Arbaclofen in Children and Adolescents with Autism Spectrum Disorder: A Randomized, Controlled, Phase 2 Trial

Neuropsychopharmacology

Volumn 42, Issue 7, 2017, Pages 1390-1398

  Veenstra Vanderweele, Jeremy ^a,b,c   Cook, Edwin H ^d   King, Bryan H ^e   Zarevics, Peter ^f   Cherubini, Maryann ^f   Walton Bowen, Karen ^g   Bear, Mark F ^h   Wang, Paul P ⁱ   Carpenter, Randall L ^f  

^a Och Spine at New York Presbyterian Hospitals   (United States)

^b NEW YORK PRESBYTERIAN HOSPITAL   (United States)

^c NEW YORK STATE PSYCHIATRIC INSTITUTE   (United States)

^d UNIVERSITY OF ILLINOIS AT CHICAGO   (United States)

^e UNIVERSITY OF WASHINGTON   (United States)

^f Seaside Therapeutics   (United States)

^g FLATIRON INSTITUTE   (United States)

^h MASSACHUSETTS INSTITUTE OF TECHNOLOGY   (United States)

ⁱ Autism Speaks Inc   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ARBACLOFEN; DIPHENHYDRAMINE; 4 AMINOBUTYRIC ACID B RECEPTOR STIMULATING AGENT; ARBACLOFEN PLACARBIL; BACLOFEN;

ABERRANT BEHAVIOR CHECKLIST; ABNORMAL SENSATION; ADOLESCENT; ADULT; AFFECT; AFFECT LABILITY; AGGRESSION; AGITATION; ANAPHYLAXIS; ANXIETY; ARTICLE; ATTENTION DISTURBANCE; AUTISM; AVOIDANCE BEHAVIOR; BODY WEIGHT DISORDER; CHILD; CLINICAL GLOBAL IMPRESSION SCALE; CONTROLLED STUDY; COUGHING; CROSSOVER PROCEDURE; DECREASED APPETITE; DIARRHEA; DISEASE SEVERITY; DOUBLE BLIND PROCEDURE; DRUG DOSE INCREASE; DRUG EFFICACY; DRUG SAFETY; DRUG WITHDRAWAL; DYSKINESIA; EMOTIONAL STRESS; FEMALE; FEVER; FRAGILE X SYNDROME; HEADACHE; HUMAN; HYPERACTIVITY; INSOMNIA; INTELLIGENCE QUOTIENT; IRRITABILITY; LETHARGY; MAJOR CLINICAL STUDY; MALE; MENTAL DISEASE ASSESSMENT; NOSE OBSTRUCTION; OCULOGYRIC CRISIS; OUTCOME ASSESSMENT; PHASE 2 CLINICAL TRIAL; PILOT STUDY; PRIORITY JOURNAL; PSYCHOSOCIAL WITHDRAWAL; RANDOMIZED CONTROLLED TRIAL; RASH; RHINOPHARYNGITIS; RHINORRHEA; SECONDARY ANALYSIS; SEDATION; SEIZURE; SIDE EFFECT; SLEEP DISORDER; SOCIALIZATION; SOMNOLENCE; SUICIDAL IDEATION; VINELAND ADAPTIVE BEHAVIOR SCALES II; VOMITING; WEIGHT REDUCTION; YOUNG ADULT; ANALOGS AND DERIVATIVES; CLINICAL TRIAL; MULTICENTER STUDY; PRESCHOOL CHILD; PSYCHOLOGY; TREATMENT OUTCOME;

ADOLESCENT; AUTISM SPECTRUM DISORDER; BACLOFEN; CHILD; CHILD, PRESCHOOL; CROSS-OVER STUDIES; FEMALE; GABA-B RECEPTOR AGONISTS; HUMANS; MALE; TREATMENT OUTCOME; YOUNG ADULT;

EID: 84994632728     PISSN: 0893133X     EISSN: 1740634X     Source Type: Journal    
DOI: 10.1038/npp.2016.237     Document Type: Article

References (49)

1. Aman M (1994). Aberrant Behavior Checklist - Community. Slosson Educational Publications: East Aurora, NY.
2. American Psychiatric Association (2000). Diagnostic and Statistical Manual of Mental Disorders-Text Revision (DSM-IV-TR), 4th edn. American Psychiatric Association Press: Washington, DC
3. American Psychiatric Association (2013). Diagnostic and Statistical Manual of Mental Disorders, 5th edn. DSM-5 American Psychiatric Publishing: Arlington, VA.
4. Anagnostou E, Jones N, Huerta M, Halladay AK, Wang P, Scahill L et al (2014). Measuring social communication behaviors as a treatment endpoint in individuals with autism spectrum disorder. Autism 19: 622-636.
5. Anderson GM (2015). Autism biomarkers: challenges, pitfalls and possibilities. J Autism Dev Disord 45: 1103-1113.
6. Berry-Kravis EM, Hessl D, Rathmell B, Zarevics P, Cherubini M, Walton-Bowen K et al (2012). Effects of STX209 (arbaclofen) on neurobehavioral function in children and adults with fragile X syndrome: a randomized, controlled, phase 2 trial. Sci Transl Med 4: 152ra127.
7. Braat S, Kooy RF (2015). The GABAA receptor as a therapeutic target for neurodevelopmental disorders. Neuron 86: 1119-1130.
8. Chang S, Bray SM, Li Z, Zarnescu DC, He C, Jin P et al (2008). Identification of small molecules rescuing fragile X syndrome phenotypes in Drosophila. Nat Chem Biol 4: 256-263.
9. Dawson G, Rogers S, Munson J, Smith M, Winter J, Greenson J et al (2010). Randomized, controlled trial of an intervention for toddlers with autism: the Early Start Denver Model. Pediatrics 125: e17-e23.
10. De Rubeis S, Buxbaum JD (2015). Genetics and genomics of autism spectrum disorder: embracing complexity. Hum Mol Genet 24 (R1): R24-R31.
11. DuPaul GJ, Power TJ, Anastopoulos AD, Reid D (1998). ADHD Rating Scale-IV: Checklists, Norms, and Clinical Interpretation. The Guilford Press: New York.
12. Emslie G, Rush A, Weinberg W, Kowatch R, Hughes C, Carmody T et al (1997). A double-blind, randomized, placebo-controlled trial of fluoxetine in children and adolescents with depression. Arch Gen Psychiatry 54: 1031-1037.
13. Erickson CA, Veenstra-Vanderweele JM, Melmed RD, McCracken JT, Ginsberg LD, Sikich L et al (2014). STX209 (arbaclofen) for autism spectrum disorders: an 8-week open-label study. J Autism Dev Disord 44: 958-964.
14. Fung LK, Mahajan R, Nozzolillo A, Bernal P, Krasner A, Jo B et al (2016). Pharmacologic treatment of severe irritability and problem behaviors in autism: a systematic review and meta-analysis. Pediatrics 137(S2): S124-S135.
15. Gaetz W, Bloy L, Wang DJ, Port RG, Blaskey L, Levy SE et al (2014). GABA estimation in the brains of children on the autism spectrum: measurement precision and regional cortical variation. Neuroimage 86: 1-9.
16. Gandal MJ, Sisti J, Klook K, Ortinski PI, Leitman V, Liang Y et al (2012). GABAB-mediated rescue of altered excitatory-inhibitory balance, gamma synchrony and behavioral deficits following constitutive NMDAR-hypofunction. Transl Psychiatry 2: e142.
17. Guy W (1976). ECDEU Assessment Manual for Psychopharmacol-ogy. United States Department of Health, Education, and Welfare, Public Health Service, Alcohol, Drug Abuse, and Mental Health, Psychopharmacology Research Branch. Division of Extramural Research Programs: Rockville, MD.
18. Henderson C, Wijetunge L, Kinoshita MN, Shumway M, Hammond RS, Postma FR et al (2012). Reversal of disease-related pathologies in the fragile X mouse model by selective activation of GABA(B) receptors with arbaclofen. Sci Transl Med 4: 152ra128.
19. Jeste SS, Geschwind DH (2014). Disentangling the heterogeneity of autism spectrum disorder through genetic findings. Nat Rev Neurol 10: 74-81.
20. Jeste SS, Tuchman R (2015). Autism spectrum disorder and epilepsy: two sides of the same coin? J Child Neurol 30: 1963-1971.
21. Kenny EM, Cormican P, Furlong S, Heron E, Kenny G, Fahey C et al (2014). Excess of rare novel loss-of-function variants in synaptic genes in schizophrenia and autism spectrum disorders. Mol Psychiatry 19: 872-879.
22. King BH, Hollander E, Sikich L, McCracken JT, Scahill L, Bregman JD et al (2009). Lack of efficacy of citalopram in children with autism spectrum disorders and high levels of repetitive behavior: citalopram ineffective in children with autism. Arch Gen Psychiatry 66: 583-590.
23. Krumm N, Turner TN, Baker C, Vives L, Mohajeri K, Witherspoon K et al (2015). Excess of rare, inherited truncating mutations in autism. Nat Genet 47: 582-588.
24. Levin AR, Nelson CA (2015). Inhibition-based biomarkers for autism spectrum disorder. Neurotherapeutics 12: 546-552.
25. Lord C, Rutter M, DiLavore P, Risi S (2000). Autism Diagnostic Observation Schedule (ADOS). Western Psychological Services: Torrance, CA.
26. Masi A, Lampit A, Glozier N, Hickie IB, Guastella AJ (2015). Predictors of placebo response in pharmacological and dietary supplement treatment trials in pediatric autism spectrum disorder: a meta-analysis. Transl Psychiatry 5: e640.
27. McPartland JC (2016). Considerations in biomarker development for neurodevelopmental disorders. Curr Opin Neurol 29: 118-122.
28. McPheeters ML, Warren Z, Sathe N, Bruzek JL, Krishnaswami S, Jerome RN et al (2011). A systematic review of medical treatments for children with autism spectrum disorders. Pediatrics 127: e1312-e1321.
29. O'Roak BJ, Vives L, Girirajan S, Karakoc E, Krumm N, Coe BP et al (2012). Sporadic autism exomes reveal a highly interconnected protein network of de novo mutations. Nature 485: 246-250.
30. Qin M, Huang T, Kader M, Krych L, Xia Z, Burlin T et al (2015). R-baclofen reverses a social behavior deficit and elevated protein synthesis in a mouse model of fragile X syndrome. Int J Neuropsychopharmacol 18.
31. Reichow B, Volkmar FR, Bloch MH (2013). Systematic review and meta-analysis of pharmacological treatment of the symptoms of attention-deficit/hyperactivity disorder in children with pervasive developmental disorders. J Autism Dev Disord 43: 2435-2441.
32. Robertson CE, Ratai EM, Kanwisher N (2016). Reduced GABAergic action in the autistic brain. Curr Biol 26: 80-85.
33. Roid GH (2003). Stanrod Binet Intelligence Scales, Fifth Edition. Riverside: Itasca, IL.
34. Rubenstein JL, Merzenich MM (2003). Model of autism: increased ratio of excitation/inhibition in key neural systems. Genes Brain Behav 2: 255-267.
35. Ruggeri B, Sarkans U, Schumann G, Persico AM (2014). Biomarkers in autism spectrum disorder: the old and the new. Psychophar-macology (Berl) 231: 1201-1216.
36. Sahin M, Sur M (2015). Genes, circuits, and precision therapies for autism and related neurodevelopmental disorders. Science 350: aab3897.
37. Sanders SJ, He X, Willsey AJ, Ercan-Sencicek AG, Samocha KE, Cicek AE et al (2015). Insights into autism spectrum disorder genomic architecture and biology from 71 risk loci. Neuron 87: 1215-1233.
38. Sansone SM, Widaman KF, Hall SS, Reiss AL, Lightbody A, Kaufmann WE et al (2012). Psychometric study of the Aberrant Behavior Checklist in Fragile X Syndrome and implications for targeted treatment. J Autism Dev Disord 42: 1377-1392.
39. Scahill L, Hallett V, Aman MG, McDougle CJ, Eugene Arnold L, McCracken JT et al (2013). Brief Report: social disability in autism spectrum disorder: results from Research Units on Pediatric Psychopharmacology (RUPP) Autism Network trials. J Autism Dev Disord 43: 739-746.
40. Shattuck PT, Narendorf SC, Cooper B, Sterzing PR, Wagner M, Taylor JL (2012). Postsecondary education and employment among youth with an autism spectrum disorder. Pediatrics 129: 1042-1049.
41. Silverman JL, Pride MC, Hayes JE, Puhger KR, Butler-Struben HM, Baker S et al (2015). GABAB receptor agonist R-baclofen reverses social deficits and reduces repetitive behavior in two mouse models of autism. Neuropsychopharmacology 40: 2228-2239.
42. Sparrow S, Balla D, Cicchetti D (1984). Vineland Scales of Adaptive Behavior, Survey Form Manual. American Guidance Service: Circle Pines, MN.
43. Sparrow SS, Cicchetti DV, Balla DA (2005a). Vineland Adaptive Behavior Scales, (Vineland-II). American Guidance Services: Circle Pines, MN.
44. Sparrow SS, Cicchetti DV, Balla DA (2005b). Vineland Adaptive Behavior Scales, Second Edition. AGS Publishing: Circle Pines.
45. Tabuchi K, Blundell J, Etherton MR, Hammer RE, Liu X, Powell CM et al (2007). A neuroligin-3 mutation implicated in autism increases inhibitory synaptic transmission in mice. Science 318: 71-76.
46. Weimer K, Gulewitsch MD, Schlarb AA, Schwille-Kiuntke J, Klosterhalfen S, Enck P (2013). Placebo effects in children: a review. Pediatr Res 74: 96-102.
47. Weitlauf AS, McPheeters ML, Peters B, Sathe N, Travis R, Aiello R et al. Therapies for Children with Autism Spectrum Disorder: Behavioral Interventions Update. AHRQ Comparative Effectiveness Reviews. Agency for Healthcare Research and Quality (US): Rockville, MD, 2014.
48. Won H, Lee HR, Gee HY, Mah W, Kim JI, Lee J et al (2012). Autistic-like social behaviour in Shank2-mutant mice improved by restoring NMDA receptor function. Nature 486: 261-265.
49. Yizhar O, Fenno LE, Prigge M, Schneider F, Davidson TJ, O'Shea DJ et al (2011). Neocortical excitation/inhibition balance in information processing and social dysfunction. Nature 477: 171-178.