Aripiprazole Overview & Mechanism of Action Aripiprazole is an atypical antipsychotic acting as a partial agonist at dopaminergic D2 and serotonergic 5-HT1A receptors, and an antagonist at 5-HT2A receptors. This unique mechanism stabilizes dopamine, limiting extrapyramidal side effects compared to older agents. It is FDA-approved for schizophrenia, bipolar I disorder, major depressive disorder (MDD) adjunct therapy, Tourette's syndrome, and autism-associated irritability.

Critical Boxed Warnings

1. Suicidality: There is an increased risk of suicidal thoughts and behaviors in children, adolescents, and young adults (up to 24 years of age) when aripiprazole is used as an antidepressant.
2. Dementia-Related Psychosis: Antipsychotics are not approved for treating dementia-related psychosis in the elderly due to significantly elevated mortality (often from heart failure or pneumonia) and cerebrovascular events like stroke.

Formulations & Administration Protocols

• Oral Options: Available as immediate-release tablets, disintegrating tablets, oral solutions, and Mycite. Mycite contains an ingestible sensor tracked via a smartphone app, though it is not recommended for "real-time" emergency tracking. All oral forms may be administered without regard to meals.
• Short-Acting IM Injection: Utilized exclusively for acute agitation in schizophrenia or bipolar mania. Inject deeply into the muscle; intravenous and subcutaneous routes are strictly contraindicated.
• Extended-Release (LAI) IM Injections: Formulations like Abilify Maintena (monthly), Abilify Asimtufii (every 2 months), and Aristada provide maintenance therapy via deep gluteal or deltoid injection. LAIs are not approved for patients under 18 years of age. Crucial Rule: Tolerability with oral aripiprazole must be established (which takes up to 2 weeks) prior to initiating long-acting injections in aripiprazole-naive patients. Initiation requires 14 to 21 days of oral overlap or the use of Aristada Initio.

Key Dosing Principles

• Schizophrenia & Bipolar I: Initiate at 10 to 15 mg/day PO for adults. The target maximum effective dose is 30 mg/day.
• MDD Adjunct: Start at 2 to 5 mg/day PO, adjusting up to 15 mg/day based on response.
• Pediatrics: Doses vary by weight and indication, with maximum PO doses of 30 mg/day for bipolar disorder, 15 mg/day for autism, and 20 mg/day for Tourette's.
• Adjustments: Aripiprazole undergoes extensive hepatic metabolism via CYP3A4 and CYP2D6. Dosages must be reduced by 50% to 75% in CYP2D6 poor metabolizers or when co-administered with strong CYP3A4 or CYP2D6 inhibitors. No hepatic or renal dose adjustments are required.

Pharmacokinetics & Safety Profile Oral aripiprazole has an 87% bioavailability, achieving steady-state within 14 days with an elimination half-life of 75 hours. LAI half-lives range widely from 30 to 57 days. Common mild-to-moderate adverse reactions include headache (0-27%), weight gain (2.2-26.3%), drowsiness (3-23%), agitation (19%), and nausea (8-15%). Severe risks include tardive dyskinesia, neuroleptic malignant syndrome, seizures, and metabolic changes.