Aripiprazole: Third-Generation Antipsychotic (Partial D2 Agonist)
Aripiprazole (Abilify) is a third-generation atypical antipsychotic acting as a partial agonist at D2 and D3 dopamine receptors and 5-HT1A receptors, and an antagonist at 5-HT2A receptors. This unique profile minimises metabolic side effects.
Approved for schizophrenia, bipolar I disorder, adjunctive therapy in MDD, and irritability associated with autism spectrum disorder. Available as oral, long-acting injectable (LAI), and patch formulations.
Mechanism of Action
Partial D2 agonism acts as a functional antagonist in hyperdopaminergic states (psychosis) and as an agonist in hypodopaminergic states (depression, negative symptoms). This 'dopamine stabiliser' profile reduces EPS and prolactin elevation.
Indications & Use
Schizophrenia (acute and maintenance), acute manic/mixed episodes in bipolar I, adjunct to antidepressants in MDD, irritability in autism (6–17 years). LAI formulation (Maintena, Aristada) for maintenance in schizophrenia.
Dosage
Schizophrenia: 10–15 mg/day (range 10–30 mg). Bipolar mania: 15–30 mg/day. MDD adjunct: 2–5 mg/day (up to 15 mg). LAI: 400 mg monthly IM. Poor CYP2D6 metabolisers: reduce dose by 50%.
Side Effects
Akathisia (common, 10–15%), insomnia, nausea, headache. Minimal weight gain and metabolic effects compared to other atypicals. Low prolactin elevation. Rare: NMS, tardive dyskinesia.
Drug Interactions
CYP2D6 inhibitors (fluoxetine, paroxetine): increase aripiprazole exposure — reduce dose by 50%. CYP3A4 inducers (carbamazepine): decrease levels — double dose. QT-prolonging drugs: additive risk (though aripiprazole has low QT effect).
Contraindications
Hypersensitivity. Caution in elderly patients with dementia-related psychosis (increased mortality risk). Monitor for suicidal ideation when used as MDD adjunct in younger patients.
Frequently Asked Questions
What is akathisia and how common is it with aripiprazole?
Akathisia is an inner restlessness/urge to move, occurring in 10–15% of patients. It can be distressing and mistaken for worsening anxiety. Beta-blockers (propranolol) or dose reduction help; switching may be necessary.
Does aripiprazole cause weight gain?
Aripiprazole has among the lowest metabolic burden of all atypicals — minimal weight gain and lipid changes. It is sometimes switched to from olanzapine or quetiapine specifically for this reason.
Can aripiprazole be used as a once-monthly injection?
Yes. Aripiprazole monohydrate (Abilify Maintena) 400 mg IM monthly is approved for maintenance of schizophrenia, improving adherence significantly.
References
- NICE NG222: Schizophrenia 2023
- Leucht S et al. Lancet 2013 (meta-analysis)
- EMA Abilify SPC 2023
Medical Disclaimer: This information is for educational purposes only and does not replace professional medical advice.