Purpose of Review
To provide an updated review of empirical evidence in support of interventions for posttraumatic fatigue.
A total of 360 articles were published between January 22, 2014 and September 23, 2016 with nine meeting inclusion criteria. Articles included in this review provided further support for behavioral, pharmacological, and physical activity interventions for fatigue. Behavioral interventions remain popular, but studies directly targeting fatigue have not yet been undertaken. Pharmacological agents, particularly those using dopaminergic agents, showed potential but had mixed results. Interventions incorporating physical activity were promising but require more rigorous investigation.
Despite promising results, there remains a need to replicate and further refine treatments using rigorous research designs and larger samples. Future studies should continue to more clearly define fatigue and use consistent subjective and objective endpoints that better capture this construct. Including imaging techniques would establish the effectiveness and mechanisms of interventions.
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Papers of particular interest, published recently, have been highlighted as: • Of importance, •• Of major importance
• Cantor JB, Gordon W, Gumber S. What is post TBI fatigue? NeuroRehabilitation. 2013;32(4):875–83. Provides an overview of post-traumatic brain injury fatigue including its epidemiology and characteristics; correlates; and its measurement, biology and treatment of PTBIF
Zumstein MA, Moser M, Mottini M, Ott SR, Sadowski-Cron C, Radanov BP, et al. Long-term outcome in patients with mild traumatic brain injury: a prospective observational study. J Trauma. 2011;71(1):120–7.
•• Cantor JB, Ashman T, Bushnik T, Cai X, Farrell-Carnahan L, Gumber S, et al. Systematic review of interventions for fatigue after traumatic brain injury: a NIDRR traumatic brain injury model systems study. J Head Trauma Rehabil. 2014;29(6):490–7. Earlier systematic review of post-traumatic brain injury fatigue. The current review sought to expand upon this previous review
Beaulieu-Bonneau S, Morin CM. Sleepiness and fatigue following traumatic brain injury. Sleep Med. 2012;13(6):598–605.
Bushnik T, Englander J, Wright J. Patterns of fatigue and its correlates over the first 2 years after traumatic brain injury. J Head Trauma Rehabil. 2008;23(1):25–32.
Lequerica AH, Botticello AL, Lengenfelder J, Chiaravalloti N, Bushnik T, Dijkers MP, et al. Factors associated with remission of post-traumatic brain injury fatigue in the years following traumatic brain injury (TBI): a TBI model systems module study. Neuropsychological rehabilitation. 2016;16:1–12.
Dahm J, Ponsford J. Long-term employment outcomes following traumatic brain injury and orthopaedic trauma: a ten-year prospective study. J Rehabil Med. 2015;47(10):932–40.
Cantor JB, Ashman T, Gordon W, Ginsberg A, Engmann C, Egan M, et al. Fatigue after traumatic brain injury and its impact on participation and quality of life. J Head Trauma Rehabil. 2008;23(1):41–51.
Chaudhuri A, Behan PO. Fatigue and basal ganglia. J Neurol Sci. 2000;179(S 1–2):34–42.
Chaudhuri A, Behan PO. Fatigue in neurological disorders. Lancet. 2004 Mar 20;363(9413):978–88.
Leavitt VM, DeLuca J. Central fatigue: issues related to cognition, mood and behavior, and psychiatric diagnoses. PM & R : the journal of injury, function, and rehabilitation. 2010 May;2(5):332–7.
Dobryakova E, Genova HM, DeLuca J, Wylie GR. The dopamine imbalance hypothesis of fatigue in multiple sclerosis and other neurological disorders. Front Neurol. 2015;6:52.
van Zomeran AH, Brouwer WH, Deelman BG. Attentional deficits: the riddles of selectivity, speed, and alertness. In: Brooks D, editor. Closed head injury: psychological, social, and family consequences. New York: Oxford University Press; 1984.
Kohl AD, Wylie GR, Genova HM, Hillary FG, Deluca J. The neural correlates of cognitive fatigue in traumatic brain injury using functional MRI. Brain Inj. 2009;23(5):420–32.
Hattori N, Swan M, Stobbe GA, Uomoto JM, Minoshima S, Djang D, et al. Differential SPECT activation patterns associated with PASAT performance may indicate frontocerebellar functional dissociation in chronic mild traumatic brain injury. Journal of nuclear medicine : official publication, Society of Nuclear Medicine. 2009;50(7):1054–61.
Ashman TA, Cantor JB, Gordon WA, Spielman L, Egan M, Ginsberg A, et al. Objective measurement of fatigue following traumatic brain injury. J Head Trauma Rehabil. 2008;23(1):33–40.
Johnson SK, Lange G, DeLuca J, Korn LR, Natelson B. The effects of fatigue on neuropsychological performance in patients with chronic fatigue syndrome, multiple sclerosis, and depression. Appl Neuropsychol. 1997;4(3):145–53.
Parmenter BA, Denney DR, Lynch SG. The cognitive performance of patients with multiple sclerosis during periods of high and low fatigue. Mult Scler. 2003;9(2):111–8.
Paul RH, Beatty WW, Schneider R, Blanco CR, Hames KA. Cognitive and physical fatigue in multiple sclerosis: relations between self-report and objective performance. Appl Neuropsychol. 1998;5(3):143–8.
Pardini M, Krueger F, Raymont V, Grafman J. Ventromedial prefrontal cortex modulates fatigue after penetrating traumatic brain injury. Neurology. 2010;74(9):749–54.
Schonberger M, Reutens D, Beare R, O'Sullivan R, Rajaratnam SM, Ponsford J. Brain lesion correlates of fatigue in individuals with traumatic brain injury. Neuropsychological rehabilitation. 2016;09:1–15.
Cools R, D'Esposito M. Inverted-U-shaped dopamine actions on human working memory and cognitive control. Biol Psychiatry. 2011;69(12):e113–25.
Fernandez-Rodriguez E, Bernabeu I, Castro AI, Kelestimur F, Casanueva FF. Hypopituitarism following traumatic brain injury: determining factors for diagnosis. Front Endocrinol. 2011;2:25.
Bavisetty S, Bavisetty S, McArthur DL, Dusick JR, Wang C, Cohan P, et al. Chronic hypopituitarism after traumatic brain injury: risk assessment and relationship to outcome. Neurosurgery. 2008;62(5):1080–93. discussion 93-4
Kelly DF, McArthur DL, Levin H, Swimmer S, Dusick JR, Cohan P, et al. Neurobehavioral and quality of life changes associated with growth hormone insufficiency after complicated mild, moderate, or severe traumatic brain injury. J Neurotrauma. 2006;23(6):928–42.
Bushnik T, Englander J, Katznelson L. Fatigue after TBI: association with neuroendocrine abnormalities. Brain Inj. 2007;21(6):559–66.
Englander J, Bushnik T, Oggins J, Katznelson L. Fatigue after traumatic brain injury: association with neuroendocrine, sleep, depression and other factors. Brain Inj. 2010;24(12):1379–88.
Schnieders J, Willemsen D, de Boer H. Factors contributing to chronic fatigue after traumatic brain injury. J Head Trauma Rehabil. 2012;27(6):404–12.
Klose M, Stochholm K, Janukonyte J, Christensen LL, Cohen AS, Wagner A, et al. Patient reported outcome in posttraumatic pituitary deficiency: results from The Danish National Study on posttraumatic hypopituitarism. Eur J Endocrinol. 2015;172(6):753–62.
Barton DJ, Kumar RG, McCullough EH, Galang G, Arenth PM, Berga SL, et al. Persistent hypogonadotropic hypogonadism in men after severe traumatic brain injury: temporal hormone profiles and outcome prediction. J Head Trauma Rehabil. 2016;31(4):277–87.
Nijhof SL, Rutten JM, Uiterwaal CS, Bleijenberg G, Kimpen JL, Putte EM. The role of hypocortisolism in chronic fatigue syndrome. Psychoneuroendocrinology. 2014;42:199–206.
•• Berginstrom N, Nordstrom P, Schuit R, Nordstrom A. The effects of (−)-OSU6162 on chronic fatigue in patients with traumatic brain injury: a randomized controlled trial. J Head Trauma Rehabil. 2016;26 One of the articles included in the current review. Described an intervention study using a monoaminergic stabiliser (–)-OSU6162 to reduce mental fatigue with negative findings, which contradicts findings from a previous study that examined the same substance.
•• Johansson B, Wentzel AP, Andrell P, Odenstedt J, Mannheimer C, Ronnback L. Evaluation of dosage, safety and effects of methylphenidate on post-traumatic brain injury symptoms with a focus on mental fatigue and pain. Brain Inj. 2014;28(3):304–10. Reviewed in current article. Examined the short-term (about 4 weeks) effects of methylphenidate on mental fatigue in individuals with TBI
•• Johansson B, Wentzel AP, Andrell P, Mannheimer C, Ronnback L. Methylphenidate reduces mental fatigue and improves processing speed in persons suffered a traumatic brain injury. Brain Inj. 2015;29(6):758–65. Reviewed in current article. Examined the short-term (about 4 weeks) effects of methylphenidate on mental fatigue in individuals with TBI
•• Johansson B, Wentzel AP, Andrell P, Ronnback L, Mannheimer C. Long-term treatment with methylphenidate for fatigue after traumatic brain injury. Acta neurologica Scandinavica. 2016 Mar 15. Reviewed in current article. Examined the long-term effects (over the course of 6 months) of methylphenidate on mental fatigue in individuals with TBI.
•• Mossberg KA, Durham WJ, Zgaljardic DJ, Gilkison C, Danesi CP, Sheffield-Moore M, et al. Functional changes after recombinant human growth hormone replacement in patients with traumatic brain injury and abnormal growth hormone secretion. Journal of neurotrauma. 2016 Sep 14. Reviewed in current article. Evaluated the effects of recombinant human growth hormone replacement therapy on physical and neuropsychological functioning, as well as fatigue in individuals who had sustained moderate to severe TBIs.
•• Lu W, Krellman JW, Dijkers MP. Can cognitive behavioral therapy for insomnia also treat fatigue, pain, and mood symptoms in individuals with traumatic brain injury?—a multiple case report. NeuroRehabilitation. 2016;38(1):59–69. Reviewed in current article. Explored whether cognitive behavioral therapy for insomnia could be an effective treatment for additional symptoms following traumatic brain injury including fatigue
•• Raina KD, Morse JQ, Chisholm D, Leibold ML, Shen J, Whyte E. Feasibility of a cognitive behavioral intervention to manage fatigue in individuals with traumatic brain injury: a pilot study. J Head Trauma Rehabil. 2016;31(5):E41–9. Reviewed in current article. Manualized behavioral intervention to teach energy conservation strategies to participants with mild, moderate, and severe TBI
•• Chin LM, Chan L, Woolstenhulme JG, Christensen EJ, Shenouda CN, Keyser RE. Improved cardiorespiratory fitness with aerobic exercise training in individuals with traumatic brain injury. J Head Trauma Rehabil. 2015;30(6):382–90. Reviewed in current article. Physical activity intervention to reduce fatigue
Edinger JD, Carvey CE. Overcoming Insomnia: a cognitive-behavioral therapy approach. 2nd ed. New York: Oxford University Press; 2008.
• Johansson B, Carlsson A, Carlsson ML, Karlsson M, Nilsson MK, Nordquist-Brandt E, et al. Placebo-controlled cross-over study of the monoaminergic stabiliser (—)-OSU6162 in mental fatigue following stroke or traumatic brain injury. Acta neuropsychiatrica. 2012;24(5):266–74. Described an intervention study using a monoaminergic stabiliser (–)-OSU6162 to reduce mental fatigue with positive findings, which contradicts findings from a study in the current review that examined the same substance
• Ouellet MC, Morin CM. Cognitive behavioral therapy for insomnia associated with traumatic brain injury: a single-case study. Arch Phys Med Rehabil. 2004;85(8):1298–302. Previously reviewed article describing an intervention using cognitive behavioral therapy for insomnia and its relationship to fatigue in a case study
• Ouellet MC, Morin CM. Efficacy of cognitive-behavioral therapy for insomnia associated with traumatic brain injury: a single-case experimental design. Arch Phys Med Rehabil. 2007;88(12):1581–92. Previously reviewed article describing an intervention using cognitive behavioral therapy for insomnia and its relationship to fatigue
Cantor JB, Bushnik T, Cicerone K, Dijkers MP, Gordon W, Hammond FM, et al. Insomnia, fatigue, and sleepiness in the first 2 years after traumatic brain injury: an NIDRR TBI model system module study. J Head Trauma Rehabil. 2012;27(6):E1–14.
Lundberg B, Bennett J, Smith S. Outcomes of adaptive sports and recreation participation among veterans returning from combat with aquired disability. The Recreation J. 2011;45(2):105–20.
Gemmell C, Leathem JM. A study investigating the effects of Tai Chi Chuan: individuals with traumatic brain injury compared to controls. Brain Inj. 2006;20(2):151–6.
Driver S, Ede A. Impact of physical activity on mood after TBI. Brain Inj. 2009;23(3):203–12.
Tulsky DS, Kisala PA, Victorson D, Carlozzi N, Bushnik T, Sherer M, et al. TBI-QOL: development and calibration of item banks to measure patient reported outcomes following traumatic brain injury. J Head Trauma Rehabil. 2016;31(1):40–51.
Shuman-Paretsky M, Zemon V, Foley FW, Holtzer R. Development and validation of the State-Trait Inventory of Cognitive Fatigue in community-dwelling older adults. Archives of physical medicine and rehabilitation. 2016 Aug 26.
• Ulrichsen KM, Kaufmann T, Dorum ES, Kolskar KK, Richard G, Alnaes D, et al. Clinical utility of mindfulness training in the treatment of fatigue after stroke, traumatic brain injury and multiple sclerosis: a systematic literature review and meta-analysis. Front Psychol. 2016;7:912. Reviews mindfulness interventions for fatigue
Moore A, Malinowski P. Meditation, mindfulness and cognitive flexibility. Conscious Cogn. 2009;18(1):176–86.
Johansson B, Bjuhr H, Ronnback L. Mindfulness-based stress reduction (MBSR) improves long-term mental fatigue after stroke or traumatic brain injury. Brain Inj. 2012;26(13–14):1621–8.
Kilpatrick LA, Suyenobu BY, Smith SR, Bueller JA, Goodman T, Creswell JD, et al. Impact of mindfulness-based stress reduction training on intrinsic brain connectivity. NeuroImage. 2011;56(1):290–8.
Bedard M, Felteau M, Marshall S, Dubois S, Gibbons C, Klein R, et al. Mindfulness-based cognitive therapy: benefits in reducing depression following a traumatic brain injury. Advances in mind-body medicine. 2012;26(1):14–20.
McMillan T, Robertson IH, Brock D, Chorlton L. Brief mindfulness training for attentional problems after traumatic brain injury: a randomized control treatment trial. Neuropsychological rehabilitation. 2002;12(2):117–25.
• Zeng EQ, Zeng BQ, Tian JL, Du B, Tian XB, Chen H. Perceived social support and its impact on mental fatigue in patients with mild traumatic brain injury. Balkan medical journal. 2016;33(2):152–7. Article describes the relationship between social support and fatigue following traumatic brain injury
• Sinclair KL, Ponsford JL, Taffe J, Lockley SW, Rajaratnam SM. Randomized controlled trial of light therapy for fatigue following traumatic brain injury. Neurorehabil Neural Repair. 2014;28(4):303–13. Previously reviewed. Describes an intervention for fatigue using light therapy
Naeser MA, Hamblin MR. Traumatic brain injury: a major medical problem that could be treated using transcranial, red/near-infrared LED photobiomodulation. Photomed Laser Surg. 2015;33(9):443–6.
Naeser MA, Hamblin MR. Potential for transcranial laser or LED therapy to treat stroke, traumatic brain injury, and neurodegenerative disease. Photomed Laser Surg. 2011;29(7):443–6.
Naeser MA, Saltmarche A, Krengel MH, Hamblin MR, Knight JA. Improved cognitive function after transcranial, light-emitting diode treatments in chronic, traumatic brain injury: two case reports. Photomed Laser Surg. 2011;29(5):351–8.
Naeser MA, Zafonte R, Krengel MH, Martin PI, Frazier J, Hamblin MR, et al. Significant improvements in cognitive performance post-transcranial, red/near-infrared light-emitting diode treatments in chronic, mild traumatic brain injury: open-protocol study. J Neurotrauma. 2014;31(11):1008–17.
Ledinek AH, Sajko MC, Rot U. Evaluating the effects of amantadin, modafinil and acetyl-L-carnitine on fatigue in multiple sclerosis—result of a pilot randomized, blind study. Clin Neurol Neurosurg. 2013;115(Suppl 1):S86–9.
Conflict of Interest
M.S.-P., S.G., and K.D.-O. declare that they have no conflict of interest.
Human and Animal Rights and Informed Consent
This article does not contain any studies with human or animal subjects performed by any of the authors.
This article is part of the Topical Collection on Traumatic Brain Injury Rehabilitation
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Shuman-Paretsky, M., Gumber, S. & Dams-O’Connor, K. Interventions for Posttraumatic Brain Injury Fatigue: An Updated Review. Curr Phys Med Rehabil Rep 5, 12–21 (2017). https://doi.org/10.1007/s40141-017-0147-8
- Posttraumatic brain injury fatigue: PTBIF
- PTBIF treatment
- Traumatic brain injury