Evaluation of the Effect and Safety of Lisdexamfetamine in Children Aged 6-12 With ADHD and Autism

Summary

The purpose of this study is to evaluate the effect and safety of Lisdexamfetamine dimesylate (Vyvanse®) in the treatment of Attention Deficit Hyperactivity Disorder (ADHD) in children and adolescents with ADHD and comorbid Autism Spectrum Disorder (ASD). This would be a novel study as there is no known safety or efficacy data for amphetamine based medications in this population. In addition, although health related quality of life and executive function are known to improve with the treatment of lisdexamfetamine dimesylate in the ADHD population (Banaschewski 2013; Findling 2009; Turgay 2010), it has not been shown in the co-morbid ADHD and ASD population. ADHD is the most common pediatric neurobiological condition affecting approximately five percent of the pediatric population (Feldman 2009). ASD is being increasingly recognized as affecting a substantial amount of the pediatric population, with recent prevalence data showing 1 in 68 affected (Baio, 2014). Prior to the introduction of DSM-5 (APA, 2013), exclusion criteria precluded the diagnosis of ADHD when ASD was present. Studies have shown that 41%-71% of children with ASD also meet criteria for ADHD (Goldstein 2004, Sturm 2004,Yoshida 2004, Gadow 2006). This means that up to 1% of the population may have co-morbid ADHD and ASD. With the official recognition of this comorbidity, treatment of comorbid ADHD when ASD is also present has been increasingly recognized as an important strategy in improving executive functioning and quality of life in those affected. Studies have indicated that some of the medications commonly used to treat ADHD, are effective and safe when used in comorbid ADHD and ASD. At this time, there have been well designed studies demonstrating safety and efficacy for methylphenidate (Ghuman et al. 2009; Handen et al. 2000; Quintana et al. 1995; RUPP 2005), guanfacine XR (Posey 2004; Scahill 2015), and atomoxetine (Arnold 2006; Harfterkamp 2012).

Timeline

Start

2018-09-26

Primary completion

2023-03-31

Completion

2023-03-31

Publications

• Background First MB. Diagnostic and statistical manual of mental disorders, 5th edition, and clinical utility. J Nerv Ment Dis. 2013 Sep;201(9):727-9. doi: 10.1097/NMD.0b013e3182a2168a. No abstract available.
• Background Arnsten AF. Modulation of prefrontal cortical-striatal circuits: relevance to therapeutic treatments for Tourette syndrome and attention-deficit hyperactivity disorder. Adv Neurol. 2001;85:333-41. No abstract available.
• Background Bhutta AT, Cleves MA, Casey PH, Cradock MM, Anand KJ. Cognitive and behavioral outcomes of school-aged children who were born preterm: a meta-analysis. JAMA. 2002 Aug 14;288(6):728-37. doi: 10.1001/jama.288.6.728.
• Background Biederman J, Krishnan S, Zhang Y, McGough JJ, Findling RL. Efficacy and tolerability of lisdexamfetamine dimesylate (NRP-104) in children with attention-deficit/hyperactivity disorder: a phase III, multicenter, randomized, double-blind, forced-dose, parallel-group study. Clin Ther. 2007 Mar;29(3):450-63. doi: 10.1016/s0149-2918(07)80083-x.
• Background Bolte S, Willfors C, Berggren S, Norberg J, Poltrago L, Mevel K, Coco C, Fransson P, Borg J, Sitnikov R, Toro R, Tammimies K, Anderlid BM, Nordgren A, Falk A, Meyer U, Kere J, Landen M, Dalman C, Ronald A, Anckarsater H, Lichtenstein P. The Roots of Autism and ADHD Twin Study in Sweden (RATSS). Twin Res Hum Genet. 2014 Jun;17(3):164-76. doi: 10.1017/thg.2014.12. Epub 2014 Apr 15.
• Background Brown K. Neuroscience. New attention to ADHD genes. Science. 2003 Jul 11;301(5630):160-1. doi: 10.1126/science.301.5630.160. No abstract available.
• Background Bruni, T., 2014. Test Review: Social Responsiveness Scale-Second Edition. (SRS-2).
• Background Coghill DR, Caballero B, Sorooshian S, Civil R. A systematic review of the safety of lisdexamfetamine dimesylate. CNS Drugs. 2014 Jun;28(6):497-511. doi: 10.1007/s40263-014-0166-2.
• Background Department of Health, E. and W., 1976. Clinical Global Impression (CGI). In Guy W. ED. ECEDEU Assessment Manual for pyschopharmacology.
• Background DuPaul, G. et al., 1998. ADHD Rating Scale IV: Checklists, Norms and Clinical Interpretation. In New York, NY: Guilford Press.
• Background Efron D, Jarman F, Barker M. Side effects of methylphenidate and dexamphetamine in children with attention deficit hyperactivity disorder: a double-blind, crossover trial. Pediatrics. 1997 Oct;100(4):662-6. doi: 10.1542/peds.100.4.662.
• Background Faraone SV, Sergeant J, Gillberg C, Biederman J. The worldwide prevalence of ADHD: is it an American condition? World Psychiatry. 2003 Jun;2(2):104-13.
• Background Faraone SV. Lisdexamfetamine dimesylate: the first long-acting prodrug stimulant treatment for attention deficit/hyperactivity disorder. Expert Opin Pharmacother. 2008 Jun;9(9):1565-74. doi: 10.1517/14656566.9.9.1565.
• Background Feldman M, Belanger S. Extended-release medications for children and adolescents with attention-deficit hyperactivity disorder. Paediatr Child Health. 2009 Nov;14(9):593-602. doi: 10.1093/pch/14.9.593.
• Background Ghuman JK, Aman MG, Lecavalier L, Riddle MA, Gelenberg A, Wright R, Rice S, Ghuman HS, Fort C. Randomized, placebo-controlled, crossover study of methylphenidate for attention-deficit/hyperactivity disorder symptoms in preschoolers with developmental disorders. J Child Adolesc Psychopharmacol. 2009 Aug;19(4):329-39. doi: 10.1089/cap.2008.0137.
• Background Gioia, G. et al., 2000. Behaviour Rating Inventory of Executive Function (BRIEF): Professional Manual,
• Background Goldstein S, Schwebach AJ. The comorbidity of Pervasive Developmental Disorder and Attention Deficit Hyperactivity Disorder: results of a retrospective chart review. J Autism Dev Disord. 2004 Jun;34(3):329-39. doi: 10.1023/b:jadd.0000029554.46570.68.
• Background Handen BL, Johnson CR, Lubetsky M. Efficacy of methylphenidate among children with autism and symptoms of attention-deficit hyperactivity disorder. J Autism Dev Disord. 2000 Jun;30(3):245-55. doi: 10.1023/a:1005548619694.
• Background Hardman, J., Limbird, L. & Gilman, A., 2001. Goodman & Gillman's The Pharmacological Basis of Therapeutics, 10th edition,
• Background Hazlett HC, Poe M, Gerig G, Smith RG, Provenzale J, Ross A, Gilmore J, Piven J. Magnetic resonance imaging and head circumference study of brain size in autism: birth through age 2 years. Arch Gen Psychiatry. 2005 Dec;62(12):1366-76. doi: 10.1001/archpsyc.62.12.1366.
• Background Heal DJ, Smith SL, Gosden J, Nutt DJ. Amphetamine, past and present--a pharmacological and clinical perspective. J Psychopharmacol. 2013 Jun;27(6):479-96. doi: 10.1177/0269881113482532. Epub 2013 Mar 28.
• Background Kratochvil CJ, Vaughan BS, Harrington MJ, Burke WJ. Atomoxetine: a selective noradrenaline reuptake inhibitor for the treatment of attention-deficit/hyperactivity disorder. Expert Opin Pharmacother. 2003 Jul;4(7):1165-74. doi: 10.1517/14656566.4.7.1165.
• Background Kahn RS, Khoury J, Nichols WC, Lanphear BP. Role of dopamine transporter genotype and maternal prenatal smoking in childhood hyperactive-impulsive, inattentive, and oppositional behaviors. J Pediatr. 2003 Jul;143(1):104-10. doi: 10.1016/S0022-3476(03)00208-7.
• Background Leitner Y. The co-occurrence of autism and attention deficit hyperactivity disorder in children - what do we know? Front Hum Neurosci. 2014 Apr 29;8:268. doi: 10.3389/fnhum.2014.00268. eCollection 2014.
• Background Lewin AH, Miller GM, Gilmour B. Trace amine-associated receptor 1 is a stereoselective binding site for compounds in the amphetamine class. Bioorg Med Chem. 2011 Dec 1;19(23):7044-8. doi: 10.1016/j.bmc.2011.10.007. Epub 2011 Oct 13.
• Background Lord C, Cook EH, Leventhal BL, Amaral DG. Autism spectrum disorders. Neuron. 2000 Nov;28(2):355-63. doi: 10.1016/s0896-6273(00)00115-x. No abstract available.
• Background Harfterkamp M, van de Loo-Neus G, Minderaa RB, van der Gaag RJ, Escobar R, Schacht A, Pamulapati S, Buitelaar JK, Hoekstra PJ. A randomized double-blind study of atomoxetine versus placebo for attention-deficit/hyperactivity disorder symptoms in children with autism spectrum disorder. J Am Acad Child Adolesc Psychiatry. 2012 Jul;51(7):733-41. doi: 10.1016/j.jaac.2012.04.011. Epub 2012 May 25.
• Background Davis NO, Kollins SH. Treatment for co-occurring attention deficit/hyperactivity disorder and autism spectrum disorder. Neurotherapeutics. 2012 Jul;9(3):518-30. doi: 10.1007/s13311-012-0126-9.
• Background Posey DJ, Puntney JI, Sasher TM, Kem DL, McDougle CJ. Guanfacine treatment of hyperactivity and inattention in pervasive developmental disorders: a retrospective analysis of 80 cases. J Child Adolesc Psychopharmacol. 2004 Summer;14(2):233-41. doi: 10.1089/1044546041649084.
• Background Posner K, Brown GK, Stanley B, Brent DA, Yershova KV, Oquendo MA, Currier GW, Melvin GA, Greenhill L, Shen S, Mann JJ. The Columbia-Suicide Severity Rating Scale: initial validity and internal consistency findings from three multisite studies with adolescents and adults. Am J Psychiatry. 2011 Dec;168(12):1266-77. doi: 10.1176/appi.ajp.2011.10111704.
• Background Quintana H, Birmaher B, Stedge D, Lennon S, Freed J, Bridge J, Greenhill L. Use of methylphenidate in the treatment of children with autistic disorder. J Autism Dev Disord. 1995 Jun;25(3):283-94. doi: 10.1007/BF02179289.
• Background Scahill L, McCracken JT, King BH, Rockhill C, Shah B, Politte L, Sanders R, Minjarez M, Cowen J, Mullett J, Page C, Ward D, Deng Y, Loo S, Dziura J, McDougle CJ; Research Units on Pediatric Psychopharmacology Autism Network. Extended-Release Guanfacine for Hyperactivity in Children With Autism Spectrum Disorder. Am J Psychiatry. 2015 Dec;172(12):1197-206. doi: 10.1176/appi.ajp.2015.15010055. Epub 2015 Aug 28.
• Background Stigler KA, Desmond LA, Posey DJ, Wiegand RE, McDougle CJ. A naturalistic retrospective analysis of psychostimulants in pervasive developmental disorders. J Child Adolesc Psychopharmacol. 2004 Spring;14(1):49-56. doi: 10.1089/104454604773840481.
• Background Thomas R, Sanders S, Doust J, Beller E, Glasziou P. Prevalence of attention-deficit/hyperactivity disorder: a systematic review and meta-analysis. Pediatrics. 2015 Apr;135(4):e994-1001. doi: 10.1542/peds.2014-3482. Epub 2015 Mar 2.
• Background Thompson T, Lloyd A, Joseph A, Weiss M. The Weiss Functional Impairment Rating Scale-Parent Form for assessing ADHD: evaluating diagnostic accuracy and determining optimal thresholds using ROC analysis. Qual Life Res. 2017 Jul;26(7):1879-1885. doi: 10.1007/s11136-017-1514-8. Epub 2017 Feb 20.
• Background U.S. Department of Health and Human Services, 2010. Prevalence of autism spectrum disorder among children aged 8 years - autism and developmental disabilities

Drugs

Indications