The Impact of Modafinil on Quality of Life in Stroke Survivors Experiencing Severe Fatigue
Fatemeh Hamzeh
1
(
Department of Neurology, Urmia University of Medical Sciences, Urmia, Iran
)
Mohammadreza Amiri Nikpour
2
(
Department of Neurology, Urmia University of Medical Sciences, Urmia, Iran
)
Arash Mosarrezaii
3
(
Department of Neurology, Urmia University of Medical Sciences, Urmia, Iran
)
Keywords: Modafinil, Stroke survivors, Post-stroke fatigue, Quality of life, Randomized controlled Trial,
Abstract :
Post-stroke fatigue has a substantial negative impact on the mental and physical health of individuals recovering from stroke. This study explored the effect of modafinil om improving quality of life for stroke patients experiencing severe fatigue. This study employed a randomized, double-blind, placebo-controlled, design that was conducted at a single center hospital. Individuals recovering from a stroke were assigned by chance, in equal proportions, to either a 200 mg dose of modafinil or an inactive substitute for the first eight weeks of the study. The primary outcome measures comprised fatigue (MFI), quality of life (SSQoL), and stroke severity (NIHSS). Eighty stroke survivors were initially assessed for eligibility, and 63 of those individuals were subsequently enrolled in the study. The mean age of participants in the modafinil group was 57.46 ± 13.23 years and 64.8 ± 14.28 years in the control group. At baseline, the two groups exhibited no statistically significant differences in fatigue levels, quality of life scores, or stroke severity (P > 0.05). Nevertheless, the modafinil group exhibited greater improvement in all outcome measures following the intervention. While modafinil treatment did not yield statistically significant between-group differences in fatigue or quality of life, the observed trends suggest a potential benefit. The modafinil group exhibited a slightly greater reduction in MFI scores and a slightly greater increase in SSQoL scores compared to the control group. This study reported that modafinil may offer a safe and beneficial approach for managing fatigue and improving quality of life in individuals recovering from stroke.
1. Hosinian M., Qujeq D., Ahmadi Ahangar A., 2016. The Relation between GABA and L-Arginine Levels with some Stroke Risk Factors in Acute Ischemic Stroke Patients. Int J Mol Cell Med. 5(2), 100-105. doi: 10.22088/acadpub.BUMS.5.2.100.
2. Mashayekhi F., Salehi Z., 2024. Mammalian gut microbiome and brain development: A comprehensive review. Casp J Environ Sci. 1-11. doi: 10.22124/cjes.2024.8158.
3. Sadeghi Moghimi E., Ghanbari Z., Mirmalek SA., Aeinfar K., Salimi Tabatabaee SA., Zaferani Arani H., Derayati F., 2024. Frequency survey of brain metastases and its associated factors among Iranian women with breast cancer: A cross-sectional study in Tehran City: Brain metastases among BC patients. Galen Med J. 13, e3238. doi: 10.31661/gmj.v13i.3238.
4. Lubis S.N., Menglikulov B., Shichiyakh R., Farrux Q., Khakimboy Ugli B.O., Karimbaevna T.M., Ulugbek K., Bakhtiyarovna S.Z., Khabiba J., Sapaev I., Jasur S., 2024. Temporal and spatial dynamics of bovine spongiform encephalopathy prevalence in Akmola Province, Kazakhstan: Implications for disease management and control. Casp J Environ Sci. 22(2), 431-442. doi: 10.22124/cjes.2024.7734.
5. Sun B., Wang Z., 2023. A short review on advances in early diagnosis and treatment of ischemic stroke: Advancements in diagnosis and treatments of ischemic stroke. Galen Med J. 12, e2993. doi: 10.31661/gmj.v12i.2993.
6. Chen W., Jiang T., Huang H., Zeng J., 2023. Post-stroke fatigue: a review of development, prevalence, predisposing factors, measurements, and treatments. Front Neurol. 21, 14, 1298915. doi: 10.3389/fneur.2023.1298915.
7. Mücke M., Mochamat Cuhls H., Peuckmann-Post V., Minton O., Stone P., Radbruch L., 2015. Pharmacological treatments for fatigue associated with palliative care. Cochrane Database Syst Rev. 30(5), CD006788. doi: 10.1002/14651858.CD006788.pub3.
8. Kutlubaev M.A., Duncan F.H., Mead G.E., 2012. Biological correlates of post-stroke fatigue: a systematic review. Acta Neurol Scand. 125(4), 219-27. doi: 10.1111/j.1600-0404.2011.01618.x.
9. Kuppuswamy A., Billinger S., Coupland K.G., English C., Kutlubaev M.A., Moseley L., 2024. Mechanisms of Post-Stroke Fatigue: A Follow-Up from the Third Stroke Recovery and Rehabilitation Roundtable. Neurorehabil Neural Repair. 38(1), 52-61. doi: 10.1177/15459683231219266.
10. Kuppuswamy A., Clark E.V., Turner I.F., Rothwell J.C., Ward N.S., 2015. Post-stroke fatigue: a deficit in corticomotor excitability? Brain. 138(1), 136-48. doi: 10.1093/brain/awu306.
11. Ormstad H., Verkerk R., Amthor K.F., Sandvik L., 2014. Activation of the kynurenine pathway in the acute phase of stroke and its role in fatigue and depression following stroke. J Mol Neurosci. 54(2), 181-7. doi: 10.1007/s12031-014-0272-0.
12. Dantzer R., Heijnen C.J., Kavelaars A., Laye S., Capuron L., 2014. The neuroimmune basis of fatigue. Trends Neurosci. 37(1), 39-46. doi: 10.1016/j.tins.2013.10.003.
13. Visser M.M., Goodin P., Parsons M.W., Lillicrap T., Spratt N.J., Levi C.R., Bivard A, 2019. Modafinil treatment modulates functional connectivity in stroke survivors with severe fatigue. Sci Rep. 4, 9(1), 9660. doi: 10.1038/s41598-019-46149-0.
14. Lillicrap T., Krishnamurthy V., Attia J., Nilsson M., Levi C.R., Parsons M.W., Bivard A., 2016. Modafinil In Debilitating Fatigue After Stroke (MIDAS): study protocol for a randomised, double-blinded, placebo-controlled, crossover trial. Trials. 17, 17(1), 410. doi: 10.1186/s13063-016-1537-4.
15. Sheng P., Hou L., Wang X., Wang X., Huang C., Yu M., Han X., Dong Y., 2013. Efficacy of modafinil on fatigue and excessive daytime sleepiness associated with neurological disorders: a systematic review and meta-analysis. PLoS One. 3, 8(12), e81802. doi: 10.1371/journal.pone.0081802.
16. Geffen S., Shum K., Tan H.M., 2013. Novel use of modafinil to treat severe physical and cognitive impairment post-stroke. Intern Med J. 43(3), 338. doi: 10.1111/imj.12073.
17. Poulsen M.B., Damgaard B., Zerahn B., Overgaard K., Rasmussen R.S., 2015. Modafinil May Alleviate Poststroke Fatigue: A Randomized, Placebo-Controlled, Double-Blinded Trial. Stroke. 46(12), 3470-7. doi: 10.1161/STROKEAHA.115.010860.
18. Borhani-Haghighi A. Review of stroke: The 2nd International and the 8th National Iranian Stroke Congress: Shiraz, Iran. Galen Med J. 5, e609. doi: 10.31661/gmj.v5i.609.
19. English C., Simpson D.B., Billinger S.A., Churilov L., Coupland K.G., Drummond A., 2024. A roadmap for research in post-stroke fatigue: Consensus-based core recommendations from the third Stroke Recovery and Rehabilitation Roundtable. Neurorehabil Neural Repair. 38(1), 7-18. doi: 10.1177/17474930231189135.
20. Thorpy M.J., Bogan R.K., 2020. Update on the pharmacologic management of narcolepsy: mechanisms of action and clinical implications. Sleep Med. 1, 68, 97-109. doi: 10.1016/j.sleep.2019.09.001
21. Ghazanfar S., Farooq M., Qazi S.U., Chaurasia B., Kaunzner U., 2024. The use of modafinil for the treatment of fatigue in multiple sclerosis: A systematic review and meta-analysis of controlled clinical trials. Brain Behav. 14(7), e3623. doi: 10.1002/brb3.3623.
22. Sheng P., Hou L., Wang X., Wang X., Huang C., Yu M., Han X., Dong Y., 2013. Efficacy of modafinil on fatigue and excessive daytime sleepiness associated with neurological disorders: A systematic review and meta-analysis. PLoS One. 8(12), e81802. doi: 10.1371/journal.pone.0081802.
23. Zhu R., Huang H., Yu Y., Bao S., Lin N., Shu M., 2024. Post-stroke fatigue and its correlation with family functioning in patients who have experienced a first episode of stroke. Front Aging Neurosci. 21, 16, 1440163. doi.org/10.3389/fnagi.2024.1440163.
24. Paudel S.K., Rolls K., Green H., Fernandez R., 2023. Prevalence and impact of poststroke fatigue on patient outcomes in the first 6 months after stroke: A systematic review and meta-analysis. J Neurosci Nurs. 1, 55(5), 178-185. doi: 10.1097/JNN.0000000000000716.
25. Sibbritt D., Bayes J., Peng W., Maguire J., Adams J., 2022. Associations between fatigue and disability, depression, health-related hardiness, and quality of life in people with stroke. J Stroke Cerebrovasc Dis. 1, 31(7), 106543. doi: 10.1016/j.jstrokecerebrovasdis.2022.10.
26. Lillicrap T.P., Levi CR., Holliday E., Parsons M.W., Bivard A., 2017. Short and long-term efficacy of modafinil for post-stroke fatigue: A randomized, placebo-controlled trial. Neurorehabil Neural Repair. 31(4), 334-341. doi: 10.1177/1545968317702541.
27. Brioschi A., Gramigna S., Werth E., Staub F., Ruffieux C., Bassetti C., Schluep M., Annoni J.M., 2009. Effect of modafinil on subjective fatigue in multiple sclerosis and stroke patients. Eur Neurol. 62(4), 243–249. doi: 10.1159/000232927.
28. Ramos-Lima M.J.M., Brasileiro I.C., Lima TL., Braga-Neto P., 2018. Quality of life after stroke: impact of clinical and sociodemographic factors. Clinics (Sao Paulo). 73, e418. doi: 10.6061/clinics/2017/e418.
29. Hashemian S.M., Farhadi T., 2020. A review on modafinil: the characteristics, function, and use in critical care. J Drug Assess. 1, 9(1), 82-6.
30. Borghol A., Aucoin M., Onor I., Jamero D., Hawawini F., 2018. Modafinil for the Improvement of Patient Outcomes Following Traumatic Brain Injury. Innov Clin Neurosci. 1, 15(3-4), 17-23. PMID: 29707422; PMCID: PMC5906085.
31. Kim D., 2012. Practical use and risk of modafinil, a novel waking drug. Environ Health Toxicol. 27, e2012007. doi: 10.5620/eht.2012.27.e2012007.
32. Cramer S.C., 2015. Drugs to Enhance Motor Recovery After Stroke. Stroke. 46(10), 2998-3005. doi: 10.1161/STROKEAHA.115.007433.
33. Bindawas S.M., Vennu V.S., 2016. Stroke rehabilitation. A call to action in Saudi Arabia. Neurosciences (Riyadh). 21(4), 297-305. doi: 10.17712/nsj.2016.4.20160075.
34. Lokk J., Roghani RS., Delbari A., 2011. Effect of methylphenidate and/or levodopa coupled with physiotherapy on functional and motor recovery after stroke–a randomized, double‐blind, placebo‐controlled trial. Acta Neurol Scand. 123(4), 266-73. doi: 10.1111/j.1600-0404.2006.00728.x.
35. Ebrahimi Y., AL-Baghdady H.F.A., Hameed N.M., Iswanto A.H., Shnain Ali M., Hammoodi H.A., Hashim Kzar H., Aravindhan S., Khodaei SM., Alikord M., Pirhadi M., 2022. Common fatty acids and polyphenols in olive oil and its benefits to heart and human health. Casp J Environ Sci. 1-7. doi: 10.22124/cjes.2022.5976.
36. Lysiuk R., 2024. The Role of Biochemicals and Phytomedicine in Complementary Medicine and Modern Drug Discovery: Bridging Tradition and Innovation. J Biochem Phytomed. 3(2), 1-3. doi: 10.34172/jbp.2024.13.
37. Okhovatfard M., Rezazadeh H., 2023. Effect of Curcuma longa and its derivatives, curcumin and curcuminoids on treatment of oral lichen planus: A systematic review of clinical evidence. Casp J Environ Sci. 1-12. doi: 10.22124/cjes.2023.6824.
38. Nazarbaghi S., Parsaei P., 2025. Traditional remedy of Parkinson's: Medicinal plants effective on Parkinson's in traditional Iranian medicine. Plant Biotechnol Persa. 7(1), 76-82. doi: 10.61186/pbp.7.1.4.
39. Emami B., Shakerian A., Sharafati Chaleshtouri R., Rahimi E., 2024. Antioxidant, antimicrobial, and anticancer effects of the Russian olive, Elaeagnus angustifolia L. fruit extracts. Casp J Environ Sci. 1-9. doi: 10.22124/cjes.2024.8006.
40. Al Meanazel O.T., Alharasees M.I., Al-Tarawneh L.M., Al-Habahbeh S., Abdelhadi NN., Sapaev I., Tilwani S.A., 2024. Hesperidin, a flavone glycoside isolated from citrus fruits, can be used to facilitate Chlorpyrifos pollution side effect. Casp J Environ Sci. 1-14. doi: 10.22124/cjes.2024.8222.
41. Rabiepour A., Babakhani A., Zakipour Rahimabadi E., 2024. Effect of extraction methods on the antioxidant properties of water hyacinth, Eichhornia crassipes. Casp J Environ Sci. 1-19. doi: 10.22124/cjes.2
024.8015