Modafinil May Alleviate Poststroke Fatigue

Abstract

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<P<0.05), which were secondary outcomes. No serious adverse reactions were observed and there was no difference in blood pressure between groups. Conclusions-There were no significant differences between the 2 groups with regard to the primary end point. There were secondary significant outcomes that should be explored in future trials.

Post-stroke Mood and Emotional Disturbances: Pharmacological Therapy Based on Mechanisms

“…Thus, SSRIs may not be effective for PSF. Modafinil, a drug originally used for patients with hypersomnia or narcolepsy, was used in a recent randomized, placebo-controlled trial [ 152 ]. Forty-one patients were treated with either 400 mg modafinil or placebo.…”

MIDAS (Modafinil in Debilitating Fatigue After Stroke)

“…A recent study of modafinil therapy in a more acute population of patients with stroke in hospital, which did not recruit to target, was not able to show a treatment effect of modafinil on the MFI. 14 Of note is that the placebo group in this study also had a decline in fatigue during their hospital stay, something often observed in the initial recovery phase after acute stroke. 23 Importantly, our study assessed patients more than 3 months post-stroke, rather than in the in-hospital setting.…”

“…Modafinil has been tested in clinical trials to alleviate fatigue in multiple sclerosis and inpatient stroke patients with mixed results in small or incomplete studies. 13,14 …”

Fatigue in Multiple Sclerosis: Assessing Pontine Involvement Using Proton MR Spectroscopic Imaging

“…On the other hand, neurons from this nucleus seem to be be the site of action for a drug used to treat narcolepsy, modafinil [ 30 ]. Modafinil is also used to treat fatigue in MS patients [ 31 ] and it has been recently shown to be effective in alleviating post-stroke fatigue [ 32 ].…”