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

Kelly Blankenship; Craig A Erickson; Kimberly A Stigler; David J Posey; Christopher J McDougle

Disclosures

Pediatr Health. 2010;4(4):375-381. 

In This Article

Introduction to Aripiprazole

Aripiprazole is a second-generation antipsychotic. Second-generation antipsychotics, often called atypical antipsychotics, have a lower propensity to cause TD and EPS.[9] Aripiprazole is approved to treat schizophrenia, mixed and manic states of bipolar I disorder (as monotherapy or as an adjunct to either lithium or valproate) and as adjunctive treatment for major depressive disorder (MDD) in adults. It is also FDA-approved to treat adolescents (aged 13–17 years) with schizophrenia and manic and mixed states of bipolar I disorder in children and adolescents (aged 10–17 years).[102]

The intramuscular formulation of aripiprazole is also indicated for the acute treatment of agitation associated with schizophrenia or manic and mixed states of bipolar I disorder in adults.

Chemistry

Aripiprazole is a quinolinone antipsychotic. The empirical formula is C23H27Cl2N3O2. It has a molecular weight of 448.38.[10,103]

Pharmacodynamics

Aripiprazole is a partial agonist at the D2 (dopamine), D3 and 5-HT1A (serotonin) receptors. It also functions as an antagonist at the 5-HT2A receptor. It exhibits high affinity for D2, D3, 5-HT1A and 5-HT2A receptors. Aripiprazole possesses moderate affinity for D4, 5-HT2C, 5-HT7, a1 adrenergic and H1 histaminic receptors. Aripiprazole does not have significant affinity for muscarinic receptors.[10,103]

Pharmacokinetics & Metabolism

Although initial studies of the pharmacokinetics of aripiprazole were performed in adults, pediatric studies have revealed similar pharmacokinetic properties.[9] 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.[104] The onset of action is 1–3 weeks.[103]

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.[104]

Aripiprazole is mainly excreted in the feces with a smaller amount excreted in the urine.[103]

Clinical Efficacy

Aripiprazole has been evaluated in several open-label studies and two large placebo-controlled trials in children with autistic disorder. In these studies, aripiprazole has been found to be effective in the treatment of children and adolescents with irritability associated with autism.

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