of patients and have those patients have access to care, fatigue will continue to be an issue.
The Q&A was edited for clarity and length.


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Reviewed October 2020