Elsevier

Journal of the Neurological Sciences

Volume 380, 15 September 2017, Pages 256-261
Journal of the Neurological Sciences

Pharmacological treatments for fatigue in patients with multiple sclerosis: A systematic review and meta-analysis

https://doi.org/10.1016/j.jns.2017.07.042Get rights and content

Highlights

  • Amantadine is effective for treatment of fatigue symptoms in MS.

  • Major drugs used for MS fatigue were relatively safe.

  • RCT studies are required to validate effectiveness.

Abstract

Background

Multiple sclerosis (MS) is a chronic immune-mediated inflammatory disease. Fatigue is the most common symptom of MS patients, affecting > 80% subjects. Medical treatment is an important method for managing fatigue. Currently, although many drugs have been tested in treatment of MS fatigue, the efficacy of these drugs remain largely unclear.

Methods

We researched available literatures in PubMed, Embase, Medline, Google Scholar, Cochrane Library (August 31, 2016). Search terms included multiple sclerosis, fatigue, medication treatments, amantadine, modafinil, aspirin, acetyl-l-carnitine, pemoline, 4-aminopyridine and randomized controlled trial (RCT). Two researchers were required to independently assess the quality of literatures, and finish data extraction. Meta-analysis was conducted using RevMan 5.3 software.

Findings

A total of 11 RCTs involving 723 patients were included. The therapeutic effects were quantified by different scales, such as Modified Fatigue Impact Scale (MFIS) or Fatigue Severity Scale (FSS). Here, meta-analysis suggested that amantadine, not modafinil, was effective for treating the fatigue in MS. Moreover, two studies implied that l-carnitine might have similar therapeutic effect with amantadine. However, the reliability of this finding was greatly weakened by the limited sample sizes. Additionally, current data could not answer whether treatment of MS fatigue using aspirin or 4-aminopyridine was beneficial. Finally, we found that all drugs except pemoline were relatively safe for treating MS fatigue.

Conclusions

Current limited data suggest that amantadine may be the only drug that has relatively sufficient evidences in treatment of fatigue symptoms in MS. Further RCT studies recruiting larger samples sizes are required to validate the therapeutic effect of these candidate drugs.

Introduction

Multiple sclerosis (MS) is a chronic immune-mediated inflammatory disease that causes demyelination of the central nervous system (CNS). The pathological cascades of MS are characterized by penetration of immune cells into the CNS, triggering inflammation, leading to demyelination of neurons, and eventually axonal degeneration. Fatigue, characterizing by tiredness, weakness or lack of energy, is the most common symptom of MS patients, affecting over 80% of MS patients [1]. Fatigue can significantly impact the quality of life in MS patients, as it greatly restricts their everyday activities, energy levels and productivity. Due to subjective nature of fatigue manifestations, symptoms of fatigue were always clinically overlooked during MS treatment.

In clinical practice, a variety of tests including Modified Fatigue Impact Scale (MFIS), Fatigue Impact Scale (FIS), Fatigue Severity Scale (FSS) and Visual Analogue Scale (VAS) are used to assess the severity of fatigue. Among these scales, FSS is the widely used as it is more easily and fast to screen MS fatigue relative to other scales.

Several drugs such as amantadine, modafinil, pemoline, aspirin, acetyl-l-carnitine and 4-aminopyridine have been used clinically on MS patients. Among these drugs, amantadine was the most widely used in treatment of MS fatigue. Additionally, other aforementioned pharmaceuticals excluding amantadine have also been used to treat fatigue by differential clinical institution. However, it is required to systematically determinate the efficacy and side effects of these drugs.

Section snippets

Search strategy

According to clinical practice experience and previous search protocols [2], these drugs (amantadine, modafinil, aspirin, acetyl-l-carnitine, pemoline and 4-aminopyridine) were selected in this study. We researched PubMed, Embase, Medline, Google Scholar, Cochrane Library (31 September 2016), the search terms included multiple sclerosis, fatigue, pharmacological treatments, amantadine, modafinil, aspirin, acetyl-l-carnitine, pemoline, 4-aminopyridine and randomized controlled trial. We

Study characteristics

A total of 690 citations were identified from the databases, of which 645 were excluded after a preliminary review. The remaining 45 studies were retrieved for detailed assessment. Upon further screening, 11 articles (total number of participants 723) were included in the review [3], [4], [5], [6], [7], [8], [9], [10], [11], [12], [13] (see Tables 1 and 2). Pharmacological treatments were recorded, including amantadine (n = 7), modafinil (n = 4), acetyl-l-carnitine (n = 2), aspirin (n = 1), pemoline (n =

Discussion

Fatigue is a common, multidimensional, complex and highly subjective symptom of MS. It significantly impedes patients' daily life, personal relationships and work quality. Therefore, effective manages of MS fatigue were of great clinical values. Currently, a few studies have examined the efficacy of amantadine, modafinil, aspirin, acetyl-l-carnitine, pemoline, and 4-aminopyridine in treatment of MS fatigue. In this review, we included 11 articles that involves these drugs, and conducted 5

Acknowledgments

This work was supported by the National Science Foundation of Chongqing Science and Technology Commission (CSTC, cstc2016jcyjA1406).

References (20)

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1

These authors contributed equally to this study.

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