A placebo-controlled, fixed-dose study of aripiprazole in children and adolescents with irritability associated with autistic disorder.
OBJECTIVE
To evaluate the short-term efficacy and safety of aripiprazole in the treatment of irritability in children and adolescents with autistic disorder.


METHODS
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 improvements 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 adolescents with irritability associated with autistic disorder.
Drs. Marcus, Owen, Kamen, and Manos are with Bristol-Myers Squibb; Drs. McQuade and Carson are with Otsuka Pharmaceutical Development & Commercialization and Dr. Aman is with Ohio State University.
Ronald N
RN
Marcus
Drs. Marcus, Owen, Kamen, and Manos are with Bristol-Myers Squibb; Drs. McQuade and Carson are with Otsuka Pharmaceutical Development & Commercialization and Dr. Aman is with Ohio State University. Electronic address: randall.owen@bms.com.
Randall
R
Owen
Drs. Marcus, Owen, Kamen, and Manos are with Bristol-Myers Squibb; Drs. McQuade and Carson are with Otsuka Pharmaceutical Development & Commercialization and Dr. Aman is with Ohio State University.
Lisa
L
Kamen
Drs. Marcus, Owen, Kamen, and Manos are with Bristol-Myers Squibb; Drs. McQuade and Carson are with Otsuka Pharmaceutical Development & Commercialization and Dr. Aman is with Ohio State University.
George
G
Manos
Drs. Marcus, Owen, Kamen, and Manos are with Bristol-Myers Squibb; Drs. McQuade and Carson are with Otsuka Pharmaceutical Development & Commercialization and Dr. Aman is with Ohio State University.
Robert D
RD
McQuade
Drs. Marcus, Owen, Kamen, and Manos are with Bristol-Myers Squibb; Drs. McQuade and Carson are with Otsuka Pharmaceutical Development & Commercialization and Dr. Aman is with Ohio State University.
William H
WH
Carson
Drs. Marcus, Owen, Kamen, and Manos are with Bristol-Myers Squibb; Drs. McQuade and Carson are with Otsuka Pharmaceutical Development & Commercialization and Dr. Aman is with Ohio State University.
Michael G
MG
Aman
D000293:Adolescent; D016907:Adverse Drug Reaction Reporting Systems; D014150:Antipsychotic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D000068180:Aripiprazole; D001321:Autistic Disorder / Q000175:diagnosis / Q000188:drug therapy* / Q000523:psychology; D002648:Child; D002653:Child Behavior Disorders / Q000175:diagnosis / Q000188:drug therapy* / Q000523:psychology; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007508:Irritable Mood / Q000187:drug effects*; D008297:Male; D010552:Personality Assessment; D010879:Piperazines / Q000008:administration & dosage* / Q000009:adverse effects; D011595:Psychomotor Agitation / Q000175:diagnosis / Q000188:drug therapy / Q000523:psychology; D015363:Quinolones / Q000008:administration & dosage* / Q000009:adverse effects; D016728:Self-Injurious Behavior / Q000175:diagnosis / Q000188:drug therapy / Q000523:psychology; D016896:Treatment Outcome
D014150:Antipsychotic Agents; D010879:Piperazines; D015363:Quinolones; D000068180:Aripiprazole