Aripiprazole for Irritability Associated with Autistic Disorder in Children and Adolescents Aged 6–17 Years

ABC-I: Aberrant Behavior Checklist Irritability subscale; CGI-I: Clinical Global Impressions-Improvement scale; EPS: Extrapyramidal symptoms.

Authors and Disclosures

Kelly Blankenship^1,2,Craig A Erickson^1,2,Kimberly A Stigler^1,2,David J Posey^1,2 & Christopher J McDougle<sup>†1,2

1</sup>Christian Sarkine Autism Treatment Center, James Whitcomb Riley Hospital for Children, IN, USA
²Department of Psychiatry, Indiana University School of Medicine, 702 Barnhill Drive, ROC 4300, Indianapolis, IN 46202, USA

^†Author for correspondence
Tel.: +1 317 274 8162 Fax: +1 317 948 0609 cmcdougl@iupui.edu

Sidebar

Executive Summary

Mechanism of action

• Aripiprazole is a partial agonist at the D ₂ (dopamine) and 5-HT _1A (serotonin) receptors.

• It also functions as an antagonist at the 5-HT _2A receptor.

Pharmacokinetic properties

• Aripiprazole and its active metabolite dehyro-aripiprazole have average elimination half-lives of 75 and 94 h, respectively.

• It has a bioavailability of 87%.

• Peak plasma concentrations are reported 3–5 h after ingestion.

• It is 99% protein bound.

• Aripiprazole is metabolized through two primary cytochromes. It is dehydrogenated and hydroxylated by cytochrome P450 3A4 and 2D6. It is N -dealkylated by cytochrome P450 3A4.

• Aripiprazole is mainly excreted in the feces with a smaller amount excreted in the urine.

Clinical efficacy

• A naturalistic, open-label study of aripiprazole in five male youths with PDDs aged 5–18 years was performed for a mean duration of 12 weeks (range: 8–16 weeks). All five youths were rated as 'much improved' or 'very much improved' on the Clinical Global Impressions-Improvement scale (CGI-I).

• In a second open-label study with aripiprazole in 25 children and adolescents (aged 5–17 years) diagnosed with PDDs, 22 (88%) were judged to be responders.

• Two large placebo-controlled studies in children and adolescents (aged 6–17 years) with autistic disorder found aripiprazole to be superior to placebo for the treatment of irritability, as judged by the Aberrant Behavior Checklist Irritability subscale and CGI-I.

Safety & tolerability

• There is the possibility of clinically significant weight gain and an increase in trigylcerides.

• Prolactin levels are reduced.

• Sedation is a frequent side effect reported with this medication.

• Extrapyramidal symptoms can occur in those treated with this medication.

• There is no clinically significant increase in blood pressure or heart rate.

Drug interactions

• Strong CYP3A4 or CYP2D6 inhibitors will increase ABILIFY drug concentrations; CYP3A4 inducers will decrease ABILIFY drug concentrations.

Dosage & administration

• Available in 2, 5, 10, 15, 20 and 30 mg tablets.

• Available as a 1 mg/ml solution.

• Available as a 9.75 mg/1.3 ml intramuscular injection.