UpToDate
Official reprint from UpToDate®
www.uptodate.com ©2016 UpToDate®

Autism spectrum disorder in children and adolescents: Pharmacologic interventions

Authors
Laura Weissman, MD
Carolyn Bridgemohan, MD
Section Editors
Marilyn Augustyn, MD
Marc C Patterson, MD, FRACP
Deputy Editor
Mary M Torchia, MD

INTRODUCTION

Autism spectrum disorder (ASD) is a biologically based neurodevelopmental disorder characterized by impairments in two major domains: (1) deficits in social communication and social interaction and (2) restricted repetitive patterns of behavior, interests, and activities [1]. ASD encompasses disorders previously known as autistic disorder (classic autism, sometimes called early infantile autism, childhood autism, or Kanner's autism), childhood disintegrative disorder, pervasive developmental disorder not otherwise specified, and Asperger disorder (also known as Asperger syndrome). (See "Autism spectrum disorder: Diagnosis", section on 'Diagnostic criteria' and "Asperger syndrome (a specific autism spectrum disorder): Clinical features and diagnosis in children and adolescents" and "Asperger syndrome (a specific autism spectrum disorder): Management and prognosis in children and adolescents".)

The discussion that follows will focus on pharmacologic interventions for autism. Related topics are presented separately:

(See "Autism spectrum disorder: Clinical features".)

(See "Autism spectrum disorder: Diagnosis".)

(See "Autism spectrum disorder in children and adolescents: Overview of management".)

                                                  

Subscribers log in here

To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information or to purchase a personal subscription, click below on the option that best describes you:
Literature review current through: Nov 2016. | This topic last updated: Wed Oct 05 00:00:00 GMT+00:00 2016.
The content on the UpToDate website is not intended nor recommended as a substitute for medical advice, diagnosis, or treatment. Always seek the advice of your own physician or other qualified health care professional regarding any medical questions or conditions. The use of this website is governed by the UpToDate Terms of Use ©2016 UpToDate, Inc.
References
Top
  1. American Psychiatric Association. Autism spectrum disorder. In: Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, American Psychiatric Association, Arlington, VA 2013. p.50.
  2. McGuire K, Fung LK, Hagopian L, et al. Irritability and Problem Behavior in Autism Spectrum Disorder: A Practice Pathway for Pediatric Primary Care. Pediatrics 2016; 137 Suppl 2:S136.
  3. Towbin KE. Strategies for pharmacologic treatment of high functioning autism and Asperger syndrome. Child Adolesc Psychiatr Clin N Am 2003; 12:23.
  4. Aman MG, Farmer CA, Hollway J, Arnold LE. Treatment of inattention, overactivity, and impulsiveness in autism spectrum disorders. Child Adolesc Psychiatr Clin N Am 2008; 17:713.
  5. Aman MG, Novotny S, Samango-Sprouse C, et al. Outcome measures for clinical drug trials in autism. CNS Spectr 2004; 9:36.
  6. Kaat AJ, Lecavalier L, Aman MG. Validity of the aberrant behavior checklist in children with autism spectrum disorder. J Autism Dev Disord 2014; 44:1103.
  7. Myers SM, Johnson CP, American Academy of Pediatrics Council on Children With Disabilities. Management of children with autism spectrum disorders. Pediatrics 2007; 120:1162.
  8. Myers SM. The status of pharmacotherapy for autism spectrum disorders. Expert Opin Pharmacother 2007; 8:1579.
  9. Scottish Intercollegiate Guidelines Network. Assessment, diagnosis and clinical interventions for children and young people with autism spectrum disorders. A national clinical guideline. Scottish Intercollegiate Guidelines Network, Edinburgh 2007. www.sign.ac.uk/guidelines/fulltext/98/index.html (Accessed on November 10, 2011).
  10. Volkmar F, Siegel M, Woodbury-Smith M, et al. Practice parameter for the assessment and treatment of children and adolescents with autism spectrum disorder. J Am Acad Child Adolesc Psychiatry 2014; 53:237.
  11. Abilify (aripiprazole). US Food & Drug Administration (FDA) approved product information. Revised July 2014. US National Library of Medicine. www.dailymed.nlm.nih.gov (Accessed on July 17, 2014).
  12. Leskovec TJ, Rowles BM, Findling RL. Pharmacological treatment options for autism spectrum disorders in children and adolescents. Harv Rev Psychiatry 2008; 16:97.
  13. West L, Waldrop J, Brunssen S. Pharmacologic treatment for the core deficits and associated symptoms of autism in children. J Pediatr Health Care 2009; 23:75.
  14. Parikh MS, Kolevzon A, Hollander E. Psychopharmacology of aggression in children and adolescents with autism: a critical review of efficacy and tolerability. J Child Adolesc Psychopharmacol 2008; 18:157.
  15. Ching H, Pringsheim T. Aripiprazole for autism spectrum disorders (ASD). Cochrane Database Syst Rev 2012; :CD009043.
  16. Oswald DP, Sonenklar NA. Medication use among children with autism spectrum disorders. J Child Adolesc Psychopharmacol 2007; 17:348.
  17. Huffman LC, Sutcliffe TL, Tanner IS, Feldman HM. Management of symptoms in children with autism spectrum disorders: a comprehensive review of pharmacologic and complementary-alternative medicine treatments. J Dev Behav Pediatr 2011; 32:56.
  18. Quintana H, Birmaher B, Stedge D, et al. Use of methylphenidate in the treatment of children with autistic disorder. J Autism Dev Disord 1995; 25:283.
  19. 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; 30:245.
  20. Research Units on Pediatric Psychopharmacology Autism Network. Randomized, controlled, crossover trial of methylphenidate in pervasive developmental disorders with hyperactivity. Arch Gen Psychiatry 2005; 62:1266.
  21. Posey DJ, Aman MG, McCracken JT, et al. Positive effects of methylphenidate on inattention and hyperactivity in pervasive developmental disorders: an analysis of secondary measures. Biol Psychiatry 2007; 61:538.
  22. Jahromi LB, Kasari CL, McCracken JT, et al. Positive effects of methylphenidate on social communication and self-regulation in children with pervasive developmental disorders and hyperactivity. J Autism Dev Disord 2009; 39:395.
  23. Hazell P. Drug therapy for attention-deficit/hyperactivity disorder-like symptoms in autistic disorder. J Paediatr Child Health 2007; 43:19.
  24. A 14-month randomized clinical trial of treatment strategies for attention-deficit/hyperactivity disorder. The MTA Cooperative Group. Multimodal Treatment Study of Children with ADHD. Arch Gen Psychiatry 1999; 56:1073.
  25. 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; 14:233.
  26. Scahill L, McCracken JT, King BH, et al. Extended-Release Guanfacine for Hyperactivity in Children With Autism Spectrum Disorder. Am J Psychiatry 2015; 172:1197.
  27. 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; 16:589.
  28. Fankhauser MP, Karumanchi VC, German ML, et al. A double-blind, placebo-controlled study of the efficacy of transdermal clonidine in autism. J Clin Psychiatry 1992; 53:77.
  29. Jaselskis CA, Cook EH Jr, Fletcher KE, Leventhal BL. Clonidine treatment of hyperactive and impulsive children with autistic disorder. J Clin Psychopharmacol 1992; 12:322.
  30. Ghanizadeh A. Atomoxetine for treating ADHD symptoms in autism: a systematic review. J Atten Disord 2013; 17:635.
  31. Harfterkamp M, van de Loo-Neus G, Minderaa RB, et al. 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; 51:733.
  32. 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; 45:1196.
  33. Svanborg P, Thernlund G, Gustafsson PA, et al. Efficacy and safety of atomoxetine as add-on to psychoeducation in the treatment of attention deficit/hyperactivity disorder: a randomized, double-blind, placebo-controlled study in stimulant-naïve Swedish children and adolescents. Eur Child Adolesc Psychiatry 2009; 18:240.
  34. Geller D, Donnelly C, Lopez F, et al. Atomoxetine treatment for pediatric patients with attention-deficit/hyperactivity disorder with comorbid anxiety disorder. J Am Acad Child Adolesc Psychiatry 2007; 46:1119.
  35. McCracken JT, McGough J, Shah B, et al. Risperidone in children with autism and serious behavioral problems. N Engl J Med 2002; 347:314.
  36. Barnard L, Young AH, Pearson J, et al. A systematic review of the use of atypical antipsychotics in autism. J Psychopharmacol 2002; 16:93.
  37. Hollander E, Dolgoff-Kaspar R, Cartwright C, et al. An open trial of divalproex sodium in autism spectrum disorders. J Clin Psychiatry 2001; 62:530.
  38. Hardan AY, Jou RJ, Handen BL. A retrospective assessment of topiramate in children and adolescents with pervasive developmental disorders. J Child Adolesc Psychopharmacol 2004; 14:426.
  39. 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; 31:175.
  40. Mahajan R, Bernal MP, Panzer R, et al. Clinical practice pathways for evaluation and medication choice for attention-deficit/hyperactivity disorder symptoms in autism spectrum disorders. Pediatrics 2012; 140:S125.
  41. Frazier TW. Friends not foes: combined risperidone and behavior therapy for irritability in autism. J Am Acad Child Adolesc Psychiatry 2012; 51:129.
  42. Aman MG, McDougle CJ, Scahill L, et al. Medication and parent training in children with pervasive developmental disorders and serious behavior problems: results from a randomized clinical trial. J Am Acad Child Adolesc Psychiatry 2009; 48:1143.
  43. Fung LK, Mahajan R, Nozzolillo A, et al. Pharmacologic Treatment of Severe Irritability and Problem Behaviors in Autism: A Systematic Review and Meta-analysis. Pediatrics 2016; 137 Suppl 2:S124.
  44. McVoy M, Findling R. Child and adolescent psychopharmacology update. Psychiatr Clin North Am 2009; 32:111.
  45. Shea S, Turgay A, Carroll A, et al. Risperidone in the treatment of disruptive behavioral symptoms in children with autistic and other pervasive developmental disorders. Pediatrics 2004; 114:e634.
  46. Nagaraj R, Singhi P, Malhi P. Risperidone in children with autism: randomized, placebo-controlled, double-blind study. J Child Neurol 2006; 21:450.
  47. Jesner OS, Aref-Adib M, Coren E. Risperidone for autism spectrum disorder. Cochrane Database Syst Rev 2007; :CD005040.
  48. McPheeters ML, Warren Z, Sathe N, et al. A systematic review of medical treatments for children with autism spectrum disorders. Pediatrics 2011; 127:e1312.
  49. Dove D, Warren Z, McPheeters ML, et al. Medications for adolescents and young adults with autism spectrum disorders: a systematic review. Pediatrics 2012; 130:717.
  50. McDougle CJ, Scahill L, Aman MG, et al. Risperidone for the core symptom domains of autism: results from the study by the autism network of the research units on pediatric psychopharmacology. Am J Psychiatry 2005; 162:1142.
  51. Levine SZ, Kodesh A, Goldberg Y, et al. Initial severity and efficacy of risperidone in autism: Results from the RUPP trial. Eur Psychiatry 2016; 32:16.
  52. Research Units on Pediatric Psychopharmacology Autism Network. Risperidone treatment of autistic disorder: longer-term benefits and blinded discontinuation after 6 months. Am J Psychiatry 2005; 162:1361.
  53. Owen R, Sikich L, Marcus RN, et al. Aripiprazole in the treatment of irritability in children and adolescents with autistic disorder. Pediatrics 2009; 124:1533.
  54. 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; 48:1110.
  55. Hirsch LE, Pringsheim T. Aripiprazole for autism spectrum disorders (ASD). Cochrane Database Syst Rev 2016; :CD009043.
  56. Findling RL, Mankoski R, Timko K, et al. A randomized controlled trial investigating the safety and efficacy of aripiprazole in the long-term maintenance treatment of pediatric patients with irritability associated with autistic disorder. J Clin Psychiatry 2014; 75:22.
  57. US Food and Drug Administration. FDA drug safety communication: FDA warns about new impulse-control problems associated with mental health drug aripiprozole (Ability, Abilify Maintena, Aristada). http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm498823.htm (Accessed on May 03, 2016).
  58. Potenza MN, Holmes JP, Kanes SJ, McDougle CJ. Olanzapine treatment of children, adolescents, and adults with pervasive developmental disorders: an open-label pilot study. J Clin Psychopharmacol 1999; 19:37.
  59. Malone RP, Cater J, Sheikh RM, et al. Olanzapine versus haloperidol in children with autistic disorder: an open pilot study. J Am Acad Child Adolesc Psychiatry 2001; 40:887.
  60. Kemner C, Willemsen-Swinkels SH, de Jonge M, et al. Open-label study of olanzapine in children with pervasive developmental disorder. J Clin Psychopharmacol 2002; 22:455.
  61. Hollander E, Wasserman S, Swanson EN, et al. A double-blind placebo-controlled pilot study of olanzapine in childhood/adolescent pervasive developmental disorder. J Child Adolesc Psychopharmacol 2006; 16:541.
  62. Malone RP, Delaney MA, Hyman SB, Cater JR. Ziprasidone in adolescents with autism: an open-label pilot study. J Child Adolesc Psychopharmacol 2007; 17:779.
  63. Chavez B, Chavez-Brown M, Sopko MA Jr, Rey JA. Atypical antipsychotics in children with pervasive developmental disorders. Paediatr Drugs 2007; 9:249.
  64. Posey DJ, Stigler KA, Erickson CA, McDougle CJ. Antipsychotics in the treatment of autism. J Clin Invest 2008; 118:6.
  65. Zuddas A, Ledda MG, Fratta A, et al. Clinical effects of clozapine on autistic disorder. Am J Psychiatry 1996; 153:738.
  66. Campbell M, Anderson LT, Small AM, et al. The effects of haloperidol on learning and behavior in autistic children. J Autism Dev Disord 1982; 12:167.
  67. Miral S, Gencer O, Inal-Emiroglu FN, et al. Risperidone versus haloperidol in children and adolescents with AD : a randomized, controlled, double-blind trial. Eur Child Adolesc Psychiatry 2008; 17:1.
  68. Campbell M, Armenteros JL, Malone RP, et al. Neuroleptic-related dyskinesias in autistic children: a prospective, longitudinal study. J Am Acad Child Adolesc Psychiatry 1997; 36:835.
  69. Hellings JA, Weckbaugh M, Nickel EJ, et al. A double-blind, placebo-controlled study of valproate for aggression in youth with pervasive developmental disorders. J Child Adolesc Psychopharmacol 2005; 15:682.
  70. Correll CU, Manu P, Olshanskiy V, et al. Cardiometabolic risk of second-generation antipsychotic medications during first-time use in children and adolescents. JAMA 2009; 302:1765.
  71. Luby J, Mrakotsky C, Stalets MM, et al. Risperidone in preschool children with autistic spectrum disorders: an investigation of safety and efficacy. J Child Adolesc Psychopharmacol 2006; 16:575.
  72. Almandil NB, Liu Y, Murray ML, et al. Weight gain and other metabolic adverse effects associated with atypical antipsychotic treatment of children and adolescents: a systematic review and meta-analysis. Paediatr Drugs 2013; 15:139.
  73. Scahill L, Jeon S, Boorin SJ, et al. Weight Gain and Metabolic Consequences of Risperidone in Young Children With Autism Spectrum Disorder. J Am Acad Child Adolesc Psychiatry 2016; 55:415.
  74. Jensen KG, Juul K, Fink-Jensen A, et al. Corrected QT changes during antipsychotic treatment of children and adolescents: a systematic review and meta-analysis of clinical trials. J Am Acad Child Adolesc Psychiatry 2015; 54:25.
  75. Arnold LE, Vitiello B, McDougle C, et al. Parent-defined target symptoms respond to risperidone in RUPP autism study: customer approach to clinical trials. J Am Acad Child Adolesc Psychiatry 2003; 42:1443.
  76. American Diabetes Association, American Psychiatric Association, American Association of Clinical Endocrinologists, North American Association for the Study of Obesity. Consensus development conference on antipsychotic drugs and obesity and diabetes. Diabetes Care 2004; 27:596.
  77. Parr J. Autism. In: Clinical Evidence Handbook, BMJ Publishing Group, London 2008. p.69.
  78. Carrasco M, Volkmar FR, Bloch MH. Pharmacologic treatment of repetitive behaviors in autism spectrum disorders: evidence of publication bias. Pediatrics 2012; 129:e1301.
  79. Chugani DC, Chugani HT, Wiznitzer M, et al. Efficacy of Low-Dose Buspirone for Restricted and Repetitive Behavior in Young Children with Autism Spectrum Disorder: A Randomized Trial. J Pediatr 2016; 170:45.
  80. Soomro GM, Altman D, Rajagopal S, Oakley-Browne M. Selective serotonin re-uptake inhibitors (SSRIs) versus placebo for obsessive compulsive disorder (OCD). Cochrane Database Syst Rev 2008; :CD001765.
  81. Williams K, Brignell A, Randall M, et al. Selective serotonin reuptake inhibitors (SSRIs) for autism spectrum disorders (ASD). Cochrane Database Syst Rev 2013; :CD004677.
  82. 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; 30:582.
  83. McDougle CJ, Kresch LE, Posey DJ. Repetitive thoughts and behavior in pervasive developmental disorders: treatment with serotonin reuptake inhibitors. J Autism Dev Disord 2000; 30:427.
  84. 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; 53:1001.
  85. McDougle CJ, Brodkin ES, Naylor ST, et al. Sertraline in adults with pervasive developmental disorders: a prospective open-label investigation. J Clin Psychopharmacol 1998; 18:62.
  86. Hellings JA, Kelley LA, Gabrielli WF, et al. Sertraline response in adults with mental retardation and autistic disorder. J Clin Psychiatry 1996; 57:333.
  87. Davanzo PA, Belin TR, Widawski MH, King BH. Paroxetine treatment of aggression and self-injury in persons with mental retardation. Am J Ment Retard 1998; 102:427.
  88. 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; 66:583.
  89. Owley T, Walton L, Salt J, et al. An open-label trial of escitalopram in pervasive developmental disorders. J Am Acad Child Adolesc Psychiatry 2005; 44:343.
  90. Clomipramine in the treatment of patients with obsessive-compulsive disorder. The Clomipramine Collaborative Study Group. Arch Gen Psychiatry 1991; 48:730.
  91. Gordon CT, State RC, Nelson JE, et al. A double-blind comparison of clomipramine, desipramine, and placebo in the treatment of autistic disorder. Arch Gen Psychiatry 1993; 50:441.
  92. Remington G, Sloman L, Konstantareas M, et al. Clomipramine versus haloperidol in the treatment of autistic disorder: a double-blind, placebo-controlled, crossover study. J Clin Psychopharmacol 2001; 21:440.
  93. Hurwitz R, Blackmore R, Hazell P, et al. Tricyclic antidepressants for autism spectrum disorders (ASD) in children and adolescents. Cochrane Database Syst Rev 2012; :CD008372.
  94. Hollander E, Soorya L, Wasserman S, et al. Divalproex sodium vs. placebo in the treatment of repetitive behaviours in autism spectrum disorder. Int J Neuropsychopharmacol 2006; 9:209.
  95. Vasa RA, Mazurek MO, Mahajan R, et al. Assessment and Treatment of Anxiety in Youth With Autism Spectrum Disorders. Pediatrics 2016; 137 Suppl 2:S115.
  96. White SW, Oswald D, Ollendick T, Scahill L. Anxiety in children and adolescents with autism spectrum disorders. Clin Psychol Rev 2009; 29:216.
  97. Ung D, Selles R, Small BJ, Storch EA. A Systematic Review and Meta-Analysis of Cognitive-Behavioral Therapy for Anxiety in Youth with High-Functioning Autism Spectrum Disorders. Child Psychiatry Hum Dev 2015; 46:533.
  98. Lickel A, MacLean WE Jr, Blakeley-Smith A, Hepburn S. Assessment of the prerequisite skills for cognitive behavioral therapy in children with and without autism spectrum disorders. J Autism Dev Disord 2012; 42:992.
  99. Ipser JC, Stein DJ, Hawkridge S, Hoppe L. Pharmacotherapy for anxiety disorders in children and adolescents. Cochrane Database Syst Rev 2009; :CD005170.
  100. Posey DJ, Guenin KD, Kohn AE, et al. A naturalistic open-label study of mirtazapine in autistic and other pervasive developmental disorders. J Child Adolesc Psychopharmacol 2001; 11:267.
  101. Buitelaar JK, van der Gaag RJ, van der Hoeven J. Buspirone in the management of anxiety and irritability in children with pervasive developmental disorders: results of an open-label study. J Clin Psychiatry 1998; 59:56.
  102. Posey DJ, Erickson CA, Stigler KA, McDougle CJ. The use of selective serotonin reuptake inhibitors in autism and related disorders. J Child Adolesc Psychopharmacol 2006; 16:181.
  103. Hollander E, Novotny S, Hanratty M, et al. Oxytocin infusion reduces repetitive behaviors in adults with autistic and Asperger's disorders. Neuropsychopharmacology 2003; 28:193.
  104. Andari E, Duhamel JR, Zalla T, et al. Promoting social behavior with oxytocin in high-functioning autism spectrum disorders. Proc Natl Acad Sci U S A 2010; 107:4389.
  105. Gordon I, Vander Wyk BC, Bennett RH, et al. Oxytocin enhances brain function in children with autism. Proc Natl Acad Sci U S A 2013; 110:20953.
  106. Yatawara CJ, Einfeld SL, Hickie IB, et al. The effect of oxytocin nasal spray on social interaction deficits observed in young children with autism: a randomized clinical crossover trial. Mol Psychiatry 2016; 21:1225.
  107. Posey DJ, Kem DL, Swiezy NB, et al. A pilot study of D-cycloserine in subjects with autistic disorder. Am J Psychiatry 2004; 161:2115.
  108. Danfors T, von Knorring AL, Hartvig P, et al. Tetrahydrobiopterin in the treatment of children with autistic disorder: a double-blind placebo-controlled crossover study. J Clin Psychopharmacol 2005; 25:485.
  109. Hardan AY, Handen BL. A retrospective open trial of adjunctive donepezil in children and adolescents with autistic disorder. J Child Adolesc Psychopharmacol 2002; 12:237.
  110. Chez MG, Aimonovitch M, Buchanan T, et al. Treating autistic spectrum disorders in children: utility of the cholinesterase inhibitor rivastigmine tartrate. J Child Neurol 2004; 19:165.
  111. Nicolson R, Craven-Thuss B, Smith J. A prospective, open-label trial of galantamine in autistic disorder. J Child Adolesc Psychopharmacol 2006; 16:621.
  112. Chez MG, Burton Q, Dowling T, et al. Memantine as adjunctive therapy in children diagnosed with autistic spectrum disorders: an observation of initial clinical response and maintenance tolerability. J Child Neurol 2007; 22:574.
  113. Erickson CA, Posey DJ, Stigler KA, et al. A retrospective study of memantine in children and adolescents with pervasive developmental disorders. Psychopharmacology (Berl) 2007; 191:141.
  114. Farmer C, Thurm A, Grant P. Pharmacotherapy for the core symptoms in autistic disorder: current status of the research. Drugs 2013; 73:303.
  115. McElhanon BO, McCracken C, Karpen S, Sharp WG. Gastrointestinal symptoms in autism spectrum disorder: a meta-analysis. Pediatrics 2014; 133:872.
  116. Buie T, Fuchs GJ 3rd, Furuta GT, et al. Recommendations for evaluation and treatment of common gastrointestinal problems in children with ASDs. Pediatrics 2010; 125 Suppl 1:S19.
  117. Brimacombe M, Chaaban J, Zimmerman-Bier B, et al. Autism spectrum disorders: concurrent clinical disorders. J Child Neurol 2008; 23:6.
  118. Elrod MG, Hood BS. Sleep differences among children with autism spectrum disorders and typically developing peers: a meta-analysis. J Dev Behav Pediatr 2015; 36:166.
  119. Johnson KP, Giannotti F, Cortesi F. Sleep patterns in autism spectrum disorders. Child Adolesc Psychiatr Clin N Am 2009; 18:917.
  120. Appleton RE, Gringras P. Melatonin: helping to MEND impaired sleep. Arch Dis Child 2013; 98:216.
  121. Appleton RE, Jones AP, Gamble C, et al. The use of MElatonin in children with neurodevelopmental disorders and impaired sleep: a randomised, double-blind, placebo-controlled, parallel study (MENDS). Health Technol Assess 2012; 16:i.
  122. Andersen IM, Kaczmarska J, McGrew SG, Malow BA. Melatonin for insomnia in children with autism spectrum disorders. J Child Neurol 2008; 23:482.
  123. Paavonen EJ, Nieminen-von Wendt T, Vanhala R, et al. Effectiveness of melatonin in the treatment of sleep disturbances in children with Asperger disorder. J Child Adolesc Psychopharmacol 2003; 13:83.
  124. Giannotti F, Cortesi F, Cerquiglini A, Bernabei P. An open-label study of controlled-release melatonin in treatment of sleep disorders in children with autism. J Autism Dev Disord 2006; 36:741.
  125. Garstang J, Wallis M. Randomized controlled trial of melatonin for children with autistic spectrum disorders and sleep problems. Child Care Health Dev 2006; 32:585.
  126. Wright B, Sims D, Smart S, et al. Melatonin versus placebo in children with autism spectrum conditions and severe sleep problems not amenable to behaviour management strategies: a randomised controlled crossover trial. J Autism Dev Disord 2011; 41:175.
  127. Guénolé F, Godbout R, Nicolas A, et al. Melatonin for disordered sleep in individuals with autism spectrum disorders: systematic review and discussion. Sleep Med Rev 2011; 15:379.
  128. Rossignol DA, Frye RE. Melatonin in autism spectrum disorders: a systematic review and meta-analysis. Dev Med Child Neurol 2011; 53:783.
  129. Wirojanan J, Jacquemont S, Diaz R, et al. The efficacy of melatonin for sleep problems in children with autism, fragile X syndrome, or autism and fragile X syndrome. J Clin Sleep Med 2009; 5:145.
  130. Wasdell MB, Jan JE, Bomben MM, et al. A randomized, placebo-controlled trial of controlled release melatonin treatment of delayed sleep phase syndrome and impaired sleep maintenance in children with neurodevelopmental disabilities. J Pineal Res 2008; 44:57.
  131. McArthur AJ, Budden SS. Sleep dysfunction in Rett syndrome: a trial of exogenous melatonin treatment. Dev Med Child Neurol 1998; 40:186.
  132. Dosman CF, Brian JA, Drmic IE, et al. Children with autism: effect of iron supplementation on sleep and ferritin. Pediatr Neurol 2007; 36:152.
  133. Johnson KP, Malow BA. Assessment and pharmacologic treatment of sleep disturbance in autism. Child Adolesc Psychiatr Clin N Am 2008; 17:773.
  134. Rossi PG, Posar A, Parmeggiani A, et al. Niaprazine in the treatment of autistic disorder. J Child Neurol 1999; 14:547.
  135. Ming X, Gordon E, Kang N, Wagner GC. Use of clonidine in children with autism spectrum disorders. Brain Dev 2008; 30:454.