Multiple sclerosis-related fatigue

Phys Med Rehabil Clin N Am. 2005 May;16(2):483-502. doi: 10.1016/j.pmr.2005.01.014.


Fatigue is a significant factor in the lives of many MS patients and the most commonly reported symptom in many studies. Fatigue is an important symptom to consider because it affects patients' social lives, occupations, and activities of daily living. Efforts to predict fatigue have been mixed, but it appears to be related to overall quality of life and mood. From a pathophysiologic perspective, fatigue in MS is multifactorial and complex,involving dysregulation of the immune system, changes in the nervous system related to the disease process, neuroendocrine and neurotransmitter changes, and other factors such as physical deconditioning, sleep disturbance, pain, and medication side effects. Various attempts to assess fatigue have been made, and many measures are now available for use in clinical practice and research. In clinical practice, these measures help guide treatment considerations. Recent research has provided valuable strategies to ameliorate fatigue in MS, and although many patients continue to experience fatigue despite interventions, many receive substantial relief.Nonpharmacologic approaches-considered the first step in treatment-include exercise programs, cooling, dietary considerations, and energy conservation strategies. For patients who continue to experience significant fatigue, several medications (although not specifically approved for use in the reduction of MS-related fatigue) have proved effective in this regard.The first-line agents include amantadine for mild fatigue and modafinil for more severe cases. Second-line agents include pemoline and antidepressant medications. Other pharmacologic agents have also shown some promise.

Publication types

  • Review

MeSH terms

  • Antidepressive Agents / therapeutic use
  • Central Nervous System Stimulants / therapeutic use
  • Cryotherapy
  • Dopamine Agents / therapeutic use
  • Exercise Therapy
  • Fatigue / physiopathology*
  • Fatigue / psychology
  • Fatigue / therapy
  • Humans
  • Multiple Sclerosis / physiopathology*
  • Patient Care Planning
  • Quality of Life


  • Antidepressive Agents
  • Central Nervous System Stimulants
  • Dopamine Agents