The atypical antipsychotic aripiprazole has been approved for treating irritability associated with autistic disorder in children and adolescents aged 6-17 years. Irritability includes symptoms of aggression toward others, deliberate self-injuriousness, temper tantrums, and quickly changing moods, the manufacturers announced.
Aripiprazole is marketed as Abilify by the manufacturers, Bristol-Myers Squibb Co. and Otsuka Pharmaceutical Co. The recommended dose for the new indication is 5 mg to 10 mg day (starting at 2 mg/day, with the maximum dose of 15 mg/day).
Since it was initially approved by the Food and Drug Administration in 2002 for schizophrenia, it has been approved for several other adult and pediatric indications, including treatment of schizophrenia in adolescents aged 13-17 years, and bipolar disorder indications down to age 10 years.
The effectiveness of aripiprazole for the autistic disorder indication was established in two 8-week multicenter studies of children and adolescents aged 6-17 years (more than 75% were younger than age 13 years), according to the revised label. They met the DSM-IV criteria for autistic disorder and exhibited behaviors that included tantrums, aggression, and/or self-injurious behavior.
In one study of 98 children and adolescents, those who were on aripiprazole (starting at a dose of 2 mg/day and increasing up to 15 mg/day based on clinical response) had significantly improved scores when compared to those on placebo at 8 weeks on two scales: the irritability subscale of the Aberrant Behavior Checklist (ABC-I), a caregiver rated assessment tool, and the Clinical Global Impression-Improvement (CGI-I) scale, a tool used to monitor treatment outcomes in psychiatric disorders.
In the second study of 218 children and adolescents, those on a fixed dose of aripiprazole (5 mg, 10 mg, or 15 mg per day) had significantly improved scores on the ABC-I subscale compared with those on placebo.
In a pooled analysis of the two studies, mean weight gain among those on aripiprazole was 1.6 kg, compared with 0.4 kg among those on placebo. During the study, 26% of those on aripiprazole and 7% of those on placebo experienced clinically significant weight gain, defined as at least a 7% change from baseline, according to the company statement.
Other adverse events more common among treated patients included sedation, affecting 21% of those on aripiprazole compared with 4% of those on placebo, fatigue (17% vs. 2%), vomiting (14% vs. 7%), somnolence (10% vs. 4%), tremor (10% vs. 0%), drooling (9% vs. 0%), and extrapyramidal disorder (6% vs. 0%).
These studies were “not designed or intended to evaluate” aripiprazole for treatment of the core symptoms of autistic disorder, the company statement said.