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Risperidone in the treatment of childhood autistic disorder: an open pilot study

Published online by Cambridge University Press:  24 June 2014

Paul Casaer
Affiliation:
Department of Pediatrics, University Hospital, Gasthuisberg, Leuven, Belgium
J. A. N. Croonenberghs*
Affiliation:
University Center of Child and Adolescent Psychiatry; A. Z. Middelheim, Antwerp, Belgium University of Antwerp, Belgium
Lieven Lagae
Affiliation:
Department of Pediatrics, University Hospital, Gasthuisberg, Leuven, Belgium
Dirk Deboutte
Affiliation:
University Center of Child and Adolescent Psychiatry; A. Z. Middelheim, Antwerp, Belgium University of Antwerp, Belgium
*
J Croonenberghs, MD, University Center of Child and Adolescent Psychiatry, A.Z. Middelheim, Lindendreef 1, 2020 Antwerp, Belgium. Tel: + 32-3-280-49 00; Fax: + 32-3-230-49 51; E-mail: [email protected]

Abstract

Objective:

To evaluate the tolerability and efficacy of risperidone in childhood autistic disorder.

Methods:

A multicenter, open-label, dose-titration study involving seven autistic children (mean age 7.6 years) receiving risperidone for 4 weeks.

Results:

Mean dose was 0.01 mg/kg/day on day 1, 0.019 mg/kg/day on day 7 (range 0.01–0.041 mg/kg/day) and 0.035 mg/kg/day on day 28 (range 0.014–0.064 mg/kg/day). Over the 4-week period, the Ritvo–Freeman Real Life Rating Scale total score measuring autistic behavior was significantly decreased (P = 0.019), as was the affectual reactions subscale (P = 0.029). Aberrant Behavior Checklist total score was significantly improved (P < 0.001), as were all subscales except inappropriate speech. Visual Analog Scale for individual target symptoms was significantly decreased (P = 0.001), and Clinical Global Impression severity of illness score was significantly improved (P = 0.006). The incidence of adverse effects was low, and no extrapyramidal symptoms were observed. No significant changes or clinically relevant abnormalities occurred in laboratory tests, vital signs or electrocardiograms. Plasma concentrations of the drug were similar to those in adult patients.

Conclusions:

These favorable results suggest that larger controlled trials of risperidone should be performed in autistic or mentally retarded patients with behavioral disturbances.

Type
Original Article
Copyright
Copyright © Acta Neuropsychiatrica 2002

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References

American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, 4th edn. (DSM-IV). Washington, DC: American Psychiatric Association, 1994: 6671. Google ScholarPubMed
Demyer, MK, Hingtgen, JN, Jackson, RK.Infantile autism reviewed. A decade of research. Schizophr Bull 1981;7: 388451.CrossRefGoogle Scholar
Volkmar, FR, Cohen, DJ.Current concepts. Infantile autism and the pervasive developmental disorders. J Dev Behav Pediatr 1986;7: 324329.CrossRefGoogle ScholarPubMed
Tsai, LY.Medical treatment in autism. In: Berkell, DE, ed. Autism: Identification, Education and Treatment. Hillside, New Jersey: Erlbaum, 1992: 151184. Google Scholar
Croonenberghs, J, Deboutte, D, Maes, M.Pathophysiology of autism: Current opinions. Acta Neuropsychiatrica 2001;00: 000000.Google Scholar
Gilman, JT, Tuchman, RF.Autism and associated behavioral disorders: Pharmacotherapeutic intervention. Ann Pharmacother 1995;29: 4756.CrossRefGoogle ScholarPubMed
Campbell, M, Cueva, JE.Psychopharmacology in child and adolescent psychiatry: a review of the past seven years. Part I. J Am Acad Child Adolesc Psychiatry 1995;34: 11241132.CrossRefGoogle Scholar
Locascio, JJ, Malone, RP, Small, AMet al. Factors related to haloperidol response and dyskinesias in autistic children. Psychopharmacol Bull 1991;27: 119126.Google Scholar
Whitaker, A, Rao, U.Neuroleptics in pediatric psychiatry. Psychiatr Clin North Am 1992;15: 243276.Google Scholar
Panksepp, J.A neurochemical theory of autism. Trends Neurosci 1979;2: 174177. CrossRefGoogle Scholar
Kolmen, BK, Feldman, HM, Handen, BL, Janosky, JE.Naltrexone in young autistic children: a double-blind, placebo-controlled crossover study. J Am Acad Child Adolesc Psychiatry 1995;34: 223231.CrossRefGoogle ScholarPubMed
Gillberg, C.Endogenous opioids and opiate antagonists in autism: Brief review of empirical findings and implications for clinicians. Dev Med Child Neurol 1995;37: 239245.CrossRefGoogle Scholar
Willemsen-Swinkels, SH, Buitelaar, JK, Nijhof, GJ, Van Engeland, H.Failure of naltrexone hydrochloride to reduce self-injurious and autistic behavior in mentally retarded adults. Double-blind, placebo-controlled studies. Arch General Psychiatry 1995;52: 766773. CrossRefGoogle Scholar
Willemsen-Swinkels, SH, Buitelaar, JK, Weijnen, FG, Van Engeland, H.Placebo-controlled acute dosage naltrexone study in young autistic children. Psychiatr Res 1995;58: 203215. CrossRefGoogle ScholarPubMed
Anderson, GM, Freedman, DX, Cohen, DJet al. Whole blood serotonin in autistic and normal subjects. J Child Psychol Psychiatry Allied Discip 1987;18: 885900. CrossRefGoogle Scholar
Anderson, GM, Horne, WC, Chatterjee, D, Cohen, DJ.The hyperserotonemia of autism. Ann NY Acad Sci 1990;600: 331340.CrossRefGoogle ScholarPubMed
Gordon, CT, State, RC, Nelson, JE, Hamburger, SD, Rapoport, JL.A double-blind comparison of clomipramine, desipramine, and placebo in the treatment of autistic disorder. Arch General Psychiatry 1993;50: 441447. CrossRefGoogle ScholarPubMed
Cook, EH, Rowlett, R, Jaselskis, C, Leventhal, BL.Fluoxetine treatment of children and adults with autistic disorder and mental retardation. J Am Acad Child Adolesc Psychiatry 1992;31: 739745.CrossRefGoogle ScholarPubMed
Piggott, LR, Gdowski, CL, Villaneuva, D, Fischhoff, J, Frohman, CF.Side-effects of fenfluramine in autistic children. J Am Acad Child Psychiatry 1986;25: 287289.CrossRefGoogle ScholarPubMed
Deutsch, SI, Campbell, M.Relative affinities for different classes of neurotransmitter receptors predict neuroleptic efficacy in infantile autism: a hypothesis. Neuropsychobiol 1986;15: 160164. CrossRefGoogle ScholarPubMed
Marder, SR, Meibach, RC.Risperidone in the treatment of schizophrenia. Am J Psychiatry 1994;151: 825835.Google ScholarPubMed
Marder, SR, Davis, JM, Chouinard, G.The effects of risperidone on the five dimensions of schizophrenia derived by factor analysis: Combined results of the North American trials. J Clin Psychiatry 1997;58: 538546.CrossRefGoogle ScholarPubMed
Peuskens, J.Risperidone in the treatment of patients with chronic schizophrenia: a multi-national, multicentre, double-blind, parallel group study versus haloperidol. Br J Psychiatry 1995;166: 712726.CrossRefGoogle Scholar
Lemmens, P, Dedeyn, PP, Desmedt, G. Risperidone in the treatment of behavioral disturbances in dementia. Presented at the Annual Meeting of the American Psychiatric Association, Toronto (Ontario), 1998. Google Scholar
Chouinard, G, Jones, B, Remington, Get al. A Canadian multicenter placebo-controlled study of fixed doses of risperidone and haloperidol in the treatment of chronic schizophrenic patients. J Clin Psychopharmacol 1993;13: 2540.CrossRefGoogle ScholarPubMed
Purdon, SE, Lit, W, Labelle, A, Jones, BD.Risperidone in the treatment of pervasive developmental disorder. Can J Psychiatry 1994;39: 400405.CrossRefGoogle Scholar
Simeon, JG, Carrey, NJ, Wiggins, DM, Milin, RP, Hosenbocus, SN.Risperidone effects in treatment-resistant adolescents: preliminary case reports. J Child Adol Psychopharmacol 1995;5: 6979. CrossRefGoogle Scholar
Croonenberghs, J. Risperdal in the treatment of 4 children with a DSM-III R Axis 2 diagnosis: ‘Autistic Disorder’ without concomitant diseases. Poster presented at the 5th International Congress of Autism Europe, Barcelona (Spain), 1996. Google Scholar
Findling, RL, Maxwell, K, Wiznitzer, M.An open clinical trial of risperidone monotherapy in young children with autistic disorder. Psychopharmacol Bull 1997;331: 155159. Google Scholar
Malone, RP, Rowan, AB, Blaney, BL, Biescker, KA, Delaney, MA.Open risperidone in pervasive developmental disorder. Psychopharmacol Bull 1997;333: 553. Google Scholar
McDougle, CJ, Holmes, JP, Bronson, MR, Anderson, GM, Volkmar, FR, Price, LH, Cohen, DJ.Risperidone treatment of children and adolescents with pervasive developmental disorders: a prospective open-label study. J Am Acad Child Adolesc Psychiatry 1997;36: 685693.CrossRefGoogle ScholarPubMed
McDougle, CJ, Holmes, JP, Carlson, DC, Pelton, GH, Cohen, DJ, Price, LH.A double-blind, placebo controlled study of risperidone in adults with autistic disorder and other pervasive developmental disorders. Arch Gen Psychiatry 1998;55: 633641.CrossRefGoogle ScholarPubMed
Mandoki, MW.Risperidone treatment of children and adolescents: Increased risk of extrapyramidal side-effects? J Child Adolesc Psychopharmacol 1995;5: 4967. CrossRefGoogle Scholar
Baldessarini, RJ, Teicher, MH.Dosing of antipsychotic agents in pediatric populations. J Child Adolesc Psychopharmacol 1995;5: 14. CrossRefGoogle Scholar
Freeman, BJ, Ritvo, ER, Yokota, A, Ritvo, A.A scale for rating symptoms for patients with the syndrome of autism in real life settings. J Am Acad Child Psychiatry 1986;25: 130136.CrossRefGoogle ScholarPubMed
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;89: 485491.Google ScholarPubMed
Aman, MG, Richmond, G, Stewart, AW, Bell, JC, Kissel, RC.The Aberrant Behavior Checklist. Factor structure and the effect of subjective variables in American and New Zealand facilities. Am J Ment Defic 1987;91: 570578.Google Scholar
Guy, W.The Clinical Global Impression. In: ECDU Assessment Manual for Psychopharmacology (Revised). Rockville (Maryland): National Institute of Mental Health. DHEW publication (ADM). 1976: 76330. Google Scholar
Lippert, HJ, Lehmann, JP.SI Units in Medicine. Baltimore: Urban and Schwarzenberg, 1978. Google Scholar