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01-06-2008 | ORIGINAL CONTRIBUTION

Comparison of long-term efficacy and safety of risperidone and haloperidol in children and adolescents with autistic disorder

An open label maintenance study

Authors: Ozlem Gencer, MD, F. Neslihan Inal Emiroglu, MD, Suha Miral, MD, Burak Baykara, MD, Aysen Baykara, MD, Eray Dirik, MD

Published in: European Child & Adolescent Psychiatry | Issue 4/2008

Abstract

Background

The aim of the study was to investigate safety, efficacy and tolerability of risperidone in comparison with haloperidol in the long-term treatment of autistic disorder.

Methods

This was an open-label continuation study of the randomized, double-blind, controlled trial of risperidone and haloperidol study for 12 week in autistic children and adolescents. A total of 28 subjects between 8 and 18 ages with autistic disorder were enrolled to the open label phase of the study. Behavioral rating scales (Clinical Global Impression Scale [CGI-I], Ritvo-Freeman Real Life Rating Scale [RF-RLRS]), Aberrant Behavior Checklist [ABC], Turgay DSM-IV Pervasive Developmental Disorder Rating Scale [TPDDRS]) and safety assessment scales (Extrapyramidal Symptoms Rating Scale [ESRS], UKU-Side Effect Rating Scale) were performed at 12, 16, 20 and 24 weeks, following the 12 week double-blind phase. Risperidone and haloperidol treatments were applied with a once daily dosage regimen as 0.01–0.08 mg/kg/day.

Results

Risperidone led to a significant greater reduction on CGI scale. There was significant improvement on RF-RLRS sensory motor and language subscale and ABC scores in risperidone group. Weight gain was observed more frequently in the haloperidol group at week 24.

Conclusions

These results demonstrate that risperidone is more efficacious and well tolerated than haloperidol in the long-term maintenance treatment of autistic disorder.

Aman MG, Singh NN, Stewart AW, Field CJ (1985) The aberrant behavior checklist: a behavior rating scale for the assessment of treatment effects. Am J Ment Defic 89:485–489PubMed

Aman MG, Singh NN (1985) Psychometric characteristics of the aberrant behavior checklist. Am J Ment Defic 89:492–502PubMed

American Psychiatric Association (1994) Diagnostic and statistical manual of mental disorders, 4th edition (DSM-IV). American Psychiatric Association, Washington DC

Anderson LT, Campbell M, Grega DM, Perry R, Small AM, Green WH (1984) Haloperidol in the treatment of infantile autism: effects on learning and behavioral symptoms. Am J Psychiatry 141:1195–1202PubMed

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 19:227–239PubMedCrossRef

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):1443–1450PubMedCrossRef

Campbell M, Schopler E, Cueva JE, Hallin A (1996) Treatment of autistic disorder. J Am Acad Child Adolesc Psychiatry 35:134–143PubMedCrossRef

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 36:835–843PubMedCrossRef

Campbell M, Rapoport JL, Simpson GM (1999) Antipsychotics in children and adolescents. J Am Acad Child Adolesc Psychiatry 38:537–545PubMedCrossRef

10.

Casaer P, Croonenberghs JAN, Lagae L, Deboutte D (2002) Risperidone in the treatment of childhood autistic disorder: an open pilot study. Acta Neuropsychiatrica 14:242–249CrossRef

11.

Chouinard G, Ross- Chouinard A, Annable L (1980) Extrapyramidal symptom rating scale. Can J Neurol Sci 7:233

12.

Chouinard G, Annable L, Ross- Chouinard A (1982) Fluphenazine enanthate and fluphenazine decanoate in the treatment of schizophrenic outpatients: extrapyramidal symptoms and therapeutic effect. Am J Psychiatry 139 (3):312–318PubMed

13.

Cohen IL, Campbell M, Posner D, Small AM, Triebel D, Anderson LT (1980) Behavioral effects of haloperİdol in young autistic children: an objective analysis using a within-subjects reversal design. J Am Acad Child Adolesc Psychiatry 19:665–667

14.

Findling RL, Maxwell K, Wiznitzer M (1997) An open clinical trial of risperidone monotherapy in young children with autistic disorder. Psychopharmacol Bull 33:155–159PubMed

15.

Findling RL, McNamara NK (2004) Atypical antipsychotics in the treatment of children and adolescents: clinical applications. J Clin Psychiatry 65(Suppl 6):30–44PubMed

16.

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 25:130–136PubMedCrossRef

17.

Gagliano A, Germano E, Pustorino G, Impallomeni C, D’Arrigo C, Calamoneri F, Spina E (2004) Risperidone treatment of children with autistic disorder: Effectiveness, tolerability, and pharmacokinetic implications. J Child Adolesc Psychopharmacol 14:39–47PubMedCrossRef

18.

Ganguli R (2000) Weight gain associated with antipsychotic drugs. J Clin Psychiatry 60(suppl 9):678CrossRef

19.

Guy W (1976) ECDEU assessment manual for psychopharmacology, revised. US Department of Health, Education and Welfare, Rockville

20.

Jensen PS, Bhatara VS, Vitiello B, Hoagwood K, Feil M, Burke L (1999) Psychoactive medication prescribing practices for US children: gaps between research and clinical practice. J Am Acad Child Adolesc Psychiatry 38:557–565PubMed

21.

Lambert TJR, Cock N, Alcock SJ, Kelly DL, Conley RR (2003) Measurement of antipsychotic-induced side effects:support for the validity of a self report (LUNSERS) versus structured interview (UKU) approach to measurement. Human Psychopharmacol Clin Exp 18:405–411CrossRef

22.

Lingjaerde O, Ahlfors UG, Bech P Dencker SJ Elgen K (1987) The UKU side effect rating scale. Acta Psychiatr Scand 334(suppl):1–100CrossRef

23.

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 41:140–147PubMedCrossRef

24.

Martin A, Scahill L, Anderson GM, Aman M, Arnold LE, McCracken J, McDougle CJ, Tierney E, Chuang S, Vitiello B (2004) Weight and leptin changes among risperidone-treated youths with autism: 6-month prospective data. Am J Psychiatry 161:1125–1127PubMedCrossRef

25.

Masi GM, Cosenza A, Mucci M, Brovedani P (2003) A 3-year naturalistic study of preschool children with pervasive developmental disorders treated with risperidone. J Clin Psychiatry 64:1039–1047PubMedCrossRef

26.

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):314–321

27.

McDougle CJ, Holmes JP, Bronson MR, Anderson GM, Volkmar FR, Price LH Cohen DJ (1997) Risperidone treatment of children and adolescents with pervasive developmental disorder: a prospective open-label study. J Am Acad Child Adolesc Psychiatry 36:685–693PubMedCrossRef

28.

McDougle CJ, Holmes JP, Carlson DC, Pelton GGH, Cohen DJ, Price LH (1998) A double-blind, placebo-controlled study of risperidone in adults with autistic disorder and other pervasive developmental disorders. Arch Gen Psychiatry 55:633–641PubMedCrossRef

29.

McDougle CJ, Scahill L, Aman MG, McCracken JT, Tierney E, Davies M, Arnold LE, Posey DJ, Martin A, Ghuman JK, Shah B, Chuang SZ, Swiezy NB, Gonzalez NM (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 162:1142–1148PubMedCrossRef

30.

Nicolson R, Awad G, Sloman L (1998) An open trial of risperidone in young autistic children. J Am Acad Child Adolesc Psychiatry 37:372–376PubMedCrossRef

31.

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 28:87–92PubMedCrossRef

32.

Ritvo ER, Freeman BJ, Yuwiler A, Geller E, Schroth P, Yokota A, Mason-Brothers A, August GJ, Klykylo W, Leventhal B, Lewis K, Piggott L, Realmuto G, Stubbs EG, Umansky R (1986) Fenfluramine treatment of autism: UCLA collaborative study of 81 patients at nine medical centers. Psychopharmacol Bull 22:133–140PubMed

33.

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 11:377–388PubMedCrossRef

34.

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 pervasive developmental disorders. Pediatrics 114:e634–e641PubMedCrossRef

35.

Taylor E (1994) Physical treatments. In: Rutter M, Taylor E, Hersov L (eds) Child and adolescent psychiatry, modern approaches, 3rd edn. Great Britain: Bath Press, pp 880–899

36.

Turgay A (1993) Turgay pervasive developmental disorders scale. Copyright and publication: Integrative Therapy Institute, West Bloomfield

37.

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 pervasive developmental disorders. New York, Wiley pp 5–40

38.

Zuddas A, Di Martino A, Muglia P, Cianchetti C (2000) Long-term risperidone for pervasive developmental disorder: efficacy, tolerability, and discontinuation. J Child Adolesc Psychopharmacol 10:79–90PubMed

Title: Comparison of long-term efficacy and safety of risperidone and haloperidol in children and adolescents with autistic disorder
An open label maintenance study
Authors: Ozlem Gencer, MD
F. Neslihan Inal Emiroglu, MD
Suha Miral, MD
Burak Baykara, MD
Aysen Baykara, MD
Eray Dirik, MD
Publication date: 01-06-2008
Publisher: D. Steinkopff-Verlag
Published in: European Child & Adolescent Psychiatry / Issue 4/2008
Print ISSN: 1018-8827
Electronic ISSN: 1435-165X
DOI: https://doi.org/10.1007/s00787-007-0656-6

At a glance: The STEP trials

Springer Medicine

Comparison of long-term efficacy and safety of risperidone and haloperidol in children and adolescents with autistic disorder

An open label maintenance study

Abstract

Background

Methods

Results

Conclusions

At a glance: The STEP trials

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

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