The Use of Methylphenidate to Improve Executive Functioning in Pediatric Traumatic Brain Injury: A Systematic Review and Meta-Analysis
Abstract
1. Introduction
2. Materials and Methods
2.1. Literature Searching
- Population: pediatric population (aged below 18 years of age) with a history of TBI.
- Intervention: MPH.
- Comparator: placebo or standard medical care.
- Primary outcome: attention.
- Secondary outcomes: other aspects of cognitive function, behaviour, and adverse events.
2.2. Search Terms
2.3. Inclusion and Exclusion Criteria
- An initial title and abstract screening performed by two independent reviewers.
- A full-text review.
2.4. Data Extraction
2.5. Quality Assessment
2.6. Statistical Analysis
3. Results
3.1. Study Selection
3.2. Study Characteristics
3.3. Risk-of-Bias Assessment
3.4. Primary Outcome
3.5. Secondary Outcomes
4. Discussion
Limitations of Individual Studies
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Population | Intervention | Injury Type |
---|---|---|
p?ediatric * child * Child/ infan * Infant/ adolescen * Adolescent/ | Methylphenidate/ Concerta Ritalin Delmosart Equasym Medikinet | traumatic brain injury brain injury head injury head trauma concussion Brain injuries, traumatic/ Craniocerebral trauma/ |
Inclusion Criteria | Exclusion Criteria | Justification |
---|---|---|
Including pediatric population aged 0–18 years | Only adult population | The focus of this review was to look at the efficacy in a pediatric population |
History of traumatic brain injury | Other forms of brain injury | The focus of this review was the efficacy in a traumatic injury population |
Studies in humans | Studies in animals | Scoping searches revealed that studies in humans were numerous enough to analyse and compare |
Methylphenidate as intervention | Medications other than methylphenidate, including those in the same drug class | The focus of the review is to compare the efficacy of methylphenidate to placebo and standard care |
Study designs meeting OCEBM levels one, two, or three, excluding reviews | Study designs meeting OCEBM level four or five and reviews | Low evidence levels would reduce the overall quality of the systematic review |
English language translation available | No English language translation available | Time and resource constraints limited translation abilities |
Full-text access available | Articles with abstract only, conference summaries, or no full-text available | Full-text was needed for a complete quality assessment and analysis of the data |
No limitation on publication dates | Unpublished results | The field is novel, and previous systematic reviews did not focus on the same research question |
Study | Study Origin | Type of Study | Number of Participants | Mean Age of Participants (Range) | Male:Female Ratio | Mean GCS (SD) | Dosing Regimen | Measurements Related to Primary and Secondary Outcomes |
---|---|---|---|---|---|---|---|---|
LeBlond et al., 2019 [23] | USA | RCT | 26 | 11.25 (6–17) | 20:6 | 11.9 (4.2) | Four weeks of one of MPH or placebo, followed by four weeks of the other condition | BRIEF parent-report and self-report CPT D-KEFS VF WISCIV-PSI |
Kurowski et al., 2019 [24] | USA | RCT | 26 (20 completed) | 11.5 (6–17) | 20:6 (15:5 completed) | 11.9 (4.2) | Four weeks of one of MPH or placebo, followed by four weeks of the other condition | VADPRS PSERS Vital signs |
Nikles et al., 2014 [25] | Australia | RCT | 10 | 12.9 (6–16) | 6:4 | Moderate to severe | Three pairs of one week treatment periods (of placebo, MPH, and dexamphetamine) | Conners’ 3 rating scales (parent and teacher) BRIEF parent-report, teacher-report, and self-report ECBI |
Baker et al., 1990 [26] | USA | RCT | 8 | 11 (7–15) | 5:3 | 11.4 (4.9) at hospital admission | Two weeks of one of MPH or placebo, followed by two weeks of the other condition | MFFT CPT Stroop test Conners’ abbreviated parent–teacher questionnaires Central-incidental method HRNB- seashore rhythm test, Trail making part A and B, progressive figures test ANSER PIC (short form) |
Clark et al., 1990 [27] | USA | RCT | 8 | 11 (7–15) | 5:3 | Unknown (had to meet baseline test requirements) | Two weeks of one of MPH or placebo, followed by two weeks of the other condition | MFFT CPT Stroop test Seashore rhythm test Trail making part A and B Abbreviated parent–teacher questionnaires |
Ekinci et al., 2017 [28] | Turkey | Prospective cohort | 20 | 12.7 (6–18) | 15:5 | 8.6 (2.7) | IR-MPH, increased to a dose of 10 mg twice daily for first week and 10 mg three times a day for second week | Turgay DSM-IV disruptive behavior disorders rating scale parent and teacher forms Conners’ 3 rating scale-revised (parent and teacher) CGI-S CGI-I Adverse effect scale |
Mahalick et al., 1998 [29] | USA | Prospective controlled trial | 14 | 10.7 (5–14.5) | 11:3 | 8.1 (4.1) | 14 days of either MPH or placebo with a washout period of 12 h, then crossed over | Gordon diagnostic system (model III) The Woodcock–Johnson psychoeducational test battery- revised Ruff 2 and 7 cancellation test |
Williams et al., 1998 [30] | USA | Prospective controlled study | 10 | 10.5 (8.3–16.7) | 9:1 | Unknown (had to meet baseline test requirements) | Two-week testing period, with four days of MPH or placebo and a three-day washout period before cross-over | Conners’ 3 rating scale (parent and teacher) SDMT CPT SMRTT SRT RANT Psychomotor skills- Purdue pegboard, finger tapping test, developmental test of VMI |
Caliendo et al., 2024 [31] | USA | Retrospective review | 234 | 11.6 median (2 months–21 years) | 146:88 | Unknown | Had been given MPH | Demographic data MPH dosing patterns, adverse events Cognitive state (at admission, discharge, and other time points) |
Patrick et al., 2003 [32] | USA | Retrospective review | 10 | 13.7 (8–19) | 7:3 | ‘Low response state’ for 30 days or more | Given a dopaminergic agonist (amantadine, pramipexole, bromocriptine, levodopa, or MPH) | WNSSP scores before and on medication |
Hornyak et al., 1997 [33] | USA | Retrospective review | 10 | 10.9 (3–16) | 7:3 | 6.2 (range 5 to 9) | Had been given MPH | Ranchos Los Amigos level of cognitive functioning Subjective/qualitative comments on results |
Study | Type of Score | Stimulant Group (Mean ± SD) | Placebo Group (Mean ± SD) |
---|---|---|---|
Nikles et al., 2014 [25] | Parent-rated | 10.9 ± 4.9 | 13.3 ± 5.4 |
Teacher-rated | 6.5 ± 4.4 | 11.0 ± 5.2 | |
Williams et al., 1998 * [30] | Parent-rated | 56.50 ± 14.71 | 56.90 ± 24.69 |
Teacher-rated | 53.83 ± 13.78 | 61.29 ± 10.68 |
Study | Type of Score | Stimulant Group (Mean ± SD) | Placebo Group (Mean ± SD) |
---|---|---|---|
LeBlond et al., 2019 [23] | Self-rated (GEC) | 41.10 ± 3.53 | 46.03 ± 3.53 |
Parent-rated (BRI mean) | 58.49 ± 1.84 | 62.88 ± 1.84 | |
Nikles et al., 2014 [25] | Parent-rated | 147.8 ± 29.8 | 152.3 ± 27.4 |
Teacher-rated | 127.4 ± 24.1 | 143.2 ± 20.2 |
Study | Stimulant Group (%) | Placebo Group (%) |
---|---|---|
Clark et al., 1990 [27] | 37.5 | 25.0 |
Ekinci et al., 2017 [28] | 55 | - |
Caliendo et al., 2024 [31] | 8.0 | - |
Study | Type of Event | Stimulant Group (Mean ± SD) | Placebo Group (Mean ± SD) |
---|---|---|---|
Kurowski et al., 2019 [24] | Change in appetite | 0.3 ± 0.5 | 0.2 ± 0.4 |
Extreme sadness | 0.0 ± 0.0 | 0.1 ± 0.2 | |
Headache | 0.1 ± 0.3 | 0.2 ± 0.4 | |
Irritability | 0.2 ± 0.4 | 0.3 ± 0.6 | |
Listless | 0.1 ± 0.3 | 0.1 ± 0.3 | |
Picking at | 0.3 ± 0.6 | 0.4 ± 0.6 | |
Repetitive movements | 0.1 ± 0.2 | 0.1 ± 0.2 | |
Sees/hears things | 0.0 ± 0.0 | 0.0 ± 0.0 | |
Shaky | 0.1 ± 0.2 | 0.1 ± 0.4 | |
Socially withdrawn | 0.0 ± 0.0 | 0.1 ± 0.2 | |
Stomach-ache | 0.2 ± 0.5 | 0.0 ± 0.0 | |
Suicidal/homicidal ideation | 0.0 ± 0.0 | 0.1 ± 0.2 | |
Trouble sleeping | 0.2 ± 0.4 | 0.2 ± 0.5 |
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Pitt-Francis, A.; Stevens, A.R.; Ahmed, Z.; Di Pietro, V. The Use of Methylphenidate to Improve Executive Functioning in Pediatric Traumatic Brain Injury: A Systematic Review and Meta-Analysis. Trauma Care 2025, 5, 1. https://doi.org/10.3390/traumacare5010001
Pitt-Francis A, Stevens AR, Ahmed Z, Di Pietro V. The Use of Methylphenidate to Improve Executive Functioning in Pediatric Traumatic Brain Injury: A Systematic Review and Meta-Analysis. Trauma Care. 2025; 5(1):1. https://doi.org/10.3390/traumacare5010001
Chicago/Turabian StylePitt-Francis, Anna, Andrew R. Stevens, Zubair Ahmed, and Valentina Di Pietro. 2025. "The Use of Methylphenidate to Improve Executive Functioning in Pediatric Traumatic Brain Injury: A Systematic Review and Meta-Analysis" Trauma Care 5, no. 1: 1. https://doi.org/10.3390/traumacare5010001
APA StylePitt-Francis, A., Stevens, A. R., Ahmed, Z., & Di Pietro, V. (2025). The Use of Methylphenidate to Improve Executive Functioning in Pediatric Traumatic Brain Injury: A Systematic Review and Meta-Analysis. Trauma Care, 5(1), 1. https://doi.org/10.3390/traumacare5010001