European, randomized, phase 3 study of lisdexamfetamine dimesylate in children and adolescents with attention-deficit/hyperactivity disorder
Open accessAbstract
This study evaluated the efficacy and safety of lisdexamfetamine dimesylate (LDX) compared with placebo in children and adolescents with attention-deficit/hyperactivity disorder (ADHD) in Europe. Osmotic-release oral system methylphenidate (OROS-MPH) was included as a reference arm. Patients (6-17 years old) with a baseline ADHD Rating Scale version IV (ADHD-RS-IV) total score ≥ 28 were randomized (1:1:1) to dose-optimized LDX (30, 50, or 70 mg/day), OROS-MPH (18, 36, or 54 mg/day) or placebo for 7 weeks. Primary and key secondary efficacy measures were the investigator-rated ADHD-RS-IV and the Clinical Global Impressions-Improvement (CGI-I) rating, respectively. Safety assessments included treatment-emergent adverse events (TEAEs), electrocardiograms, and vital signs. Of 336 patients randomized, 196 completed the study. The difference between LDX and placebo in least squares mean change in ADHD-RS-IV total score from baseline to endpoint was -18.6 (95% confidence interval [CI]: -21.5 to -15.7) (p<0.001; effect size, 1.80). The difference between OROS-MPH and placebo in least squares mean change in ADHD-RS-IV total score from baseline to endpoint was -13.0 (95% CI: -15.9 to -10.2) (p<0.001; effect size, 1.26). The proportions (95% CI) of patients showing improvement (CGI-I of 1 or 2) at endpoint were 78% (70-86), 14% (8-21), and 61% (51-70) for LDX, placebo, and OROS-MPH. The most common TEAEs for LDX were decreased appetite, headache, and insomnia. Mean changes in vital signs were modest and consistent with the known profile of LDX. LDX was effective and generally well tolerated in children and adolescents with ADHD.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
RCTs showed efficacy and tolerability of LDX in child and adolescent ADHD, but each trial had a limited sample size.
“Although randomized controlled trials (RCTs) showed the efficacy and tolerability of LDX in child and adolescent ADHD,10–13 each trial had a limited sample size.”
From Comparative efficacy, acceptability, and tolerability of lisdexamfetamine in child and adolescent ADHD: a meta-analysis of randomized, controlled trials (2015) · cites this paper as [12]
The Discussion reports that this randomized trial found LDX more effective than placebo and well tolerated in children and adolescents with ADHD. The Patient disposition section reports 336 randomized patients, but the paper does not characterize its sample as limited or establish that each of the other cited trials had a limited sample size. Page numbers were not available in our copy. (LLM, conf=0.83)
Experimental — accuracy not yet measuredPrevious studies documented that LDX was an effective, safe, and well-tolerated stimulant in the treatment of ADHD in children and adolescents.
“Previous studies documented that LDX was an effective, safe, and well-tolerated stimulant in the treatment of ADHD in children and adolescents.10–13”
From Comparative efficacy, acceptability, and tolerability of lisdexamfetamine in child and adolescent ADHD: a meta-analysis of randomized, controlled trials (2015) · cites this paper as [12]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR)
American Psychiatric Association (2000) · doi:10.1176/appi.books.9780890423349 · Cited by 11,069 · see citing works
Adler, L. A., Goodman, D. W., Kollins, S. H., Weisler, R. H., Krishnan, S., Zhang, Y., & Biederman, J. (2008) · The Journal of Clinical Psychiatry · doi:10.4088/jcp.v69n0903 · Cited by 218 · see citing works
Absorption of lisdexamfetamine dimesylate and its enzymatic conversion to d-amphetamine
Pennick (2010) · Neuropsychiatric Disease and Treatment · doi:10.2147/ndt.s9749 · Cited by 170 · cited 2× · see citing works
“The intact parent molecule requires enzymatic hydrolysis to yield the therapeuticallyactive metabolite d-amfetamine (Pennick, 2010).”
BackgroundWigal, T., Brams, M., Gasior, M., Gao, J., Squires, L., Giblin, J., & 316 Study Group (2010) · Behavioral and Brain Functions · doi:10.1186/1744-9081-6-34 · Cited by 136 · cited 2× · see citing works
“Studies in a laboratory school setting and in a simulated adult workplace environment have demonstrated that the therapeutic benefits of LDX are ongoing at 13 h post-dose in children (Wigal et al., 2009) and 14 h post-dose in adults (Wigal et al., 2010).”
BackgroundSelf-citationthe 311 Study Group, Wigal, S. B., Kollins, S. H., Childress, A. C., & Squires, L. (2009) · Child and Adolescent Psychiatry and Mental Health · doi:10.1186/1753-2000-3-17 · Cited by 112 · see citing works
Self-citation
Flagged first, then by citations
Research works printed but not linked: 3
- Banaschewski, T., Coghill, D., Santosh, P., Zuddas, A., Asherson, P., Buitelaar, J., Danckaerts, M., Dopfner, M., Faraone, S.V., Rothenberger, A., Sergeant, J., Steinhausen, H.C., Sonuga- Barke, E.J., Taylor, E., 2006. Long-acting medications for the hyperkinetic disorders. A systematic review and European treatment guideline. Eur. Child Adolesc. Psychiatry 15, 476-495.
- NHS Quality Improvement Scotland, 2008. Attention Deficit and Hyperkinetic Disorders. Services Over Scotland. Report of the Implementation Review Exercise. Edinburgh, UK, p. 11876. /http://www.healthcareimprovementscotland.org/default.aspx?S (accessed 16.05.2012).
- Polanczyk, G., de Lima, M.S., Horta, B.L., Biederman, J., Rohde, L.A., 2007. The worldwide prevalence of ADHD: a systematic review and metaregression analysis. Am. J. Psychiatry 164, 942-948.
Cited by
Sorted by citations
Associations of sleep disturbance with ADHD: implications for treatment
Hvolby, A. (2015) · ADHD Attention Deficit and Hyperactivity Disorders · doi:10.1007/s12402-014-0151-0 · Cited by 339 · see citing works
Methylphenidate for children and adolescents with attention deficit hyperactivity disorder (ADHD)
Storebø, O. J., Ramstad, E., Krogh, H. B., Nilausen, T. D., Skoog, M., Holmskov, M., Rosendal, S., Groth, C., Magnusson, F. L., Moreira-Maia, C. R., et al. (2015) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd009885.pub2 · Cited by 347 · see citing works
Tarver, J., Daley, D., & Sayal, K. (2014) · Child: Care, Health and Development · doi:10.1111/cch.12139 · Cited by 234 · see citing works
Stimulant medications and sleep for youth with ADHD: a meta-analysis
Kidwell, K. M., Van Dyk, T. R., Lundahl, A., & Nelson, T. D. (2015) · Pediatrics · doi:10.1542/peds.2015-1708 · Cited by 133 · see citing works
Sleep disturbances in adolescents with ADHD: A systematic review and framework for future research
Lunsford-Avery, J. R., Krystal, A. D., & Kollins, S. H. (2016) · Clinical Psychology Review · doi:10.1016/j.cpr.2016.10.004 · Cited by 131 · see citing works
Dittmann, R. W., Cardo, E., Nagy, P., Anderson, C. S., Bloomfield, R., Caballero, B., Higgins, N., Hodgkins, P., Lyne, A., Civil, R., et al. (2013) · CNS Drugs · doi:10.1007/s40263-013-0104-8 · Cited by 88 · see citing works
Self-citationCerrillo-Urbina, A. J., García-Hermoso, A., Pardo-Guijarro, M. J., Sánchez-López, M., Santos-Gómez, J. L., & Martínez-Vizcaíno, V. (2018) · Journal of Child and Adolescent Psychopharmacology · doi:10.1089/cap.2017.0151 · Cited by 44 · see citing works
Coghill, D. R., Banaschewski, T., Nagy, P., Otero, I. H., Soutullo, C., Yan, B., Caballero, B., & Zuddas, A. (2017) · CNS Drugs · doi:10.1007/s40263-017-0443-y · Cited by 45 · see citing works
Self-citationRoskell, N. S., Setyawan, J., Zimovetz, E. A., & Hodgkins, P. (2014) · Current Medical Research and Opinion · doi:10.1185/03007995.2014.904772 · Cited by 42 · see citing works
Banaschewski, T., Johnson, M., Lecendreux, M., Zuddas, A., Adeyi, B., Hodgkins, P., Squires, L. A., & Coghill, D. R. (2014) · CNS Drugs · doi:10.1007/s40263-014-0193-z · Cited by 41 · see citing works
Self-citationCoghill, D. R., Banaschewski, T., Lecendreux, M., Zuddas, A., Dittmann, R. W., Otero, I. H., Civil, R., Bloomfield, R., & Squires, L. A. (2014) · European Child & Adolescent Psychiatry · doi:10.1007/s00787-013-0421-y · Cited by 33 · see citing works
Self-citationWeiss, M., Childress, A., Mattingly, G., Nordbrock, E., Kupper, R. J., & Adjei, A. L. (2018) · Journal of Child and Adolescent Psychopharmacology · doi:10.1089/cap.2017.0166 · Cited by 30 · see citing works
Maneeton, N., Maneeton, B., Likhitsatian, S., Suttajit, S., Narkpongphun, A., Srisurapanont, M., & Woottiluk, P. (2015) · Drug Design, Development and Therapy · doi:10.2147/dddt.s79071 · Cited by 23 · see citing works
“However, freedom of selective reporting was determined in three studies (see Table 2).(11,12,34)”
Brams, M., Childress, A. C., Greenbaum, M., Yu, M., Yan, B., Jaffee, M., & Robertson, B. (2018) · Journal of Child and Adolescent Psychopharmacology · doi:10.1089/cap.2017.0053 · Cited by 12 · see citing works
Luan, R., Mu, Z., Yue, F., & He, S. (2017) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2017.00229 · Cited by 11 · see citing works
- Authors
- Coghill, D., Banaschewski, T., Lecendreux, M., Soutullo, C., Johnson, M., Zuddas, A., Anderson, C., Civil, R., Higgins, N., Lyne, A., & Squires, L.
- Affiliations
- University of Dundee (GB)
- Heidelberg University (DE)
- Hôpital Robert-Debré (FR)
- Drottning Silvias barn- och ungdomssjukhus (SE)
- University of Cagliari (IT)
- Shire (United Kingdom) (GB)
- Corresponding author
- Coghill, David
- ORCID
- Venue
- European Neuropsychopharmacology
- Publisher
- Elsevier BV
- Published
- 2013-10
- Volume
- 23
- Issue
- 10
- Pages
- 1208-1218
- ISSN
- 0924-977X (ISSN-L)
- OpenAlex
- W2086997214
- Cited by
- 123
- References
- 5
- Citations by year
- 2026: 3 · 2025: 9 · 2024: 4 · 2023: 7 · 2022: 5 · 2021: 5 · 2020: 5 · 2019: 6 · 2018: 10 · 2017: 8 · 2016: 13 · 2015: 16 · 2014: 23 · 2013: 9
- FWCI
- 14.46
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- European Neuropsychopharmacology (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Discovery Research Portal (University of Dundee) (submittedVersion)
- UNICA IRIS Institutional Research Information System (University of Cagliari) (submittedVersion)
- INFM-OAR (INFN Catania) (submittedVersion, cc-by-nc-nd)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Attention Deficit Hyperactivity Disorder
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Pharmaceutical studies and practices
- Health Sciences › Medicine › Pharmacology › Pharmacology and Obesity Treatment
- Keywords
- lisdexamfetamine dimesylate, attention deficit hyperactivity disorder, children and adolescents, OROS methylphenidate, ADHD-RS-IV, treatment efficacy, drug safety, stimulant medication, adverse events, vital signs, electrocardiogram
- MeSH terms
- Lisdexamfetamine Dimesylate, Adolescent, Adolescent Behavior, Central Nervous System Stimulants, Appetite Regulation, Attention Deficit Disorder with Hyperactivity, Child, Child Behavior, Dextroamphetamine, Dose-Response Relationship, Drug, Double-Blind Method, Drug Resistance, Europe, Female, Follow-Up Studies, Humans, Impulsive Behavior, Male, Methylphenidate, Patient Dropouts, Psychiatric Status Rating Scales, Severity of Illness Index, Diagnostic and Statistical Manual of Mental Disorders
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
