Multiple Sclerosis Journal - October 2017 - 1439

R Moss-Morris and S Norton
longer term treatments or booster treatment sessions.
Perhaps combining CBT and exercise would provide
greater benefits. We also need more mechanistic studies of fatigue in MS to design more optimal approaches.
Future studies also need to be considerably larger than
the three reported here. Power calculations need to
account for larger attrition and number of primary
outcomes. The TREFAMS-ACE protocol suggests
there may be secondary papers from these three trials
exploring possible mechanisms of the treatment
effects. While these future papers may be informative
in terms of next steps, these trials are not well powered for mediation and moderation analyses. Large
trials with clearly embedded process analyses will
help us to refine and personalise treatments.16
Future RCTs in this area also need to be more pragmatic and consider broader generalisability. These
three trials were largely efficacy trials. Patients with
high Hospital Anxiety and Depression Scale17 scores
were excluded. Although this makes sense in trying to
rule out the possibility of the effects of depression on
fatigue, it limits the generalisability of findings. In
addition, the patients in these three RCTs had low
mean disability scores (Expanded Disability Status
Scale)18 and the majority had relapsing remitting MS
(see Table 1). Fatigue occurs across the board in MS
and effective interventions are needed for people with
higher levels of disability including reduced mobility.
Finally, implementation of these interventions in normal everyday health-care needs to be more carefully
considered. The CBT protocol here included 12 faceto-face sessions with an experienced CBT therapist.
Bearing in mind effects were not sustained at longterm follow-up, this is unlikely to be a cost-effective
treatment. CBT therapists experienced in treating
fatigue are also not readily available to most patients
with MS fatigue. The exercise intervention included
the provision of home training equipment, but only
for the duration of the study and only one type of
exercise. Any exercise programme needs to consider
how to embed exercise as a habitual part of an everyday lifestyle that can be sustained once the intervention is finished. To do this, exercise needs to consider
personal preference (enjoyment) of type of exercise
and tailoring of exercise during times of symptom
fluctuation or more serious relapse.
Declaration of Conflicting Interests
The author(s) declared the following potential
conflicts of interest with respect to the research,
authorship and/or publication of this article: RMM

journals.sagepub.com/home/msj

has developed protocols for CBT for MS fatigue and
published RCTs of CBT for MS fatigue.
Funding
The author(s) received no financial support for the
research, authorship and/or publication of this article.
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