Innovations In Clinical Neuroscience

MAR-APR 2018

A peer-reviewed, evidence-based journal for clinicians in the field of neuroscience

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17 ICNS INNOVATIONS IN CLINICAL NEUROSCIENCE March-April 2018 • Volume 15 • Number 3–4 R E V I E W E Each year in the United States, as many as 1.7 million individuals are thought to experience some form of a traumatic brain injury (TBI)- inducing event. 1,2 Falls appear to be the most common cause of head injury leading to TBI (28%). 3 Other medical events can also result in TBI, such as stroke, automotive accidents, and neurologic degenerative diseases. Two of the most commonly reported complications following TBI are fatigue and excessive daytime sleep (EDS), and the prevalence rate for these complications varies widely from 21 to 70 percent. 4,5 A study by Gardani et al 5 suggests that these sleep disturbances are common in patients with TBI undergoing rehabilitation activities and notes that clinicians often perceive sleep disorders to have an overall negative impact on rehabilitation progress. Furthermore, symptoms of fatigue/EDS are known to be associated with reduced quality of life. 4 Fatigue is often defined as an overall lack of physical and/or mental energy, ordinarily stemming from inadequate nighttime sleep or excessive exercise. 6,7 EDS, on the other hand, is a symptom normally present in narcolepsy, a chronic condition comprising some combination of the following four symptoms: 1) EDS, 2) cataplexy, 3) hallucinations, and 4) sleep paralysis. 8 Patients suffering from this disorder will have difficulty staying awake during the day and will awaken multiple times in the middle of the night, disrupting the body's circadian rhythm. The cause of EDS is unclear, though it is thought to be associated with decreased production of a wake- promoting hypocretin (orexin) from neuronal cells in the hypothalamus in TBI patients. 9 Treatment for narcolepsy is currently focused on correcting EDS and rapid eye motion (REM) sleep patterns, and several drug classes have been used for that purpose (e.g., methylphenidates, amphetamines, modafinil, and sodium oxybate). 8,10,11 The same medication classes are used for fatigue, as these disorders are often difficult to distinguish from each other. The classical psychostimulants—amphetamines and methylphenidates—work by increasing central nervous system (CNS) secretion of catecholamines (dopamine and norepinephrine). 12 These stimulants are often used to treat attention deficit hyperactivity disorder (ADHD) and narcolepsy, but they might show promise in the treatment of patients with TBI, who often experience attention deficits. 13 A meta-analysis conducted by Huang et al 14 demonstrated statistical significance with regard to enhancing attention in patients with TBIs through 10 randomized, controlled trials utilizing A B S T R A C T Objective: The authors sought to assess the literature evidence on the efficacy of modafinil use in patients with fatigue or excessive daytime sleepiness (EDS) secondary to traumatic brain injury (TBI). Method of Research: A literature search of Medline and PubMed was performed using the EBSCOhost database. Primary literature, observational studies, meta-analyses, case reports, and systematic reviews were assessed for content regarding modafinil and psychostimulant use in patients with TBI. Of the 23 articles collected, three randomized, controlled studies, three observational studies, one case report, and two systematic reviews gave a description of modafinil use in TBI patients. Results and Conclusion: Modafinil is a central nervous system stimulant with well-established effectiveness in the treatment of narcolepsy and shift-work sleep disorder. There is conflicting evidence about the benefits of modafinil in the treatment of fatigue and EDS secondary to TBI. One randomized, controlled study states that modafinil does not significantly improve patient wakefulness, while another concludes that modafinil corrects EDS but not fatigue. An observational study provides evidence that modafinil increases alertness in fatigued patients with past medical history of brainstem diencephalic stroke or multiple sclerosis. Modafinil appears to have the potential to improve wakefulness in patients with TBI. A prospective, double-blinded, randomized, crossover trial of modafinil for the management of fatigue in ischemic stroke patients is currently being conducted, and further studies demonstrating consistent results are needed before making a conclusive decision. Keywords: Traumatic brain injury, TBI, excessive daytime sleep, modafinil, fatigue, stroke, head injury Modafinil for the Improvement of Patient Outcomes Following Traumatic Brain Injury by AMNE BORGHOL, PharmD, BCPS, BCGP; MICHAEL AUCOIN, PharmD; IFEANYICHUKWU ONOR, PharmD, BCPS; DANA JAMERO, PharmD, BCOP; and FADI HAWAWINI, DO, CMD Drs. Borghol, Onor, and Jamero are with the College of Pharmacy at Xavier University of Louisiana in New Orleans, Louisiana. Dr. Aucoin is with the Woman's Hospital in Baton Rouge, Louisiana. Dr. Hawawini is with the Geriatric and Extended Care Service at Southeast Louisiana Veterans Health Care System in New Orleans, Louisiana. Innov Clin Neurosci. 2018;15(3–4):17–23 FUNDING: This research did not receive any specific grant from funding agencies in the public, commercial, or not-for- profit sectors. DISCLOSURES: The authors have no conflicts of interest relevant to the content of this article. CORRESPONDENCE: Amne Borghol, PharmD, BCPS, BCGP; Email:

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