Ontario Neurotrauma Foundation

Clinical Practice Guideline

For the rehabilitation of Adults with Moderate to Severe TBI

Ontario Neurotrauma Foundation INESSS
SECTION 2: Assessment and Rehabilitation of Brain Injury Sequelae > O. Fatigue and Sleep Disorders

O. Fatigue and Sleep Disorders

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Brain injury frequently causes changes in sleep patterns likely through injury to brainstem functions that affect the daily circadian rhythms. Individuals with brain injury frequently complain of fatigue that is likely partially due to decreased nerve function and connectivity in the brain and the extra effort required for cognition. These issues may be combined with other causes of fatigability such as deconditioning and other concomitant medical conditions. Individuals with complaints of fatigue and sleep disturbance require a medical and sleep workup to rule out treatable causes. People with traumatic brain injury (TBI) should be taught strategies to optimize fatigue (e.g. energy conservation, pacing) and good sleep hygiene. In those with persistent fatigue where TBI is believed to be the main cause medications may be considered. 

The rehabilitation team should have a structured and systematic process for assessing sleep disturbances and fatigue in individuals with traumatic brain injury. Clinicians with expertise in non-pharmacological therapeutic approaches for sleep-related disturbance, particularly cognitive behavioral therapy, should be available early on in the rehabilitation process. The rehabilitation environment and schedule should facilitate adequate sleep hygiene.


Indicators exemples

  • Proportion of individuals with TBI formally assessed for fatigue and sleep disorders.

  • Proportion of individuals with TBI and fatigue and/or sleep disorder who received at least one of the following five non-pharmacological interventions:

    1. Cognitive behavioural therapy (CBT);

    2. Light therapy;

    3. Regular exercise;

    4. Energy conservation strategies;

    5. Sleep hygiene

The following are suggestions of tools and resources that can be used to support the implementation of the recommendations in this section. Healthcare professionals must respect the legal and normative regulations of the regulatory bodies, in particular with regards to scopes of practice and restricted/protected activities, as these may differ provincially

Clinical Tools:

Patient and Family Resources:

Wiseman-Hakes et al. (2013) states that sleep disturbances associated with TBI can exacerbate cognitive, communication and mood deficits that are trauma-related. Similarly, Bushnik, Englander, and Wright (2008) found that when fatigue worsened over the course of 2 years, it was accompanied by poorer cognitive and motor outcomes as well as reduced levels of general functioning. Dealing with sleep disturbances is necessary for optimal recovery and fatigue and sleep disorders should be assessed. Common objective assessments for fatigue and sleep disorders included questionnaires, polysomnography, actigraphy, multiple sleep latency tests and maintenance of wakefulness tests (Mollayeva, Colantonio, Mollayeva, & Shapiro, 2013).

In terms of treatment, both pharmacological and non-pharmacological options have been studied:

Non-pharmacological interventions may include pacing, cognitive behavioural therapy (CBT), or light therapy, among others. A pre-post case series found that 8 sessions of CBT improved sleep disturbances by improving total wake time (p<0.001), sleep efficacy (p=0.01), fatigue (p<0.012), and insomnia (p<0.01) but not total sleep time (Ouellet & Morin, 2007). No additional significant gains were made once the treatment had concluded, although gains were maintained at a 3-month follow-up.

A RCT conducted by Sinclair, Ponsford, Taffe, Lockley, and Rajaratnam (2014) examined the effectiveness of blue and yellow light therapy versus a control group. The blue light therapy was shown to significantly decrease fatigue (p<0.001) and daytime sleepiness (p<0.01) but yellow light therapy did not show improvements compared to the control group. The improvements measured during the treatment phase did not persist at follow-up (week 8).

Pharmacological treatments to improve sleep quality have also been suggested. In research in cats, Aton et al. (2009) found that trazodone administration did not affect EEG but may have affected cortical plasticity. While trazodone has been found to be commonly prescribed in humans for insomnia, and shown some benefit, in other study populations, the research supporting trazodone’s effects on insomnia among a brain injury population is minimal (Larson & Zollman, 2010). Shan and Ashworth (2004) compared lorazepam with zopiclone to assess the effects of these medications on sleep and cognition in a randomized, double-blinded, crossover trial. There was no difference in average sleep duration or in subjective measures of sleep. Cognition as assessed by the Mini Mental Status Exam revealed no difference in the zopiclone arm compared with the lorazepam arm.

The indolamine melatonin is a hormone secreted or synthesized by pineal gland in the brain which helps to regulate sleep and wake cycle. Melatonin production has been found to be associated with REM sleep (Shekleton et al., 2010). Melatonin has been shown to be a versatile hormone having antioxidative, antiapoptotic, neuroprotective, and anti-inflammatory properties (Naseem & Parvez, 2014). Further, melatonin production levels were lower in individuals with TBI compared to healthy controls which suggests the disruption of the circadian regulation of melatonin synthesis (Shekleton et al., 2010). (Ponsford & Sinclair, 2014; Ponsford, Ziino, et al., 2012) conducted a large cohort study of community-based patients with TBI, recruited from a TBI rehabilitation program, completed measures of subjective fatigue and sleep disturbances, as well as attentional measures. A subgroup of participants completed polysomnography and assessment of dim light melatonin onset. They found that objective sleep studies show reduced sleep efficiency, increased sleep onset latency, and increased time awake after sleep onset. Depression and pain exacerbate but cannot entirely account for these problems. Individuals with TBI show lower levels of evening melatonin production, associated with less rapid-eye movement sleep (Ponsford & Sinclair, 2014; Ponsford, Ziino, et al., 2012). There are, however, limited studies examining the administration of exogenous melatonin among a brain injury population. (Kemp et al., 2004) conducted a RCT cross-over trial comparing melatonin and amitriptyline for a month for those with TBI (n=7). No significant improvements were found for either group on any of the sleep variables examined: latency, duration, quality or daytime alertness; however, it was found that melatonin had a moderate effect on daytime alertness (Kemp et al., 2004).

Pharmacological treatments to reduce fatigue are also an option if sleep disturbances have been ruled out and brain injury is suspected as the cause. Modafinil has been studied in two RCTs and although both studies found no significant difference between groups in fatigue, as measured by the Fatigue Severity Scale, the treatment groups both showed a significantly greater decrease in Epworth Sleepiness Scale scores when compared to controls, representing a greater improvement in excessive daytime sleepiness (Jha et al., 2008; Kaiser et al., 2010).

Aton, S. J., Seibt, J., Dumoulin, M. C., Coleman, T., Shiraishi, M., & Frank, M. G. (2009). The sedating antidepressant trazodone impairs sleep-dependent cortical plasticity. PLoS One, 4(7), e6078.

Bushnik, T., Englander, J., & Wright, J. (2008). Patterns of fatigue and its correlates over the first 2 years after traumatic brain injury. J Head Trauma Rehabil, 23(1), 25-32.

Evidence-Based Review of Moderate To Severe Acquired Brain Injury (ERABI). (2016). http://www.abiebr.com/.   

Jha, A., Weintraub, A., Allshouse, A., Morey, C., Cusick, C., Kittelson, J., . . . Gerber, D. (2008). A randomized trial of modafinil for the treatment of fatigue and excessive daytime sleepiness in individuals with chronic traumatic brain injury. J Head Trauma Rehabil, 23(1), 52-63.

Kaiser, P. R., Valko, P. O., Werth, E., Thomann, J., Meier, J., Stocker, R., . . . Baumann, C. R. (2010). Modafinil ameliorates excessive daytime sleepiness after traumatic brain injury. Neurology, 75(20), 1780-1785.

Kemp, S., Biswas, R., Neumann, V., & Coughlan, A. (2004). The value of melatonin for sleep disorders occurring post-head injury: a pilot RCT. Brain Inj, 18(9), 911-919.

Larson, E. B., & Zollman, F. S. (2010). The effect of sleep medications on cognitive recovery from traumatic brain injury. J Head Trauma Rehabil, 25(1), 61-67.

Mollayeva, T., Colantonio, A., Mollayeva, S., & Shapiro, C. M. (2013). Screening for sleep dysfunction after traumatic brain injury. Sleep Med, 14(12), 1235-1246.

Naseem, M., & Parvez, S. (2014). Role of melatonin in traumatic brain injury and spinal cord injury. ScientificWorldJournal, 2014, 586270.

Ouellet, M. C., & Morin, C. M. (2007). Efficacy of cognitive-behavioral therapy for insomnia associated with traumatic brain injury: a single-case experimental design. Arch Phys Med Rehabil, 88(12), 1581-1592.

Ponsford, J., & Sinclair, K. (2014). Sleep and fatigue following traumatic brain injury. Psychiatr Clin North Am, 37(1), 77-89.

Ponsford, J., Ziino, C., Parcell, D. L., Shekleton, J. A., Roper, M., Redman, J. R., . . . Rajaratnam, S. M. (2012). Fatigue and sleep disturbance following traumatic brain injury--their nature, causes, and potential treatments. J Head Trauma Rehabil, 27(3), 224-233.

Shan, R. S., & Ashworth, N. L. (2004). Comparison of Lorazepam and Zopiclone for Insomnia in Patients with Stroke and Brain Injury: A Randomized, Crossover, Double-Blinded Trial. American Journal of Physical Medicine & Rehabilitation, 83(6), 421-427.

Shekleton, J. A., Parcell, D. L., Redman, J. R., Phipps-Nelson, J., Ponsford, J. L., & Rajaratnam, S. M. (2010). Sleep disturbance and melatonin levels following traumatic brain injury. Neurology, 74(21), 1732-1738.

Sinclair, K. L., Ponsford, J. L., Taffe, J., Lockley, S. W., & Rajaratnam, S. M. (2014). Randomized controlled trial of light therapy for fatigue following traumatic brain injury. Neurorehabil Neural Repair, 28(4), 303-313.

Wiseman-Hakes, C., Murray, B., Moineddin, R., Rochon, E., Cullen, N., Gargaro, J., & Colantonio, A. (2013). Evaluating the impact of treatment for sleep/wake disorders on recovery of cognition and communication in adults with chronic TBI. Brain Injury, 27(12), 1364-1376.

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P Priority F Fundamental New Level of evidence A B C

O 1.1 P icon C

All individuals who have sustained a traumatic brain injury should be assessed for fatigue and sleep disorders and offered appropriate treatment.

(INESSS-ONF, 2015)


- ERABI Module 15-Fatigue and Sleep Disorders - 15.2 

O 1.2 B

Clinicians should consider the possibility of sleep disorders related to traumatic brain injury as a cause of cognitive and other behavioural changes.

(Adapted from ABIKUS 2007, G13, p. 18)

Medications should only be prescribed by qualified physicians, and guideline users should consult the section on "Principles of medication management" before prescribing.
P Priority F Fundamental New Level of evidence A B C

O 2.1 P icon B

Non-pharmacological interventions should be considered in the treatment of fatigue and sleep disorders for individuals with traumatic brain injury. Interventions may include: cognitive behaviour therapy (CBT) [for insomnia], light therapy, regular exercise, energy conservation strategies and sleep hygiene.

(INESSS-ONF, 2015)


- ERABI Module 15-Fatigue and Sleep Disorders - 15.4

O 2.2 icon B

Consider use of melatonin 2–5 mg for insomnia following traumatic brain injury.

(INESSS-ONF, 2015)

Suggested tool: Health Canada Indications of Use


- Shekleton et al. (2010)
- Kemp et al. (2004)
- Ponsford et al. (2012)
- Colantonio et al. (2010)
- Glassner et al. (2013)

O 2.3 icon C

Consider use of trazodone 25–100 mg for insomnia post traumatic brain injury.

(INESSS-ONF, 2015)

Suggested tool: Health Canada Indications of Use


- Larson and Zollman (2010)

O 2.4 P icon C

Benzodiazepines (lorazepam) and other non-benzodiazepine hypnotic (zopiclone) medications should be considered as last resort for the treatment of sleep disorders in individuals with traumatic brain injury, and it should be prescribed for no longer than 7 days.

(INESSS-ONF, 2015)

Suggested tool: Health Canada Indications of Use


- ERABI Module 15-Fatigue and Sleep Disorders - 15.5
- Li Pi Shan and Ashworth (2004)
- Kemp et al. (2004)
- Aton et al. (2009)


O 2.5 icon C

Consider short-term treatment with methylphenidate to reduce excess daytime sleepiness in individuals with traumatic brain injury.

(INESSS-ONF, 2015)

Suggested tool: Health Canada Indications of Use


- ERABI Module 15-Fatigue and Sleep Disorders - 15.5.2 

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