Aripiprazole

Neuroleptic, Atypical neuroleptic, Third-generation neuroleptic, Mood stabilizer

Aripiprazole

Abilify (oral), Abilify Maintena (monthly IM LAI), Aristada (aripiprazole lauroxil IM LAI), Abilify Asimtufii (bi-monthly IM LAI), Abilify MyCite (digital ingestion sensor)

Experience

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Problems

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Titration strategies

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Effects

In May 2016 the FDA warned that aripiprazole can cause intense, uncontrollable urges, most often compulsive gambling, but also compulsive eating, shopping, and hypersexuality; these urges can arise at any dose, are easily missed, and generally resolve when the dose is lowered or the medicine is stopped. The association is commonly linked to aripiprazole's dopamine D2 partial agonism, though the FDA stated the mechanism is not established. This is a labeled Warning, separate from the medicine's boxed warnings.

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Pharmacy

Starting dose

Schizophrenia/bipolar mania: 10-15 mg PO once daily, target 15-30 mg. MDD adjunct: 2-5 mg/day, target 5-15 mg. Pediatric autism irritability: 2 mg, titrate to 5-15 mg. Maintena LAI: 400 mg IM every 4 weeks after oral overlap

Preparations

Tablets 2, 5, 10, 15, 20, 30 mg; ODT 10, 15 mg; oral solution 1 mg/mL; acute IM injection 9.75 mg/1.3 mL; Maintena LAI 300, 400 mg monthly; Aristada LAI 441, 662, 882, 1064 mg (4-8 week dosing); Asimtufii bi-monthly

US FDA Max

30 mg/day (adult schizophrenia); 15 mg/day (MDD adjunct)

Common uses

Classification(s)

Classes

Neuroleptic, Atypical neuroleptic, Third-generation neuroleptic, Mood stabilizer

Pharmacology

Routes

Oral, intramuscular (acute and long-acting)

Onset

Neuroleptic effect emerges over days to weeks; activation symptoms (akathisia, insomnia) often within days

Duration

24 hours (oral); 4-8 weeks (LAI)

Half-life

~75 hours (long, accumulates over weeks)

Bioavailability

~87% (oral)

Pregnancy

Limited human data; signal for neonatal extrapyramidal symptoms and withdrawal with third-trimester exposure.^{[citation needed]}

Legal status

Rx-only in US. Carries the atypical-neuroleptic Boxed Warning for increased mortality in elderly patients with dementia-related psychosis, and the antidepressant suicidality Boxed Warning when used for MDD adjunct in patients under 24

Purported mechanism

D2 and D3 dopamine receptor partial agonist (the third-generation neuroleptic signature, distinct from olanzapine/risperidone full D2 antagonism), with additional 5-HT1A partial agonism and 5-HT2A receptor antagonism. The D2 partial agonism is the "dopamine system stabilizer" rationale: in hyperdopaminergic states (psychosis, mania) aripiprazole functions as a partial antagonist; in hypodopaminergic states (prefrontal cortex, MDD adjunct) it functions as a partial agonist.▲0▼ Akathisia is the most common dose-limiting adverse effect, particularly with the MDD-adjunct dose range. Lower weight gain, lower metabolic burden, and lower prolactin elevation than most second-generation neuroleptics, the principal pharmacological selling points. CYP2D6 and CYP3A4 metabolism; CPIC PGx guidance applies for CYP2D6 dose individualization.

Pharmacopedia is intended for reference. Nothing here is advice. In an emergency call 911; US Poison Control 1-800-222-1222. See the full disclaimer.