Lisdexamfetamine Dimesylate and Mixed Amphetamine Salts Extended-Release in Children with ADHD: A Double-Blind, Placebo-Controlled, Crossover Analog Classroom Study
Abstract
Background Lisdexamfetamine dimesylate is a therapeutically inactive prodrug in which d-amphetamine is covalently bound to l-lysine, a naturally occurring amino acid. Pharmacologically active d-amphetamine is released from lisdexamfetamine following oral ingestion.Methods This phase 2, randomized, double-blind, placebo- and active-controlled crossover study compared the efficacy and safety of lisdexamfetamine (LDX: 30, 50, or 70 mg) with placebo, with mixed amphetamine salts extended-release (MAS XR: 10, 20, or 30 mg) included as a reference arm of the study, in 52 children aged 6 to 12 years with attention-deficit/hyperactivity disorder (ADHD) in an analog classroom setting. The primary efficacy measure was the Swanson, Kotkin, Agler, M-Flynn, and Pelham (SKAMP) Rating Scale; secondary efficacy measures included the Permanent Product Measure of Performance (PERMP) Derived Measures, and the Clinical Global Impression (CGI) Scale.Results LDX treatment significantly improved scores on SKAMP-deportment, SKAMP-attention, PERMP-attempted, PERMP-correct, and CGI-improvement from baseline. Adverse events were similar for both active treatments.Conclusions In a laboratory classroom environment, LDX significantly improved ADHD symptoms versus placebo in school-age children with ADHD.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
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?
LDX was generally well tolerated with adverse events (AEs) similar to those seen with other once-daily stimulants.
“LDX was generally well tolerated with adverse events (AEs) similar to those seen with other once-daily stimulants [13].”
From A 13-hour laboratory school study of lisdexamfetamine dimesylate in school-aged children with attention-deficit/hyperactivity disorder (2009) · cites this paper as [13]
Efficacy in LDX-treated subjects compared with placebo was significant beginning at 2 hours postdose and lasted up to 12 hours postdose, the last time point measured.
“Efficacy in LDX-treated subjects compared with placebo was significant beginning at 2 hours postdose and lasted up to 12 hours postdose, the last time point measured.”
From A 13-hour laboratory school study of lisdexamfetamine dimesylate in school-aged children with attention-deficit/hyperactivity disorder (2009) · cites this paper as [13]
In a previous laboratory school study, LDX demonstrated efficacy 2 hours postdose with duration of efficacy through 12 hours.
“In a previous laboratory school study, LDX demonstrated efficacy 2 hours postdose with duration of efficacy through 12 hours.”
From A 13-hour laboratory school study of lisdexamfetamine dimesylate in school-aged children with attention-deficit/hyperactivity disorder (2009) · cites this paper as [13]
A 6-week, randomized, double-blind, crossover study in a laboratory school setting showed that LDX was significantly more effective in reducing ADHD symptoms compared with placebo (P < .0001), as measured by SKAMP-D throughout the day.
“A 6-week, randomized, double-blind, crossover study in a laboratory school setting [13] similar to the current study showed that LDX was significantly more effective in reducing ADHD symptoms compared with placebo (P < .0001), as measured by the Swanson, Kotkin, Agler, M-Flynn, and Pelham deportment (SKAMP-D) subscale throughout the day [14].”
From A 13-hour laboratory school study of lisdexamfetamine dimesylate in school-aged children with attention-deficit/hyperactivity disorder (2009) · cites this paper as [13]
In the previous laboratory school study, treatment effects were observed beginning at 2 hours postdose and continued until 12 hours postdose.
“In the previous study, treatment effects were observed beginning at 2 hours postdose and continued until 12 hours postdose.”
From A 13-hour laboratory school study of lisdexamfetamine dimesylate in school-aged children with attention-deficit/hyperactivity disorder (2009) · cites this paper as [13]
This study expanded and further refined findings from a previous laboratory school study due to a larger sample size (129 vs 52) and additional time points assessed predose and 13-hour measurements (-0.5 to 13 hours vs 1 to 12 hours).
“This study expanded and further refined findings from a previous laboratory school study, due to a larger sample size (129 vs 52), and additional time points assessed predose and 13-hour measurements (-0.5 to 13 hours in this study vs 1 to 12 hours) [13].”
From A 13-hour laboratory school study of lisdexamfetamine dimesylate in school-aged children with attention-deficit/hyperactivity disorder (2009) · cites this paper as [13]
The adverse events reported in this study were similar in nature to those reported in studies of other stimulants and included decreased appetite, insomnia, headache, irritability, upper abdominal pain, and affect lability.
“The AEs reported here were similar in nature to those reported in studies of other stimulants and included decreased appetite, insomnia, headache, irritability, upper abdominal pain, and affect lability [10,13,27-29].”
From A 13-hour laboratory school study of lisdexamfetamine dimesylate in school-aged children with attention-deficit/hyperactivity disorder (2009) · cites this paper as [13]
Low interpatient variability of d-amphetamine plasma levels from LDX has been suggested by consistent delivery of d-amphetamine from patient to patient in a study in children with ADHD and, similarly, within and between subjects in a clinical trial in healthy adults.
“Low interpatient variability of d-amphetamine plasma levels from LDX has been suggested by consistent delivery of d-amphetamine from patient to patient in a study in children with ADHD and, similarly, within and between subjects in a clinical trial in healthy adults. 2,3”
From Absorption of lisdexamfetamine dimesylate and its enzymatic conversion to d-amphetamine (2010) · cites this paper as [2]
The dual findings of high-capacity absorption and enzymatic conversion may contribute to the consistent and reproducible pharmacokinetic profile of LDX in humans.
“The dual findings of high-capacity absorption and enzymatic conversion may contribute to the consistent and reproducible pharmacokinetic profile of LDX in humans. 2,3”
From Absorption of lisdexamfetamine dimesylate and its enzymatic conversion to d-amphetamine (2010) · cites this paper as [2]
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 [10]
Previous 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 [10]
In Biederman et al Phase II trial of 52 children aged 6-12 years with ADHD, both MAS XR and lisdexamfetamine produced statistically significant improvement (P < 0.001) measured by SKAMP, PERMP, and CGI.
“There was a statistically significant improvement (P < 0.001) in both the MAS XR and lisdexamfetamine groups. This was measured using the Swanson, Kotkin, Agler, M-Flynn, and Pelham (SKAMP), Permanent Product Measure of Performance (PERMP), and the Clinical Global Impression (CGI) rating scales.”
From Update on optimal use of lisdexamfetamine in the treatment of ADHD (2013) · cites this paper as [17]
In that trial, insomnia, decreased appetite, and anorexia were the most common adverse effects noticed with lisdexamfetamine.
“Insomnia, decreased appetite, and anorexia were the most common adverse effects noticed with lisdexamfetamine.”
From Update on optimal use of lisdexamfetamine in the treatment of ADHD (2013) · cites this paper as [17]
In that trial, small changes in diastolic blood pressure and pulse rate, along with changes in the QTc interval, were noted but were not clinically or statistically significant.
“Small changes in diastolic blood pressure and pulse rate, along with changes in the QTc interval, were noted but were not clinically or statistically significant.”
From Update on optimal use of lisdexamfetamine in the treatment of ADHD (2013) · cites this paper as [17]
Multiple randomized, double-blind, placebo-controlled trials have shown LDX to be an effective treatment for children, adolescents and adults with ADHD, with a tolerability and safety profile consistent with the known effects of psychostimulant therapy.
“Multiple randomized, double-blind, placebo-controlled trials have shown LDX to be an effective treatment for children, adolescents and adults with ADHD, with a tolerability and safety profile consistent with the known effects of psychostimulant therapy [9–15].”
Cites
Diagnostic and Statistical Manual of Mental Disorders
Williams, J. B. W., & First, M. B. (2013) · Oxford University Press eBooks · doi:10.1093/acrefore/9780199975839.013.104 · Cited by 109,841 · see citing works
(1976) · Medical Entomology and Zoology · Cited by 8,899 · see citing works
Pliszka, S. (2007) · Journal of the American Academy of Child & Adolescent Psychiatry · doi:10.1097/chi.0b013e318054e724 · Cited by 1,765 · see citing works
Attention-deficit hyperactivity disorder
Biederman, J., & Faraone, S. V. (2005) · The Lancet · doi:10.1016/s0140-6736(05)66915-2 · Cited by 1,463 · see citing works
Self-citationDulcan, M. (1997) · Journal of the American Academy of Child & Adolescent Psychiatry · doi:10.1097/00004583-199710001-00007 · Cited by 628 · see citing works
Epidemiology of Adhd in School-Age Children
Scahill, L., & Schwab‐Stone, M. (2000) · Child and Adolescent Psychiatric Clinics of North America · doi:10.1016/s1056-4993(18)30106-8 · Cited by 528 · see citing works
PLISZKA, S. R., CRISMON, M. L., HUGHES, C. W., CORNERS, C. K., EMSLIE, G. J., JENSEN, P. S., McCRACKEN, J. T., SWANSON, J. M., & LOPEZ, M. (2006) · Journal of the American Academy of Child & Adolescent Psychiatry · doi:10.1097/01.chi.0000215326.51175.eb · Cited by 442 · see citing works
Biederman, J., Krishnan, S., Zhang, Y., McGough, J. J., & Findling, R. L. (2007) · Clinical Therapeutics · doi:10.1016/s0149-2918(07)80083-x · Cited by 404 · see citing works
Self-citationDarpö, B., Nebout, T., & Sager, P. T. (2006) · The Journal of Clinical Pharmacology · doi:10.1177/0091270006286436 · Cited by 316 · see citing works
(1998) · PubMed · Cited by 130 · see citing works
MCCRACKEN, J. T., BIEDERMAN, J., GREENHILL, L. L., SWANSON, J. M., MCGOUGH, J. J., SPENCER, T. J., POSNER, K., WIGAL, S., PATAKI, C., ZHANG, Y., et al. (2003) · Journal of the American Academy of Child & Adolescent Psychiatry · doi:10.1097/01.chi.0000046863.56865.fe · Cited by 116 · see citing works
Self-citationVoeller, K. K. S. (2000) · Pediatric Neurology · doi:10.1016/s0887-8994(00)00149-1 · Cited by 105 · see citing works
Swanson, J. M., Wigal, S. B., Greenhill, L. L., Browne, R., WASLICK, B. D., Lerner, M., Williams, L., Flynn, D., AGLER, D., Crowley, K., et al. (1998) · PubMed · Cited by 72 · see citing works
Greenhill, L. L., & Osman, B. B. (2000) · Cited by 71 · see citing works
Disorders usually first diagnosed in infancy, childhood, or adolescence.
Popper, C. W., Gammon, G. D., West, S. A., & Bailey, C. E. (1994) · Cited by 69 · see citing works
Disorders usually first diagnosed in infancy, childhood or adolescence
Wood, C., & Green, D. (2011) · Swinburne figshare (Swinburne University of Technology) · Cited by 15 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Bolea-Alamañac, B., Nutt, D. J., Adamou, M., Asherson, P., Bazire, S., Coghill, D., Heal, D., Müller, U., Nash, J., Santosh, P., et al. (2014) · Journal of Psychopharmacology · doi:10.1177/0269881113519509 · Cited by 287 · see citing works
Attention-deficit-hyperactivity disorder and reward deficiency syndrome
Oscar Berman, M., Blum, K., Chen, T. J., Braverman, E., Waite, R., Downs, W., Arcuri, V., Notaro, A., Palomo, T., & Comings (2008) · Neuropsychiatric Disease and Treatment · doi:10.2147/ndt.s2627 · Cited by 248 · see citing works
“…crossover study compared the effi cacy and safety of LDX (30, 50, or 70 mg) with placebo, with mixed amphetamine salts (extended-release 10, 20, or 30 mg) included as a reference arm of the study, in 52 ADHD children aged 6–12 years in an analog classroom setting (Biederman et al 2007a).”
BackgroundMethodAdler, 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
Self-citationThe neuropharmacology of ADHD drugs in vivo: Insights on efficacy and safety
Heal, D. J., Cheetham, S. C., & Smith, S. L. (2009) · Neuropharmacology · doi:10.1016/j.neuropharm.2009.08.020 · Cited by 198 · 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 · see citing works
ADHD Treatments, Sleep, and Sleep Problems: Complex Associations
Stein, M. A., Weiss, M., & Hlavaty, L. (2012) · Neurotherapeutics · doi:10.1007/s13311-012-0130-0 · Cited by 165 · see citing works
Jasinski, D., & Krishnan, S. (2009) · Journal of Psychopharmacology · doi:10.1177/0269881109103113 · Cited by 149 · see citing works
Self-citationWigal, 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 · see citing works
“LDX demonstrated efficacy compared with placebo by the Permanent Product Measure of Performance (PERMP) and other assessments in the laboratory school setting at 12 and 13 hours postdose in children with ADHD [ 15 ,16].”
BackgroundMethodInfluentialFindling, R. L., Childress, A. C., Cutler, A. J., Gasior, M., Hamdani, M., Ferreira-Cornwell, M. C., & Squires, L. (2011) · Journal of the American Academy of Child & Adolescent Psychiatry · doi:10.1016/j.jaac.2011.01.007 · Cited by 120 · see citing works
Self-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-citationWeisler, R., Young, J., Mattingly, G., Gao, J., Squires, L., Adler, L., & 304 Study Group (2009) · CNS Spectrums · doi:10.1017/s1092852900024056 · Cited by 94 · see citing works
New treatment approaches for severe and enduring eating disorders
Treasure, J., Cardi, V., Leppanen, J., & Turton, R. (2015) · Physiology & Behavior · doi:10.1016/j.physbeh.2015.06.007 · Cited by 91 · 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
Ermer, J., Homolka, R., Martin, P., Buckwalter, M., Purkayastha, J., & Roesch, B. (2010) · The Journal of Clinical Pharmacology · doi:10.1177/0091270009357346 · Cited by 72 · see citing works
Boellner, S. W., Stark, J. G., Krishnan, S., & Zhang, Y. (2010) · Clinical Therapeutics · doi:10.1016/j.clinthera.2010.02.011 · Cited by 72 · see citing works
Self-citationMultiple daily-dose pharmacokinetics of lisdexamfetamine dimesylate in healthy adult volunteers
Krishnan, S. M., & Stark, J. G. (2008) · Current Medical Research and Opinion · doi:10.1185/030079908x242737 · Cited by 55 · see citing works
Self-citationKollins, S. H., López, F. A., Vince, B. D., Turnbow, J. M., Farrand, K., Lyne, A., Wigal, S. B., & Roth, T. (2011) · Journal of Child and Adolescent Psychopharmacology · doi:10.1089/cap.2010.0064 · Cited by 53 · see citing works
Self-citationFindling, R. L., Ginsberg, L. D., Jain, R., & Gao, J. (2009) · Journal of Child and Adolescent Psychopharmacology · doi:10.1089/cap.2008.0165 · Cited by 45 · 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
López, F. A., & Leroux, J. R. (2013) · ADHD Attention Deficit and Hyperactivity Disorders · doi:10.1007/s12402-013-0106-x · Cited by 43 · see citing works
Najib, J. (2009) · Clinical Therapeutics · doi:10.1016/j.clinthera.2009.01.015 · Cited by 40 · see citing works
Effects of Lisdexamfetamine Dimesylate Treatment for ADHD on Growth
Faraone, S. V., Spencer, T. J., Kollins, S. H., & Glatt, S. J. (2010) · Journal of the American Academy of Child & Adolescent Psychiatry · doi:10.1097/00004583-201001000-00006 · Cited by 39 · see citing works
Effect of Lisdexamfetamine Dimesylate on Sleep in Children With ADHD
Giblin, J. M., & Strobel, A. L. (2011) · Journal of Attention Disorders · doi:10.1177/1087054710371195 · Cited by 38 · see citing works
Ermer, J. C., Dennis, K., Haffey, M. B., Doll, W. J., Sandefer, E. P., Buckwalter, M., Page, R. C., Diehl, B., & Martin, P. T. (2011) · Clinical Drug Investigation · doi:10.2165/11588190-000000000-00000 · Cited by 35 · see citing works
Faraone, S. V. (2008) · Expert Opinion on Pharmacotherapy · doi:10.1517/14656566.9.9.1565 · Cited by 33 · see citing works
Upadhyaya, H. P. (2008) · The Primary Care Companion to The Journal of Clinical Psychiatry · doi:10.4088/pcc.v10n0306 · Cited by 31 · see citing works
Lisdexamfetamine Dimesylate: A New Therapeutic Option for Attention-Deficit Hyperactivity Disorder
Steer, C., Froelich, J., Soutullo, C. A., Johnson, M., & Shaw, M. (2012) · CNS Drugs · doi:10.2165/11634340-000000000-00000 · Cited by 30 · see citing works
Changes in Emotions Related to Medication Used to Treat ADHD. Part I: Literature Review
Manos, M. J., Brams, M., Childress, A. C., Findling, R. L., López, F. A., & Jensen, P. S. (2011) · Journal of Attention Disorders · doi:10.1177/1087054710381230 · Cited by 28 · see citing works
Self-citationManeeton, 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, two studies had the lack of clearness of a risk of bias in two or more domains (see Table 2).(10,34)”
InfluentialWigal, S. B., Kollins, S. H., Childress, A. C., & Adeyi, B. (2010) · Child and Adolescent Psychiatry and Mental Health · doi:10.1186/1753-2000-4-32 · Cited by 23 · see citing works
Self-citationUpdate on optimal use of lisdexamfetamine in the treatment of ADHD
Madaan, V., Kolli, V., Bestha, D., & Shah, M. (2013) · Neuropsychiatric Disease and Treatment · doi:10.2147/ndt.s34092 · Cited by 19 · see citing works
Weisler, R., Childress, A., Adler, L., Kollins, S., Goodman, D., Hamdani, & Dirks, B. (2013) · Neuropsychiatric Disease and Treatment · doi:10.2147/ndt.s47087 · Cited by 16 · see citing works
Self-citationWigal, S. B., Maltas, S., Crinella, F., Stehli, A., Steinhoff, K., Lakes, K., & Schuck, S. (2012) · Journal of Attention Disorders · doi:10.1177/1087054710378008 · Cited by 14 · see citing works
Lisdexamfetamine dimesylate: a new option in stimulant treatment for ADHD
Dew, R. E., & Kollins, S. H. (2010) · Expert Opinion on Pharmacotherapy · doi:10.1517/14656566.2010.531009 · Cited by 14 · see citing works
Jain, R., Babcock, T., Burtea, T., Dirks, B., Adeyi, B., Scheckner, B., Lasser, R., Renna, J., & Duncan, D. (2013) · Advances in Therapy · doi:10.1007/s12325-013-0027-2 · Cited by 9 · see citing works
Antonucci, D., Kunins, C., Manos, M., López, F. A., & Kerney, D. L. (2010) · CNS Spectrums · doi:10.1017/s1092852900000080 · Cited by 6 · see citing works
- Authors
- Biederman, J., Boellner, S. W., Childress, A., Lopez, F. A., Krishnan, S., & Zhang, Y.
- Affiliations
- Harvard University (US)
- Center for Psychiatry and Behavioral Medicine (US)
- Corresponding author
- Biederman, Joseph
- Venue
- Biological Psychiatry
- Publisher
- Elsevier BV
- Published
- 2007-11
- Volume
- 62
- Issue
- 9
- Pages
- 970-976
- ISSN
- 0006-3223 (ISSN-L)
- OpenAlex
- W1992488678
- Semantic Scholar
- d36d110009ae7a939cea1c85575af3dd12d6a288
- Cited by
- 356
- References
- 16
- Citations by year
- 2026: 1 · 2025: 6 · 2024: 10 · 2023: 2 · 2022: 5 · 2021: 3 · 2020: 162 · 2019: 4 · 2018: 6 · 2017: 3 · 2016: 7 · 2015: 8 · 2014: 13 · 2013: 17 · 2012: 19
- FWCI
- 14.18
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Biological Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- 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, prodrugs, academic performance, adverse events
- MeSH terms
- Lisdexamfetamine Dimesylate, Amphetamine, Central Nervous System Stimulants, Attention Deficit Disorder with Hyperactivity, Child, Delayed-Action Preparations, Dextroamphetamine, Double-Blind Method, Female, Humans, Male, Psychiatric Status Rating Scales, Time Factors, Treatment Outcome, Cross-Over Studies
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
