Safety and Tolerability of Aripiprazole in the Treatment of Irritability Associated With Autistic Disorder in Pediatric Subjects (6–17 Years Old)

With increasing use of atypical antipsychotics among pediatric patients, detailed information about safety and tolerability is crucial.Data were pooled from two 8-week, randomized, double-blind, multicenter, parallel-group trials comparing aripiprazole versus placebo in subjects aged 6 to 17 years with irritability associated with DSM-IV-TR-diagnosed autistic disorder: one flexibly dosed (aripiprazole 2-15 mg/d; target of 5, 10, or 15 mg/d), the other fixed-dose (aripiprazole 5, 10, or 15 mg/d). The first was conducted from June 2006-April 2008, and the second, from June 2006-June 2008. Adverse events were characterized with respect to incidence, duration, severity, timing of peak incidence of onset, and dose-response relationship. Extrapyramidal symptoms, drooling, and metabolic parameters were evaluated.Three hundred thirteen subjects comprised the safety sample (aripiprazole 212, placebo 101). Discontinuations due to adverse events with aripiprazole versus placebo were, overall, 10.4% versus 6.9%; subjects 6-12 years: 10.8% versus 5.1%; and subjects 13-17 years: 8.9% versus 13.6%. Common adverse events with aripiprazole versus placebo included sedation (20.8% vs 4.0%), fatigue (16.5% vs 2.0%), vomiting (13.7% vs 6.9%), increased appetite (12.7% vs 6.9%), somnolence (10.4% vs 4.0%), and tremor (9.9% vs 0.0%). Most adverse events were mild or moderate and occurred early. Only fatigue showed a dose-response relationship (P < .05). Mean body weight change (last observation carried forward, 1.6 vs 0.4 kg) was higher with aripiprazole than placebo (P < .001). There were no between-treatment differences in metabolic changes. The extrapyramidal symptom-related adverse event incidence with aripiprazole versus placebo was, overall, 20.8% vs 9.9%; the incidence of akathisia-related events was 3.3% vs 8.9%.Aripiprazole was generally safe and well tolerated in subjects (6-17 years) with irritability associated with autistic disorder in these 8-week studies; clinicians should be aware of this clinical profile and strategies to manage adverse events if they occur.clinicaltrials.gov Identifiers NCT00332241 and NCT00337571.