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Treating fatigue in multiple sclerosis


Clinical bottom line

There is no good research underpinning treatment of fatigue in patients with multiple sclerosis. There are some clinical trials for some interventions, but these show no conclusive effects on fatigue outcomes or quality of life. For most interventions there is no research at all.


P Branas et al. Treatments for fatigue in multiple sclerosis: a rapid and systematic review. Health Technology Assessment 2000 4 (27).(

Patients with multiple sclerosis suffer from a variety of common symptoms, and a recent survey conducted by the MS Society in the UK shows that the three most common symptoms were fatigue, balance problems and muscle weakness, but others affect over half of patients (Table 1).

Table 1: Common symptoms in patients with multiple sclerosis


MS patients currently with the symptom (%)



Balance problems


Muscle weakness


Bladder or bowel problem


Numbness or tingling


Muscle stiffness




Muscle spasms


The review has a searched for studies examining fatigue and its measurement, and the prevalence of fatigue in MS patients was high (53-92%) in all studies.


There was an extensive search conducted for studies examining treatment for fatigue in MS. Initial searches were wide, but for a detailed examination an intervention had to have evidence available, defined as at least two rigorous evaluations. For inclusion trials had to be controlled, with a placebo or alternate intervention, in patients with clinically defined MS, and where fatigue was an outcome.


A number of potential interventions were found, and references are given for all of them. They included interventions from recognised pharmaceuticals, to cooling systems, pulsed magnetic fields, and bee venom. Only two, amantadine and pemoline, were taken for further review.


Four trials (10, 29, 82, and 115 patients) were found, of adequate quality, all of which compared amantadine with placebo in parallel or crossover designs. All the trials reported a statistically significant result in favour of amantadine based on at least one outcome of fatigue or patient preference.

Using realistic assumptions on the true results of the trials, there was no difference between amantadine and control on patient preference. amantadine was favoured by 64/157 patients (41%) and placebo by 82/161 (51%); relative risk 0.8 (95% confidence interval 0.6 to 1.1).


Two trials (46 and 82 patients) were found, of adequate quality, and comparing pemoline with placebo in parallel or crossover designs. There was no statistically significant difference on any outcome.


This is a scintillating excellent systematic review, that also takes into account health economic factors. It comes from the UK Health Technology Assessment authority, and is exactly what HTA is all about. The 60+ page report is freely available to download as a PDF from the Internet, and could be used as a terrific teaching aid.

The real disappointment, though, is the negative conclusion. Not just the negative conclusion about amantadine and pemoline, but that there is so little information about this important symptom for important patients. There are times when saying that more research is needed shames us all.