Aripiprazole for Irritability Associated with Autistic Disorder in Children and Adolescents Aged 6–17 Years

Kelly Blankenship; Craig A Erickson; Kimberly A Stigler; David J Posey; Christopher J McDougle

Pediatr Health. 2010;4(4):375-381.

Abstract and Introduction

Abstract

Aripiprazole was recently US FDA-approved to treat irritability in children and adolescents with autistic disorder aged 6–17 years. There are currently only two psychotropics approved by the FDA to treat irritability in the autistic population. This drug profile will discuss available studies of aripiprazole in individuals with pervasive developmental disorders, two of which led to its recent FDA approval. We will discuss the efficacy, as well as the safety and tolerability of the drug documented in these studies. In addition, the chemistry, pharmacokinetics, metabolism and mechanism of action of aripiprazole will be reviewed.

Introduction

Autistic disorder (autism) is a neuropsychiatric syndrome characterized by deficits in social interaction, qualitative impairments in communication and restricted repetitive and stereotyped patterns of behavior, interests or activities. It is classified as a type of pervasive developmental disorder (PDD). PDD not otherwise specified, Asperger's disorder, Rett's disorder and childhood disintegrative disorder represent the other diagnostic types of PDDs.^[1] All types of PDDs have a qualitative impairment in social relatedness. However, many individuals with PDDs also have other interfering symptoms, including irritability (aggression, self-injurious behavior and severe tantrums). Behavioral therapy is often helpful in decreasing these behaviors; however, sometimes medications are needed adjunctively owing to the intensity and severity of the irritability.^[2]

The typical antipsychotics were one of the initial classes of medication to be studied for the treatment of irritability in autism.^[2,3] However, concerns regarding their propensity to cause extrapyramidal symptoms (EPS) limited their use.^[2,4–7] Atypical antipsychotics have largely replaced the use of typical antipsychotics to treat irritability in autism.^[3] Atypical antipsychotics are thought to result in less tardive dyskinesia (TD) and EPS compared with typical antipsychotics owing to differences in D₂-receptor affinity.

Until recently, risperidone was the most studied and the only psychotropic approved by the US FDA to treat irritability related to autism. Aripiprazole has recently undergone several placebo-controlled studies validating its use in individuals with irritability associated with autistic disorder, leading to its recent US FDA approval.

1 2 3 4 5 6 7 8 9

Next Section

Cite this: Aripiprazole for Irritability Associated with Autistic Disorder in Children and Adolescents Aged 6–17 Years - Medscape - Aug 01, 2010.

Table 1. Prospective, systematic trials of aripiprazole in individuals with pervasive developmental disorder.
Study type	Sample, n (age in years)	Mean dose (mg/day)	Duration (weeks)	Results	Side effects	Ref.
Open-label	n = 5 (5–18)	10–15	12	5/5 (100%) responded	2/5 reported somnolence, 1/5 gained weight	^[15]
Open-label	n = 25 (5–17)	7.8	14	22/25 (88%) responded	19/25 experienced an increase in BMI, 9/25 reported EPS	^[16]
Double-blind	n = 218 (6–17)	5, 10 and 15 fixed dosing	8	17/49 (35%), 29/52 (56%), 29/59 (49%) and 28/53 (53%) responded to placebo, aripiprazole 5, 10 and 15 mg, respectively; all doses demonstrated significantly greater improvement than placebo on ABC-I and CGI-I	For the placebo, 5, 10 and 15 mg groups, respectively, an increase in BMI was experienced by 1/49, 4/52, 1/59 and 2/53; EPS was reported by 1/49, 2/52, 4/59 and 6/53; and sedation was reported by 3/49, 9/52, 17/59 and 13/53	^[13]
Double-blind	n = 98 (6–17)	8.6	8	Aripiprazole demonstrated significantly greater improvement compared with placebo on the ABC-I and CGI-I (67% were rated as improved or much improved)	For the aripiprazole and placebo groups, respectively, there was an increase in weight (2.0 and 0.8 kg); EPS (7/47 and 4/50); and sedation (5/47 and 1/50)	^[14]

ABC-I: Aberrant Behavior Checklist Irritability subscale; CGI-I: Clinical Global Impressions-Improvement scale; EPS: Extrapyramidal symptoms.

Comments

Commenting is limited to medical professionals. To comment please Log-in.

Comments on Medscape are moderated and should be professional in tone and on topic. You must declare any conflicts of interest related to your comments and responses. Please see our Commenting Guide for further information. We reserve the right to remove posts at our sole discretion.