People with MS often suffer from a sometimes very debilitating physical and mental fatigue, which is referred to in clinical practice as “fatigue”. Despite its importance for many MS patients, “fatigue” is not well defined, which may be related to the fact that its delineation from “cognitive impairments” and “depression” – also two very common symptoms in MS – can be difficult in individual cases. The extent of fatigue can be measured with scale systems, such as the Modified Fatigue Impact Scale (MFIS). These scales consist of questions, for which a certain point value is awarded, from which a fatigue score is then calculated. Since the development of fatigue is also increasingly important for estimating the effect of immunotherapy, it would be desirable if these scales were used widely in therapy monitoring (analogous to the measurement of walking distance or finger dexterity).
So what can be done when the disease has already led to debilitating abnormal fatigue? As strange as it may sound – an integral part of any therapy against fatigue is physical training. Various forms of training, especially aerobic endurance sports, lead to a significant improvement in physical well-being. Our working group was recently able to show that particularly in poorly trained MS patients, a clear effect of physical training on the measurements of the fatigue scales could be demonstrated. So – physical fitness is a basic requirement for combating fatigue. This may in part be due to the fact that physical fitness increases heat tolerance and heat is a factor that negatively affects fatigue. Conversely, therefore, body cooling – as a simple mechanical measure – can lead to a reduction in fatigue. There are studies that have been able to show that after cooling for 30 – 45 minutes, a reduction in fatigue can be observed for several hours.
If fatigue continues to be a problem despite good training status, medication strategies can be used. I often start here with the prescription of a mild antidepressant. Substances such as citalopram (Cipramil®) or sertraline (Zoloft®) have proven to be very helpful. These drugs belong to the group of so-called serotonin reuptake inhibitors (SSRI) – they have a quite favorable side effect profile and in addition to their mood-enhancing effect, they also have a certain drive-enhancing component, which we use in the treatment of fatigue. Due to the frequent overlap between fatigue and depressive mood, the mood-enhancing aspect of these drugs is also helpful for many patients. If no success is achieved with the SSRIs, a trial of therapy with amantadine (PK Merz®) can be undertaken. Amantadine is actually a Parkinson’s medication, but has shown a moderate improvement in fatigue compared to placebo in studies of MS patients. Therefore, its use is worth a try, even though the drug has been officially classified as ineffective by the joint federal committee. Therefore, its prescription – even if the preparation is already generic – can sometimes cause problems with cost reimbursement.
Another substance that can be considered especially after testing other strategies is modafinil (Vigil®), which is approved for the treatment of narcolepsy. The therapy studies with modafinil in MS were not unequivocally positive. However, we often observe on an individual basis that modafinil has a really good effect on fatigue in some people with MS. If this can secure a stay in professional life, then the prescription of this substance is certainly justified. However, a prerequisite for the prescription of this relatively expensive drug is a clear documentation that no success has been achieved with other concepts, despite consistent application.
Fampridine (Fampyra®) is now a well-established symptomatic therapy for MS to improve an MS-related gait disorder. However, reports in the literature are increasingly showing that taking fampridine can also lead to a reduction in fatigue. Therefore, fampridine is also a possible option for the drug treatment of fatigue, especially when there is a gait disorder. Last but not least, I would like to mention that I personally believe that the extent of fatigue correlates with the degree of inflammatory activity/tissue destruction in MS. Therefore, I am of the opinion that the most effective treatment of fatigue is probably good drug control of the underlying disease MS with immunomodulatory therapies.
