Fatigue and multiple sclerosis
People with MS nominate fatigue as one of the most common and disabling symptoms of their disease. Studies indicate that as many as 95 per cent of individuals with MS experience fatigue. Fatigue in MS, also known as lassitude, is defined as ‘a subjective lack of physical and/or mental energy that is perceived by the individual or caregiver to interfere with usual and desired activities’. This fatigue does not appear to be related to the type of MS, disease severity or duration; and, to date, the underlying mechanism is poorly understood.
In this article, the treatment of primary MS fatigue is considered. Other articles in this magazine discuss alternative causes of fatigue that can confuse and even compound the problem, such as existing medical conditions, the side effects of medications or sleep problems.
Recent studies have reinforced that there is a definite role for the use of medications in the treatment of primary fatigue in MS, by way of altering the brain chemistry. The newer agents focus on promoting normal wakefulness rather than stimulating the central nervous system.
Amantadine
Amantadine is an antiviral medication and it has been used in the treatment of MS fatigue since the 1980s. Its method of action in reducing fatigue is not known. It is considered a first-line treatment and is recommended for mild fatigue. Amantadine has been shown in studies to benefit about one third of patients with MS. A positive benefit is usually seen within one week. Amantadine is relatively safe, well tolerated and inexpensive. Its side effects are usually mild and may include dreams, hallucinations, hyperactivity and nausea.
Modafinal
Modafinal is a wake-promoting agent used in the treatment of excessive daytime sleepiness. Recent studies using modafinal for MS fatigue have shown positive benefits in about two-thirds of subjects after about two weeks of therapy. Its use is recommended for those with moderate to severe fatigue or mild fatigue that has not responded to amantadine. Modafinal is relatively safe and well tolerated. Its side effects include headache, nausea and weakness at higher doses.
Pemoline
Pemoline is a central nervous system stimulant and has been used to treat MS fatigue, but studies have failed to show significant benefit using fatigue assessment scales. Pemoline is poorly tolerated in about 25 per cent of patients and, as higher doses can cause liver damage, careful monitoring by regular blood tests is required. It is not recommended as a first-line treatment for MS fatigue.
Other Medications
Aminopyridines (4-aminopyridine and 3,4-aminopyridine) are drugs that improve nerve conduction in nerves with damage to their protective myelin sheath (demyelination) and have shown some benefits in MS fatigue related mainly to heat sensitivity.
Their use is not advocated as side effects include the risk of seizures, trigeminal neuralgia* and heart problems.
Central Nervous System stimulants have a very limited role in the treatment of MS fatigue. Side effects include agitation, anxiety and high blood pressure and the added risk of addiction.
Antidepressants
There is little evidence to support the use of antidepressants in MS fatigue but they may be of benefit in some individuals.
Summary
Fatigue is a complex and common symptom of MS and recent advances in the treatment of fatigue are proving beneficial. As our understanding of the underlying mechanisms increases, so will the potential to develop more tailored and effective treatments.
* Trigeminal neuralgia is a disorder of the sensory nerve of the face, in which sudden episodes of excruciating stabbing pain occur in the cheek, lips, gums, chin or tongue.
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