BACKGROUND: With increasing use of atypical antipsychotics among pediatric patients, detailed information about safety and tolerability is crucial. METHOD: 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. RESULTS: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%. CONCLUSIONS: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. TRIAL REGISTRATION: clinicaltrials.gov Identifiers NCT00332241 and NCT00337571.
RCT Entities:
BACKGROUND: With increasing use of atypical antipsychotics among pediatric patients, detailed information about safety and tolerability is crucial. METHOD: 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. RESULTS: 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%. CONCLUSIONS: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. TRIAL REGISTRATION: clinicaltrials.gov Identifiers NCT00332241 and NCT00337571.
Authors: Randall Owen; Linmarie Sikich; Ronald N Marcus; Patricia Corey-Lisle; George Manos; Robert D McQuade; William H Carson; Robert L Findling Journal: Pediatrics Date: 2009-12 Impact factor: 7.124
Authors: Ronald N Marcus; Randall Owen; Lisa Kamen; George Manos; Robert D McQuade; William H Carson; Michael G Aman Journal: J Am Acad Child Adolesc Psychiatry Date: 2009-11 Impact factor: 8.829
Authors: Tatiana M Kazdoba; Prescott T Leach; Mu Yang; Jill L Silverman; Marjorie Solomon; Jacqueline N Crawley Journal: Curr Top Behav Neurosci Date: 2016
Authors: José María Martínez-Ortega; Silvia Funes-Godoy; Francisco Díaz-Atienza; Luis Gutiérrez-Rojas; Lucía Pérez-Costillas; Manuel Gurpegui Journal: Eur Child Adolesc Psychiatry Date: 2013-03-17 Impact factor: 4.785
Authors: E Lemonnier; C Degrez; M Phelep; R Tyzio; F Josse; M Grandgeorge; N Hadjikhani; Y Ben-Ari Journal: Transl Psychiatry Date: 2012-12-11 Impact factor: 6.222
Authors: Sahar A Jallaq; Mark Verba; Jeffrey R Strawn; Lisa J Martin; Melissa P DelBello; Laura B Ramsey Journal: J Child Adolesc Psychopharmacol Date: 2020-08-25 Impact factor: 2.576