Fatigue in multiple sclerosis: a rational approach to evaluation and treatment.

With the publication of the Multiple Sclerosis Council Guideline on the management of multiple sclerosis (MS) fatigue, there has been increased appreciation for the role fatigue can play in MS. Secondary fatigue is fatigue caused by other etiologies than those directly related to MS. Once these causes are ruled out, fatigue is related to MS. Secondary MS-related fatigue comes as result of the symptoms of MS that drain energy. Once secondary MS causes are ruled out, then the patient is deemed as having primary MS fatigue. Fatigue management is both nonpharmacologic and pharmacologic. Occupational therapists are the major allied health providers that address the role fatigue plays in MS patients. Over the past two decades, numerous clinical trials have been conducted on drugs for treating MS-related fatigue. Of these agents, amantadine has been studied for the longest period, and has shown efficacy in about one third of patients with MS-related fatigue on several commonly used scales. Two randomized -trials of the central nervous system stimulant pemoline have yielded unimpressive results; efficacy was seen at higher doses but coupled with an unacceptable risk of adverse events. The wake-promoting agent modafinil is the only agent to show efficacy compared with placebo on the Fatigue Severity Scale, a measure that is highly resistant to "impulse answering" and is thus viewed as one of the most difficult scales on which to show -benefit. This article reviews fatigue in MS and proposes a rational strategy for evaluation and management of this most common MS symptom.