European Child & Adolescent Psychiatry

, Volume 17, Issue 1, pp 1–8 | Cite as

Risperidone versus haloperidol in children and adolescents with AD

A randomized, controlled, double-blind trial
  • Suha Miral
  • Ozlem Gencer
  • F. Neslihan Inal-Emiroglu
  • Burak Baykara
  • Aysen Baykara
  • Eray Dirik



The aim of the study was to compare safety, efficacy and tolerability of risperidone with haloperidol in the treatment of Autistic Disorder (AD).


This study was designed as a double-blind, prospective, for a 12-week period. A total of 30 subjects, between the ages of 8 and 18 with AD based on DSM IV criteria, were included in the study. Behavioral Rating Scales were performed by the investigators and the parents. Safety assessment included vital signs, electrocardiogram, electroencephalogram, adverse events, laboratory tests, extrapyramidal symptoms and the side effects. Both treatments were applied in a once daily dosage regimen of 0.01–0.08 mg/kg/day.


The reduction from baseline in Ritvo–Freeman Real Life Rating Scale (RF-RLRS), sensory motor (subscale I) and language (subscale V) scores were significant in risperidone group (P < 0.05). Compared to haloperidol, risperidone led to a significantly greater reduction in the Aberrant Behavior Checklist (ABC) and Turgay DSM-IV Pervasive Developmental Disorder (PDD) scale scores (P < 0.05 and P < 0.01). There was a greater increase of prolactin in the risperidone group, while alanine amino transferase (ALT) had further increased in the haloperidol group. Sensory motor behaviors (subscale I) and language at the end of the 12th week, RF-RLRS sensory motor and language subscale scores decreased in the risperidone group further than the other group (P < 0.05).


Risperidone was found to be more effective than haloperidol in the treatment of behavioral symptoms, impulsivity, language skills, and impaired social relations in children with AD. These results demonstrated that both drugs were safe and well tolerated in the treatment of AD.


autistic disorder risperidone haloperidol treatment 



This research was supported in part by Janssen and Cilag Drug Company and presented as poster presentation in ESCAP 2003, Paris.


  1. 1.
    Aman MG, Singh NN (1985) Psychometric characteristics of the Aberrant Behavior Checklist. Am J Ment Defic 89:492–502PubMedGoogle Scholar
  2. 2.
    American Psychiatric Association (1994) Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV). American Psychiatric Association, Washington DCGoogle Scholar
  3. 3.
    Anderson L, Campbell, M Adams P, Small AM, Perry R, Shell J (1989) The effects of haloperidol on discrimination learning and behavioral symptoms in autistic children. J Autism Dev Disord 19:227–239Google Scholar
  4. 4.
    Arnold LE, Vitiello B, McDougle C, Scahill L, Shah B, Gonzalez NM, Chuang S, Davies M, Hollway J, Aman MG, Cronin P, Koenig K, Kohn AE, McMahon DJ, Tierney E (2003) Parent defined target symptoms respond to risperidone in RUPP autism study: customer approach to clinical trials. J Am Acad Child Adolesc Psychiatry 42(12):1443–1450PubMedCrossRefGoogle Scholar
  5. 5.
    Barnard L, Young AH, Pearson C, Geddes J, O’Brien G (2003) A systematic review of the use of atypical antipsychotics in autism. J Psychopharmacol 16(1):93–101Google Scholar
  6. 6.
    Buitelaar JK, Willemsen-Swinkels SHN (2000) Medication treatment in subjects with autistic spectrum disorders. Eur Child Adolesc Psychiatry 9:I/85–I/97CrossRefGoogle Scholar
  7. 7.
    Campbell M, Geller B, Cohen IL (1977) Current status of drug research and treatment with autistic children. J Pediatr Psychol 4:153–161CrossRefGoogle Scholar
  8. 8.
    Campbell M, Adams P, Perry R, Spencer EK, Overall JE (1988) Tardive and withdrawal dyskinesia in autistic children: a prospective study. Psychopharmacol Bull 24:251–255PubMedGoogle Scholar
  9. 9.
    Campbell M, Schopler E, Cueva JE, Hallin A (1996) Treatment of AD. J Am Acad Child Adolesc Psychiatry 35:134–143PubMedCrossRefGoogle Scholar
  10. 10.
    Campbell M, Armentos JL, Malone RP, Adams PB, Eisenberg ZW, Overall JE (1997) Neuroleptic- related dyskinesias in autistic children: a prospective, longitudinal study. J Am Acad Child Adolesc Psychiatry 36:835–843PubMedCrossRefGoogle Scholar
  11. 11.
    Campbell M, Rapoport JL, Simpson GM (1999) Antipsychotics in children and adolescents. J Am Acad Child Adolesc Psychiatry 38:537–545PubMedCrossRefGoogle Scholar
  12. 12.
    Chouinard G, Ross-Chouinard A, Annable L (1980) Extrapyramidal symptom rating scale. Can J Neurol Sci 7:233Google Scholar
  13. 13.
    Cohen IL, Campbell M, Posner D, Small AM, Triebel D, Anderson LT (1980) Behavioral effects of haloperidol in young autistic children: an objective analysis using a within-subjects reversal design. J Am Acad Child Adolesc Psychiatry 19:665–677Google Scholar
  14. 14.
    Findling RL, Maxwell K, Wiznitzer M (1997) An open clinical trial of risperidone monotherapy in young children with AD. Psychopharmacol Bull 33:155–159PubMedGoogle Scholar
  15. 15.
    Findling RL, McNamara NK (2004) Atypical antipsychotics in the treatment of children and adolescents: clinical applications. J Clin Psychiatry 65(Suppl 6):30–44PubMedGoogle Scholar
  16. 16.
    Fisman S, Steele M (1996) Use of risperidone in PDDs: a case series. J Child Adolesc Psychopharmacol 6:177–190PubMedGoogle Scholar
  17. 17.
    Freeman BJ, Ritvo ER, Yokota A, Ritvo A (1986) A scale for rating symptoms of patients with the syndrome of autism in real life settings. J Am Acad Child Psychiatry 25:130–136PubMedCrossRefGoogle Scholar
  18. 18.
    Gagliano A, Germano E, Pustorino G, Impallomeni C, D’Arrigo C, Calamoneri F, Spina E (2004) Risperidone treatment of children with AD: Effectiveness, tolerability, and pharmacokinetic implications. J Child Adolesc Psychopharmacol 14:39–47PubMedCrossRefGoogle Scholar
  19. 19.
    Gillberg C (2000) Typical neuroleptics in child and adolescent psychiatry. Eur Child Adolesc Psychiatry 9:I/2–I/8Google Scholar
  20. 20.
    Guy W (1976) ECDEU assessment manual for psychopharmacology, revised. US Department of Health, Education and Welfare, Rockville, MDGoogle Scholar
  21. 21.
    Hellings JA, Zarcone JR, Crandall KI, Wallace D, Schraeder SR (2001) Weight gain in a controlled study of risperidone in children adolescents and adults with mental retardation and autism. J Child Adolesc Psychopharmacol 11:229–238PubMedCrossRefGoogle Scholar
  22. 22.
    Lingjaerde O, Ahlfors UG, Bech P Dencker SJ Elgen K (1987) The UKU side effect rating scale. Acta Psychiatr Scand (suppl) 334:1–100CrossRefGoogle Scholar
  23. 23.
    Locascio J, Malone R, Small A, Kafantaris V, Ernst M, Lynch NS, Overall JE, Campbell M (1991) Factors related to haloperidol response and dyskinesias in autistic children. Psychopharmacol Bull 27:119–126PubMedGoogle Scholar
  24. 24.
    Malone RP, Maislin G, Choudhury MS, Gifford C, Delaney MA (2002) Risperidone treatment in children and adolescents with autism: short- and long-term safety and effectiveness. J Am Acad Child Adolesc Psychiatry 41:140–147PubMedCrossRefGoogle Scholar
  25. 25.
    Masi GM, Cosenza A, Mucci M (2001) Prolactin levels in young children with PDDs during risperidone treatment. J Child Adolesc Psychopharmacol 11:389–394PubMedCrossRefGoogle Scholar
  26. 26.
    Masi GM, Cosenza A, Mucci M, Brovedani P (2001) Open trial of risperidone in 24 young children with PDDs. J Am Acad Child Adolesc Psychiatry 40:1206–1214PubMedCrossRefGoogle Scholar
  27. 27.
    Masi GM, Cosenza A, Mucci M, Brovedani P (2003) A 3-year naturalistic study of preschool children with PDDs treated with risperidone. J Clin Psychiatry 64:1039–1047PubMedCrossRefGoogle Scholar
  28. 28.
    McCracken JT, McGough J, Shah B, Cronin P, Hong D, Aman MG, Arnold LE, Lindsay R, Nash P, Hollway J, McDougle CJ, Posey D, Swiezy N, Kohn A, Scahill L, Martin A, Koenig K, Volkmar F, Carroll D, Lancor A, Tierney E, Ghuman J, Gonzalez NM, Grados M, Vitiello B, Ritz L, Davies M, Robinson J, McMahon D (2002) Risperidone in children with autism and serious behavioral problems. N Engl J Med 5:314–321CrossRefGoogle Scholar
  29. 29.
    McDougle CJ, Holmes JP, Bronson MR, Anderson GM, Volkmar FR, Price LH, Cohen DJ (1997) Risperidone treatment of children and adolescents with PDDs: a prospective, open-label study. J Am Acad Child Adolesc Psychiatry 36:685–693PubMedCrossRefGoogle Scholar
  30. 30.
    McDougle CJ, Holmes JP, Carlson DC, Pelton GH, Cohen DJ, Price LH (1998) A double-blind, placebo controlled study of risperidone in adults with AD and the other PDDs. Arch Gen Psychiatry 55:633–641PubMedCrossRefGoogle Scholar
  31. 31.
    McDougle CJ, Scahill L, McCracken JT, Aman MG, Tierney E, Arnold LE, Freeman BJ, Martin A, McGough JJ, Cronin P, Posey DJ, Riddle MA, Ritz L, Swiezy NB, Vitiello B, Volkmar FR, Votolato NA, Walson P (2000) Research Units on Pediatric Psychopharmacology (RUPP)—Autism Network: background and rationale for an initial controlled study of risperidone. Child Adolesc Psychiatr Clin N Am 9:201–224PubMedGoogle Scholar
  32. 32.
    McDougle CJ, Scahill L, Aman MG, McCracken JT, Davies M, Arnold LE, Posey DJ, Martin A, Ghuman JK, Shah B, Chuang SZ, Swiezy NB, Gonzalez NM, Hollway J, Koenig K, McGough JJ, Ritz L, Vitiello B (2005) 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 162:1142–1148PubMedCrossRefGoogle Scholar
  33. 33.
    Nicolson R, Awad G, Sloman L (1998) An open trial of risperidone in young autistic children. J Am Acad Child Adolesc Psychiatry 37:372–376PubMedCrossRefGoogle Scholar
  34. 34.
    Perry R, Campbell M, Adams P, Lynch N, Spencer EK, Curren EL, Overall JE. (1989) Long-term efficacy of haloperidol in autistic children: continuous versus discontinuous drug administration. J Am Acad Child Adolesc Psychiatry 28:87–92PubMedCrossRefGoogle Scholar
  35. 35.
    Remschmidt H, Hennighausen K, Clement HW, Heiser P, Schulz E (2000) Atypical neuroleptics in child and adolescent psychiatry. Eur Child Adolesc Psychiatry 9:I/9–I/19CrossRefGoogle Scholar
  36. 36.
    Scahill L, McCracken J, McDougle CJ, Aman M, Arnold LE, Tierney E, Cronin P, Davies M, Ghuman J, Gonzalez N, Koenig K, Lindsay R, Martin A, McGough J, Posey DJ, Swiezy N, Volkmar F, Ritz L, Vitiello B (2001) Methodological issues in designing a multisided trial of risperidone in children and adolescents with autism. J Child Adolesc Psychopharmacol 11:377–388PubMedCrossRefGoogle Scholar
  37. 37.
    Shea S, Turgay A, Carroll A, Schulz M, Orlik H, Smith I, Dunbar F (2004) Risperidone in the treatment of disruptive behavioral symptoms in children with autistic and other PDDs. Pediatrics 114:634–641CrossRefGoogle Scholar
  38. 38.
    Turgay A (1993) Turgay PDDs scale. Copyright and publication: Integrative Therapy Institute, West Bloomfield, MichiganGoogle Scholar
  39. 39.
    Vasconcelos SM, Pereira RF, Alves RS Arruda Filho AC, Aguiar LM, Macedo DS, Freitas RM, Queiroz MG, Sousa FC, Viana GS (2004) Effects of ethanol and haloperidol on plasma levels of hepatic enzymes, lipid profile, and apolipoprotein in rats. Biochem Cell Biol 82(2):315–320PubMedCrossRefGoogle Scholar
  40. 40.
    Volkmar FR, Klin A, Cohen DJ (1997) Diagnosis and classification of autism and related conditions. In: Volkmar FR, Cohen DJ (eds) Handbook of Autism and PDDs. New York, Wiley pp 5–40Google Scholar
  41. 41.
    Zuddas A, Di Martino A, Muglia P, Cianchetti C (2000) Long-term risperidone for PDD: efficacy, tolerability, and discontinuation. J Child Adolesc Psychopharmacol 10:79–90PubMedGoogle Scholar

Copyright information

© Steinkopff Verlag 2008

Authors and Affiliations

  • Suha Miral
    • 1
  • Ozlem Gencer
    • 1
  • F. Neslihan Inal-Emiroglu
    • 1
  • Burak Baykara
    • 1
  • Aysen Baykara
    • 1
  • Eray Dirik
    • 2
  1. 1.Department of Child and Adolescent PsychiatryDokuz Eylul University Faculty of MedicineNarlidere, IzmirTurkey
  2. 2.Department of Child NeurologyDokuz Eylul University Faculty of MedicineNarlidere, IzmirTurkey

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