A Systematic Review of Psychological Interventions for Sleep and Fatigue after Mild Traumatic Brain Injury

Abstract

This review evaluated the evidence for psychological interventions to improve sleep and reduce fatigue after mild traumatic brain injury (mTBI). Eight electronic databases were searched up until August 2016 for studies that: 1) included adults; 2) tested intervention effectiveness on sleep quality and fatigue post-acutely; and 3) applied a broadly-defined psychological intervention (e.g., cognitive behavioral therapy [CBT], counseling, or education). Only randomized controlled trials were eligible for inclusion. Of the 698 studies identified, four met the eligibility criteria and underwent data extraction. These studies were assessed for risk of bias by two independent reviewers using the Scottish Intercollegiate Guidelines Network Methodology Checklist 2 for randomized controlled trials. One study applied CBT and three studies used enhanced education to improve outcomes. Limited evidence and methodological bias prevents strong conclusions about the effectiveness of psychological interventions for sleep and fatigue after mTBI. All but one study targeted general post-concussion symptoms rather than sleep or fatigue specifically. This runs the risk that the potential benefits of a targeted approach are underestimated in this literature, and future sleep- and fatigue-focused interventions are recommended. It is tentatively concluded that compared with standard care or the provision of generic advice, small improvements in sleep and fatigue are observed through psychological intervention post-mTBI.

Introduction

Traumatic brain injury (TBI) is a complex injury that is associated with a broad constellation of symptoms.¹ Of all injury types, TBI is the leading cause of disability worldwide.² TBI occurs as the result of a forceful blow or jolt to the head or body and is associated with diminished or altered state of consciousness.³ The severity of TBI can vary from mild to severe, with up to 80–95% of TBIs classified as mild.^4,5

Mild TBI (mTBI) in particular poses a diagnostic challenge because there is no universally applied classification. The World Health Organization Collaborating Centre Task Force on Mild Traumatic Brain Injury attempted to synthesize the numerous case definitions to provide a common operational classification that required one or more of the following criteria to be met for a clinical diagnosis to be made: i) disorientation or confusion, loss of consciousness for 30 min or less, post-traumatic amnesia (PTA) for less than 24 h, and/or other transient neurological abnormalities such as seizures, focal signs, and intracranial lesions not requiring surgery; and ii) Glasgow Coma Scale (GCS) score of 13–15 thirty minutes following the injury or when presenting for healthcare.⁶ These symptoms cannot be the result of using alcohol, illicit drugs, or other medications, other injuries or the treatment of other injuries, or other psychological, medical, or contextual factors.

Following an insult to the head, a person may experience nausea, fatigue, slowed cognition, headaches, and poor concentration. For mild injuries, these symptoms typically resolve within 7 to 10 days.⁵ A small subgroup of individuals, however, continue to experience ongoing symptoms that can last months or years.^7,8 These residual symptoms impair cognitive (e.g., poor concentration, memory difficulties), physical (e.g., headaches, sleep disturbance, double vision) and affective (e.g., irritability, anxiety, depression) functioning.

Residual symptoms following mTBI are commonly referred to as persistent post-concussion symptoms (PPCS). These symptoms pose a significant public health concern due to the negative impact they have on an individual's life, including preventing return to work or study and reducing social participation.^9,10 Such impairment leads to a reduced quality of life for the individual and creates significant costs to society due to loss of productivity and greater burden on the healthcare system.¹¹

Despite the variable presentation of PPCS, sleep disturbance is one of the most commonly reported symptoms. A meta-analysis conducted by Mathias and Alvaro¹² investigated sleep complaints in a mixed-severity TBI sample. They showed that 50% the sample reported disturbed sleep, while up to 30% had a diagnosable sleep disorder. In mTBI more specifically, 40 to 65% of individuals had some type of sleep disorder.¹³ Further, Chaput and colleagues¹⁴ observed a significant increase in the prevalence of sleep disturbance in patients from 11 days to 6 weeks post-injury.

Sleep disturbance may present acutely after the injury or later during recovery. The mechanism through which mTBI affects sleep is not yet fully understood.¹⁵ Several explanations have been proposed that take into account trauma-induced physical and biochemical changes post-mTBI, the influence of co-morbidities such as anxiety and depression, and pre-morbid sleep disturbance.¹⁶ It is well established that disturbed sleep post-mTBI has the potential to compromise an individual's recovery by causing or exacerbating co-morbidities (e.g., anxiety, depression, fatigue, pain), impeding return to pre-injury activity levels, and reducing quality of life.^{17, 18}

The exact nature of the sleep and fatigue complaint experienced after mTBI has traditionally been poorly characterized, but this is changing. For example, in a study by Orff and colleagues,¹⁹ a combination of polysomnographic recordings and self-reported ratings of sleep quality showed that individuals who had sustained mTBI had lower sleep efficiency, greater nocturnal wake time, and more night-time awakenings lasting longer than 3 min. Consistent with this research, Perlis and colleagues²⁰ found that individuals with chronic PCS had greater difficulty initiating and maintaining sleep and increased sleepiness during the day at 2 years post-injury. It also has been suggested that the change in sleep after mild TBI should be characterized according to multiple dimensions, including quality, quantity, or duration of sleep and presence of daytime impairment.²¹ On balance, the close study of the nature of sleep disturbances after mild TBI identifies clinically significant insomnia as one of the most frequently experienced diagnoses,¹⁹ which is important for informing management and treatment.

Further, although it is recognized that sleep and fatigue complaints may co-occur, overlap, or interact²² and that clearer distinctions between problems with sleep versus fatigue are needed, such distinctions are still relatively uncommon in this literature. Traumatic brain injury–related fatigue is differentiated by some authors from sleep-related complaints on the basis that it may be experienced as a primarily cognitive problem whereby additional effort is required,²³ and by others as having both cognitive and physical aspects, such as feelings of “weakness.”^22,24 The study of post-traumatic brain injury fatigue suggests that it too is significant in contributing to patients' quality of life.²³

Despite the debilitating nature of sleep and fatigue problems following mTBI, research into the management and treatment of these problems appears limited.¹⁹ The most common sleep treatment has been prescription and over-the-counter medications.^{19, 22} However, some medications can cause daytime drowsiness, dizziness, and cognitive impairments, which may exacerbate existing symptoms in individuals with PCS.²⁵ Further, the nature of the sleep problem in people with mild TBI appears particularly complex, and this could suggest the need for non-pharmacological approaches, which are effective for improving sleep in the context of other injuries.²¹ Sleep problems can be compounded in people with mild TBI because of social, economic, and emotional pressures that are different from the pressures experienced by individuals with moderate or severe brain injuries¹³ (such as early pressures associated with returning to work, play, or study). It also has been speculated that poor post-injury sleep could interfere with and prolong recovery, making addressing it a rehabilitation priority.²⁶ For these reasons, sleep disturbance and clinical sleep disorders within the mTBI population may benefit from specialist psychological intervention. Interventions for traumatic brain injury-related fatigue also have not been extensively studied.²² Although pharmacological options may be considered (such as stimulant prescription), some authors recommend non-pharmacological interventions, such as education and changes to diet and lifestyle, as the first line of treatment for this complaint.²²

To the authors' knowledge, there have not been any previous systematic reviews examining psychological interventions designed to prevent, treat, or manage sleep- and fatigue-related symptoms following mTBI. Therefore, the aim of this review was to evaluate the evidence for psychological interventions to improve sleep- and fatigue-related symptoms after mTBI. We sought to perform an extensive formal search of the literature and evaluate its quality; provide an integrated review of the extracted data, including a pooled analysis (if possible); and, make recommendations for future research in this area.

Methods

Protocol and registration

The review followed the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRIMSA) guidelines.²⁷ The review protocol was registered by KS on the PROSPERO International prospective register of systematic reviews in August 2015 (Registration no. 42015025234).

Search strategy and eligibility criteria

The search strategy was developed by CH in consultation with the other authors and the searches were run on August 23, 2016, in the following databases: CINAHL (on EBSCOhost 1982–2016); PsycINFO (on EBSCOhost 1887–2016); PubMed (1946–2016), SPORTDiscus (on EBSCOhost 1975–2016); Embase (Embase.com 1966–2016); Cochrane Central Register of Controlled Trials (The Cochrane Library 2016, Issue 8); and AMED—The Allied and Complementary Medicine Database (on EBSCOhost 1985–2016). A search for doctoral dissertations also was also in ProQuest Dissertation and Theses Global database. The searches used a combination of subject headings and keywords. The precise language and syntax used to search each database is provided in the Appendix. The keywords of the search strategy and the study inclusion and exclusion criteria are provided in Tables 1 and 2, respectively.

Table 1.

Search Terms

	Search terms
Post-concussion symptoms	(MTBI OR TBI OR “brain injury” OR “brain injuries” OR “head injury” OR “head injuries” OR “brain contusion” OR “brain damage” OR postconcussion OR postconcussive OR postconcussion OR post-concussive OR concussion OR concussive)
Sleep- and fatigue-specific symptoms	(insomnia OR hypersomnia OR hyposomnia OR dyssomnia OR parasomnia OR fatigue OR sleepiness OR somnolence OR sleep OR sleep-wake OR sleep/wake OR drowsiness OR nightmares OR sleepwalking OR somnambulism OR “periodic limb movement” OR “Nocturnal Myoclonus Syndrome” OR narcolepsy OR “phase shift disorder” OR “restless legs” OR circadian OR apnoea OR apnea)
Treatment	(management OR counselling OR counseling OR intervention OR therapy OR CBT OR CBTi OR treatment OR psychotherapy OR education OR instruction OR mindfulness OR rehabilitation OR “bio feedback” OR biofeedback OR “neuro feedback” OR neurofeedback OR prevention OR relaxation OR remediation OR psychology OR psychoeducation OR psychosocial OR biopsychosocial OR bibliotherapy OR “rational emotive” OR self-instruction OR self-management OR self-attribution OR “self attribution” OR “non-surgical interventions” OR ACT OR “stimulus control” OR “sleep restriction” OR “bedtime restriction”)
Study design	(rct OR “controlled trial” OR “control trial” OR “controled trial” OR “randomised trial” OR “randomized trial”)

Table 2.

Inclusion and Exclusion Criteria

	Inclusion criteria	Exclusion criteria
Publication type	Original research published in peer-reviewed journals	Narrative reviews, letters, editorials, commentaries, unpublished manuscripts, dissertations, government reports, books and book chapters, conference proceedings, meeting abstracts, lectures and addresses, and consensus statements (including clinical practice guidelines or recommendations.
Study design	Randomized controlled trials	Cross-sectional studies; case reports and series; qualitative studies, reviews, and meta-analyses; case–control studies and cohort studies.
Case definition	Studies must clearly state a case definition for mild TBI that falls within the definition provided by the CDC.^* OR Studies must clearly state a case definition for moderate or severe TBI.	Neck fracture or open and penetrating injury, non-traumatic brain injury; primary diagnosis for a condition other than mild TBI (e.g., PTSD or chronic pain).
Study outcome	Outcome: patient-reported post-concussive sleep symptom(s) or disorder(s). Assessed using a standardized “symptom based questionnaire” measure or relevant caseness criterion for a diagnosis of the post-concussional sleep disorder are met. May include a standardized measure of or a single standardized item to assess sleep-related symptom(s). May include objective sleep outcome measures derived from actigraphy, polysomnography, or DLMO (for circadian). May include other outcomes but results must be stratified by outcome.	Only carer, close-other, or clinician symptom ratings (or observations) were used. Carer or service impacts due to post-concussion symptoms. Studies of outcomes on a pre-existing sleep complaint/diagnosis. Studies of other outcomes (e.g., quality of life, psychosocial adjustment, return to work/sport/study) or objective assessment of post-concussion symptoms (e.g., neurocognitive test results). Studies with other outcomes (e.g., neuroimaging, feasibility, cost-effectiveness).
Intervention type	The study employed a psychological approach to the treatment, management, or prevention of post-concussion sleep-related symptoms and/or disorders (may have to define eligible approaches). A multimodal intervention was considered only if results were stratified for the psychological component. Studies that did not alter or control pre-existing use of medications for sleep would be included (e.g., if it was treatment as usual).	Pharmacological intervention, surgical, undifferentiated multimodal interventions, physical activity, exercise, physiotherapy-base (including rest); device, dietary, or hyperbaric oxygen therapies; “outdoors experiences.” The intervention does not target sleep-related symptom(s). The intervention was applied more than 2 years post-injury^** or the period in which it was applied is unclear, or the timing is not stratified.
Study population	Studies of adults (ages between 15 and 70 inclusive), may consist of a mixed group of TBI severity only if the results are stratified by severity and the subjects with a mild injury can be clearly identified); injury from any cause.	Pediatric, adolescent (< 15 years), or older adult (age >70 years) participants; animal studies.
Publication period	Published up to July 2016 (including in press)	Nil
Publication language	Language any	If an English translation is not available after contacting the authors or using available translation methods.

For presentation purposes, this table contains minor modifications from the original form.

The CDC injury criteria stipulate the following⁶: “MTBI [mild traumatic brain injury] is an acute brain injury resulting from mechanical energy to the head from external physical forces. Operational criteria for clinical identification include: (i) 1 or more of the following: confusion or disorientation, loss of consciousness for 30 minutes or less, post-traumatic amnesia for less than 24 hours, and/or other transient neurological abnormalities such as focal signs, seizure, and intracranial lesion not requiring surgery; (ii) Glasgow Coma Scale score of 13–15 after 30 minutes post-injury or later upon presentation for healthcare. These manifestations of MTBI must not be due to drugs, alcohol, medications, caused by other injuries or treatment for other injuries (e.g. systemic injuries, facial injuries or intubation), caused by other problems (e.g. psychological trauma, language barrier or coexisting medical conditions) or caused by penetrating craniocerebral injury.”

A maximum 2-year period was specified between the index injury and the intervention. This criterion was initially proposed as 1 year. This criterion was extended by 1 year to enable an additional study to be reviewed. This study applied an intervention to people who screened positive for injury during military service in the prior 24 months.³⁴ Further extension would not have captured other studies.

TBI, traumatic brain injury; CDC, Centers for Disease Control and Prevention; PTSD, post-traumatic stress disorder; DLMO, dim light melatonin onset .

Screening and selection

In total, 698 articles were identified in the search. After duplicates were removed, 547 articles remained. The titles were then independently screened by HB and SK. Articles identified as relevant by either of the reviewers were retained for abstract screening. HB and SK then independently screened the eligible abstracts. Any differences in interpretations were discussed between HB and SK and were mutually agreed upon. Figure 1 outlines the study selection process.

FIG. 1.

Flow diagram of literature selection.

Data extraction

Data were extracted for 15 articles using a data extraction sheet that had been previously piloted and used to extract data for another review. Data extraction was carried out independently by SK and checked by HB. Differences in interpretation between these authors were discussed and resolved. Of the 15 articles, six articles were then selected by SK and HB for further consideration and reviewed by KS, SS, and AT. A further two studies were excluded at this stage as it was agreed by all reviewers that they did not meet the intervention inclusion criterion.^28,29 If eligible articles did not include effect sizes (only one reported Cohen's d), this was calculated where possible and reported in Table 2. The data were not provided in a form that allowed for meta-analysis or similar methods of comparison.

Risk of bias

An adapted version of the Scottish Intercollegiate Guidelines Network Methodology Checklist 2 for randomized controlled trials³⁰ was used to assess risk of bias for each of the eligible studies (see Table 3 for details of the items and rating scale). The standard checklist was modified to include a small number of additional items for the assessment of critical variables (e.g., the quality of the mild TBI definition). The quality assessment was independently performed by HB and SK on the four studies. The consistency of the quality ratings was high (e.g., the ratings of both reviewers were identical for approximately 70% of the internal validity items) and where differences occurred, these were mainly minor (i.e., only three internal validity ratings spanned non-adjacent categories; Table 3). This assessment revealed that all of the eligible studies had a risk of bias. Specifically, all of the studies were found to have a potential performance and/or detection bias. A potential performance bias was identified if the participants knew their group allocation, and a potential detection bias was identified if the assessors knew the group allocation for participants. Assessors were blind to group assignment at follow-up in the studies by Mittenberg and colleagues³² and in Vuletic and colleagues.³⁴

Table 3.

Completed Study Quality Evaluation Checklist

Criteria
1. Study identification	Matuseviciene and colleagues (2013)	Mittenberg and colleagues (1996)	Ponsford and colleagues (2002)	Vuletic and colleagues (2016)
Internal validity
2.1. This study addresses an appropriate and clearly focused question.	Well covered	Well covered Adequately addressed^a	Well covered	Well covered
2.2. The definition of mTBI is clear.	Well covered Adequately addressed^a	Adequately addressed	Well covered Adequately addressed^a	Well covered Adequately addressed^a
2.3. The assignment of subjects to treatment groups is randomized.	Adequately addressed	Adequately addressed	Poorly addressed	Well covered
2.4. An adequate concealment method is used.	Not addressed	Not addressed	Not addressed	Not addressed
2.5. Subjects and investigators are kept “blind” to the treatment allocation.	Not addressed	Poorly addressed	Not addressed	Well covered
2.6. The treatment and control groups are similar at the start of the trial.	Adequately addressed	Well covered Adequately addressed^a	Adequately addressed	Well covered
2.7. The only difference between groups is the treatment under investigation.	Well covered Adequately addressed^a	Poorly addressed Not reported^a	Poorly addressed	Well covered
2.8. All relevant outcomes are measured in a reliable way.	Well covered	Adequately addressed Poorly addressed^b	Well covered	Well covered
2.9. All relevant outcomes are measured in a valid way.	Well covered	Adequately addressed Not reported^c	Well covered Adequately addressed^a	Well covered
2.10. What percentage of the individuals or clusters recruited into the study dropped out before the study was complete?	17%	No details provided	38%	22% at 6 months Additional 13% at 12 months
2.11. All the subjects were analyzed in the groups.	Well covered	Well covered Not reported^c	Not addressed	Well covered
2.12. Where the study is carried out at more than one site, results are comparable for all sites.	Not addressed	n/a	Not addressed	Not addressed
Overall assessment of the study.
3.1. How well was the study done to minimize bias?	++	+	+	++
3.2. If coded + or −, what is the likely direction in which bias might affect the study results?		Overestimate	Overestimate
3.3. Taking into account clinical considerations, your evaluation of the methodology used, and the statistical power of the study, are you certain that the overall effect is due to the study intervention?	Yes	Yes	Yes	Yes
3.4. Are the results of this study directly applicable to the patient group targeted?	Yes	Yes	Yes	Yes
3.5. Is the analysis appropriate (e.g., does it align with the research question)?	Yes	Yes	Yes	Yes
3.6. Main strengths (All studies were RCTs, and therefore this was a strength for all research presented.)	Multi-site, community sample recruited from hospital setting.Valid and reliable outcome measures.Standard treatment—ecological validity.Early intervention/follow-up.	Standardized treatment—ecological validity (CBT).Early intervention/follow-up mTBI patients only.	Multi-site, community sample recruited from hospital setting.Valid and reliable outcome measures.Standard treatment—ecological validity.Early intervention/follow up.mTBI patients only—strict inclusion/exclusion criteria	Valid and reliable outcome measures—specific focus on sleep.Standard treatment—ecological validity.mTBI patients only.
3.7. Main weaknesses	Didn't separate results based on site of recruitment/intervention.	Does not state PCS outcome measure used.Does not provide much information on the delivering of treatment.Does not report power.Study conducted prior to Carroll and colleagues (2004) mTBI criteria (does not refer to LOC and disorientation, but does report an injury history, GCS, and PTA, consistent with those criteria).	Limited information on randomization of sample and intervention procedure.No information on why participants dropped out from week 1 to 3-month follow-up (? Recovery).	Time frame of intervention—2 years following mTBI.Did not separate results based on site of recruitment/intervention.Military sample - ? generalizable to community sample given presence of PTSD and mechanism of injury (i.e., blast injuries).
Additional comments
4.1. What percentage of selected individuals agreed to participate (i.e., response rate)?	n = 76	Not reported.	Not reported.	Not reported.
4.2. Is non-randomized treatment allocation adequate?	Yes	n/a	n/a	n/a
4.3. Comment on the length and completeness of follow-up.	3 month follow-up; no details provided on drop-out rates.	6-month follow-up; unsure about dropout rates.	3-month follow-up.	6 months and 12 months post-intervention.
4.4. Can we generalize the results? (external validity)?	Yes	Yes	Yes	Military sample—may not generalize to community/hospital based demographic.

Two independent reviewers (SK and HB) completed the study quality evaluation form for each study. This form was based on the Scottish Intercollegiate Guidelines Network [SIGN] Methodology Checklist 2 for randomized controlled trials. The study criterion was reported as well covered, adequately addressed, poorly addressed, not addressed, not reported, or not applicable (n/a). Where there was general consensus ratings between the two reviewers, the study criterion are stated.

Small discrepancy (i.e., well covered vs. adequately addressed; poorly addressed vs. not reported).

Medium discrepancy (i.e., adequately addressed vs. poorly addressed).

Large discrepancy (i.e., adequately addressed vs. poorly addressed; well covered vs. not reported).

Overall assessment was assessed with the following symbols: ++ = all or most of the criteria has been fulfilled. Where they have not been fulfilled the conclusions of the study or review are through very unlikely to alter; + = some of the criteria has been fulfilled. Those criteria that have not been fulfilled or not adequately described are through unlikely to alter the conclusions; - = few or no criteria fulfilled. The conclusions of the study are thought likely or very likely to alter.

mTBI, mild traumatic brain injury; RCT, randomized controlled trial; CBT, cognitive behavioral therapy; PCS, post-concussion symptoms; LOC, loss of consciousness; GCS, Glasgow Coma Scale; PTA, post-traumatic amnesia; PTSD, post-traumatic stress disorder.

Results

Four studies were included in the current review.^31

–34 Of those studies, Vuletic and colleagues³⁴ was the only study that specifically targeted sleep-related symptoms. The remaining studies used interventions for post-concussion symptoms (e.g., headaches, irritability, and dizziness), which include sleep-related problems (e.g., fatigue). Given that the objective of this review was to evaluate the evidence for psychological interventions to improve sleep and fatigue after a mild traumatic brain injury, we only extracted findings where sleep and/or fatigue was specifically assessed as an outcome measure. An overview of each of the four studies is provided in Table 4, highlighting the sample size, methodology, and main findings.

Table 4.

Studies Using Psychological Interventions to Improve Sleep after mTBI

Author(s)	Relevant research objective(s) and study design	Participants	Intervention details	PCS sleep-related symptom evaluation^*	Sleep-related results^*
Matuseviciene and colleagues (2013)	Objective:Assess effects of written information and treatment on treating mTBI symptoms.Study design: Two-group RCT1. Early intervention (education)2. Treatment as usual	Individuals presented to emergency departments with mTBI N = 173; only those high-risk patients who reported three or more symptoms were randomly allocated to intervention or treatment-as-usual condition.Intervention: n = 48 (mean age = 41.1; 31% male).Treatment as usual: n = 49 (mean age = 37.5; 47% male).Low-risk participants who were not randomized: n = 76 (mean age = 39.6; 53% male).	Early intervention:Delivered by physician in rehabilitation medicine (14–21 days post-injury). Participants were first screened for anxiety and depression, followed by partaking in a detailed interview. Interview included current symptoms and treatments. Next, participants received information about mTBI (e.g., current symptoms, expected favorable outcome).Treatment as usual:Provided with usual written information at discharge.	Rivermead Postconcussion Symptom Questionnaire. Included the following sleep-related symptoms:1. Fatigue.2. Sleep disturbances.	Fatigue and sleep disturbances decreased from baseline to 3 months follow-up in both groups; no significant differences in self-reported fatigue or self-reported sleep disturbances between the early intervention condition and treatment-as-usual condition at 3 months.
Mittenberg and colleagues (1996)	Objective:Assess effectiveness of CBT for prevention of post-concussion symptoms.Study design:Two-group RCT1. Single session CBT2. Control condition	Individuals presented to general hospital with mTBI.Total sample: N = 58.Intervention condition: (n = 29; mean age = 43.35; 66% male)Control condition:(n = 29; mean age = 49.35; 75% male)	1. Single session CBT: Received a printed 10-page manual about recovering from brain injury. Single session with therapist to discuss nature of and expected mTBI symptoms.2. Control condition: Standardized treatment.	InterviewedSleep-related symptom:1. Fatigue.	Control group significantly more likely to report fatigue (82% of the condition sample) than experimental group (47% of the condition sample) at 6 months post-treatment.Effect sizes were not reported and were unable to be calculated based on the data presented in this article.
Ponsford and colleagues (2002)	Objectives:Assess impact of early intervention (information booklet) following mTBI.Study design:Two-group RCT1. Intervention condition (provided with information booklet)2. Control condition	Individuals presented to emergency department with mTBI.Total sample: N = 202Intervention condition (n = 79; mean age = 24.1)Control condition (n = 123; mean age = 28.1)	1. Intervention condition: Participants provided a detailed history and undertook neuropsychological assessments. Provided with information booklet that addresses common mTBI symptoms.2. Control condition: Standard emergency department treatment.	Measured as part of the Symptom Checklist-90-Revised.PCS sleep-related symptoms:1. Fatigue.2. Sleeping difficulty.	Control group significantly more likely to report difficulties in sleeping, compared with intervention group, at 3 month post-injury.No significant differences in fatigue ratings between the two conditions.Effect sizes were not reported and were unable to be calculated based on the data presented in this article.
Vuletic and colleagues (2016)	Objective:1. Assess the rate of sleep disturbances of those individuals with mTBI in deployment services.2. Assess development of mTBI over time and the association of mTBI with other symptoms and disorders.3. Impact of telephone-based problem-solving treatment.Study design:Two-group RCT1. Education-only condition.2. Problem-solving treatment condition. Also received same education material as education-only condition.	Active duty post-deployment service members (returning from Iraq and Afghanistan) with combat mTBI.Total sample: N = 356, Ages 20–54 years (mean age = 29.35; 93% male). n = 179 in each condition.26% of the sample with PTSD.	1. Education only:Received 12 informational brochures addressing common mTBI symptoms (baseline). Received additional brochures biweekly.2. Problem-solving treatment:Received brochures as reported above. In addition, received 12 biweekly telephone calls over 6 months from trained master's-level counselors. Focused on participant-related problems.	Primary measure: Pittsburgh Sleep Quality Index (PSQI).	6-month follow-up:Overall PSQI score (Cohen's d = 0.35), sleep quality (Cohen's d = 0.31), sleep latency (Cohen's d = 0.26), sleep duration (Cohen's d = 0.26), and habitual sleep efficiency sleep duration (Cohen's d = 0.27) significantly improved in problem-solving treatment condition, compared with education-only condition.Issues that interfered with sleep: waking in middle of night sleep duration (Cohen's d = 0.46), not getting to sleep within 30 min sleep duration (Cohen's d = 0.50), and having pain sleep duration (Cohen's d = 0.65) significantly improved for problem-solving condition, compared with education-only condition.Clinical improvements in sleep quality for 30.8% of participants in problem-solving treatment condition and 13.7% of participants in education-only condition12-month follow-up:No significant differences in total PSQI score or individual sleep disturbance items between individuals allocated to the problem-solving treatment condition, compared with individuals allocated to the education-only condition.Clinical improvement in sleep quality for 22.2% of participants in problem-solving treatment condition and 20.7% of participants in education-only condition.

Focus is on sleep-related symptom evaluations and results. Other measures and findings were included in each individual article; however, only those that relate to sleep are reported here.

mTBI, mild traumatic brain injury; PCS, post-concussion symptoms; RCT, randomized controlled trial; CBT, cognitive behavioral therapy; PTSD, post-traumatic stress disorder.

Study characteristics

Two studies were conducted in the U.S.^32,34 and one each in Sweden³² and Australia.³³ Sample sizes in the individual studies were low to moderate, ranging from 58 to 356 participants. All participants (N = 789) were age 15 years or older and overall included a greater proportion of male (73%) than female participants. The age range was only reported in Matuseviciene and colleagues (15–70 years)³¹ and Vuletic and colleagues (20–54 years).³⁴ However, based on the age-related means and standard deviations reported in the remaining two studies, it was concluded that the age ranges were between 15–70 years. The sex of the participants was not reported in Ponsford and colleagues.³³

Of the 789 participants, 334 (42%) were randomly allocated to the intervention condition. All remaining participants were randomized into the control condition (usual care). Seventy-six low-risk patients were not randomized in Matuseviciene and colleagues.³¹ Matuseviciene and colleagues only randomized patients who reported three or more symptoms. Participants were recruited from emergency departments^31

–34 and army medical centers.³⁴ Three studies recruited participants from the general population.^31

–34 Participants in the study by Vuletic and colleagues³⁴ comprised military and National Guard personnel, all recruited post-deployment. Injury cause was reported in all studies; with blast, vehicular or traffic road accidents, and fall being the three most commonly reported causes of injury. One study reported that patients were seeking litigation (38% of participants).³¹ The majority of patients in Vuletic and colleagues³⁴ reported blast as an injury cause. In this study, patients were able to report several causes of injury as some patients had received multiple TBIs. Blast was not reported as an injury cause in any other study.

Type of TBI

All studies included only those participants who had sustained a mild TBI injury. In two studies, mild TBI was defined using time of injury reports of loss of consciousness (LOC) of less than 30 min, PTA of less than 1 hour, and a GCS score of 13–15.^31,33 In Mittenberg and colleagues,³² some injury characteristics were not reported (see Table 2); but this study was included in a prior review.³⁵ We sought further detail on the participant characteristics; however, none were able to be provided by the authors. In Vuletic and colleagues³⁴, participants were screened for mild TBI at a post-deployment examination. This process included a TBI screening questionnaire and a military acute concussion evaluation. Injury definition was consistent with the Centers for Disease Control and Prevention definition of mTBI.

Interventions

Intervention delivery ranged from 5 days to more than 24 months post-injury. Three intervention approaches were used across the four studies: psycho-educational,^31,33 cognitive behavioral therapy,³² and counseling.³⁴ As shown in Table 4, the interventions within each of these four categories were highly variable, including in terms of their format, duration, intensity, and staffing. All interventions targeted individuals (there were no group interventions nor programs that included caregivers).

Outcomes

A variety of measures were used to report outcomes. Vuletic and colleagues³⁴ used the Pittsburgh Sleep Quality Index (PSQI)³⁶ as the primary measure of sleep quality. In the remaining studies, outcomes were reported using individual item(s) of sleeping difficulty and/or fatigue from various well established post-concussion questionnaires (i.e., Rivermead Postconcussion Symptom Questionnaire³¹ and the Postconcussion Syndrome Checklist³³) and via interviews with a structured checklist.³²

Results of interventions

Cognitive behavioral therapy (CBT)

One study applied CBT³² and three studies used enhanced education.^31,33,34 In Mittenberg and colleagues,³² participants in the treatment condition met with a therapist for 1 h to discuss symptoms and treatments to reduce self-reported symptoms. Participants also were provided with a 10-page information booklet on post-concussion symptoms to review when required. Those randomly allocated to the treatment condition received standard care. At 6 months follow-up, the control condition was significantly more likely to report symptoms of fatigue (82%) than participants in the treatment condition (47%).

Enhanced education

Matuseviviene and colleagues³¹ randomly allocated high-risk participants (i.e., those who reported three or more post-concussion symptoms) to an early intervention condition or treatment as usual condition. Participants in the early intervention condition met with a physician 14–21 days post-injury. As part of this visit, participants received verbal information about mTBI symptoms and were notified of an expected favorable outcome. Self-reported symptoms of fatigue and sleep disturbances decreased relative to baseline for both the treatment and control conditions at 3 months. There were, however, no significant differences in these symptoms between the two conditions at follow-up.

Similarly to Matusevivine and colleagues,³¹ Ponsford and colleagues³³ examined the effects of early invention on post-concussion symptoms. Participants randomly allocated to the treatment condition were provided with an information booklet 5 to 7 days post-injury. This booklet contained information on post-concussion symptoms and coping strategies. Participants also completed a range of neuropsychological tests. Neuropsychological tests also were included at 3-month follow-up to assess any changes in attention, memory, and information processing. Participants in the control condition received standard care and were only seen at the 3-month follow-up. At follow-up, the data revealed that participants in the treatment condition were significantly less likely to report symptoms relating to sleeping difficulty, compared with participants in the control condition. There were no significant differences in fatigue ratings between the two conditions.

Vuletic and colleagues³⁴ assessed whether a telephone-based problem-solving treatment improved sleep quality at 6 and 12 months post-intervention. Active duty post-deployment service members were randomly allocated to the education-only condition or the problem-solving treatment condition. In the education-only condition, participants were provided with informational brochures on mTBI symptoms, including sleep-related symptoms, at baseline and on a biweekly basis. In the problem-solving treatment condition, participants received the same educational material as those in the education-only condition, as well as 12 biweekly telephone calls. At the 6-month follow-up, participants in the problem-solving treatment condition showed significant improvements in subjective sleep quality, sleep latency, sleep duration, and habitual sleep efficiency, compared with participants in the education-only condition. Further, participants in the problem-solving treatment condition showed significant reductions in waking up in the middle of the night or early morning, inability to fall asleep within 30 min, and pain, compared with participants in the education-only condition. Clinically significant improvements (reduction of total PSQI score by 1 or more standard deviation) in sleep were observed in 30.8% and 13.7% of participants in the problem-solving treatment and education conditions, respectively. At the 12-month follow-up, similar scores on the PSQI composite and components were found for both conditions. Overall, these findings suggest that problem-solving treatment improves sleep quality at 6 months post-intervention; however, treatment gains reduce at 12 months post-intervention (relative to those who received education).

Discussion

This systematic review aimed to evaluate the evidence from RCTs for psychological interventions to improve sleep and fatigue following mild TBI. Adult mild TBI patients describe sleep and fatigue problems as among the most debilitating of the symptoms they experience,³⁷ leaving a gap for clinicians who need to recommend an effective treatment.³⁸ Although several interventions for this problem have now been tested in randomized controlled trials, a comparison of these programs has not previously been undertaken.

We identified only a small body of literature (four studies), including only one RCT of a sleep-specific intervention for sleep problems following mild TBI. A more common approach in the identified studies was to implement a general intervention for post-concussion symptoms and report findings for sleep- or fatigue-specific items that were drawn from a general symptom questionnaire. Given that sleep changes post-injury are measurable across numerous dimensions (e.g., quality, quantity, and timing) and there are numerous dimensions of fatigue,²² the use of a single item to measure sleep dysfunction could miss or underestimate the effect of the intervention. Future studies would benefit from adopting an approach as per Vuletic and colleagues³⁴ who used multiple measures (subjective and objective) to test the effect of their intervention on a range of sleep parameters. Further, there is a need to separate out the effects on sleep versus the effects of fatigue.³⁹ We encourage the further exploration of both factors (and associated sub-factors such as physical and cognitive fatigue) and the potential interactions. This multidimensional approach of sleep and fatigue assessment would advance our understanding of the way in which post-injury sleep and fatigue can be improved.

Despite the relative scarcity of research and allowing that only tentative conclusions can be drawn, the available evidence suggests that sleep and fatigue symptoms after mild TBI can effectively be treated by psychological interventions. CBT has been used for the successful treatment of traumatic brain injury–related fatigue, and problem-solving via telephone counseling has been used successfully for sleep problems. With one exception,³¹ the effects of enhanced-education approaches on sleep symptoms was generally more favorable than treatment-as-usual or the provision of standard (general) information about post-concussion symptoms. Such enhancements included the addition of a neuropsychological assessment³³ or consultation with a therapist.³² Unfortunately, effect size data often were not reported or could not be calculated; however, at least one study showed the potential for small-to-medium sized benefits of a focused sleep intervention on a range of sleep outcomes (e.g., quality, duration, efficiency, and sleep onset latency), with the strongest effects (medium effects) for issues that interfere with sleep (such as night-time waking). As noted, this conclusion is tentative given the number of studies on which it is based. This review should be updated when further studies become available.

This review has a number of limitations. This review did not specifically target treatments for clinical sleep disorders, sleep or fatigue problems after multiple mild TBIs (repeat concussions), the potential for multiple (comorbid) sleep or fatigue disorders or problems, or the likely effectiveness of interventions in non-treatment seeking mild TBI samples. This review does not address the effects of psychological interventions on chronic symptoms (with the likely exception of one study³⁴; these studies were “early” interventions for sub-acute symptoms), or interventions for the sleep complaints of injured children (age <15 years) or people age older than 70 years, or pharmacological treatments to improve sleep or fatigue after mild TBI (for more information about pharmacotherapy see Vaishnavi and colleagues²² and Dikmen and colleagues⁴⁰). The injury–intervention period was both variable and wider than initially proposed, and this could affect the interpretation of results. Further, all of the available studies did not distinguish between pre- and post-injury sleep or fatigue complaints; thus, the strength of the potential benefits might be underestimated because the interventions could be “correcting” a long-standing or exacerbated sleep or fatigue problem⁴⁰ as opposed to a new complaint from the injury; we strongly recommend that future studies draw this distinction.³⁹ The studies contained potential biases, there could be a file drawer problem, and the data are currently insufficient for funnel plots or other analyses.⁴¹

A related issue is that few of the identified studies utilized a sleep- or fatigue-specific intervention, and there was high variability in the approaches. It is possible that the use of non-specific interventions underestimated the potential benefits. For example, trials of individual, group, and web-based interventions for insomnia have shown sustained improvements in sleep quality over the longer-term in people with this condition. These targeted interventions may demonstrate superior benefit to the more general interventions reviewed here, and it is encouraging to see that such trials are underway (https://clinicaltrials.gov/ct2/show/NCT02658669; ACTRN12616001218482; ACTRN12614000787684). A further limitation is that non-English studies were not identified, which gives rise to another potential publication bias. This review was scoped on mild TBI only (as opposed to mild and moderate TBI), and this may be interpreted as overly exclusive, or conversely, as insufficiently refined⁴²; however, this approach is used in other reviews^43,44 and it was considered important to reduce the heterogeneity of the primary studies. Additionally, although we trained our raters, this did not eliminate discrepancies; thus, coding or classification errors could have occurred.

Until recently, the clinical management of sleep and fatigue problems after mild TBI was largely ignored in clinical management guidelines for mild TBI (for an exception, see the recently launched specialist guidelines from the U.S.)⁴⁵ or it was recognized only as a subcomponent of general treatment guidelines for post-concussion symptoms.^46,47 This review shows that there are relatively few high quality RCTs of interventions for sleep and fatigue problems after mild TBI. This inevitably limits the quality of the evidence on which treatment guidelines can be based. Despite an extensive and systematic search of the published literature, only a handful of studies were identified. These contained potential biases, some of which are avoidable, and the available evidence is not yet sufficient to permit pooled data analysis. Further, interventions for other types of sleep disorders (including obstructive sleep apnea, narcolepsy, and circadian phase disorders) have an evidence base, but their value in mild TBI is currently limited by lack of definition of the nature of the sleep complaint. This means that if patients complain of a sleep or fatigue problem following mild TBI, this should prompt a thorough clinical assessment and if warranted, a laboratory assessment of the problem. Nevertheless, it can still be tentatively concluded that psychological interventions, especially those with an enhanced educative component or that use CBT, appear promising for sleep and fatigue complaints after mild TBI.

This review strongly demonstrates the need for further research on sleep and fatigue after mild TBI; however this research must adopt stronger designs and include pragmatic trials. Future studies require the following: improved sample description (including the chronicity of symptoms and the period between injury and the intervention) and stratification of results by demographics, where appropriate); multidimensional assessment of sleep and fatigue; application of standardized diagnostic criteria, common outcome metrics, and cost measures, (where appropriate); use of data repositories (or the inclusions of additional detail) to enable better data extraction for pooled analyses, and to calculate clinically-relevant metrics; and improved reporting to trials standards (such as Consolidated Standards Of Reporting Trials [CONSORT]). Traumatic brain injury–related sleep disturbance and fatigue are associated with and can be comorbid with myriad other clinical conditions, including depression. Untreated problems can hamper recovery and rehabilitation^37,39 and reduce quality of life.²³ Finding effective solutions for this problem is a growing and important priority because the successful treatment of sleep and fatigue complaints delivers specific benefits, and it could fast track recovery from mild TBI by preventing symptom persistence.

Footnotes

Author Disclosure Statement

No competing financial interests exist.

Appendix Table AT1

Search Strategy

Database	Search strategy	Results
PubMed	(((((((((“Brain Injuries”[Mesh]) OR “Head Injuries, Closed”[Mesh]) OR “Brain Concussion”[Mesh]) OR “Postconcussion Syndrome”[Mesh])) OR ((mtbi OR TBI OR brain injury OR brain injuries OR head injury OR head injuries OR brain contusion OR brain damage OR postconcussion OR postconcussive OR postconcussion OR post-concussive OR concussion OR concussive)))) AND ((((((((((((((((“Sleep Initiation and Maintenance Disorders”[Mesh]) OR “Disorders of Excessive Somnolence”[Mesh]) OR “Dyssomnias”[Mesh]) OR “Parasomnias”[Mesh]) OR “Fatigue”[Mesh]) OR “Sleep”[Mesh]) OR “Sleep-Wake Transition Disorders”[Mesh]) OR “Sleep Stages”[Mesh]) OR “Somnambulism”[Mesh]) OR “Nocturnal Myoclonus Syndrome”[Mesh]) OR “Narcolepsy”[Mesh]) OR “Sleep Disorders, Circadian Rhythm”[Mesh]) OR “Restless Legs Syndrome”[Mesh]) OR “Sleep Apnea Syndromes”[Mesh])) OR (insomnia OR hypersomnia OR hypersomnia OR dyssomnias OR parasomnia OR fatigue OR sleepiness OR somnolence OR sleep OR sleep-wake OR sleep/wake OR drowsiness OR nightmares OR sleepwalking OR somnambulism OR periodic limb movement OR nocturnal myoclonus syndrome OR narcolepsy OR phase shift disorder OR restless legs OR circadian OR apnoea OR apnea))) AND ((((((((((((((“Counseling”[Mesh]) OR “Cognitive Therapy”[Mesh]) OR “Psychotherapy”[Mesh]) OR “Education”[Mesh]) OR “Rehabilitation”[Mesh]) OR “Biofeedback, Psychology”[Mesh]) OR “Neurofeedback”[Mesh]) OR “Relaxation Therapy”[Mesh]) OR “Psychology”[Mesh]) OR “Psychotherapy, Rational-Emotive”[Mesh]) OR “Mindfulness”[Mesh]) OR “Diffuse Noxious Inhibitory Control”[Mesh])) OR ((management OR counselling OR counseling OR intervention OR therapy OR CBT OR cbti OR treatment OR psychotherapy OR education OR instruction OR mindfulness OR rehabilitation OR bio feedback OR biofeedback OR neuro feedback OR neuro feedback OR prevention OR relaxation OR remediation OR psychology OR psychoeducation OR psychosocial OR biopsychosocial OR bibliotherapy OR rational emotive OR self-instruction OR self-management OR self-attribution OR self attribution OR non-surgical interventions OR ACT OR mindfulness OR stimulus control OR sleep restriction OR bedtime restriction)))) AND ((“Randomized Controlled Trial”[Publication Type]) OR ((rct OR controlled trial OR control trial OR controlled trial OR randomised trial OR randomized trial)))	144
Embase on Embase.com	(('traumatic brain injury'/exp OR 'brain injury'/exp OR 'head injury'/exp OR 'brain contusion'/exp OR 'brain damage'/exp OR 'postconcussion syndrome'/exp OR 'concussion'/exp) OR (mtbi OR tbi OR 'brain injury' OR 'brain injuries' OR 'head injury' OR 'head injuries' OR 'brain contusion' OR 'brain damage' OR postconcussion OR postconcussive OR 'post concussion' OR 'post concussive' OR concussion OR concussive)) AND (('insomnia'/exp OR 'hypersomnia'/exp OR 'sleep disorder'/exp OR 'parasomnia'/exp OR 'fatigue'/exp OR 'somnolence'/exp OR 'sleep'/exp OR 'sleep waking cycle'/exp OR 'drowsiness'/exp OR 'nightmare'/exp OR 'sleep walking'/exp OR 'periodic limb movement disorder'/exp OR 'narcolepsy'/exp OR 'restless legs syndrome'/exp OR 'circadian rhythm'/exp OR 'apnea'/exp) OR (insomnia OR hypersomnia OR hyposomnia OR dyssomnia OR parasomnia OR fatigue OR sleepiness OR somnolence OR sleep OR 'sleep wake' OR drowsiness OR nightmares OR sleepwalking OR somnambulism OR 'periodic limb movement' OR 'nocturnal myoclonus syndrome' OR narcolepsy OR 'phase shift disorder' OR 'restless legs' OR circadian OR apnoea OR apnea)) AND (('management'/exp OR 'counseling'/exp OR 'therapy'/exp OR 'cognitive therapy'/exp OR 'psychotherapy'/exp OR 'education'/exp OR 'rehabilitation'/exp OR 'psychophysiology'/exp OR 'neurofeedback'/exp OR 'prevention'/exp OR 'cognitive remediation therapy'/exp OR 'psychology'/exp OR 'psychoeducation'/exp OR 'psychosocial disorder'/exp OR 'bibliotherapy'/exp OR 'acceptance and commitment therapy'/exp OR 'mindfulness'/exp) OR (management OR counselling OR counseling OR intervention OR therapy OR cbt OR cbti OR treatment OR psychotherapy OR education OR instruction OR mindfulness OR rehabilitation OR 'bio feedback' OR biofeedback OR 'neuro feedback' OR neurofeedback OR prevention OR relaxation OR remediation OR psychology OR psychoeducation OR psychosocial OR biopsychosocial OR bibliotherapy OR 'rational emotive' OR 'self instruction' OR 'self management' OR 'self attribution' OR 'non-surgical interventions' OR act OR 'stimulus control' OR 'sleep restriction' OR 'bedtime restriction')) AND ('randomized controlled trial'/exp OR (rct OR 'controlled trial' OR 'control trial' OR 'controled trial' OR 'randomised trial' OR 'randomized trial')) AND [embase]/lim	353
PsycINFO (on EBSCOhost)	S1 ((DE “Traumatic Brain Injury”) OR (DE “Brain Damage”)) OR (DE “Brain Concussion”) OR (MTBI OR TBI OR “brain injury” OR “brain injuries” OR “head injury” OR “head injuries” OR “brain contusion” OR “brain damage” OR postconcussion OR postconcussive OR postconcussion OR post-concussive OR concussion OR concussive)) AND S2 ((((((((((((DE “Insomnia”) OR (DE “Hypersomnia”)) OR (DE “Parasomnias”)) OR (DE “Fatigue”)) OR (DE “Sleepiness”)) OR (DE “Sleep”)) OR (DE “Sleep Wake Cycle”)) OR (DE “Nightmares”)) OR (DE “Sleepwalking”)) OR (DE “Narcolepsy”)) OR (DE “Restless Leg Syndrome”)) OR (DE “Human Biological Rhythms”)) OR (DE “Sleep Apnea”) OR (insomnia OR hypersomnia OR hyposomnia OR dyssomnia OR parasomnia OR fatigue OR sleepiness OR somnolence OR sleep OR sleep-wake OR sleep/wake OR drowsiness OR nightmares OR sleepwalking OR somnambulism OR “periodic limb movement” OR “Nocturnal Myoclonus Syndrome” OR narcolepsy OR “phase shift disorder” OR “restless legs” OR circadian OR apnoea OR apnea)) AND S3 (((((((((((((((((((((DE “Management”) OR (DE “Counseling”)) OR (DE “Intervention”)) OR (DE “Treatment”)) OR (DE “Cognitive Therapy”)) OR (DE “Cognitive Behavior Therapy”)) OR (DE “Psychotherapy”)) OR (DE “Education”)) OR (DE “Mindfulness”)) OR (DE “Rehabilitation”)) OR (DE “Biofeedback”)) OR (DE “Neurotherapy”)) OR (DE “Prevention”)) OR (DE “Relaxation”)) OR (DE “Psychology”)) OR (DE “Psychoeducation”)) AND (DE “Psychosocial Readjustment” OR DE “Psychosocial Rehabilitation” OR DE “Therapeutic Social Clubs” OR DE “Vocational Rehabilitation”)) OR (DE “Biopsychosocial Approach”)) OR (DE “Bibliotherapy”)) OR (DE “Rational Emotive Behavior Therapy”)) OR (DE “Acceptance and Commitment Therapy”)) OR (DE “Stimulus Control”) OR (management OR counselling OR counseling OR intervention OR therapy OR CBT OR CBTi OR treatment OR psychotherapy OR education OR instruction OR mindfulness OR rehabilitation OR” bio feedback” OR biofeedback OR “neuro feedback” OR neurofeedback OR prevention OR relaxation OR remediation OR psychology OR psychoeducation OR psychosocial OR biopsychosocial OR bibliotherapy OR “rational emotive” OR self-instruction OR self-management OR self-attribution OR “self attribution” OR “non-surgical interventions” OR ACT OR “stimulus control” OR “sleep restriction” OR “bedtime restriction”) AND S4 (rct OR “controlled trial” OR “control trial” OR “controled trial” OR “randomised trial” OR “randomized trial”)	102
CINAHL (on EBSCOhost)	S1 ((DE “Traumatic Brain Injury”) OR (DE “Brain Damage”)) OR (DE “Brain Concussion”)	5
	S2 (MTBI OR TBI OR “brain injury” OR “brain injuries” OR “head injury” OR “head injuries” OR “brain contusion” OR “brain damage” OR postconcussion OR postconcussive OR postconcussion OR post-concussive OR concussion OR concussive)S3 (S1 OR S2)S4 ((((((((((((DE “Insomnia”) OR (DE “Hypersomnia”)) OR (DE “Parasomnias”)) OR (DE “Fatigue”)) OR (DE “Sleepiness”)) OR (DE “Sleep”)) OR (DE “Sleep Wake Cycle”)) OR (DE “Nightmares”)) OR (DE “Sleepwalking”)) OR (DE “Narcolepsy”)) OR (DE “Restless Leg Syndrome”)) OR (DE “Human Biological Rhythms”)) OR (DE “Sleep Apnea”)
	S5 (insomnia OR hypersomnia OR hyposomnia OR dyssomnia OR parasomnia OR fatigue OR sleepiness OR somnolence OR sleep OR sleep-wake OR sleep/wake OR drowsiness OR nightmares OR sleepwalking OR somnambulism OR “periodic limb movement” OR “Nocturnal Myoclonus Syndrome” OR narcolepsy OR “phase shift disorder” OR “restless legs” OR circadian OR apnoea OR apnea)S6 (S4 OR S5)S7 (((((((((((((((((((((DE “Management”) OR (DE “Counseling”)) OR (DE “Intervention”)) OR (DE “Treatment”)) OR (DE “Cognitive Therapy”)) OR (DE “Cognitive Behavior Therapy”)) OR (DE “Psychotherapy”)) OR (DE “Education”)) OR (DE “Mindfulness”)) OR (DE “Rehabilitation”)) OR (DE “Biofeedback”)) OR (DE “Neurotherapy”)) OR (DE “Prevention”)) OR (DE “Relaxation”)) OR (DE “Psychology”)) OR (DE “Psychoeducation”)) AND (DE “Psychosocial Readjustment” OR DE “Psychosocial Rehabilitation” OR DE “Therapeutic Social Clubs” OR DE “Vocational Rehabilitation”)) OR (DE “Biopsychosocial Approach”)) OR (DE “Bibliotherapy”)) OR (DE “Rational Emotive Behavior Therapy”)) OR (DE “Acceptance and Commitment Therapy”)) OR (DE “Stimulus Control”)S8 (management OR counselling OR counseling OR intervention OR therapy OR CBT OR CBTi OR treatment OR psychotherapy OR education OR instruction OR mindfulness OR rehabilitation OR” bio feedback” OR biofeedback OR “neuro feedback” OR neurofeedback OR prevention OR relaxation OR remediation OR psychology OR psychoeducation OR psychosocial OR biopsychosocial OR bibliotherapy OR “rational emotive” OR self-instruction OR self-management OR self-attribution OR “self attribution” OR “non-surgical interventions” OR ACT OR “stimulus control” OR “sleep restriction” OR “bedtime restriction”) S9 (S7 OR S8)S10 (rct OR “controlled trial” OR “control trial” OR “controled trial” OR “randomised trial” OR “randomized trial”)S11 (S3 AND S6 AND S9 AND S10)
SPORTDiscus (on EBSCOhost)	S1 (DE “BRAIN – Wounds & injuries” OR DE “BRAIN – Concussion” OR DE “BRAIN damage” OR DE “CHRONIC traumatic encephalopathy” OR DE “BRAIN injury patients – Rehabilitation” OR DE “BRAIN injury patients” OR DE “BRAIN – Concussion” OR DE “POSTCONCUSSION syndrome”) OR (DE “HEAD injuries”)	6
	S2 (MTBI OR TBI OR “brain injury” OR “brain injuries” OR “head injury” OR “head injuries” OR “brain contusion” OR “brain damage” OR postconcussion OR postconcussive OR postconcussion OR post-concussive OR concussion OR concussive)S3 (S1 OR S2)S4 (((DE “FATIGUE” OR DE “CHRONIC fatigue syndrome”) AND (DE “SLEEP” OR DE “SLEEP – Health aspects” OR DE “SLEEP disorders” OR DE “SLEEP – Health aspects”)) OR (DE “CIRCADIAN rhythms”)) OR (DE “APNEA”)S5 (insomnia OR hypersomnia OR hyposomnia OR dyssomnia OR parasomnia OR fatigue OR sleepiness OR somnolence OR sleep OR sleep-wake OR sleep/wake OR drowsiness OR nightmares OR sleepwalking OR somnambulism OR “periodic limb movement” OR “Nocturnal Myoclonus Syndrome” OR narcolepsy OR “phase shift disorder” OR “restless legs” OR circadian OR apnoea OR apnea)S6 (S4 OR S5)S7 ((((DE “PSYCHOLOGY” OR DE “PSYCHOTHERAPY”) OR (DE “COGNITIVE therapy”)) AND (DE “THERAPEUTICS” OR DE “CATHETERIZATION” OR DE “DANCE therapy” OR DE “DIETETICS” OR DE “DRUG therapy” OR DE “FLUID therapy” OR DE “GENE therapy” OR DE “HEALING” OR DE “HEMODIALYSIS” OR DE “HORMONE therapy” OR DE “IMMOBILIZATION (Therapeutics)” OR DE “IMMUNIZATION” OR DE “INVESTIGATIONAL therapies” OR DE “OCCUPATIONAL therapy” OR DE “PHYSICAL therapy” OR DE “PHYSIOLOGICAL therapeutics” OR DE “PLACEBOS (Medicine)” OR DE “PSYCHOTHERAPY” OR DE “RECREATIONAL therapy” OR DE “TREATMENT effectiveness” OR DE “TREATMENT programs” OR DE “ULTRASONIC therapy” OR DE “TREATMENT programs” OR DE “SUBSTANCE abuse – Treatment”)) OR (DE “REHABILITATION” OR DE “AQUATIC exercises – Therapeutic use” OR DE “MEDICAL rehabilitation” OR DE “NEUROPSYCHOLOGICAL rehabilitation”)) OR (DE “BIOFEEDBACK training”)S8 (management OR counselling OR counseling OR intervention OR therapy OR CBT OR CBTi OR treatment OR psychotherapy OR education OR instruction OR mindfulness OR rehabilitation OR” bio feedback” OR biofeedback OR “neuro feedback” OR neurofeedback OR prevention OR relaxation OR remediation OR psychology OR psychoeducation OR psychosocial OR biopsychosocial OR bibliotherapy OR “rational emotive” OR self-instruction OR self-management OR self-attribution OR “self attribution” OR “non-surgical interventions” OR ACT OR “stimulus control” OR “sleep restriction” OR “bedtime restriction”) S9 (S7 OR S8)S10 (rct OR “controlled trial” OR “control trial” OR “controled trial” OR “randomised trial” OR “randomized trial”)S11 (S3 AND S6 AND S9 AND S10)
AMED - The Allied and Complementary Medicine Database on EBSCOhost	S1 (MTBI OR TBI OR “brain injury” OR “brain injuries” OR “head injury” OR “head injuries” OR “brain contusion” OR “brain damage” OR postconcussion OR postconcussive OR postconcussion OR post-concussive OR concussion OR concussive)S2 (DE “INSOMNIA”)S3 (DE “FATIGUE”)S4 (DE “SLEEP”)S5 (insomnia OR hypersomnia OR hyposomnia OR dyssomnia OR parasomnia OR fatigue OR sleepiness OR somnolence OR sleep OR sleep-wake OR sleep/wake OR drowsiness OR nightmares OR sleepwalking OR somnambulism OR “periodic limb movement” OR “Nocturnal Myoclonus Syndrome” OR narcolepsy OR “phase shift disorder” OR “restless legs” OR circadian OR apnoea OR apnea)S6 (S2 OR S3 OR S4 OR S5)S7 (DE “COUNSELING”)S8 (DE “THERAPY”)S9 (DE “COGNITIVE THERAPY”)S10 (DE “PSYCHOTHERAPY”)S11 (DE “EDUCATION”)S12 (DE “REHABILITATION”)S13 (DE “BIOFEEDBACK”)S14 (DE “PREVENTION”)S15 (DE “RELAXATION”)S16 (DE “PSYCHOLOGY”)S17 (DE “PSYCHOEDUCATION”)S18 (management OR counselling OR counseling OR intervention OR therapy OR CBT OR CBTi OR treatment OR psychotherapy OR education OR instruction OR mindfulness OR rehabilitation OR” bio feedback” OR biofeedback OR “neuro feedback” OR neurofeedback OR prevention OR relaxation OR remediation OR psychology OR psychoeducation OR psychosocial OR biopsychosocial OR bibliotherapy OR “rational emotive” OR self-instruction OR self-management OR self-attribution OR “self attribution” OR “non-surgical interven …S19 (S7 OR S8 OR S9 OR S10 OR S11 OR S12 OR S13 OR S14 OR S15 OR S16 OR S17 OR S18)S20 (rct OR “controlled trial” OR “control trial” OR “controled trial” OR “randomised trial” OR “randomized trial”)S21 S1 AND S6 AND S19 AND S20	5
Cochrane Central Register of Controlled Trials	(MTBI OR TBI OR “brain injury” OR “brain injuries” OR “head injury” OR “head injuries” OR “brain contusion” OR “brain damage” OR postconcussion OR postconcussive OR postconcussion OR post-concussive OR concussion OR concussive) in Title, Abstract, Keywords and (insomnia OR hypersomnia OR hyposomnia OR dyssomnia OR parasomnia OR fatigue OR sleepiness OR somnolence OR sleep OR sleep-wake OR drowsiness OR nightmares OR sleepwalking OR somnambulism OR “periodic limb movement” OR “Nocturnal Myoclonus Syndrome” OR narcolepsy OR “phase shift disorder” OR “restless legs” OR circadian OR apnoea OR apnea) in Title, Abstract, Keywords and (management OR counselling OR counseling OR intervention OR therapy OR CBT OR CBTi OR treatment OR psychotherapy OR education OR instruction OR mindfulness OR rehabilitation OR “bio feedback” OR biofeedback OR “neuro feedback” OR neurofeedback OR prevention OR relaxation OR remediation OR psychology OR psychoeducation OR psychosocial OR biopsychosocial OR bibliotherapy OR “rational emotive” OR self-instruction OR self-management OR self-attribution OR “self attribution” OR “non-surgical interventions” OR ACT OR “stimulus control” OR “sleep restriction” OR “bedtime restriction”) in Title, Abstract, Keywords and (rct OR “controlled trial” OR “control trial” OR “controled trial” OR “randomised trial” OR “randomized trial”) in Title, Abstract, Keywords in Trials'	83
ProQuest Dissertations and Theses Global	ab((Mtbi OR tbi OR “brain injury” OR “brain injuries” OR “head injury” OR “head injuries” OR “brain contusion” OR “brain damage” OR postcondition OR concussive OR postconcussion OR post-concussive OR concussion OR concussive)) AND ab((insomnia OR hypersomnia OR hypersomnia OR dysphonia OR parasomnia OR fatigue OR sleepiness OR somnolence OR sleep OR sleep-wake OR sleep/wake OR drowsiness OR nightmares OR sleepwalking OR somnambulism OR “periodic limb movement” OR “Nocturnal clonus Syndrome” OR narcolepsy OR “phase shift disorder” OR “restless legs” OR circadian OR apnoea OR apnea)) AND ab((management OR counselling OR counseling OR intervention OR therapy OR cot OR coti OR treatment OR psychotherapy OR education OR instruction OR mindfulness OR rehabilitation OR “bio feedback” OR biofeedback OR “neuro feedback” OR biofeedback OR prevention OR relaxation OR remediation OR psychology OR coeducation OR psychosocial OR psychosocial OR bibliotherapy OR “rational emotive” OR self-instruction OR self-management OR self-attribution OR “self attribution” OR “non-surgical interventions” OR pact OR “stimulus control” OR “sleep restriction” OR “bedtime restriction”)) AND (rut OR “controlled trial” OR “control trial” OR “controlled trial” OR “randomised trial” OR “randomized trial”)2015-01-01 – present and limited to doctoral dissertations	13

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