Effect of Modafinil on Subjective Fatigue in Multiple Sclerosis and Stroke Patients

Brioschi, Andrea; Gramigna, Sandrine; Werth, Esther; Staub, F.; Ruffieux, Christiane; Bassetti, Claudio L.; Schluep, Myriam; Annoni, Jean‐Marie

doi:10.1159/000232927

Cited by 64 publications

(38 citation statements)

References 55 publications

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“…14 Several small studies have found that treatment with modafinil, a wake-promoting agent, improved symptoms of MS fatigue, although in a larger randomized controlled trial there was no difference. [15][16][17] These studies did not use objective measures of alertness. Beyond these pharmaceutical studies, little research has been conducted into whether poor sleep and decreased alertness are major determinants of MS fatigue.…”

Section: Original Articlementioning

confidence: 99%

Multiple Sclerosis Fatigue is Associated with Reduced Psychomotor Vigilance

Rotstein

O’Connor²,

Lee³

et al. 2012

Can. J. Neurol. Sci.

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Fatigue is a common and disabling symptom in those who suffer from multiple sclerosis (MS). Studies indicate that more than 75% of MS patients suffer from fatigue. 1-3 Two-thirds of MS patients rank fatigue as one of their three most debilitating symptoms. 1 Multiple sclerosis fatigue is particularly aggravated by heat and can significantly impair physical activity. 1 It is one of the main causes of work absenteeism in individuals with MS. 4 Yet fatigue is a lay term that remains subjectively defined and assessment of fatigue is therefore dependent on self-report. Perhaps as a result, the physiologic substrates of MS fatigue are not well-described. The subjective experience of fatigue is multifactorial and has been correlated with factors such as disability, depression, and pain. [5][6][7] Interestingly, no clear association has been established between MS fatigue and demographic factors, such as age and gender; lesion burden; or the clinical form of MS. 1,[7][8][9] ABSTRACT: Background: Fatigue is common and disabling in multiple sclerosis, yet its physiologic substrates remain poorly defined. The aim of this study was to determine the relationship between fatigue and an objective measure of alertness in MS patients. Methods: This study enrolled 49 consecutive MS clinic patients at two academic hospitals in Toronto. Alertness was assessed with the psychomotor vigilance test (PVT), a ten-minute reaction-time test that measures attention and is sensitive to sleep loss. Patients with visual impairment or arm weakness were excluded. Validated tools were used to assess fatigue, disability, mood, and pain. Results: The average age was 43; 65% were women. Median EDSS was 2.0 (range 0-7.5). Fifty-five percent reported a high impact of fatigue on their lives. Psychomotor vigilance test performance was worse than in an age-and sex-matched population, with a mean reaction time of 315 msecs and 3.98 lapses >500 msec (p<0.001). In a multiple regression analysis, fatigue was the most significantly correlated factor with mean PVT reaction time (p<0.05), and disability was also significantly correlated (p<0.01). Mood and pain did not correlate with the PVT. Eighteen (37%) reported often experiencing restlessness in their legs at night. Conclusion: Subjective fatigue and disability were associated with poor performance on alertness testing in MS patients. This research highlights a potential role for psychomotor vigilance testing in providing a standardized assessment tool for an important aspect of MS-related fatigue.RÉSUMÉ: La fatigue dans la sclérose en plaques est associée à une diminution de la vigilance psychomotrice. Contexte : La fatigue est un symptôme fréquent et invalidant chez les patients atteints de la sclérose en plaques (SP) et sa cause physiologique demeure mal définie. Le but de cette étude était de déterminer la relation entre la fatigue et une mesure objective de vigilance chez des patients atteints de la SP. Méthode : Nous avons inclus 49 patients consécutifs de cliniques de SP situées dans deux hôpitaux ac...

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Section: Original Articlementioning

confidence: 99%

Multiple Sclerosis Fatigue is Associated with Reduced Psychomotor Vigilance

Rotstein

O’Connor²,

Lee³

et al. 2012

Can. J. Neurol. Sci.

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“…The earlier modafinil trial in patients with stroke had a dropout rate because of side effects of 25% despite a lower dosage. 19 Therefore, our use of the maximum allowed dose of 400 mg in patients aged <65 years does not seem to have had influenced the amount of adverse effects, but adverse events seem to be a consistent problem.…”

Section: Discussionmentioning

confidence: 86%

“…Investigators found a positive effect on patients with brain stem and diencephalic strokes, but not on patients with cortical stroke. 19 Because of different end points and the uncontrolled design, the effect size cannot be directly compared with our trial. Because of the few included patients in our trial, it did not make sense to compare patients with, for example, brain stem and cortical strokes.…”

Section: Discussionmentioning

confidence: 99%

“…14 To our knowledge, modafinil has only been used for poststroke fatigue treatment in a small trial without placebo control. 19 The aim of this study was to evaluate the effect of treatment with modafinil on fatigue after stroke. The primary end point was to reduce fatigue measured by the general fatigue domain on the Multidimensional Fatigue Inventory-20 general fatigue domain (MFI-20 GF), whereas secondary end points included improvements on the Fatigue Severity Scale (FSS) and of neurological outcome, quality of life, cognition, reaction times, depression, bone density, and muscle mass.…”

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confidence: 99%

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Modafinil May Alleviate Poststroke Fatigue

Poulsen

Damgaard

Zerahn

et al. 2015

Stroke

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Modafinil is a wake promoting drug useful for treatment of excessive sleepiness in narcolepsy, shift work sleep disorder, and obstructive sleep apnea. Numerous other indications, including treatment of fatigue in multiple sclerosis, have been suggested but are still debated.14 The neurobiochemical effects of modafinil are complex and not fully understood. 15 The primary effects seem to involve inhibiting reuptake by dopamine and norepinephrine transporters. Furthermore, it is known to have some effects on serotonin, glutamate, gamma-aminobutyric acid, orexin, and histamine systems, but it is unknown Background and Purpose-Poststroke fatigue is common and reduces quality of life. Current evidence for intervention is limited, and this is the first placebo-controlled trial to investigate treatment of poststroke fatigue with the wakefulness promoting drug modafinil. Methods-The trial was randomized, double-blinded, and placebo-controlled. Patients were treated with 400-mg modafinil or placebo for 90 days. Assessments were done at inclusion, 30, 90, and 180 days. The primary end point was fatigue at 90 days measured by the Multidimensional Fatigue Inventory-20 general fatigue domain. Secondary end points included the Fatigue Severity Scale, the Montreal Cognitive Assessment, the modified Rankin Scale and the Stroke-specific quality of Life questionnaire. Adult patients with a recent stroke achieving a score of ≥12 on the Multidimensional Fatigue Inventory-20 general fatigue domain were consecutively included. Exclusion criteria were severe cognitive disabilities and contraindications for modafinil treatment. Results-One thousand one hundred twenty-one patients with stroke were screened and 41 patients included, 21 received modafinil. The primary end point, the Multidimensional Fatigue Inventory-20 general fatigue score, did not differ between groups. Patients in the modafinil group obtained better scores on the Fatigue Severity Scale (P=0.02) and in some subscales of the stroke-specific quality of life questionnaire (0.001

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“…203 Modafinil was studied in 23 young patients (aged <70 years) with mild strokes 12 to 48 months from the acute event; the study was limited by a high dropout rate, and treatment was found to be effective only in a subgroup of stroke patients. 204 Amantadine and methylphenidate have been used to treat cancer fatigue or fatigue in other neurological conditions 205 but have not been studied for fatigue in the stroke population.…”

Section: Fatiguementioning

confidence: 99%

Palliative and End-of-Life Care in Stroke

Holloway¹,

Arnold²,

Creutzfeldt³

et al. 2014

Stroke

218

120

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Background and Purpose-The purpose of this statement is to delineate basic expectations regarding primary palliative care competencies and skills to be considered, learned, and practiced by providers and healthcare services across hospitals and community settings when caring for patients and families with stroke. Methods-Members of the writing group were appointed by the American Heart Association Stroke Council's Scientific Statement Oversight Committee and the American Heart Association's Manuscript Oversight Committee. Members were chosen to reflect the diversity and expertise of professional roles in delivering optimal palliative care. Writing group members were assigned topics relevant to their areas of expertise, reviewed the appropriate literature, and drafted manuscript content and recommendations in accordance with the American Heart Association's framework for defining classes and level of evidence and recommendations. Results-The palliative care needs of patients with serious or life-threatening stroke and their families are enormous: complex decision making, aligning treatment with goals, and symptom control. Primary palliative care should be available to all patients with serious or life-threatening stroke and their families throughout the entire course of illness. To optimally deliver primary palliative care, stroke systems of care and provider teams should (1) promote and practice patient-and family-centered care; (2) effectively estimate prognosis; (3) develop appropriate goals of care; (4) be familiar with the evidence for common stroke decisions with end-of-life implications; (5) assess and effectively manage emerging stroke symptoms; (6) possess experience with palliative treatments at the end of life; (7) assist with care coordination, including referral to a palliative care specialist or hospice if necessary; (8) provide the patient and family the opportunity for personal growth and make bereavement resources available if death is anticipated; and (9) actively participate in continuous quality improvement and research. Conclusions-Addressing the palliative care needs of patients and families throughout the course of illness can complement

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Effect of Modafinil on Subjective Fatigue in Multiple Sclerosis and Stroke Patients

Cited by 64 publications

References 55 publications

Multiple Sclerosis Fatigue is Associated with Reduced Psychomotor Vigilance

Multiple Sclerosis Fatigue is Associated with Reduced Psychomotor Vigilance

Modafinil May Alleviate Poststroke Fatigue

Palliative and End-of-Life Care in Stroke

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