FDA Approves Aripiprazole to Treat Irritability in Autistic Children

Yael Waknine

November 24, 2009

November 24, 2009 — The US Food and Drug Administration (FDA) has approved an expanded indication for the oral formulation of aripiprazole (Abilify tablets, orally disintegrating tablets, and oral solution, Bristol-Myers Squibb Co) for the treatment of irritability associated with autism spectrum disorder in children aged 6 to 17 years.

According to a company news release, the atypical antipsychotic is intended for use as part of a total pediatric treatment program that includes psychological, educational, and social interventions.

The approval was based on data from two 8-week, randomized, placebo-controlled multicenter studies that evaluated the efficacy of oral aripiprazole for improving mean scores on the caregiver-rated Irritability subscale of the Aberrant Behavior Checklist (ABC-I). The ABC-I measures irritability symptoms associated with autistic disorder, such as aggression toward others, deliberate self-injuriousness, temper tantrums, and quickly changing moods.

For the first study, aripiprazole was initiated at a dose of 2 mg/day and titrated weekly for the first 6 weeks to a mean of 8.6 mg/day, with most patients receiving either 5 or 10 mg/day. Results showed that aripiprazole was significantly more effective than placebo for improving mean scores on the ABC-I subscale (P < .001). Adjusted mean scores on the Clinical Global Impression Improvement scale, a secondary outcome measure, were likewise significantly improved (P < .001).

The second study was a fixed-dose trial in which patients were randomly assigned to receive 1 of 3 aripiprazole doses (5, 10, or 15 mg/day) or placebo; active treatment was initiated at dose of 2 mg/day and titrated by 5 mg weekly until the assigned dose was achieved.

Results showed that all aripiprazole doses were more effective than placebo for improving mean ABC-I subscale scores (5 mg, P < .05; 10 mg, P < .01; 15 mg, P = .001). Differences between dose groups were not evaluated.

For both studies, the most frequently reported aripiprazole-related adverse events (incidence > 10%, twice that of placebo) were sedation (21% vs 4%), fatigue (17% vs 2%), vomiting (14% vs 7%), somnolence (10% vs 4%), and tremor (10% vs 0%). The most common reasons for discontinuation of aripiprazole were sedation, drooling, tremor, vomiting, and extrapyramidal disorder.

Clinically significant weight gain (>7 pounds) occurred in 26% of patients receiving aripiprazole compared with 7% of those receiving placebo (mean gain, 1.6 kg vs 0.4 kg, respectively). A statistically significant decrease in mean prolactin levels was also observed.

The recommended starting dose of aripiprazole for autistic pediatric patients is 2 mg/day, increasing to 5 mg/day, with subsequent increases to 10 or 15 mg/day as needed. Dose adjustments of up to 5 mg/day should occur gradually at intervals of 1 week or greater.

Routine monitoring for metabolic effects should include periodic evaluations of patient weight, waist circumference, blood pressure, fasting plasma-glucose level, and fasting lipid profile.

The FDA notes that the efficacy of aripiprazole for the maintenance treatment of autistic irritability has not been evaluated; patients should be periodically reassessed to determine the need for continued treatment. Aripiprazole is not indicated for the treatment of core autistic symptoms such as abnormalities in social interaction and communication and the presence of restricted, repetitive, and stereotyped patterns of behaviors, activities, or interests.

Oral aripiprazole was previously approved as adjunctive therapy to antidepressants in the acute treatment of major depressive disorder in adults, acute and maintenance treatment (with or without lithium or valproate) of manic and mixed episodes of bipolar disorder in patients aged 10 years and older, and acute and maintenance treatment of schizophrenia in patients aged 13 years and older. Aripiprazole intramuscular injection may be used for the acute treatment of agitation associated with schizophrenia or bipolar disorder in adults.

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