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Advanced Neurology Fatigue management in patients with MS

or thyroid dysfunction, should be treated if present. In several associated side effects. Studies exploring the effect
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addition, identifying and addressing factors that exacerbate of fampridine, a drug commonly used for gait disorders,
fatigue, such as depression and sleep disorders, is crucial. It on fatigue have yielded mixed results, with some indicating
is worth noting that fatigue and depression often co-occur effectiveness and others showing no significant effect.
in individuals with MS, complicating the identification Similarly, investigations into the efficacy of oral salbutamol,
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and treatment of fatigue. Therefore, it is important to memantine, and methylphenidate in reducing fatigue
inquire about fatigue in individuals with MS and utilize have not yielded positive outcomes. 29,31,32 While one study
both pharmacological and non-pharmacological methods noted the positive effect of low-dose ketamine infusion,
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for its management. While certain methods for managing drawing definitive conclusions regarding the effectiveness
fatigue in MS have been scarcely researched, others have of pharmacological methods (Table 1) remains challenging.
strong literature evidence supporting their efficacy. Given the potential for side effects associated with these
drugs, prioritizing non-pharmacological methods for
3.1. Pharmacological management managing fatigue may offer a more reliable strategy.

Amantadine and modafinil are commonly prescribed to
manage fatigue in patients with MS. Despite their common 3.2. Non-pharmacological management
use, the precise mechanism of action of these drugs on Non-pharmacological methods are commonly used to
fatigue remains incompletely understood. Modafinil exerts manage fatigue in MS patients. These methods include
a psychostimulant effect, purportedly enhancing alertness exercise, dietary regulation, cooling therapies, transcranial
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by increasing noradrenergic and dopaminergic activity. direct stimulation, cognitive behavioral therapy,
On the other hand, amantadine, an antiviral agent, affects acupuncture, and acupressure. However, the effectiveness
fatigue through its antiviral and immune-mediated of certain methods has not been fully established and
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activity, or its amphetamine-like properties. Although requires further investigation through randomized
previous studies have reported a positive effect on fatigue controlled studies.
with modafinil, 26-28 its superiority over placebo was not
confirmed in a recent study. Similarly, a 2007 Cochrane 3.2.1. Non-pharmacological management: Exercise
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Review of amantadine reported no superiority of the Exercise is a non-pharmacological method for fatigue
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drug and recommended further investigation. Recent management in MS patients. It is the most extensively
research aligns with this finding, with a 2021 study failing studied and proven effective method, regardless of the
to demonstrate superiority over placebo and reporting exercise modality employed (aerobic, endurance, resistance,

Table 1. Review of the effect of pharmacological methods on fatigue in patients with multiple sclerosis
Study Intervention Proven effectiveness Outcome analysis
Morrow et al. 34 Fampridine sustained release No (i) No significant effect on fatigue has been reported.
tablet (ii) It has a significant effect on information processing speed and
cognitive functions.
(iii) It should be studied in larger groups.
Broicher et al. 35 Prolong released fampridine Yes Reported to be effective in improving depressed mood in addition to
fatigue.
Falsafi et al. 31 Memantine No (i) Superiority over placebo has not been proven.
(ii) Side effects such as sedation and headache have been reported.
Almeida et al. 32 Oral salbutamol No Oral salbutamol has not been proven to be superior to placebo in
reducing fatigue.
Nourbakhsh Amantadine, modafinil, and No (i) Amantadine, modafinil, and methylphenidate are not superior to
et al. 29 methylphenidate placebo in improving fatigue in patients with multiple sclerosis.
(ii) The drugs cause frequent side effects.
(iii) It is important to be cautious when using amantadine, modafinil,
or methylphenidate to treat fatigue in multiple sclerosis.
Fitzgerald et al. 33 Low-dose ketamine infusion Yes (i) No effect on patients’ fatigue was found in the first week.
(ii) However, a significant decrease in fatigue severity was reported
after one month.
(iii) No serious side effects were reported.
Natsheh et al. 36 Methylphenidate Yes Its superiority to placebo in reducing fatigue has been proven.

Volume 3 Issue 2 (2024) 3 doi: 10.36922/an.2576