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Sleep–Wake Disturbances in Pediatric Traumatic Brain Injury: A Systematic Review and Meta‐Analysis of Interventions
Open accessAbstract
Background: Sleep–wake disturbances (SWD) are frequent and persistent complications following pediatric traumatic brain injury (TBI), negatively affecting cognitive, emotional, and academic outcomes. This systematic review and meta‐analysis aimed to evaluate the effectiveness of behavioral, pharmacological, and emerging interventions for SWD in children and adolescents with mild to severe TBI and examined related sleep outcomes and functional measures. Method: Following PRISMA guidelines, a systematic search was conducted across PubMed, Web of Science, and ScienceDirect for studies published between 1998 and 2025. Nineteen studies ( N = 1113) met inclusion criteria, encompassing cognitive behavioral therapy for insomnia (CBT‐I), sleep hygiene, mindfulness, pharmacological treatments (melatonin, branched‐chain amino acids), physical activity, and family‐based interventions. Meta‐analytic models using random effects were employed to calculate pooled standardized mean differences and mean raw scores across sleep, cognitive, and quality‐of‐life outcomes. Results: CBT‐I demonstrated efficacy in reducing persistent post‐concussion symptoms and improving subjective sleep outcomes, although heterogeneity varied across outcomes. In contrast, melatonin did not produce statistically significant pooled effects on persistent post‐concussion symptoms or cognitive outcomes, and treatment effects varied across dosage groups. Few studies examined mindfulness or educational outcomes, revealing key research gaps. Discrepancies between objective (actigraphy) and subjective (self‐report) measures emphasized the need for multi‐method sleep assessment. Conclusion: CBT‐I is the most consistently effective intervention for sleep problems following pediatric TBI. Melatonin showed mixed and nonsignificant pooled effects, indicating that its role in pediatric TBI recovery requires further investigation. Future research should focus on personalized, multidisciplinary treatment models integrating behavioral, pharmacological, and rehabilitative approaches to optimize long‐term neurocognitive and educational outcomes.
Overview
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TL;DR
This systematic review and meta-analysis of 19 studies (N = 1113) found CBT-I to be the most consistently effective intervention for sleep and persistent post-concussion symptoms in pediatric TBI, while melatonin showed mixed and nonsignificant pooled effects. Objective actigraphy and subjective sleep measures often disagreed, and educational outcomes were not directly evaluated.
Key findings
- Across 19 studies (N = 1113), CBT-I was most consistently effective: pooled post-CBT-I persistent post-concussion symptoms had a mean raw score of 9.05 (95% CI 5.41–12.68; I² = 62.3%), and subjective sleep problem scores had a mean raw score of 7.28 (95% CI 5.40–9.16; I² = 0%).
- Melatonin did not show statistically significant pooled effects: 3 mg vs. control on persistent post-concussion symptoms SMD = 0.45 (95% CI −0.00 to 0.91; I² = 31.7%); 10 mg SMD = 0.35 (95% CI −0.39 to 1.08; I² = 74.4%); cognitive outcomes were SMD = −0.31 (95% CI −0.68 to 0.06; I² = 0%) for 3 mg and SMD = 0.01 (95% CI −0.36 to 0.38; I² = 0%) for 10 mg.
- Post-intervention quality of life had a mean raw score of 78.44 (95% CI 74.31–82.56; I² = 0%); the highest BCAA dose group (54 g/day) had higher sleep efficiency (93.2% vs. 91.4%) and longer total sleep time (536.7 min vs. 468.1 min) than placebo, with no significant cognitive changes.
- Discrepancies between objective actigraphy and subjective self-report were prominent: among six actigraphy studies, only one found significant sleep efficiency improvement after 10 mg melatonin, while another found no group differences; few studies examined mindfulness or educational outcomes.
Methods
- Following PRISMA and Cochrane guidelines with a PROSPERO-registered protocol, the authors searched PubMed, Web of Science, and ScienceDirect for English peer-reviewed studies published 1998–2025, including participants aged 0–17 years with mild to severe TBI and interventions such as CBT-I, sleep hygiene, mindfulness, melatonin or related sleep medications, physical activity, or family-based approaches; 19 studies (N = 1113) met inclusion criteria.
- Two independent reviewer groups screened records; inter-rater agreement was reported as Cohen’s k = 0.71 at title/abstract screening and k = 0.86 at the full-text stage.
- Meta-analyses used random-effects models with the inverse variance method, calculating pooled standardized mean differences or mean raw scores with 95% CIs; heterogeneity was assessed with I², and subgroup analyses examined intervention type, melatonin dosage (3 vs. 10 mg), and objective vs. subjective sleep measurement. Publication bias tests were not performed except where at least 10 studies were available for an outcome.
Limitations
- Stated: formal subgroup or meta-regression analyses by TBI severity were constrained by inconsistent reporting of severity indices and small numbers of studies within severity strata, so the authors could not reliably quantify whether intervention effects differed by severity.
- Stated: the review included heterogeneous study designs (RCTs, observational studies, pilot studies, and study protocols), limiting causal inference and possibly contributing to variability; no eligible studies directly evaluated the correlation between sleep interventions and school functioning, and few studies per outcome domain limited publication bias testing.
- Evident from the text: many included studies had small samples and missing data (e.g., “n/r” for demographics, severity, time since injury, gender, or comorbidities), and some pooled analyses relied on few studies (e.g., CBT-I sleep outcomes n = 28; melatonin groups n = 58), making estimates imprecise.
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In the paper
“In contrast, melatonin did not produce statistically significant pooled effects on persistent post‐concussion symptoms or cognitive outcomes, and treatment effects varied across dosage groups.”
§ Sleep–Wake Disturbances in Pediatric Traumatic Brain Injury: A Systematic Review and Meta‐Analysis of Interventions > Abstract > Results
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Melatonin showed mixed and nonsignificant pooled effects, indicating that its role in pediatric TBI recovery requires further investigation.”
§ Sleep–Wake Disturbances in Pediatric Traumatic Brain Injury: A Systematic Review and Meta‐Analysis of Interventions > Abstract > Conclusion
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper states — it cites no source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Discrepancies between objective (actigraphy) and subjective (self‐report) measures emphasized the need for multi‐method sleep assessment.”
§ Sleep–Wake Disturbances in Pediatric Traumatic Brain Injury: A Systematic Review and Meta‐Analysis of Interventions > Abstract > Results
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In contrast, melatonin did not produce statistically significant pooled effects on persistent post‐concussion symptoms or cognitive outcomes, and treatment effects varied across dosage groups.”
§ Sleep–Wake Disturbances in Pediatric Traumatic Brain Injury: A Systematic Review and Meta‐Analysis of Interventions > Abstract > Results
plainstates an association- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
None of the sources cited for this claim could be matched to a paper in Crossref, so there is nothing to check it against.
In the paper
“In both trials by Barlow et al. (Barlow et al. 2020; Barlow et al. 2021) participants initiated treatment in the subacute phase following injury (mean 38 days post‐injury).”
§ Sleep–Wake Disturbances in Pediatric Traumatic Brain Injury: A Systematic Review and Meta‐Analysis of Interventions > Results > Study Characteristics and Sleep Outcomes
What the sources say
- Not matchedcites Barlow et al. 2020
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Not matchedcites Barlow et al. 2021
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plain- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
Each contradiction between two passages listed here was confirmed by an independent check.
Rated major: it would touch a result — a value a result rests on, reported and recomputed p-values on opposite sides of the significance level, two passages that conflict with no sign which is right, or a cited work retracted before this paper was published.
In the paper
§ Sleep–Wake Disturbances in Pediatric Traumatic Brain Injury: A Systematic Review and Meta‐Analysis of Interventions > Discussion > Possible Explanations and Mechanisms
“only one found significant improvement in sleep efficiency after 10 mg melatonin (Barlow et al. 2020), while another found no group differences (Barlow et al. 2021).”
§ Sleep–Wake Disturbances in Pediatric Traumatic Brain Injury: A Systematic Review and Meta‐Analysis of Interventions > Results > Study Characteristics and Sleep Outcomes
“The study found that melatonin significantly improved SWD in children and adolescents with PPCS after mTBI, decreasing subjective (self‐report) sleep problems, increasing total sleep time and efficiency, and reducing depression symptoms, but it had no significant effect on pain, anxiety, or cognitive function.”
Rated minor: it would not touch a result — a value no result rests on, a p-value that stays on the same side of the significance level, or a conflict that is clerical, resolved elsewhere in the paper, or outside its own findings.
In the paper
§ Sleep–Wake Disturbances in Pediatric Traumatic Brain Injury: A Systematic Review and Meta‐Analysis of Interventions > Results > Study Characteristics and Sleep Outcomes
“10. Barlow et al. (2021) | PPCS ≥ 10 point PCSI increase | 8–18 years, mean age 13.8 (SD: 2.6) years | 4–6 weeks | 57F, 42M | Previous concussion, migraine, ADHD, learning support, previous counselor, PCSI‐Y score pre‐injury. Excluded significant medical/psych histories. Excluded previous concussion (3 months). | Placebo, melatonin 3 mg, melatonin 10 mg | 99”
§ Sleep–Wake Disturbances in Pediatric Traumatic Brain Injury: A Systematic Review and Meta‐Analysis of Interventions > Results > Study Characteristics and Sleep Outcomes
“Barlow et al. (2021) | N = 72 (placebo: n = 22, melatonin 3 mg: n = 25, melatonin 10 mg: n = 25)”
Rated minor: it would not touch a result — a value no result rests on, a p-value that stays on the same side of the significance level, or a conflict that is clerical, resolved elsewhere in the paper, or outside its own findings.
In the paper
“42F, 30M | ADHD, previous TBI, headaches and migraines | Physical activity | 55”
§ Sleep–Wake Disturbances in Pediatric Traumatic Brain Injury: A Systematic Review and Meta‐Analysis of Interventions > Results > Study Characteristics and Sleep Outcomes
Reported 55 · recomputed 72
Rated minor: it would not touch a result — a value no result rests on, a p-value that stays on the same side of the significance level, or a conflict that is clerical, resolved elsewhere in the paper, or outside its own findings.
In the paper
§ Sleep–Wake Disturbances in Pediatric Traumatic Brain Injury: A Systematic Review and Meta‐Analysis of Interventions > Results > Study Characteristics and Sleep Outcomes
“9. Barlow et al. (2020) | PSCI ≥ 10 increase post‐injury | 8–18 years, mean age 14.0 (SD: 2.6) years | 4–6 weeks | 52F, 20M | NCI, anxiety, depression, headaches, QRHL scores are similar. | Placebo, melatonin 3 mg, melatonin 10 mg | 72”
§ Sleep–Wake Disturbances in Pediatric Traumatic Brain Injury: A Systematic Review and Meta‐Analysis of Interventions > Results > Study Characteristics and Sleep Outcomes
“Barlow et al. (2020) | N = 99 (placebo: n = 33, melatonin 3 mg: n = 33, melatonin 10 mg: n = 33)”
Rated minor: it would not touch a result — a value no result rests on, a p-value that stays on the same side of the significance level, or a conflict that is clerical, resolved elsewhere in the paper, or outside its own findings.
In the paper
§ Sleep–Wake Disturbances in Pediatric Traumatic Brain Injury: A Systematic Review and Meta‐Analysis of Interventions > Discussion
“preliminary findings suggest that mindfulness techniques may offer an alternative behavioral approach for improving sleep in this population (Ledoux et al. 2024).”
§ Sleep–Wake Disturbances in Pediatric Traumatic Brain Injury: A Systematic Review and Meta‐Analysis of Interventions > References
““ Smartphone App–Delivered Mindfulness‐Based Intervention for Mild Traumatic Brain Injury in Adolescents: Protocol for a Feasibility Randomized Controlled Trial.””
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Citations
Cites
Diagnostic and Statistical Manual of Mental Disorders
American Psychiatric Association (2013) · doi:10.1176/appi.books.9780890425596 · Cited by 116,369
The PRISMA 2020 statement: An updated guideline for reporting systematic reviews
Page, M. J., McKenzie, J. E., Bossuyt, P. M., Boutron, I., Hoffmann, T. C., Mulrow, C. D., Shamseer, L., Tetzlaff, J. M., Akl, E. A., Brennan, S. E., et al. (2021) · BMJ · doi:10.1136/bmj.n71 · Cited by 108,283
PRISMA-P Group, Moher, D., Shamseer, L., Clarke, M., Ghersi, D., Liberati, A., Petticrew, M., Shekelle, P., & Stewart, L. A. (2015) · Systematic Reviews · doi:10.1186/2046-4053-4-1 · Cited by 26,223
Validation of the Insomnia Severity Index as an outcome measure for insomnia research
Bastien, C. (2001) · Sleep Medicine · doi:10.1016/s1389-9457(00)00065-4 · Cited by 8,067
Qaseem, A., Kansagara, D., Forciea, M. A., Cooke, M., Denberg, T. D., & for the Clinical Guidelines Committee of the American College of Physicians* (2016) · Annals of Internal Medicine · doi:10.7326/m15-2175 · Cited by 1,965
Reliability and validity of a computerized neurocognitive test battery, CNS vital signs
GUALTIERI, C., & JOHNSON, L. (2006) · Archives of Clinical Neuropsychology · doi:10.1016/j.acn.2006.05.007 · Cited by 873
Functional consequences of inadequate sleep in adolescents: A systematic review
Shochat, T., Cohen-Zion, M., & Tzischinsky, O. (2014) · Sleep Medicine Reviews · doi:10.1016/j.smrv.2013.03.005 · Cited by 837
Mindfulness Interventions with Youth: A Meta-Analysis
Zoogman, S., Goldberg, S. B., Hoyt, W. T., & Miller, L. (2015) · Mindfulness · doi:10.1007/s12671-013-0260-4 · Cited by 760
Cognitive, behavioral, and functional consequences of inadequate sleep in children and adolescents
Beebe, D. W. (2011) · Pediatric Clinics of North America · doi:10.1016/j.pcl.2011.03.002 · Cited by 638
Jacobs, G. D., Pace-Schott, E. F., Stickgold, R., & Otto, M. W. (2004) · Archives of Internal Medicine · doi:10.1001/archinte.164.17.1888 · Cited by 579
Research works printed but not linked: 6
- American Academy of Sleep Medicine, 2014, International Classification of Sleep Disorders‐Third Edition
- Higgins J., 2022, Cochrane Handbook for Systematic Reviews of Interventions (Version 6.3)
- 10.1080/09602011.2024.2383337 · DOI
- Rao V., 2015, Sleep Disturbances After Traumatic Brain Injury, Psychiatric Times, 32, 30
- Rhythms C., 2024, Circadian Rhythm Sleep‐Wake Disorders: Diagnosis and Treatment, Principles and Practice of Pediatric Sleep Medicine, 549, 21
- Weber M., 2013, A Brief and Selective Review of Treatment Approaches for Sleep Disturbance Following Traumatic Brain Injury, Journal of Sleep Disorders and Therapy, 2013, 1
Cited by
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Metadata
- Authors
- Lofitou, K., Kouki, E. P., Gavriel, C., Achilleos, H., Themistokleous, V., Bargiotas, P., Haarbauer‐Krupa, J., Paraskevopoulos, E., & Constantinidou, F.
- Affiliations
- University of Cyprus (CY)
- University of Limassol (CY)
- Nicosia General Hospital (CY)
- Department of Pediatrics Emory University School of Medicine Atlanta Georgia USA
- Corresponding author
- Lofitou, K.
- Venue
- Brain and Behavior
- Publisher
- Wiley
- Published
- 2026-09
- Volume
- 16
- Issue
- 9
- Pages
- e71556-e71556
- ISSN
- 2157-9032 (ISSN-L)
- 2162-3279
- PMC
- PMC13594777
- OpenAlex
- W6943967921
- Semantic Scholar
- 0dd8b92f49620fac98cc277a077b391c4b72394a
- Cited by
- 0
- References
- 67
- FWCI
- 0.00
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by
- creativecommons.org/licenses/by/4.0/ (vor, 20 d)
- doi.wiley.com/10.1002/tdm_license_1.1 (tdm)
- Locations
- Brain and Behavior (publishedVersion, cc-by)
- PubMed (publishedVersion)
- PubMed Central (publishedVersion, cc-by)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- OSF Preprints (OSF Preprints) (submittedVersion)
- Open Science Framework
- Funders
- University of Cyprus
- Topics
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Sleep and related disorders
- Health Sciences › Medicine › Clinical Neurology › Traumatic Brain Injury Research
- Health Sciences › Medicine › Clinical Neurology › Traumatic Brain Injury and Neurovascular Disturbances
- Keywords
- sleep-wake disturbances, pediatric traumatic brain injury, cognitive behavioral therapy for insomnia, melatonin, post-concussion symptoms, sleep hygiene, mindfulness, branched-chain amino acids, physical activity, family intervention, sleep outcomes, cognitive outcomes, quality of life, actigraphy, children and adolescents
- MeSH terms
- Brain Injuries, Traumatic, Adolescent, Child, Humans, Melatonin, Sleep Wake Disorders, Cognitive Behavioral Therapy
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