DOI QR코드

DOI QR Code

Risperidone Monotherapy in Children and Adolescents with Autism Spectrum Disorders : A Naturalistic Study

  • Won, Eun-Kyung (Department of Child Psychiatry, Center for Child and Adolescent Psychiatry, Seoul National Hospital) ;
  • Park, Jin-Park (Division of Planning and Public Relations, Seoul National Hospital) ;
  • Lee, Young-Ryul (Center for Child and Adolescent Psychiatry, Seoul National Hospital) ;
  • Nam, Yoon-Young (Division of Planning and Public Relations, Seoul National Hospital) ;
  • Min, He-Ji (Department of Adolescent Psychiatry, Center for Child and Adolescent Psychiatry, Seoul National Hospital) ;
  • Kim, Yeni (Department of Child Psychiatry, Center for Child and Adolescent Psychiatry, Seoul National Hospital)
  • 투고 : 2015.08.26
  • 심사 : 2015.10.21
  • 발행 : 2015.12.31

초록

Objectives : We retrospectively investigated the efficacy and tolerability of risperidone monotherapy in subjects with autism spectrum disorder (ASD). In addition, we did mixed effect model analysis of the effects of risperidone in patients with ASDs naturalistically treated in a routine clinical setting to determine whether the clinical effects were maintained and the side effects were tolerable. Methods : This retrospective study assessed children and adolescents with ASD, who were on risperidone monotherapy from July 2010 to July 2011 at the Child and Adolescent ASD Clinic at Seoul National Hospital. Outcome measures included the Clinical Global Impression-Severity of Illness (CGI-S) and the CGI-Improvement (CGI-I) scales along with other clinical indices: dosage, target symptoms, and side effects. Results : The mean dose of risperidone in 47 children and adolescents with ASD (40 males, 7 females; age range 5-19 years) who were on risperidone monotherapy was $1.6{\pm}0.8mg/day$, and the mean duration of the treatment period was $20.2{\pm}17.3months$. Aggressive behavior, stereotypic behavior, irritability, and self-injurious behavior were the most frequent target symptoms of risperidone. The most common side effects were weight gain followed by somnolence and extrapyramidal symptoms. In a mixed effects model analysis of CGI-I scores, the mean CGI-I score at the 1 month follow-up was significantly different from the mean CGI-I score of the 3-month follow-up (p=.046), and the CGI-I scores were equally maintained over 3 to 48 months [F(6, 28.9)=4.393, p=.003]. Of the 47 patients, 33 patients (70.2%) were identified as the response group, showing an end point CGI-I rating of 3 or under and having continued risperidone treatment for at least 6 months. The baseline CGI-S score showed significant association with clinical response to risperidone (p=.005), the mean baseline CGI-S was higher in the response group compared to the non-response group. Conclusion : In this study, clinical improvement of risperidone stabilized around 3 months and was equally maintained up to 48 months with tolerable side effects, supporting maintenance of risperidone treatment in children and adolescents with ASDs.

키워드

참고문헌

  1. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders: DSM-4-TR. 4th ed., text revision. Washington, DC: American Psychiatric Association;2000.
  2. Autism and Developmental Disabilities Monitoring Network Surveillance Year 2008 Principal Investigators; Centers for Disease Control and Prevention. Prevalence of autism spectrum disorders--Autism and Developmental Disabilities Monitoring Network, 14 sites, United States, 2008. MMWR Surveill Summ 2012;61:1-19.
  3. Fombonne E. Epidemiology of pervasive developmental disorders. Pediatr Res 2009;65:591-598. https://doi.org/10.1203/PDR.0b013e31819e7203
  4. Canitano R, Scandurra V. Psychopharmacology in autism: an update. Prog Neuropsychopharmacol Biol Psychiatry 2011;35:18-28. https://doi.org/10.1016/j.pnpbp.2010.10.015
  5. McDougle CJ, Stigler KA, Erickson CA, Posey DJ. Atypical antipsychotics in children and adolescents with autistic and other pervasive developmental disorders. J Clin Psychiatry 2008;69 Suppl 4:15-20. https://doi.org/10.4088/JCP.0508e15
  6. Malone RP, Waheed A. The role of antipsychotics in the management of behavioural symptoms in children and adolescents with autism. Drugs 2009;69:535-548. https://doi.org/10.2165/00003495-200969050-00003
  7. Canitano R, Scandurra V. Risperidone in the treatment of behavioral disorders associated with autism in children and adolescents. Neuropsychiatr Dis Treat 2008;4:723-730.
  8. Pandina GJ, Bossie CA, Youssef E, Zhu Y, Dunbar F. Risperidone improves behavioral symptoms in children with autism in a randomized, double-blind, placebo-controlled trial. J Autism Dev Disord 2007;37:367-373. https://doi.org/10.1007/s10803-006-0234-7
  9. Shea S, Turgay A, Carroll A, Schulz M, Orlik H, Smith I, et al. Risperidone in the treatment of disruptive behavioral symptoms in children with autistic and other pervasive developmental disorders. Pediatrics 2004;114:e634-e641. https://doi.org/10.1542/peds.2003-0264-F
  10. Akhondzadeh S, Fallah J, Mohammadi MR, Imani R, Mohammadi M, Salehi B, 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;34:32-36. https://doi.org/10.1016/j.pnpbp.2009.09.012
  11. Aman MG, McDougle CJ, Scahill L, Handen B, Arnold LE, Johnson C, 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;48:1143-1154. https://doi.org/10.1097/CHI.0b013e3181bfd669
  12. Troost PW, Lahuis BE, Steenhuis MP, Ketelaars CE, Buitelaar JK, van Engeland H, et al. Long-term effects of risperidone in children with autism spectrum disorders: a placebo discontinuation study. J Am Acad Child Adolesc Psychiatry 2005;44:1137-1144. https://doi.org/10.1097/01.chi.0000177055.11229.76
  13. 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;162:1361-1369. https://doi.org/10.1176/appi.ajp.162.7.1361
  14. Schopler E, Reichler RJ, DeVellis RF, Daly K. Toward objective classification of childhood autism: Childhood Autism Rating Scale (CARS). J Autism Dev Disord 1980;10:91-103. https://doi.org/10.1007/BF02408436
  15. Guy W. ECDEU assessment manual for psychopharmacology revised. Rockville, MD: US Department of Health, Education, and Welfare Public Health Service Alcohol, Drug Abuse, and Mental Health Administration;1976.
  16. Choque Olsson N, Bolte S. Brief report: "Quick and (not so) dirty" assessment of change in autism: cross-cultural reliability of the Developmental Disabilities CGAS and the OSU autism CGI. J Autism Dev Disord 2014;44:1773-1778. https://doi.org/10.1007/s10803-013-2029-y
  17. Memarzia J, Tracy D, Giaroli G. The use of antipsychotics in preschoolers: a veto or a sensible last option? J Psychopharmacol 2014; 28:303-319. https://doi.org/10.1177/0269881113519506
  18. Lemmon ME, Gregas M, Jeste SS. Risperidone use in autism spectrum disorders: a retrospective review of a clinic-referred patient population. J Child Neurol 2011;26:428-432. https://doi.org/10.1177/0883073810382143
  19. Arnold LE, Farmer C, Kraemer HC, Davies M, Witwer A, Chuang S, et al. Moderators, mediators, and other predictors of risperidone response in children with autistic disorder and irritability. J Child Adolesc Psychopharmacol 2010;20:83-93. https://doi.org/10.1089/cap.2009.0022
  20. McCracken JT, McGough J, Shah B, Cronin P, Hong D, Aman MG, et al. Risperidone in children with autism and serious behavioral problems. N Engl J Med 2002;347:314-321. https://doi.org/10.1056/NEJMoa013171
  21. Doyle CA, McDougle CJ. Pharmacologic treatments for the behavioral symptoms associated with autism spectrum disorders across the lifespan. Dialogues Clin Neurosci 2012;14:263-279.
  22. Martin A, Scahill L, Anderson GM, Aman M, Arnold LE, McCracken J, et al. Weight and leptin changes among risperidone-treated youths with autism: 6-month prospective data. Am J Psychiatry 2004;161:1125-1127. https://doi.org/10.1176/appi.ajp.161.6.1125