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A Placebo-Controlled, Fixed-Dose Study of Aripiprazole in Children and Adolescents With Irritability Associated With Autistic Disorder

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Abstract

Objective

To evaluate the short-term efficacy and safety of aripiprazole in the treatment of irritability in children and adolescents with autistic disorder.

Method

Two hundred eighteen children and adolescents (aged 6–17 years) with a diagnosis of autistic disorder, and with behaviors such as tantrums, aggression, self-injurious behavior, or a combination of these symptoms, were randomized 1:1:1:1 to aripiprazole (5, 10, or 15 mg/day) or placebo in this 8-week double-blind, randomized, placebo-controlled, parallel-group study. Efficacy was evaluated using the caregiver-rated Aberrant Behavior Checklist Irritability subscale (primary efficacy measure) and the clinician-rated Clinical Global Impressions–Improvement score. Safety and tolerability were also assessed.

Results

At week 8, all aripiprazole doses produced significantly greater improvement than placebo in mean Aberrant Behavior Checklist Irritability subscale scores (5 mg/day, −12.4; 10 mg/day, −13.2; 15 mg/day, −14.4; versus placebo, −8.4; all p < .05). All aripiprazole doses demonstrated significantly greater im provements in mean Clinical Global Impressions–Improvement score than placebo at week 8. Discontinuation rates due to adverse events were as follows: placebo 7.7%, aripiprazole 5 mg/day 9.4%, 10 mg/day 13.6%, and 15 mg/day 7.4%. The most common adverse event leading to discontinuation was sedation. There were two serious adverse events: presyncope (5 mg/day) and aggression (10 mg/day). At week 8, mean weight change (last observation carried forward) was as follows: placebo +0.3 kg, aripiprazole 5 mg/day +1.3 kg, 10 mg/day +1.3 kg, and 15 mg/day +1.5 kg; all p < .05 versus placebo.

Conclusions

Aripiprazole was efficacious and generally safe and well tolerated in the treatment of children and adol escents with irritability associated with autistic disorder. J. Am. Acad. Child Adolesc. Psychiatry, 2009;48(11):1110–1119.

Section snippets

Study Design and Treatment

This multicenter, randomized, double-blind, placebo-controlled trial was conducted at 37 sites in the United States between June 2006 and June 2008 in accordance with the Declaration of Helsinki. Sites were composed of independent research centers and research centers with a hospital affiliation. The institutional review board at each site approved the protocol. All parents/guardians provided written informed consent to participate, and subjects provided written informed assent when possible.

Subject Disposition and Demographics

A total of 368 subjects were enrolled in this study. Of these, 218 were randomized to double-blind treatment (placebo, n = 52; aripiprazole 5 mg/day, n =53; aripiprazole 10 mg/day, n = 59; and aripiprazole 15 mg/day, n = 54); subject disposition is shown in Figure 1. The randomized, double-blind treatment phase was completed by 82% (n = 178) of the subjects and completion rates were similar between treatment arms (Fig. 1). The most common reason for withdrawal in all the treatment groups was

Discussion

In this 8-week study, aripiprazole was effective at reducing irritability in children and adolescents with autistic disorder who also demonstrate irritability, agitation, self-injurious behavior, or a combination of these symptoms. At all doses, aripiprazole produced significantly greater improvements in irritability than the placebo, as measured on the caregiver-rated ABC Irritability subscale. Furthermore, improvements in irritability were rapid, with all treatment arms producing

References (26)

  • L Scahill et al.

    Children's Yale-Brown Obsessive Compulsive Scale: reliability and validity

    J Am Acad Child Adolesc Psychiatry

    (1997)
  • APA

    Diagnostic and Statistical Manual of Mental Disorders

    (2000)
  • S Chakrabarti et al.

    Pervasive developmental disorders in preschool children: confirmation of high prevalence

    Am J Psychiatry

    (2005)
  • E Fombonne et al.

    Pervasive developmental disorders in Montreal, Quebec, Canada: prevalence and links with immunizations

    Pediatrics

    (2006)
  • F Volkmar et al.

    Summary of the practice parameters for the assessment and treatment of children, adolescents, and adults with autism and other pervasive developmental disorders

    JAm Acad Child Adolesc Psychiatry

    (1999)
  • L Lecavalier

    Behavioral and emotional problems in young people with pervasive developmental disorders: relative prevalence, effects of subject characteristics, and empirical classification

    J Autism Dev Disord

    (2006)
  • L Lecavalier et al.

    The impact of behaviour problems on caregiver stress in young people with autism spectrum disorders

    J Intellect Disabil Res

    (2006)
  • SM Myers et al.

    Management of children with autism spectrum disorders

    Pediatrics

    (2007)
  • Research Units on Pediatric Psychopharmacology Autism Network

    Risperidone in children with autism and serious behavioral problems

    N Engl J Med

    (2002)
  • S Shea et al.

    Risperidone in the treatment of disruptive behavioral symptoms in children with autistic and other pervasive developmental disorders

    Pediatrics

    (2004)
  • RL Findling et al.

    Tolerability and pharmacokinetics of aripiprazole in children and adolescents with psychiatric disorders: an open-label, dose-escalation study

    J Clin Psychopharmacol

    (2008)
  • RL Findling et al.

    A multiple-center, randomized, double-blind, placebo-controlled study of oral aripiprazole for treatment of adolescents with schizophrenia

    Am J Psychiatry

    (2008)
  • J Biederman et al.

    An open-label trial of aripiprazole monotherapy in children and adolescents with bipolar disorder

    CNS Spectr

    (2007)
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    This study was supported by Bristol-Myers Squibb (Princeton, NJ) and Otsuka Pharmaceutical Co., Ltd. (Tokyo, Japan). Editorial support for the preparation of this article was provided by Suzanne Patel and Anna Howarth at Ogilvy Healthworld Medical Education. Bristol-Myers Squibb provided funding for the editorial support. Additional editorial support was provided by Raymond Mankoski of Bristol-Myers Squibb.

    The authors thank Dan A. Oren, M.D., and Patricia Corey-Lisle, Ph.D. The authors also thank the patients and their caregivers for their participation in this study.

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