Aripiprazole (Abilify)

Primer

Aripiprazole (Trade name: Abilify) is an antipsychotic in the atypical antipsychotic class commonly used in the treatment of schizophrenia and bipolar disorder. It is also used as an adjunctive medication in major depressive disorder.

Pharmacokinetics

Pharmacokinetics of Aripiprazole

Absorption Peak plasma concentrations occurring within 3 to 5 hours. Oral bioavailability is 87%.
Distribution 4.9 L/kg (99% bound to serum
proteins, primarily albumin)
Metabolism Hepatic
Elimination Hepatic (minimal renal)
Half-life 75 to 94 hours (long half life!)

Aripiprazole: Cytochrome P450 Metabolism

Substrate of (Metabolized by) 2D6, 3A4
Induces -
Inhibits -

Pharmacodynamics

Mechanism of Action

Toxicity

Indications

Dosing

Dosing for Aripiprazole

Starting 2 mg PO qAM
Titration 2-5 mg increments every 2-3 weeks
Maximum 30 mg (though 20 mg is a typical dose)
Taper

Formulations

  • Aripiprazole comes in oral and intramuscular formulations.

Abilify Maintena (1-month Long-Acting Injectable)

  • Abilify Maintena is an extended-release (also known as long-acting) injectable suspension available in 400 mg or 300 mg formulations, given once every 4 weeks.
    • Requires a period of 2 weeks of oral dosing (“oral bridge”) with oral aripiprazole
    • Can be given via deep intramuscular (IM) deltoid or gluteal injection

Monitoring

Contraindications

Absolute

Relative

Drug-Drug Interactions

  • Any drugs that are CYP 2D6 inhibitors (e.g. - bupropion) can increase aripiprazole levels, which can cause akathisia, nausea/vomiting, and insomnia.[1]

Side Effects

  • There does not appear to be a bleeding risk although there are other possible haematological side effects, i.e. leucopenia, neutropenia or thrombocytopenia (incidence; 0.1% to 1%). CBC should be monitored.
  • Urinary retention has been rarely reported.[2]

Adverse Events

Impusle-Control Disorders

  • Since aripiprazole is a partial dopamine agonist it is possible that the increased dopaminergic activity may induce impulsivity (similar to what is seen in patients on dopamine agonists like L-dopa).
  • Rare but serious impulse-control problems, such as pathological gambling, compulsive eating, compulsive shopping, and compulsive sexual behavior have been reported in patients treated with aripiprazole.[3]

Clinical Pearls

Special Populations

Geriatric

Pediatric

Obstetric and Fetal

Medically Ill

Resources

References

1) Kotlyar, M., Brauer, L. H., Tracy, T. S., Hatsukami, D. K., Harris, J., Bronars, C. A., & Adson, D. E. (2005). Inhibition of CYP2D6 activity by bupropion. Journal of clinical psychopharmacology, 25(3), 226-229.
2) Hsu, W. Y., Chang, T. G., & Chiu, N. Y. (2013). Aripiprazole associated urine retention in a male schizophrenia patient. General hospital psychiatry, 35(6), 680-e11.
3) Grall-Bronnec, M., Sauvaget, A., Perrouin, F., Leboucher, J., Etcheverrigaray, F., Challet-Bouju, G., ... & Victorri-Vigneau, C. (2016). Pathological gambling associated with aripiprazole or dopamine replacement therapy: do patients share the same features? A review. Journal of clinical psychopharmacology, 36(1), 63.