Evaluation of Outcomes in Patients Receiving Modafinil to Improve Alertness after Traumatic Brain Injury

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Amne Borghol, Pharm.D., BCPS Dana Jamero, Pharm.D., BCOP Fahamina Ahmed, Pharm.D. Rim M. Hadgu, Pharm.D., BCPS Candice Wilson, MPH Nicole Fabre’-LaCoste, Pharm.D., BCPS, BCGP, DPLA Ann Dinh, Pharm.D. Jayla Thompson, Pharm.D. Mikee Castro, Pharm.D. Amid Paudyal, MS, Pharm.D. Emily Corvers, Pharm.D. Candidate 2022 Ifeanyi Iwuchukwu, M.D. IfeanyiChukwu O. Onor, Pharm.D., BCPS, FNKF


Background: Modafinil is used for improving wakefulness associated with narcolepsy, obstructive sleep apnea, and shift work sleep disorder. The goal of this study is to evaluate alertness and participation in physical therapy and occupational therapy in patients with a first-time diagnosis of traumatic brain injury using modafinil.

Methods: This was a single-center, retrospective, chart review, cohort study of Ochsner Medical Center patients from January 2016 to December 2018. Patients included in the study were 18 years of age or older who were hospitalized due to a traumatic brain injury and received modafinil either by mouth, nasogastric, or enteral feeding tube to help improve alertness. The primary outcome is the change in Glasgow Coma Scale (GCS) score from baseline to 72 hours after initiating modafinil.

Results: One-hundred and Forty patients were included with a mean age of 67.8 years and 59.3% were male. The majority of the patients (52.9 %) were predominantly patients who suffered ischemic stroke. The mean change in GCS score in 72 hours was +0.35 (95% CI [-0.16, 0.88], p=0.177). One of the secondary endpoints was the mean change in course of therapy GCS score which showed significant improvement in neurological function after initiation of modafinil: +1.22 (95% CI [0.64, 1.80], p=0.0001). The percent physical therapy/occupational therapy (PT/OT) session participation at 72-hour post-modafinil initiation was 96.7% compared to 95.7% during the course of therapy. The correlation between increase in GCS score and percent PT/OT therapy session participation was analyzed at 72 hours and throughout the course of therapy, which revealed no significant association (r=0.14 [p=0.0911] and -0.06 [p=0.4881], respectively).

Conclusion: Our study did not find a significant increase in the mean change of GCS score at 72 hours of modafinil use. Although, there were high percentage of patients participated in PT/OT in 72 hours and course of therapy (96.7% and 95.7%), there was no significant statistical correlation between increase in GCS score and PT/OT participation. Randomized studies are needed to further assess the impact of modafinil for treating traumatic brain injury associated sleep-wake disturbances while considering factors such as medication initiation time, appropriate dosage, GCS score, and long-term outcomes.

Keywords: Modafinil, traumatic brain injury, sleep-wake disturbances, stroke, alertness, excessive daytime sleepiness

Article Details

How to Cite
BORGHOL, Amne et al. Evaluation of Outcomes in Patients Receiving Modafinil to Improve Alertness after Traumatic Brain Injury. Medical Research Archives, [S.l.], v. 10, n. 10, oct. 2022. ISSN 2375-1924. Available at: <https://esmed.org/MRA/mra/article/view/3150>. Date accessed: 19 june 2024. doi: https://doi.org/10.18103/mra.v10i10.3150.
Research Articles


1. Peterson AB, Xu L, Daugherty, Breiding MJ. Surveillance report of traumatic brain injury-related emergency department visits, hospitalizations, and deaths. United States, 2014. Center for Disease Control. 2019. https://www.cdc.gov/traumaticbraininjury/pdf/TBI-Surveillance-Report-FINAL_508.pdf
2. Katz DI, Cohen SI, Alexander MP. Mild traumatic brain injury. Handbook of Clinical neurology. 2015; 27:131-156.
3. Sommerauer M, Valko PO, Werth E, Baumann CR. Excessive sleep need following traumatic brain injury: a case–control study of 36 patients. Journal of sleep research. 2013; 22(6): 634-639. Doi: 10.1111/jsr.12068
4. Sandsmark DK, Elliott JE, Lim MM. Sleep-wake disturbances after traumatic brain injury: synthesis of human and animal studies. Sleep. 2017; 40(5): 1-18. doi.org/10.1093/sleep/zsx044
5. Imbach LL, Valko PO, Li T, et al. Increased sleep need and daytime sleepiness 6 months after traumatic brain injury: a prospective controlled clinical trial. Brain. 2015; 138(3): 726-735. doi:10.1093/brain/awu391
6. Baumann CR, werth E, Stocker R, Ludwig S, Bassetti CL. Sleep–wake disturbances 6 months after traumatic brain injury: a prospective study. Brain. 2007. 130(7): 1873-1883. doi:10.1093/brain/awm109
7. McMahon MA, Vargus-Adams JN, Michaud LJ, Bean J. Effects of amantadine in children with impaired consciousness caused by acquired brain injury: A pilot study. Am J Phys Med Rehabil. 2009; 88(7):525-532. doi:10.1097/PHM.0b013e3181a5ade3
8. Nakase-Richardson R, Sherer M, Barnett SD, et al. Prospective evaluation of the nature, course, and impact of acute sleep abnormality after traumatic brain injury. Archives of physical medicine and rehabilitation. 2013; 94(5): 875-882. doi.org/10.1016/j.apmr.2013.01.001
9. Zunzunegui C, Gao B, Cam E, et al. Sleep disturbance impairs stroke recovery in the rat. Sleep. 2011; 34(9): 1261-1269. doi: 10.5665/sleep.1252
10. Parry SM, Puthucheary ZA. The impact of extended bed rest on the musculoskeletal system in the critical care environment. Extreme physiology & medicine. 2015; 4(1):16. DOI 10.1186/s13728-015-0036-7
11. Minzenberg MJ, Carter CS. Modafinil: a review of neurochemical actions and effects on cognition. Neuropsychopharmacology. 2008; 33(7):1477-1502. doi:10.1038/sj.npp.1301534
12. Elkbuli A, fanfan D, Sutherland M, et al. The association between early versus late physical therapy initiation and outcomes of trauma patients with and without traumatic brain injury. Journal of surgical research. 2022; 273:34-43. doi.org/10.1016/j.jss.2021.11.011
13. Teasdale G, Jennett B. Assessment of coma and impaired consciousness. A practical scale. Lancet. 1974; 2(7872): 81-4.
14. Moore L, Lavoie A, LeSage N, et al. Statistical validation of the Glasgow Coma Score. J Trauma. 2006; 60(6):1238-43. DOI: 10.1097/01.ta.0000200840.89685.b0
15. Grima N, Ponsford J, Rajaratnam SM, Mansfield D, Pase MP. Sleep disturbances in traumatic brain injury: a meta-analysis. Journal of clinical sleep medicine. 2016; 12(03): 419-428. doi.org/10.5664/jcsm.5598
16. Czeisler CA, Walsj JK, Roth T, et al. Modafinil for excessive sleepiness associated with shift-work sleep disorder. N Engl J Med. 2005; 353(5): 476-486. DOI:10.1056/NEJMoa041292
17. Lexicomp Online, Modafinil Lexi-Drugs Online. 2019, UpToDate, Inc.: Hudson, Ohio.
18. Karabacak Y, Sase S, Aher YD, et al. The effect of modafinil on the rat dopamine transporter and dopamine receptors D1–D3 paralleling cognitive enhancement in the radial arm maze. Frontiers in behavioral neuroscience 2015; 9 (article 215):1-11. doi:10.3389/fnbeh.2015.00215
19. Baranski JV, Pigeau R, Dinich P, Jacobs I. Effects of modafinil on cognitive and meta‐cognitive performance. Human Psychopharmacology: Clin Exp. 2004; 19(5):323-332. DOI: 10.1002/hup.596
20. Willie J, renthal W, Chemelli RM, et al. Modafinil more effectively induces wakefulness in orexin-null mice than in wild-type littermates. Neuroscience. 2005; 130(4): p. 983-995. doi:10.1016/j
21. Billiard M, Besset A, Montplaisir J, et al. Modafinil: a double-blind multicentric study. Sleep. 1994; 17(8): S107-S112. DOI: 10.1093/sleep/17.suppl_8.s107
22. Visser MM, Goodin P, Parsons MW, et al. Modafinil treatment modulates functional connectivity in stroke survivors with severe fatigue. Scientific reports. 2019; 9(1): 1-9. doi.org/10.1038/s41598-019-46149-0
23. Bivard A, Lillicrap T, Krishnamurthy V, et al. MIDAS (Modafinil in Debilitating Fatigue After Stroke) A Randomized, Double-Blind, Placebo-Controlled, Cross-Over Trial. Stroke. 2017; 48(5): 1293-1298. DOI: 10.1161/STROKEAHA.116.016293
24. Kaiser PR, Valko PO, Thomann J, et al. Modafinil ameliorates excessive daytime sleepiness after traumatic brain injury. Neurology. 2010; 75(20): 1780-1785. doi.org/10.1212/WNL.0b013e3181fd62a2
25. Viola-Saltzman M, Musleh C. Traumatic brain injury-induced sleep disorders. Neuropsychiatr Dis Treat. 2016; 12: 339-348. doi: 10.2147/NDT.S69105
26. Castriotta RJ, Wilde MC. Treatment of sleep disorders after traumatic brain injury. Sleep Medicine. 2015. Springer: 319-330. 10.1007/978-1-4939-2089-1_36
27. Dhamapurkar SK, Wilson BA, Rose A, Watson P, Shiel A. Does Modafinil improve the level of consciousness for people with a prolonged disorder of consciousness? a retrospective pilot study. Disability and Rehabilitation. 2016; 39(26): 2633-2639. doi.org/10.1080/09638288.2016.1236414
28. StataCorp, Stata Statistical Software: Release 12. 2011, StataCorp LP: College Station, TX.
29. Moncrieff J, Cohen D, Porter S. The psychoactive effects of psychiatric medication: the elephant in the room. J Psychoactive Drugs, 2013. 45(5): p. 409-15. DOI: 10.1080/02791072.2013.845328
30. Miller R. Mechanisms of action of antipsychotic drugs of different classes, refractoriness to therapeutic effects of classical neuroleptics, and individual variation in sensitivity to their actions: Part I. Curr Neuropharmacol. 2009; 7(4): 302-14. doi:10.2174/157015909790031229
31. Carney N, Totten AM, O’Reilly C, et al. Guidelines for the Management of Severe Traumatic Brain Injury, Fourth Edition. Neurosurgery. 2017; 80(1): 6-15. DOI:10.1227/NEU.0000000000001432
32. Horn SD, Corrigan JD, Beaulieu CL, et al. Traumatic Brain Injury Patient, Injury, Therapy, and Ancillary Treatments Associated With Outcomes at Discharge and 9 Months Postdischarge. Arch Phys Med Rehabil. 2015; 96(8 0): S304-S329. doi:10.1016/j.apmr.2014.11.030
33. Majdan M, Steyerberg EW, Nieboer D, Mauritz W, Rusnak M, Lingsma HF. Glasgow coma scale motor score and pupillary reaction to predict six-month mortality in patients with traumatic brain injury: comparison of field and admission assessment. Journal of Neurotrauma. 2015; 32(2): 101-108. DOI: 10.1089/neu.2014.3438
34. Teasdale G, Maas A, Lecky F, Manley G, Stocchetti N, Murray G. The Glasgow Coma Scale at 40 years: standing the test of time. Lancet Neurol. 2014; 13(8): 844-54. doi: 10.1016/S1474-4422(14)70120-6
35. Perel P, et al., Predicting outcome after traumatic brain injury: practical prognostic models based on large cohort of international patients. Bmj. 2008; 336: 425-9. doi:10.1136/bmj.39461.643438.25