Cited by 209Attention Deficit Hyperactivity DisorderBehavioral and Psychological StudiesPharmaceutical studies and practices

Methylphenidate for attention-deficit/hyperactivity disorder in children and adolescents: Cochrane systematic review with meta-analyses and trial sequential analyses of randomised clinical trials

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Storebø, Ole Jakob, Krogh, Helle B, Ramstad, Erica, Moreira-Maia, Carlos R, Holmskov, Mathilde, Skoog, Maria, Nilausen, Trine Danvad, Magnusson, Frederik L +10 more·2015·BMJ

Abstract

STUDY QUESTION: Is methylphenidate beneficial or harmful for the treatment of attention-deficit/hyperactivity disorder (ADHD) in children and adolescents? METHODS: Electronic databases were searched up to February 2015 for parallel and crossover randomised clinical trials comparing methylphenidate with placebo or no intervention in children and adolescents with ADHD. Meta-analyses and trial sequential analyses (TSA) were conducted. Quality was assessed using GRADE. Teachers, parents, and observers rated ADHD symptoms and general behaviour. STUDY ANSWER AND LIMITATIONS: The analyses included 38 parallel group trials (n=5111, median treatment duration 49 days) and 147 crossover trials (n=7134, 14 days). The average age across all studies was 9.7 years. The analysis suggested a beneficial effect of methylphenidate on teacher rated symptoms in 19 parallel group trials (standardised mean difference (SMD) -0.77, n=1698), corresponding to a mean difference of -9.6 points on the ADHD rating scale. There was no evidence that methylphenidate was associated with an increase in serious adverse events (risk ratio 0.98, nine trials, n=1532; TSA adjusted intervention effect RR 0.91). Methylphenidate was associated with an increased risk of non-serious adverse events (1.29, 21 trials, n=3132; TSA adjusted RR 1.29). Teacher rated general behaviour seemed to improve with methylphenidate (SMD -0.87, five trials, n=668) A change of 7 points on the child health questionnaire (CHQ) has been deemed a minimal clinically relevant difference. The change reported in a meta-analysis of three trials corresponds to a mean difference of 8.0 points on the CHQ (range 0-100 points), which suggests that methylphenidate may improve parent reported quality of life (SMD 0.61, three trials, n=514). 96.8% of trials were considered high risk of bias trials according to the Cochrane guidelines. All outcomes were assessed very low quality according to GRADE. WHAT THIS STUDY ADDS: The results suggest that among children and adolescents with a diagnosis of ADHD, methylphenidate may improve teacher reported symptoms of ADHD and general behaviour and parent reported quality of life. However, given the risk of bias in the included studies, and the very low quality of outcomes, the magnitude of the effects is uncertain. Methylphenidate is associated with an increased risk of non-serious but not serious adverse events. FUNDING, COMPETING INTERESTS, DATA SHARING: Region Zealand Research Foundation and Copenhagen Trial Unit. Competing interests are given in the full paper on bmj.com. Full data are available in the version of this review published in The Cochrane Library.

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  • Methylphenidate is the most common prescribed drug for treatment of ADHD and can improve cognitive function through a dopaminergic effect.

    “The most common prescribed drug for treatment of ADHD is methylphenidate (MPH) and it is believed that it can improve cognitive function through a dopaminergic effect (Storebø et al. 2015).”

    From <i>Crocus sativus</i> L. Versus Methylphenidate in Treatment of Children with Attention-Deficit/Hyperactivity Disorder: A Randomized, Double-Blind Pilot Study (2019) · cites this paper as Storebø et al. 2015

    The Introduction (page unavailable) calls methylphenidate globally the most common drug treatment for ADHD. The Results and Discussion report possible improvements in ADHD symptoms and general behaviour in children and adolescents, but do not establish improved cognitive function through a dopaminergic effect; searches for that mechanism found only related reference titles. (LLM, conf=0.88)

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  1. [27]Storebø O, Pedersen N, Krogh H, et al. Methylphenidate for attention deficit hyperactivity disorder (ADHD) in children and adolescents—assessment of harms in observational studies. Cochrane Database Syst Rev 2015; (In press). PMC6494554 29744873
  2. [59]Gluud C, Nikolova D, Klingenberg SL. Cochrane Hepato-Biliary About the Cochrane Collaboration (Cochrane Review Groups (CRGs). Cochrane Rev Groups 2015;1(Art.No:LIVER). www.cochranelibrary.com/about/cochrane-review-groups.html.

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Authors
Storebø, O. J., Krogh, H. B., Ramstad, E., Moreira-Maia, C. R., Holmskov, M., Skoog, M., Nilausen, T. D., Magnusson, F. L., Zwi, M., Gillies, D., Rosendal, S., Groth, C., Rasmussen, K. B., Gauci, D., Kirubakaran, R., Forsbøl, B., Simonsen, E., & Gluud, C.
Affiliations
  • University of Southern Denmark (DK)
  • Region Zealand (DK)
  • Copenhagen University Hospital (DK)
  • Whittington Hospital (GB)
  • Western Sydney Local Health District (AU)
  • Capital Region of Denmark (DK)
  • Herlev Hospital (DK)
  • Ministry for Health (MT)
  • Christian Medical College, Vellore (IN)
  • University of Copenhagen (DK)
Corresponding author
Storebø, Ole Jakob
Venue
BMJ
Publisher
BMJ
Published
2015-11-25
Volume
351
Pages
h5203
ISSN
1756-1833 (ISSN-L)
OpenAlex
W2179260900
Cited by
209
References
77
Citations by year
2026: 8 · 2025: 8 · 2024: 11 · 2023: 14 · 2022: 17 · 2021: 24 · 2020: 16 · 2019: 18 · 2018: 25 · 2017: 36 · 2016: 28 · 2015: 4
FWCI
4.27
Type
journal article
Language
en
Open access
Locations
  • BMJ (publishedVersion, cc-by-nc)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by-nc)
  • PubMed (publishedVersion)
  • Research at the University of Copenhagen (University of Copenhagen) (publishedVersion, cc-by-nc)
  • OAR@UM (University of Malta) (submittedVersion, other-oa)
  • University of Southern Denmark Research Portal (University of Southern Denmark) (submittedVersion, cc-by-nc)
Funders
  • Gentofte Hospital
  • Syddansk Universitet
  • Region Sjælland
  • Copenhagen Trial Unit, Centre for Clinical Intervention Research
Topics
  • Health Sciences › Medicine › Psychiatry and Mental health › Attention Deficit Hyperactivity Disorder
  • Social Sciences › Psychology › Developmental and Educational Psychology › Behavioral and Psychological Studies
  • Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Pharmaceutical studies and practices
Keywords
methylphenidate, attention deficit hyperactivity disorder, children, adolescents, ADHD symptoms, quality of life, adverse events, stimulant medication, teacher ratings, parent ratings, trial sequential analysis, risk of bias, quality of evidence, minimal clinically important difference, Child Health Questionnaire
MeSH terms
Adolescent, Central Nervous System Stimulants, Attention Deficit Disorder with Hyperactivity, Child, Drug Administration Schedule, Humans, Methylphenidate, Quality of Life, Randomized Controlled Trials as Topic, Treatment Outcome, Cross-Over Studies

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