Multiple sclerosis (MS) is an inflammatory-demyelinating disease of the central nervous system that may entail severe levels of disability in the long term. However, independently of the level of disability, MS patients frequently experience severe fatigue that can be as disabling as objective neurological deficits. For that reason, it is mandatory to perform an early diagnosis of MS-related fatigue and start a suitable treatment as soon as possible. In clinical practice, MS-related fatigue should be assessed and managed by a multidisciplinary team involving neurologists, MS nurses, occupational therapists, and physiotherapists. When assessing a person with MS-related fatigue, the first step is to rule out potential triggers or causes of fatigue, which may be related to MS, such as urinary dysfunction, pain, or muscular spasms leading to a sleep disorder, or unrelated to it. Once these causes have been ruled out and appropriately tackled, a careful therapeutic intervention needs to be decided. Therapeutic interventions for MS-related fatigue can be pharmacological or non-pharmacological. Regarding the pharmacological treatments, although many drugs have been tested in clinical trials, only amantadine is currently recommended for this indication. Regarding the non-pharmacological approaches, they can be broadly divided into physical, psychological, and mixed physical/psychological interventions. Several studies, many of them randomised clinical trials, support the use of all these types of non-pharmacological interventions to treat MS-related fatigue. Recent publications suggest that the implementation of mixed approaches, which have a naturally comprehensive nature, may have excellent results in clinical practice, in relation not only to fatigue levels but also to more general aspects of MS.
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