Emerging drugs for the treatment of symptoms associated with autism spectrum disorders

Expert Opinion on Emerging Drugs

Volumn 15, Issue 3, 2010, Pages 481-494

  Wink, Logan K ^a   Plawecki, Martin H ^a   Erickson, Craig A ^a,b   Stigler, Kimberly A ^a   McDougle, Christopher J ^a,b  

^a INDIANA UNIVERSITY SCHOOL OF MEDICINE   (United States)

^b RILEY HOSPITAL FOR CHILDREN   (United States)

Author keywords

Aripiprazole; Autism; Autistic disorder; Methylphenidate; PDDs; Risperidone; Treatment

Indexed keywords

2 METHYL 6 (PHENYLETHYNYL)PYRIDINE; 4 AMINOBUTYRIC ACID; 4 AMINOBUTYRIC ACID B RECEPTOR STIMULATING AGENT; AFQ 056; AMANTADINE; ARBACLOFEN; ARIPIPRAZOLE; ATOMOXETINE; CHLORIDE; CITALOPRAM; CM AT; CYCLOSERINE; FLUOXETINE; FLUVOXAMINE; GLUTAMATE RECEPTOR ANTAGONIST; GLUTAMIC ACID; GUANFACINE; LAMOTRIGINE; MEMANTINE; METHYLPHENIDATE; MONOAMINE DERIVATIVE; OXYTOCIN; PALIPERIDONE; PLACEBO; RILUZOLE; RISPERIDONE; SECRETIN; UNCLASSIFIED DRUG;

ALZHEIMER DISEASE; AMYOTROPHIC LATERAL SCLEROSIS; ASPERGER SYNDROME; AUTISM; CLINICAL FEATURE; CLINICAL TRIAL; COMPULSION; CONCENTRATION LOSS; DIARRHEA; DIZZINESS; DROWSINESS; DRUG MECHANISM; DRY SKIN; FATIGUE; HUMAN; HYPERACTIVITY; IMPULSIVENESS; INSOMNIA; IRRITABILITY; NAUSEA; NONHUMAN; REVIEW; SCHIZOPHRENIA; SEDATION; SIDE EFFECT; SOCIAL STATUS; STEREOTYPY; TUBERCULOSIS; WEIGHT GAIN;

ADULT; ANIMALS; CENTRAL NERVOUS SYSTEM AGENTS; CHILD; CHILD DEVELOPMENT DISORDERS, PERVASIVE; DRUG DELIVERY SYSTEMS; DRUG DESIGN; HUMANS;

EID: 77955871463     PISSN: 14728214     EISSN: None     Source Type: Journal    
DOI: 10.1517/14728214.2010.487860     Document Type: Review

References (101)

1. American Psychiatric Association. Diagnostic and statistical manual of mental disorders. 4th edition. American Psychiatric Press, Washington DC; 1994
2. Howlin P, Magiati I, Charman T. Systematic review of early intensive behavioral interventions for children with autism. Am J Intellect Dev Disabil 2009;114(1):23-41
3. Posey DJ, Erickson CA, McDougle CJ. Developing drugs for core social and communication impairment in autism. Child Adolesc Psychiatr Clin N Am 2008;17(4):787-801, viii-ix
4. Centers for Disease Control and Prevention. Prevalence of Autism Spectrum Disorders-Autism and Devlopmental Disabilities Monitoring Nework, United States, 2006. Surveillance Summaries, December 19. MMWR 2009;58(SS-10):1-20
5. King BH, Hollander E, Sikich L, et al. 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 2009;66(6):583-590
6. Gibson E. The Hunt for an Autism Drug. Business Week 14 January 2010
7. McDougle CJ, Naylor ST, Cohen DJ, et al. A double-blind, placebo-controlled study of fluvoxamine in adults with autistic disorder. Arch Gen Psychiatry 1996;53(11):1001-1008
8. Hollander E, Phillips A, Chaplin W, et al. A placebo controlled crossover trial of liquid fluoxetine on repetitive behaviors in childhood and adolescent autism. Neuropsychopharmacology 2005;30(3):582-589
9. Autism Speaks Announces Results Reported for the Study of Fluoxetine in Autism (SOFIA), First Industry-Sponsored Trial for the Autism Clinical Trials Network (ACTN) 2009; Available from: http://www.autismspeaks.org/press/as- announces-sofia-results.php. [Cited 22 February 2010]
10. Research Units on Pediatric Psychopharmacology Autism N. Risperidone in children with autism and serious behavioral problems. N Engl J Med 2002;347(5):314-321
11. Marcus RN, Owen R, Kamen L, et al. A placebo-controlled, fixed-dose study of aripiprazole in children and adolescents with irritability associated with autistic disorder. J Am Acad Child Adolesc Psychiatry 2009;48(11):1110-1119
12. Owen R, Sikich L, Marcus RN, et al. Aripiprazole in the treatment of irritability in children and adolescents with autistic disorder. Pediatrics 2009;124(6):1533-1540
13. Posey DJ, Kem DL, Swiezy NB, et al. A pilot study of D-cycloserine in subjects with autistic disorder. Am J Psychiatry 2004;161(11):2115-2117
14. Belsito KM, Law PA, Kirk KS, et al. Lamotrigine therapy for autistic disorder: a randomized, double-blind, placebo-controlled trial. J Autism Dev Disord 2001;31(2):175-181
15. King BH, Wright DM, Handen BL, et al. Double-blind, placebo-controlled study of amantadine hydrochloride in the treatment of children with autistic disorder. J Am Acad Child Adolesc Psychiatry 2001;40(6):658-665
16. Erickson CA, Posey DJ, Stigler KA, et al. A retrospective study of memantine in children and adolescents with pervasive developmental disorders. Psychopharmacology (Berl) 2007;191(1):141-147
17. Bill BR, Geschwind DH. Genetic advances in autism: heterogeneity and convergence on shared pathways. Curr Opin Genet Dev 2009;19(3):271-278
18. McDougle CJ, Erickson CA, Stigler KA, Posey DJ. Neurochemistry in the pathophysiology of autism. J Clin Psychiatry 2005;66(Suppl 10):9-18
19. Stigler KA, Sweeten TL, Posey DJ, McDougle CJ. Autism and immune factors: a comprehensive review. Res Autism Spectr Disord 2009;3(4):840-860
20. Theoharides TC, Kempuraj D, Redwood L. Autism: an emerging 'neuroimmune disorder' in search of therapy. Expert Opin Pharmacother 2009;10(13):2127-2143
21. Posey DJ, Stigler KA, Erickson CA, McDougle CJ. Antipsychotics in the treatment of autism. J Clin Invest 2008;118(1):6-14
22. Schain RJ, Freedman DX. Studies on 5-hydroxyindole metabolism in autistic and other mentally retarded children. J Pediatr 1961;58:315-320
23. Anderson GM, Freedman DX, Cohen DJ, et al. Whole blood serotonin in autistic and normal subjects. J Child Psychol Psychiatry 1987;28(6):885-900
24. Leboyer M, Philippe A, Bouvard M, et al. Whole blood serotonin and plasma beta-endorphin in autistic probands and their first-degree relatives. Biol Psychiatry 1999;45(2):158-163
25. Hoshino Y, Tachibana J, Watanabe M, et al. Serotonin metabolism and hypothalamic-pituitary function in children with infantile autism and minimal brain dysfunction. Jpn J Psychiatry Neurol 1984;26:937-945
26. McBride PA, Anderson GM, Hertzig ME, et al. Serotonergic responsivity in male young adults with autistic disorder. Results of a pilot study. Arch Gen Psychiatry 1989;46(3):213-221
27. McDougle CJ, Naylor ST, Cohen DJ, et al. Effects of tryptophan depletion in drug-free adults with autistic disorder. Arch Gen Psychiatry 1996;53(11):993-1000
28. Novotny S, Hollander E, Allen A, et al. Increased growth hormone response to sumatriptan challenge in adult autistic disorders. Psychiatry Res 2000;94(2):173-177
29. Hollander E, Novotny S, Allen A, et al. The relationship between repetitive behaviors and growth hormone response to sumatriptan challenge in adult autistic disorder. Neuropsychopharmacology 2000;22(2):163-167
30. Cook EH Jr, Courchesne R, Lord C, et al. Evidence of linkage between the serotonin transporter and autistic disorder. Mol Psychiatry 1997;2(3):247-250
31. Klauck SM, Poustka F, Benner A, et al. Serotonin transporter (5-HTT) gene variants associated with autism? Hum Mol Genet 1997;6(13):2233-2238
32. Nabi R, Serajee FJ, Chugani DC, et al. Association of tryptophan 2,3 dioxygenase gene polymorphism with autism. Am J Med Genet B Neuropsychiatr Genet 2004;125B(1):63-68
33. McCauley JL, Olson LM, Dowd M, et al. Linkage and association analysis at the serotonin transporter (SLC6A4) locus in a rigid-compulsive subset of autism. Am J Med Genet B Neuropsychiatr Genet 2004;127B(1):104-112
34. Mulder EJ, Anderson GM, Kema IP, et al. Serotonin transporter intron polymorphism associated with rigid-compulsive behaviors in Dutch individuals with pervasive developmental disorder. Am J Med Genet B Neuropsychiatr Genet 2005;133B(1):93-96
35. Chugani DC, Muzik O, Rothermel R, et al. Altered serotonin synthesis in the dentatothalamocortical pathway in autistic boys. Ann Neurol 1997;42(4):666-669
36. Chugani DC, Muzik O, Behen M, et al. Developmental changes in brain serotonin synthesis capacity in autistic and nonautistic children. Ann Neurol 1999;45(3):287-295
37. Launay JM, Bursztejn C, Ferrari P, et al. Catecholamines metabolism in infantile autism: a controlled study of 22 autistic children. J Autism Dev Disord 1987;17(3):333-347
38. Minderaa RB, Anderson GM, Volkmar FR, et al. Neurochemical study of dopamine functioning in autistic and normal subjects. J Am Acad Child Adolesc Psychiatry 1989;28(2):190-194
39. Martineau J, Barthelemy C, Jouve J, et al. Monoamines (serotonin and catecholamines) and their derivatives in infantile autism: age-related changes and drug effects. Dev Med Child Neurol 1992;34(7):593-603
40. Gillberg C, Svennerholm L. CSF monoamines in autistic syndromes and other pervasive developmental disorders of early childhood. Br J Psychiatry 1987;151:89-94
41. Cohen DJ, Shaywitz BA, Johnson WT, Bowers M Jr. Biogenic amines in autistic and atypical children. Cerebrospinal fluid measures of homovanillic acid and 5-hydroxyindoleacetic acid. Arch Gen Psychiatry 1974;31(6):845-853
42. Cohen DJ, Caparulo BK, Shaywitz BA, Bowers MB Jr. Dopamine and serotonin metabolism in neuropsychiatrically disturbed children. CSF homovanillic acid and 5-hydroxyindoleacetic acid. Arch Gen Psychiatry 1977;34(5):545-550
43. Ross D, Klykylo W, Anderson G. Cerebrospinal fluid indoleamine and monoamine effects in fenfluramine treatment of autism. Ann Neurol 1985;18:394
44. Arnold LE, Aman MG, Cook AM, et al. Atomoxetine for hyperactivity in autism spectrum disorders: placebo-controlled crossover pilot trial. J Am Acad Child Adolesc Psychiatry 2006;45(10):1196-1205
45. Comings DE, Comings BG, Muhleman D, et al. The dopamine D2 receptor locus as a modifying gene in neuropsychiatric disorders. JAMA 1991;266(13):1793-1800
46. Feng J, Sobell JL, Heston LL, et al. Scanning of the dopamine D1 and D5 receptor genes by REF in neuropsychiatric patients reveals a novel missense change at a highly conserved amino acid. Am J Med Genet 1998;81(2):172-178
47. Ernst M, Zametkin AJ, Matochik JA, et al. Low medial prefrontal dopaminergic activity in autistic children. Lancet 1997;350(9078):638
48. Nakamura K, Sekine Y, Ouchi Y, et al. Brain serotonin and dopamine transporter bindings in adults with high-functioning autism. Arch Gen Psychiatry 2010;67(1):59-68
49. Lake CR, Ziegler MG, Murphy DL. Increased norepinephrine levels and decreased dopamine-beta-hydroxylase activity in primary autism. Arch Gen Psychiatry 1977;34(5):553-556
50. Young JG, Cohen DJ, Hattox SE, et al. Plasma free MHPG and neuroendocrine responses to challenge doses of clonidine in Tourette's syndrome: preliminary report. Life Sci 1981;29(14):1467-1475
51. Minderaa RB, Anderson GM, Volkmar FR, et al. Noradrenergic and adrenergic functioning in autism. Biol Psychiatry 1994;36(4):237-241
52. Young JG, Cohen DJ, Kavanagh ME, et al. Cerebrospinal fluid, plasma, and urinary MHPG in children. Life Sci 1981;28(25):2837-2845
53. Aldred S, Moore KM, Fitzgerald M, Waring RH. Plasma amino acid levels in children with autism and their families. J Autism Dev Disord 2003;33(1):93-97
54. Moreno-Fuenmayor H, Borjas L, Arrieta A, et al. Plasma excitatory amino acids in autism. Invest Clin 1996;37(2):113-128
55. Rolf LH, Haarmann FY, Grotemeyer KH, Kehrer H. Serotonin and amino acid content in platelets of autistic children. Acta Psychiatr Scand 1993;87(5):312-316
56. Dhossche D, Applegate H, Abraham A, et al. Elevated plasma gamma-aminobutyric acid (GABA) levels in autistic youngsters: stimulus for a GABA hypothesis of autism. Med Sci Monit 2002;8(8):PR1-6
57. Jamain S, Betancur C, Quach H, et al. Linkage and association of the glutamate receptor 6 gene with autism. Mol Psychiatry 2002;7(3):302-310
58. Philippe A, Martinez M, Guilloud-Bataille M, et al. Genome-wide scan for autism susceptibility genes. Paris Autism Research International Sibpair Study. Hum Mol Genet 1999;8(5):805-812
59. Cook EH Jr, Courchesne RY, Cox NJ, et al. Linkage-disequilibrium mapping of autistic disorder, with 15q11-13 markers. Am J Hum Genet 1998;62(5):1077-1083
60. Salmon B, Hallmayer J, Rogers T, et al. Absence of linkage and linkage disequilibrium to chromosome 15q11-q13 markers in 139 multiplex families with autism. Am J Med Genet 1999;88(5):551-556
61. Martin ER, Menold MM, Wolpert CM, et al. Analysis of linkage disequilibrium in gamma-aminobutyric acid receptor subunit genes in autistic disorder. Am J Med Genet 2000;96(1):43-48
62. Menold MM, Shao Y, Wolpert CM, et al. Association analysis of chromosome 15 gabaa receptor subunit genes in autistic disorder. J Neurogenet 2001;15(3-4):245-259
63. McCauley JL, Olson LM, Delahanty R, et al. A linkage disequilibrium map of the 1-Mb 15q12 GABA(A) receptor subunit cluster and association to autism. Am J Med Genet B Neuropsychiatr Genet 2004;131B(1):51-59
64. Purcell AE, Jeon OH, Zimmerman AW, et al. Postmortem brain abnormalities of the glutamate neurotransmitter system in autism. Neurology 2001;57(9):1618-1628
65. Fatemi SH, Halt AR, Stary JM, et al. Glutamic acid decarboxylase 65 and 67 kDa proteins are reduced in autistic parietal and cerebellar cortices. Biol Psychiatry 2002;52(8):805-810
66. Blatt GJ, Fitzgerald CM, Guptill JT, et al. Density and distribution of hippocampal neurotransmitter receptors in autism: an autoradiographic study. J Autism Dev Disord 2001;31(6):537-543
67. Macdonald K, Macdonald TM. The peptide that binds: a systematic review of oxytocin and its prosocial effects in humans. Harv Rev Psychiatry 2010;18(1):1-21
68. Hollander E, Bartz J, Chaplin W, et al. Oxytocin increases retention of social cognition in autism. Biol Psychiatry 2007;61(4):498-503
69. Jacob S, Brune CW, Carter CS, et al. Association of the oxytocin receptor gene (OXTR) in Caucasian children and adolescents with autism. Neurosci Lett 2007;417(1):6-9
70. Wu S, Jia M, Ruan Y, et al. Positive association of the oxytocin receptor gene (OXTR) with autism in the Chinese Han population. Biol Psychiatry 2005;58(1):74-77
71. Andari E, Duhamel JR, Zalla T, et al. Promoting social behavior with oxytocin in high-functioning autism spectrum disorders. Proc Natl Acad Sci USA 2010;107(9):4389-4394
72. Tordjman S, Anderson GM, McBride PA, et al. Plasma beta-endorphin, adrenocorticotropin hormone, and cortisol in autism. J Child Psychol Psychiatry 1997;38(6):705-715
73. Curin JM, Terzic J, Petkovic ZB, et al. Lower cortisol and higher ACTH levels in individuals with autism. J Autism Dev Disord 2003;33(4):443-448
74. Koves K, Kausz M, Reser D, et al. Secretin and autism: a basic morphological study about the distribution of secretin in the nervous system. Regul Pept 2004;123(1-3):209-216
75. Koves K, Kausz M, Reser D, Horvath K. What may be the anatomical basis that secretin can improve the mental functions in autism? Regul Pept 2002;109(1-3):167-172
76. Yung WH, Leung PS, Ng SS, et al. Secretin facilitates GABA transmission in the cerebellum. J Neurosci 2001;21(18):7063-7068
77. Boris M, Kaiser CC, Goldblatt A, et al. Effect of pioglitazone treatment on behavioral symptoms in autistic children. J Neuroinflammation 2007;4:3
78. Akhondzadeh S, Fallah J, Mohammadi MR, et al. Double-blind placebo-controlled trial of pentoxifylline added to risperidone: effects on aberrant behavior in children with autism. Prog Neuropsychopharmacol Biol Psychiatry 2010;34(1):32-36
79. Rilutek Prescribing Information. Available from: . sanofi-aventis.us/ rilutek/riluteck.html. [Cited 31 January 2010]
80. Grant P, Lougee L, Hirschtritt M, Swedo S. An open-label trial of riluzole, a glutamate antagonist, in children with treatment-resistant obsessive-compulsive disorder. J Child Adolesc Psychopharmacol 2007;17(6):761-767
81. Grant P, National Institutes of Health. Riluzole to Treat Child and Adolescent Obsessive-Compulsive Disorder With or Without Autism Spectrum Disorders. Available from: http://clinicaltrials.gov/ct2/show/NCT/00251303?term [Last accessed 31 January 2010]
82. Silverman JL, Tolu SS, Barkan CL, Crawley JN. Repetitive Self-Grooming Behavior in the BTBR Mouse Model of Autism is Blocked by the mGluR5 Antagonist MPEP. Neuropsychopharmacology 2009;35(4):976-989
83. Research Units on Pediatric Psychopharmacology Autism N. Randomized, controlled, crossover trial of methylphenidate in pervasive developmental disorders with hyperactivity. Arch Gen Psychiatry 2005;62(11):1266-1274
84. Jou RJ, Handen BL, Hardan AY. Retrospective assessment of atomoxetine in children and adolescents with pervasive developmental disorders. J Child Adolesc Psychopharmacol 2005;15(2):325-330
85. Posey DJ, Wiegand RE, Wilkerson J, et al. Open-label atomoxetine for attention-deficit/ hyperactivity disorder symptoms associated with high-functioning pervasive developmental disorders. J Child Adolesc Psychopharmacol 2006;16(5):599-610
86. Posey DJ, Puntney JI, Sasher TM, et al. Guanfacine treatment of hyperactivity and inattention in pervasive developmental disorders: a retrospective analysis of 80 cases. J Child Adolesc Psychopharmacol 2004;14(2):233-241
87. Scahill L, Aman MG, McDougle CJ, et al. A prospective open trial of guanfacine in children with pervasive developmental disorders. J Child Adolesc Psychopharmacol 2006;16(5):589-598
88. Handen BL, Sahl R, Hardan AY. Guanfacine in children with autism and/ or intellectual disabilities. J Dev Behav Pediatr 2008;29(4):303-308
89. Stigler KA. Study of Paliperidone ER in Adolescents and Young Adults With Autism. Available from: http://www.clinicaltrials.gov/ct2/show/NCT00549562? term=paliperidone +and+autism&rank=1. [Cited 14 February 2010]
90. Seaside, Therapeutics. An Open Label Extension Study of STX209 in Subjects With Autism Spectrum Disorders. Available from: . gov/ct2/show/ NCT01064973?term=arba- clofen+and+autism&rank=1. [Cited 14 February 2010]
91. Toda Y, Mori K, Hashimoto T, et al. Administration of secretin for autism alters dopamine metabolism in the central nervous system. Brain Dev 2006;28(2):99-103
92. Ratliff-Schaub K, Carey T, Reeves GD, Rogers MA. Randomized controlled trial of transdermal secretin on behavior of children with autism. Autism 2005,9(3): 256-265
93. Coplan J, Souders MC, Mulberg AE, et al. Children with autistic spectrum disorders. II: parents are unable to distinguish secretin from placebo under double-blind conditions. Arch Dis Child 2003;88(8):737-739
94. Levy SE, Souders MC, Wray J, et al. Children with autistic spectrum disorders. I: comparison of placebo and single dose of human synthetic secretin. Arch Dis Child 2003;88(8):731-736
95. Williams KW, Wray JJ, Wheeler DM. Intravenous secretin for autism spectrum disorder. Cochrane Database Syst Rev 2005;(3):CD003495
96. Sturmey P. Secretin is an ineffective treatment for pervasive developmental disabilities: a review of 15 double-blind randomized controlled trials. Res Dev Disabil 2005;26(1):87-97
97. Kern JK, Espinoza E, Trivedi MH. The effectiveness of secretin in the management of autism. Expert Opin Pharmacother 2004;5(2):379-387
98. Esch BE, Carr JE. Secretin as a treatment for autism: a review of the evidence. J Autism Dev Disord 2004;34(5):543-556
99. Goff DC, Tsai G, Levitt J, et al. A placebo-controlled trial of D-cycloserine added to conventional neuroleptics in patients with schizophrenia. Arch Gen Psychiatry 1999;56(1):21-27
100. Horvath K, Stefanatos G, Sokolski KN, et al. Improved social and language skills after secretin administration in patients with autistic spectrum disorders. J Assoc Acad Minor Phys 1998;9(1):9-15
101. Synthetic Human Secretin in Children With Autism. Available from: http://www.clinicaltrials.gov/ct2/show/NCT00036244?term= secretin+and+autism&rank=2. [Cited 14 February 2010]