Hostname: page-component-78c5997874-mlc7c Total loading time: 0 Render date: 2024-11-15T15:49:43.609Z Has data issue: false hasContentIssue false
  • English
  • Français

Lisdexamfetamine Dimesylate: A Prodrug Stimulant for the Treatment of ADHD in Children and Adults

Published online by Cambridge University Press:  07 November 2014

Gregory Mattingly
Gregory Mattingly*
Affiliation:
Washington University
*
Dr. Gregory Mattingly, MD, Washington University School of Medicine, Department of Psychiatry and Behavioral Neurosciences, 330 First Capitol Drive, #390, St. Charles, MO, 63301; Tel: 636-949-3894, Fax:, 636-949-0729; e-mail:, greg@mattingly.com.
Get access Rights & Permissions [Opens in a new window]

Abstract

Attention-deficit/hyperactivity disorder (ADHD) is a highly genetic neuropsychiatric disorder that can cause impairment at school, work, home, and in social relationships. Once considered a childhood disorder, as many as 65% of children with ADHD continue to exhibit symptoms into adulthood. While a mainstay of ADHD patient care, immediate-release stimulant use has been constrained by concerns about safety, tolerability, and issues related to nonmedical use and abuse. These concerns have prompted interest in developing modified versions or new delivery systems for stimulants. Prodrugs have been used in pharmaceutical development to optimize delivery of an active drug or to minimize toxicity. Prodrugs are pharmacologically inactive compounds that require in vivo conversion to release therapeutically active medications. Lisdexamfetamine dimesylate (LDX) is an inactive, water-soluble prodrug in which d-amphetamine is bonded to l-lysine, a naturally occurring amino acid. After oral ingestion, LDX is metabolized into l-lysine and active d-amphetamine. This review of LDX presents the efficacy, safety, and pharmacokinetic profile of this novel stimulant medication, and is intended to help clinicians understand its role in treating children and adults with ADHD.

Type
Review Article
Information
CNS Spectrums , Volume 15 , Issue 5 , May 2010 , pp. 315 - 325
Copyright
Copyright © Cambridge University Press 2010

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

REFERENCES

1.Faraone, SV. Etiology and pathophysiology of adult attention-deficit/hyperactivity disorder. Primary Psychiatry. 2004;11:28–40.Google Scholar
2.Pliszka, S, Bernet, W, Bukstein, O, et al.AACAP Work Group on Quality Issues. Practice parameter for the assessment and treatment of children and adolescents with attention-deficit/hyperactivity disorder. J Am Acad Child Adolesc Psychiatry. 2007;46:894–921.CrossRefGoogle Scholar
3.Diagnostic and Statistical Manual of Mental Disorders, 4th edition, text revision. Arlington, VA: American Psychiatric Association; 2000.Google Scholar
4.Faraone, SVPerlis, RH, Doyle, AE, et al.Molecular genetics of attention-deficit/hyper-activity disorder. Biol Psychiatry. 2005;57:1313–1323.CrossRefGoogle Scholar
5.Spencer, TJ. Mixed amphetamine salts extended release for the treatment of ADHD in adolescents: current evidence. CNS Spectr. 2005;10(suppl 15):5.CrossRefGoogle Scholar
6.Dulcan, M, Dunne, JE, Ayres, W, et al.Work Group on Quality Issues. Practice parameters for the assessment and treatment of children, adolescents, and adults with attention-deficit/ hyperactivity disorder. J Am Acad Child Adolesc Psychiatry. 1997;36(suppl 10):85S–121S.CrossRefGoogle Scholar
7.Kessler, RC, Adler, L, Ames, M, et al.The World Health Organization adult ADHD self-report scale IASRS): a short screening scale for use in the general population. Psychol Med. 2005;35:245–256.CrossRefGoogle Scholar
8.Adler, L, Cohen, J. Diagnosis and evaluation of adults with attention-deficit/hyperactivity disorder. Psychiatr Clin North Am. 2004;27:187–201.CrossRefGoogle ScholarPubMed
9.Kessler, RC, Adler, L, Barkley, R, et al.The prevalence and correlates of adult ADHD in the United States: results from the National Comorbidity Survey Replication. Am J Psychiatry. 2006;163:716–723.CrossRefGoogle ScholarPubMed
10.Shaw, P, Eckstrand, K, Sharp, W, et al.Attention-deficit/hyperactivity disorder is characterized by a delay in cortical maturation. Proc Natl Acad Sci. 2007;104:19649–19654.CrossRefGoogle ScholarPubMed
11.Pelham, WE, Gnagy, EM, Burrows-Maclean, L, et al.Once-a-day Concerta methylphe-nidate versus three-times-daily methylphenidate in laboratory and natural settings. Pediatrics. 2001;107:e105–e119.CrossRefGoogle ScholarPubMed
12.Biederman, J, Lopez, FA, Boellner, SW, Chandler, MC. A randomized, double-blind, placebo-controlled, parallel-group study of SLI381 (Adderall XR) in children with attention-deficit/hyperactivity disorder. Pediatrics. 2002,110:258–266.CrossRefGoogle ScholarPubMed
13.Vyvanse (lisdexamfetamine dimesylate) capsules [package insert], Wayne, PA: Shire US Inc; 2009.Google Scholar
14.Krishnan, S, Zhang, Y. Relative bioavailability of lisdexamfetamine 70-mg capsules in fasted and fed healthy adult volunteers and in solution: a single-dose, crossover pharmacokinetic study. J Clin Pharmacol. 2008;48:293–302.CrossRefGoogle ScholarPubMed
15.Pennick, M. Hydrolytic conversion of lisdexamfetamine dimesylate to the active moiety, d-amphetamine. Presented at: Society of Biological Psychiatry Annual Scientific Convention and Meeting; May 14-16, 2009; Vancouver, British Columbia, Canada.Google Scholar
16.Pennick, M. Absorption of lisdexamfetamine dimesylate and hydrolysis to form the active moiety, d-amphetamine. Poster presented at: Annual Meeting of the New Clinical Drug Evaluation Unit; June 29-July 2,2009; Hollywood, FL.Google Scholar
17.Krishnan, SM, Pennick, M, Stark, JG. Metabolism, distribution and elimination of lisdexamfetamine dimesylate: open-label, single-centre, phase I study in healthy adult volunteers. Clin Drug Invest. 2008;28:745–755.CrossRefGoogle ScholarPubMed
18.Shojaei, A, Ermer, JC, Krishnan, S. Lisdexamfetamine dimesylate as a treatment for ADHD: dosage formulation and pH effects. Presented at: American Psychiatric Association Annual Meeting; May 19-24,2007; San Diego, CA. Poster NR740.Google Scholar
19.Markowitz, JS, Straughn, AB, Patrick, KS. Advances in the pharmacotherapy of attention-deficit-hyperactivity disorder: focus on methylphenidate formulations. Pharmacotherapy. 2003;23(10):1281–1299.CrossRefGoogle ScholarPubMed
20.Adderall XR (mixed salts of a single-entity amphetamine product) capsules [package insert]. Wayne, PA: Shire US Inc; 2009.Google Scholar
21.Haffey, M, Buckwalter, M, Zhang, P, et al.Effects of omeprazole on the pharmacokinetic profiles of lisdexamfetamine dimesylate and extended-release mixed amphetamine salts in adults. Postgrad Med. 2009;121:11–19.CrossRefGoogle ScholarPubMed
22.Krishnan, S, Moncrief, S, Ermer, JC. Lisdexamfetamine dimesylate |NRP104)-GLP in vitro human cytochrome P450 inhibitory drug-drug interaction study. Presented at: 61 st Annual Convention and Scientific Program of the Society of Biological Psychiatry; May 20,2006; Toronto, Canada.Google ScholarPubMed
23.Biederman, J, Boellner, SW, Childress, A, Lopez, FA, Krishnan, S, Zhang, Y. Lisdexamfetamine dimesylate and mixed amphetamine salts extended-release in children with ADHD: a double-blind, placebo-controlled, crossover analog classroom study. Biol Psychiatry. 2007;62:970–976.CrossRefGoogle ScholarPubMed
24.Ermer, JC, Shojaei, AH, Biederman, J, Krishnan, S. Improved interpatient pharmacokinetic variability of lisdexamfetamine dimesylate compared with mixed amphetamine salts extended release in children aged 6 to 12 years with attention-deficit/hyperac-tivity disorder. Presented at: American Psychiatric Association Annual Meeting; May 19-24, 2007; San Diego, CA. Poster NR750.Google Scholar
25.Ermer, J, Homolka, R, Martin, P, Buckwalter, M, Purkayastha, J, Roesch, BG. Linear dose proportionality, low inter- and intrasubject variability, and safety of lisdexamfetamine dimesylate in an open-label single-dose pharmacokinetic study in healthy adult volunteers. Presented at: American College of Clinical Pharmacy Annual Meeting; October 19-22, 2008; Louisville, KY. Poster 201.Google Scholar
26.Biederman, J, Krishnan, S, Zhang, Y, McGough, JJ, Findling, RL. Efficacy and tolerability of lisdexamfetamine dimesylate (NRP-104) in children with attention-deficit/hyper-activity disorder: a phase III, multicenter, randomized, double-blind, forced-dose, parallel-group study. Clin Ther. 2007;29:450–463.CrossRefGoogle Scholar
27.Wigal, SB, Kollins, SH, Childress, AC, Squires, LA. A 13-hour laboratory school study of lisdexamfetamine dimesylate in school-aged children with attention-deficit/hyperactivity disorder. Child Adolesc Psychiatry Ment Health. 2009;3:17.CrossRefGoogle ScholarPubMed
28.Findling, RL, Childress, AC, Krishnan, S, McGough, JJ. Long-term effectiveness and safety of lisdexamfetamine dimesylate in school-aged children with attention-deficit/ hyperactivity disorder. CNS Spectr. 2008;13:614–620.CrossRefGoogle ScholarPubMed
29.Findling, R, Jain, R, Gao, J, Richards, C, Ginsberg, L. A dose-optimization study of the efficacy, safety, and tolerability of lisdexamfetamine dimesylate in children aged 6 to 12 years with attention-deficit/hyperactivity disorder. Presented at: American Academy of Child and Adolescent Psychiatry Annual Meeting; October 28-November 2,2008; Chicago, IL. Poster 1.10.Google Scholar
30.Adler, LA, Goodman, DW, Kollins, SH, et al.303 Study Group. Double-blind, placebo-controlled study of the efficacy and safety of lisdexamfetamine dimesylate in adults with attention-deficit/hyperactivity disorder. J Clin Psychiatry. 2008;69:1364–1373.CrossRefGoogle Scholar
31.Brams, M. Efficacy and safety of lisdexamfetamine dimesylate in adults with attention, deficit/hyperactivity disorder in the adult workplace environment. Presented at: Annual Meeting of the New Clinical Drug Evaluation Unit; June 29-July 2, 2009; Hollywood, FL.Google Scholar
32.Weisler, R, Young, J, Mattingly, G, Gao, J, Squires, L, Adler, L; on behalf of the 304 Study Group. Long-term safety and effectiveness of lisdexamfetamine dimesylate in adults with attention-deficit/hyperactivity disorder. CNS Spectr. 2009;14:573–585.CrossRefGoogle Scholar
33.Wigal, SB, Gupta, S, Guinta, D, Swanson, JM. Reliability and validity of the SKAMP rating scale in a laboratory school setting. Psychopharmacol Bull. 1998;34:47–53.Google Scholar
34.Swanson, J, Wigal, S, Greenhill, L, et al.Objective and subjective measures of the pharmacodynamic effects of Adderall in the treatment of children with ADHD in a controlled laboratory classroom setting. Psychopharmacol Bull. 1998;34:55–60.Google Scholar
35.Guy, W, ed. ECDEU Assessment Manual for Psychopharmacology Revised. Rockville, MD: National Institute of Mental Health; DHEW publication no. ADM 76-338; 1976:218–222.Google Scholar
36.Lopez, FA, Childress, AC, Curtiss, S. Improvement in attention-deficit/hyperactivity disorder symptoms in children with lisdexamfetamine dimesylate versus extended-release mixed amphetamine salts and placebo in an analog classroom. Presented at: American College of Clinical Pharmacy Annual Meeting; October 19-22, 2008; Louisville, KY. Poster 206E.Google Scholar
37.Scheckner, B, Schreckengost, J, Favit, A. Physician perception of clinical improvement with lisdexamfetamine dimesylate in children aged 6 to 12 years with attention-deficit/hyperactivity disorder. Presented at: American Psychiatric Association Annual Meeting; May 3-8, 2008; Washington, DC. Poster NR6-003.Google Scholar
38.DuPaul, GJ, Power, TJ, Anastopoulos, AD, Reid, R. ADHD Bating Scale-IV: Checklists, Norms, and Clinical Interpretations. New York, NY: Guilford Press; 1998.Google Scholar
39.Conners, CK, Sitarenios, G, Parker, JDA, Epstein, JN. The revised Conners' Parent Rating Scale (CPRS-R): factor structure, reliability, and criterion validity. J Abnorm Child Psychol. 1998;26:257–268.CrossRefGoogle ScholarPubMed
40.Faraone, SV, Schreckengost, J. Lisdexamfetamine dimesylate effect size in children with attention-deficit/hyperactivity disorder. Presented at: American Academy of Child & Adolescent Psychiatry Annual Meeting; October 23-28, 2007; Boston, MA. Poster E58.Google Scholar
41.Mares, D, McLuckie, A, Schwartz, M, Saini, M. Executive function impairments in children with attention-deficit hyperactivity disorder: do they differ between school and home environments? Can J Psychiatry. 2007;52:527–534.CrossRefGoogle ScholarPubMed
42.Strine, TW, Lesesne, CA, Okoro, CA, et al.Emotional and behavioral difficulties and impairments in everyday functioning among children with a history of attention-deficit/hyperactivity disorder. Prev Chronic Dis. 2006;3:A52.Google ScholarPubMed
43.Perwien, AR, Kratochvil, CJ, Faries, D, et al.Emotional expression in children treated with ADHD medication: development of a new measure. J Atten Disord. 2008;11:568–579.CrossRefGoogle ScholarPubMed
44.Gioia, GA, Isquith, PK, Retzlaff, PD, Espy, KA. Confirmatory factor analysis of the Behavior Rating Inventory of Executive Function (BRIEF) in a clinical sample. Child Neuropsychol. 2002;8:249–257.CrossRefGoogle Scholar
45.Adler, LA, Goodman, D, Weisler, R, Hamdani, M, Roth, T. Effect of lisdexamfetamine dimesylate on sleep in adults with attention-deficit/hyperactivity disorder. Behav Brain Funct. 2009; 5:34.CrossRefGoogle ScholarPubMed
46.Favit, A, Schreckengost, J, Richards, C. Efficacy and safety of lisdexamfetamine dimesylate in adults with attention-deficit/hyperactivity disorder and a history of depression. Presented at: American Psychiatric Association Annual Meeting; May 3-8, 2008; Washington, DC. Poster NR6-002.Google Scholar
47.Upadhyaya, H, Schreckengost, J, Youcha, S. Efficacy and safety of lisdexamfetamine dimesylate in adults with attention-deficit/hyperactivity disorder and a history of substance use disorder. Presented at: American Psychiatric Association Annual Meeting; May 3-8, 2008; Washington, DC. Poster NR6-015.Google Scholar
48.Childress, AC, Wigal, SB, Greenbaum, M, Biederman, J. Efficacy and safety of lisdexamfetamine dimesylate in the treatment of female children and adults with attention-deficit/hyperactivity disorder. Presented at: American Psychiatric Association Annual Meeting; May 3-8, 2008; Washington, DC. Poster NR6-001.Google Scholar
49.Niebier, G, Wilens, TE, Weisler, R, Goodman, D, Adler, L, Biederman, J. Evaluation of cardiovascular effects of lisdexamfetamine dimesylate treatment in adults with attention-deficit/hyperactivity disorder. Presented at: American Psychiatric Association Annual Meeting; May 3-8, 2008; Washington, DC. Poster NR6-013.Google Scholar
50.Jasinski, DR, Krishnan, S. Human pharmacology of intravenous lisdexamfetamine dimesylate: abuse liability in adult stimulant abusers. J Psychopharmacol. 2009;23:410–418.CrossRefGoogle ScholarPubMed
51.Jasinski, DR. Krishnan, S. Abuse liability and safety of oral lisdexamfetamine dimesylate in individuals with a history of stimulant abuse. J Psychopharmacol. 2009;23:419–427.CrossRefGoogle ScholarPubMed