Skip to main content
PMC home page
Neurotherapeutics logoLink to Neurotherapeutics
. 2010 Jul;7(3):258–263. doi: 10.1016/j.nurt.2010.04.001

Aripiprazole in autism spectrum disorders and fragile X syndrome

Craig A Erickson 1,2,✉, Kimberly A Stigler 1,2, David J Posey 1,2, Christopher J McDougle 1,2
PMCID: PMC2911359  NIHMSID: NIHMS204519  PMID: 20643378

Summary

Autism spectrum disorders (ASDs) are childhood onset developmental disorders characterized by impairment of social skills and repetitive behavior, and also for classic autistic disorder, a significant impairment of communication. In addition to these core symptom domains, persons with ASDs frequently exhibit interfering behavioral symptoms, including irritability marked by aggression, self-injurious behavior, and severe tantrums. Aripiprazole is an atypical or newer generation antipsychotic with a unique mechanism of action impacting dopaminergic and serotonergic neurotransmission. The drug has been found efficacious for several indications, including most recently for use targeting irritability associated with autistic disorder in youth. Fragile X syndrome is the most common inherited cause of developmental disability and the most common known single gene cause of ASDs. As in idiopathic ASDs, irritable behavior is often exhibited by persons with fragile X syndrome. However, research to date in this disorder has not focused on this target symptom cluster. An initial pilot study has begun to assess the impact of aripiprazole on irritability in youth with fragile X syndrome.

Key Words: Aripiprazole, autistic disorder, irritability, fragile X syndrome

References

  • 1.American Psychiatric Association . Diagnostic and Statistical Manual of Mental Disorders. 4th Ed. Washington, D.C.: American Psychiatric Association; 2000. [Google Scholar]
  • 2.Kogan MD, Blumberg SJ, Schieve LA, et al. Prevalence of parent-reported diagnosis of autism spectrum disorder among children in the US, 2007. Pediatrics. 2009;124:1395–1403. doi: 10.1542/peds.2009-1522. [DOI] [PubMed] [Google Scholar]
  • 3.Erickson CA, Posey DJ, Stigler KA, McDougle CJ. Pharmacologic treatment of autism and related disorders. Pediatr Ann. 2007;36:575–585. doi: 10.3928/0090-4481-20070901-09. [DOI] [PubMed] [Google Scholar]
  • 4.Berry-Kravis E, Potanos K. Psychopharmacology in fragile X syndrome—present and future. Ment Retard Dev Disabil Res Rev. 2004;10:42–48. doi: 10.1002/mrdd.20007. [DOI] [PubMed] [Google Scholar]
  • 5.Hatton DD, Sideris J, Skinner M, et al. Autistic behavior in children with fragile X syndrome: prevalence, stability, and the impact of FMRP. Am J Med Genet A. 2006;140A:1804–1813. doi: 10.1002/ajmg.a.31286. [DOI] [PubMed] [Google Scholar]
  • 6.Bailey DB, Hatton DD, Skinner M, Mesibov G. Autistic behavior, FMR1 protein, and developmental trajectories in young males with fragile X syndrome. J Autism Dev Disord. 2001;31:165–174. doi: 10.1023/A:1010747131386. [DOI] [PubMed] [Google Scholar]
  • 7.Bailey DB, Raspa M, Olmsted M, Holiday DB. Co-occurring conditions associated with FMR1 gene variations: findings from a national parent survey. Am J Med Genet A. 2008;146A(16):2060–2069. doi: 10.1002/ajmg.a.32439. [DOI] [PubMed] [Google Scholar]
  • 8.Erickson CA, Stigler KA, Posey D, McDougle C. Managing maladaptive behaviors in fragile X patients. Curr Psychiatry. 2006;5:80–92. [Google Scholar]
  • 9.Hessl D, Rivera S, Koldewyn K, et al. Amygdala dysfunction in men with the fragile X premutation. Brain. 2007;130:404–416. doi: 10.1093/brain/awl338. [DOI] [PubMed] [Google Scholar]
  • 10.Hessl D, Tassone F, Loesch DZ, et al. Abnormal elevation of FMR1 mRNA is associated with psychological symptoms in individuals with the fragile X premutation. Am J Med Genet B Neuropsychiatr Genet. 2005;139B:115–121. doi: 10.1002/ajmg.b.30241. [DOI] [PubMed] [Google Scholar]
  • 11.Johnston C, Eliez S, Dyer-Friedman J, et al. Neurobehavioral phenotype in carriers of the fragile X premutation. Am J Med Genet. 2001;103:314–319. doi: 10.1002/ajmg.1561. [DOI] [PubMed] [Google Scholar]
  • 12.Shapiro DA, Renock S, Arlington E, et al. Aripiprazole, a novel atypical antipsychotic drug with a unique and robust pharmacology. Neuropsychopharmacology. 2003;28:1400–1411. doi: 10.1038/sj.npp.1300203. [DOI] [PubMed] [Google Scholar]
  • 13.Bums KD, Molski TF, Xu C, et al. Aripiprazole, a novel antipsychotic, is a high-affinity partial agonist at human dopamine D2 receptors. J Pharmacol Exp Ther. 2002;302:381–389. doi: 10.1124/jpet.102.033175. [DOI] [PubMed] [Google Scholar]
  • 14.Jordan S, Koprivica V, Chen R, Tottori K, Kikuchi T, Altar CA. The antipsychotic aripiprazole is a potent, partial agonist at the human 5-HT1A receptor. Eur J Pharmacol. 2002;441:137–140. doi: 10.1016/S0014-2999(02)01532-7. [DOI] [PubMed] [Google Scholar]
  • 15.Amt J, Skarsfeldt T. Do novel antipsychotics have similar pharmacological characteristics? A review of the evidence. Neuropsychopharmacology. 1998;18:63–101. doi: 10.1016/S0893-133X(97)00112-7. [DOI] [PubMed] [Google Scholar]
  • 16.Kikuchi T, Tottori K, Uwahodo Y, et al. 7-(4-[4-(2,3-Dichlorophenyl)-1-piperazinyl]butyloxy)-3,4-dihydro-2(1H)-qui nolinone (OPC-14597), a new putative antipsychotic drug with both presynaptic dopamine autoreceptor agonistic activity and postsynaptic D2 receptor antagonistic activity. J Pharmacol Exp Ther. 1995;274:329–336. [PubMed] [Google Scholar]
  • 17.Inoue A, Nakata Y. Strategy for modulation of central dopamine transmission based on the partial agonist concept in schizophrenia therapy. Jpn J Pharmacol. 2001;86:376–380. doi: 10.1254/jjp.86.376. [DOI] [PubMed] [Google Scholar]
  • 18.Casey DE, Carson WH, Saha AR, et al. Switching patients to aripiprazole from other antipsychotic agents: a multicenter randomized study. Psychopharmacology (Berl) 2003;166:391–399. doi: 10.1007/s00213-002-1344-3. [DOI] [PubMed] [Google Scholar]
  • 19.Bristol-Myers_Squibb, Otsuka_America_Pharmaceutical_Inc. Aripiprazole prescribing information. Otsuka Pharmaceuticals Co., Ltd. Tokyo: Otsuka Pharmaceuticals Co., Ltd.; 2009. pp. 1–77. [Google Scholar]
  • 20.Stigler KA, Posey DJ, McDougle CJ. Aripiprazole for maladaptive behavior in pervasive developmental disorders. J Child Adolesc Psychopharmacol. Fall. 2004;14:455–463. doi: 10.1089/cap.2004.14.455. [DOI] [PubMed] [Google Scholar]
  • 21.Guy W. ECDEU assessment manual for psychopharmacology, Publication No. 76-338. Washington, DC: U.S. DHEW, NIMH; 1976. [Google Scholar]
  • 22.Stigler KA, Diener JT, Kohn AE, et al. Aripiprazole in pervasive developmental disorder not otherwise specified and Asperger’s disorder: a 14-week, prospective, open-label study. J Child Adolesc Psychopharmacol. 2009;19:265–274. doi: 10.1089/cap.2008.093. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 23.Aman MG, Singh NN, Stewart AW, Field CJ. The aberrant behavior checklist: a behavior rating scale for the assessment of treatment effects. Am J Ment Defic. 1985;5:485–491. [PubMed] [Google Scholar]
  • 24.Valicenti-McDermott MR, Demb H. Clinical effects and adverse reactions of off-label use of aripiprazole in children and adolescents with developmental disabilities. J Child Adolesc Psychopharmacol. 2006;16:549–560. doi: 10.1089/cap.2006.16.549. [DOI] [PubMed] [Google Scholar]
  • 25.Masi G, Cosenza A, Millepiedi S, Muratori F, Pari C, Salvadori F. Aripiprazole monotherapy in children and young adolescents with pervasive developmental disorders: a retrospective study. CNS Drugs. 2009;23:511–521. doi: 10.2165/00023210-200923060-00005. [DOI] [PubMed] [Google Scholar]
  • 26.Owen R, Sikich L, Marcus RN, et al. Aripiprazole in the treatment of irritability in children and adolescents with autistic disorder. Pediatrics. 2009;124:1533–1540. doi: 10.1542/peds.2008-3782. [DOI] [PubMed] [Google Scholar]
  • 27.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;48:1110–1119. doi: 10.1097/CHI.0b013e3181b76658. [DOI] [PubMed] [Google Scholar]
  • 28.Aman MG, Kasper W, Manos G, et al. Aripiprazole in the treatment of irritability associated with autistic disorder in children and adolescents (6–17 years old): Line-item analysis of the Aberrant Behavior Checklist Irritability Subscale. 56th American Academy of Child & Adolescent Psychiatry Meeting. Honolulu, HI; 2009.
  • 29.Mankoski R, Manos G, Chambers J, et al. Effect of cognitive ability on aripiprazole treatment of irritability associated with autistic disorder. 56th American Academy of Child & Adolescent Psychiatry Meeting. Honolulu, HI; 2009.
  • 30.Robb A, Rojas-Femandez C, Mankoski R, et al. Safety and tolerability of aripiprazole in the treatment of irritability associated with autistic disorder. 56th American Academy of Child and Adolescent Psychiatry Meeting. Honolulu, HI; 2009.
  • 31.McCracken JT, McGough J, Shah B, et al. Risperidone in children with autism and serious behavioral problems. N Engl J Med. 2002;347:314–321. doi: 10.1056/NEJMoa013171. [DOI] [PubMed] [Google Scholar]
  • 32.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:e634–641. doi: 10.1542/peds.2003-0264-F. [DOI] [PubMed] [Google Scholar]
  • 33.Anderson GM, Scahill L, McCracken JT, et al. Effects of short- and long-term risperidone treatment on prolactin levels in children with autism. Biol Psychiatry. 2007;61:545–550. doi: 10.1016/j.biopsych.2006.02.032. [DOI] [PubMed] [Google Scholar]
  • 34.Amaria R, LL B, R H Medication use in fragile X syndrome. Mental Health Asp Dev Dis. 2001;4:89–93. [Google Scholar]
  • 35.Hagerman RJ, Berry-Kravis E, Kaufmann WE, et al. Advances in the treatment of fragile X syndrome. Pediatrics. 2009;123:378–390. doi: 10.1542/peds.2008-0317. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 36.Erickson CA, Mullett J, Diener JT, et al. Open-label aripiprazole in Fragile X Syndrome. National Clinical and Translational Research Annual Meeting. Washington, D.C.; 2009.
  • 37.McDougle CJ, Erickson CA, Stigler KA, Posey DJ. Neurochemistry in the pathophysiology of autism. J Clin Psychiatry. 2005;66(suppl 10):9–18. [PubMed] [Google Scholar]
  • 38.United States National Institutes of Health. Clinicaltrials.gov. Available at: http://www.clinicalaials.gov/ct2/show/NCT00198107. Accessed February 9, 2010.
  • 39.United States National Institutes of Health. Clinicaltrials.gov. Available at: http://www.clinicalaials.gov/ct2/show/NCT00870727. Accessed February 9, 2010.

Articles from Neurotherapeutics are provided here courtesy of Elsevier

RESOURCES