Fatigue in multiple sclerosis (MS) is defined as mental or physical exhaustion that prevents a person from performing everyday activities. It is one of the most common symptoms in MS, affecting more than 80 percent of patients, and a major cause of under-employment, early retirement, and a reduced quality of life.

MS-related fatigue could be “primary,” also called lassitude, which is a direct result of myelin damage. This fatigue is unique to MS and different from that experienced by non-MS patients. It is sudden, more severe, aggravated by heat or humidity, and unaffected by restful sleep.

“Secondary” MS-related fatigue is an indirect result of such MS symptoms as depression, stress, recent relapses, the side effects of medication, and sleeps disorders.

Various causes can be behind sleep disorders in MS, such as nocturia (frequent urination at night), nighttime muscle spasms, insomnia, restless legs syndrome (RLS), and obstructive sleep apnea (OSA).

The underlying causes of MS-related fatigue are not properly understood. The criteria to distinguish primary and secondary MS-related fatigue are still lacking.

Managing fatigue in Multiple Sclerosis

Experts recommend several fatigue management strategies that include evaluating and treating any secondary causes (such as drug side effects, depression, sleep disorders, etc.), followed by drug therapy, exercise, and self-management (diet changes, taking naps, relaxing exercises, a cool shower, etc.).

There is limited information about the effects of disease-modifying therapies (DMTs) on MS-related fatigue. Some studies suggest interferon-β (brand names, Avonex, Betaferon, Plegridy or Rebif) and glatiramer acetate (brand names, Copaxone or Glatopa) as effective DMTs to reduce fatigue. No such effect has been observed with teriflunomide, dimethyl fumarate, or alumtuzumab.

A published trial showed that alfacalcidol (a vitamin D analog) reduced fatigue. Carnitine (involved in energy metabolism) was also shown to improve fatigue in another study.

The FDA-approved therapy 4-aminopyridine (fampridine; brand name, Ampyra) is used to treat MS-related walking ability, and has been shown to improve fatigue in studies such as this one.

Other effective strategies include rehabilitation (exercise, self-management, mindfulness training) and cognitive behavioral therapy (CBT).

Fatigue can also be significantly eased by treating underlying sleep disorders, like using continuous positive air pressure (CPAP) for sleep apnea, drug therapy or CBT for insomnia, and medications for restless leg syndrome or other and nighttime limb movements.

A 2016 study gave an overview of both the challenges in treating fatigue in MS patients, and the various approaches shown to be effective. Its authors suggested “a comprehensive approach, including self-management strategies, rehabilitation, CBT, and the treatment of underlying sleep disorders and potentially other comorbidities.”

The researchers also recommended an algorithm (a practical set of instructions), which they called the Berlin Treatment Algorithm, that clinicians might use to identify the causes of fatigue in MS patients and to arrive at appropriate and individually tailored treatments.