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.
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American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, 4th Ed, text revision. Washington, D.C.: American Psychiatric Association; 2000.
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.
Erickson CA, Posey DJ, Stigler KA, McDougle CJ. Pharmacologic treatment of autism and related disorders. Pediatr Ann 2007;36: 575–585.
Berry-Kravis E, Potanos K. Psychopharmacology in fragile X syndrome—present and future. Ment Retard Dev Disabil Res Rev 2004;10: 42–48.
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.
Bailey DB, Jr., 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.
Bailey DB, Jr., 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.
Erickson CA, Stigler KA, Posey D, McDougle C. Managing maladaptive behaviors in fragile X patients. Curr Psychiatry 2006;5: 80–92.
Hessl D, Rivera S, Koldewyn K, et al. Amygdala dysfunction in men with the fragile X premutation. Brain 2007;130(Pt 2): 404–416.
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(1): 115–121.
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.
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.
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.
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.
Amt J, Skarsfeldt T. Do novel antipsychotics have similar pharmacological characteristics? A review of the evidence. Neuropsychopharmacology 1998;18: 63–101.
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.
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.
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.
Bristol-Myers_Squibb, Otsuka_America_Pharmaceutical_Inc. Aripiprazole prescribing information. Otsuka Pharmaceuticals Co., Ltd. Tokyo: Otsuka Pharmaceuticals Co., Ltd.; 2009: 1–77.
Stigler KA, Posey DJ, McDougle CJ. Aripiprazole for maladaptive behavior in pervasive developmental disorders. J Child Adolesc Psychopharmacol. Fall 2004;14: 455–463.
Guy W. ECDEU assessment manual for psychopharmacology, Publication No. 76-338. Washington, DC: U.S. DHEW, NIMH; 1976.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Amaria R, LL B, R H. Medication use in fragile X syndrome. Mental Health Asp Dev Dis 2001;4: 89–93.
Hagerman RJ, Berry-Kravis E, Kaufmann WE, et al. Advances in the treatment of fragile X syndrome. Pediatrics 2009;123: 378–390.
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.
McDougle CJ, Erickson CA, Stigler KA, Posey DJ. Neurochemistry in the pathophysiology of autism. J Clin Psychiatry 2005;66(suppl 10): 9–18.
United States National Institutes of Health. Clinicaltrials.gov. Available at: http://www.clinicalaials.gov/ct2/show/NCT00198107. Accessed February 9, 2010.
United States National Institutes of Health. Clinicaltrials.gov. Available at: http://www.clinicalaials.gov/ct2/show/NCT00870727. Accessed February 9, 2010.
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Erickson, C.A., Stigler, K.A., Posey, D.J. et al. Aripiprazole in autism spectrum disorders and fragile X syndrome. Neurotherapeutics 7, 258–263 (2010). https://doi.org/10.1016/j.nurt.2010.04.001
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DOI: https://doi.org/10.1016/j.nurt.2010.04.001