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aripiprazole

Last reviewed 2025-12-28

Reviewed by PsychMed Editorial Team.

Compare aripiprazole with other medsReview recent evidence
Related hubs: Schizophrenia hub · Bipolar hub · LAI hub
AntipsychoticLAI available

Brands: ABILIFY

Sources updated 2026 • 6 references

Quick summary

General Information

Aripiprazole (Abilify; oral and several long-acting injectable forms) is a second-generation antipsychotic.

This profile focuses on serious mental illness uses: schizophrenia and bipolar I disorder (acute manic or mixed episodes), with LAI maintenance options.

The compare view can help contrast EPS, metabolic, and LAI-readiness profiles with other SGAs, and the drug-specific evidence summaries can help when switching formulations or depot schedules.

The schizophrenia hub and bipolar disorder hub can help coordinate cross-setting care when planning adherence support, LAI transitions, or mood-stabiliser combinations.

U.S. approvals

  • Schizophrenia (adults) (2002)
  • Schizophrenia (adolescents ≥13 years) (2006)
  • Acute manic or mixed episodes in bipolar I disorder (monotherapy) (2004)
  • Adjunctive therapy to lithium or valproate in bipolar I disorder (2004)
  • Maintenance treatment in bipolar I disorder (Abilify Maintena) (2013)
  • Maintenance treatment (Abilify Asimtufii every two months) (2023)

Formulations & strengths

  • Oral tablets: 2 mg, 5 mg, 10 mg, 15 mg, 20 mg, 30 mg.
  • Orally disintegrating tablets: 10 mg, 15 mg.
  • Oral solution: 1 mg/mL.
  • Short-acting intramuscular injection for agitation: 9.75 mg/1.3 mL vial.
  • Long-acting injectables: Abilify Maintena (300 mg, 400 mg monthly), Abilify Asimtufii (720 mg, 960 mg every two months), Aristada (441 mg, 662 mg, 882 mg monthly; 1064 mg every two months; 720 mg every six weeks) with Aristada Initio loading option.

Generic availability

  • Generics exist for tablets, ODT, oral solution, and short-acting IM formulations (manufacturers include Teva, Alembic, Apotex, Lupin, Mylan/Viatris).
  • Long-acting injectables remain brand-only as of 2025.

Aripiprazole is widely used because it is often less sedating and has a lower metabolic and prolactin burden than some other SGAs, and it is available in multiple oral and LAI formulations. Common reasons for discontinuation include akathisia/restlessness, insomnia, and anxiety; routine metabolic monitoring remains important.

View labelExact

Mechanism of Action

Refer to the Glossary entry on Neurotransmitters for background on receptor systems involved in serious mental illness.

Aripiprazole stabilizes dopamine and serotonin signaling through partial agonism and selective antagonism.

Dopamine D2/D3 partial agonism allows aripiprazole to attenuate hyperdopaminergic pathways driving positive symptoms while modestly enhancing hypodopaminergic cortical circuits linked to negative symptoms. Serotonin 5-HT1A partial agonism and 5-HT2A/5-HT2B antagonism complement this effect and support mood stabilization.

  • Strong partial agonist at dopamine D2 and D3 receptors.
  • Partial agonist at serotonin 5-HT1A and antagonist at 5-HT2A/5-HT2B receptors.
  • Moderate antagonist at adrenergic α1 and histamine H1 receptors.
  • Minimal muscarinic receptor affinity.

Metabolism and Pharmacokinetics

  • Oral bioavailability ≈87% with Tmax 3–5 hours; food has minimal effect on exposure.
  • Volume of distribution ≈4.9 L/kg with ~99% protein binding.
  • Metabolized hepatically through CYP2D6 and CYP3A4 to the active metabolite dehydro-aripiprazole, which supplies ~40% of total exposure and maintains receptor occupancy.
  • Parent half-life ≈75 hours (up to 146 hours in CYP2D6 poor metabolizers); dehydro-aripiprazole half-life ≈94 hours.
  • Eliminated predominantly via feces (~60%) and urine (~27%) as metabolites.

Dosing and Administration

  • Schizophrenia (adults): start 10–15 mg once daily; therapeutic range 10–30 mg/day. Doses above 30 mg rarely add benefit.
  • Bipolar I acute manic/mixed episodes: start 15 mg once daily as monotherapy or adjunct to lithium/valproate; some patients require 30 mg/day for acute control.
  • Maintenance: continue the effective acute dose; for LAIs follow labeled initiation (e.g., Abilify Maintena requires 14-day oral overlap; Asimtufii combines a one-time 20 mg oral dose with the first injection; Aristada requires either Aristada Initio or a 21-day oral overlap).
  • Therapeutic drug monitoring is not routine, but AGNP consensus cites a reference trough range of 120–270 ng/mL (aripiprazole + dehydro-aripiprazole) when evaluating adherence or response.
  • Dose adjustments are recommended with strong CYP2D6 or CYP3A4 inhibitors/inducers; LAIs have specific labeling when combined with inducers.

Adverse Effects

FDA boxed warnings

  • Increased mortality in elderly patients with dementia-related psychosis (antipsychotic class warning).
  • Suicidal thoughts and behaviors in children, adolescents, and young adults when used as an antidepressant adjunct (shared antidepressant class warning).

Common side effects (≥10%)

  • Akathisia/restlessness: Up to 16% in oral trials; 11% vs 4% placebo with Abilify Maintena. Most frequent reason for discontinuation.
  • Insomnia: Reported in up to 17% of patients.
  • Anxiety: As high as 17% in some studies.
  • Nausea: Approximately 10–12% of adults.
  • Headache: ≥10% of adults.
  • Somnolence/sedation: Up to 18% depending on formulation and dose.
  • Dizziness: At least 10%.
  • Constipation: At least 10%.
  • Weight gain: 7–12% experience ≥7% weight gain; generally modest compared with other SGAs.

Other notable effects

  • Impulse control disorders (pathological gambling, hypersexuality, compulsive shopping or eating) <1% but clinically significant.
  • Hyperglycemia and new-onset diabetes, including rare cases of ketoacidosis.
  • Orthostatic hypotension and syncope, especially during titration or when combined with antihypertensives.
  • Tardive dyskinesia risk lower than FGAs but present with long-term therapy.
  • Neuroleptic malignant syndrome (rare).
  • Leukopenia or neutropenia in susceptible patients.
  • Injection-site pain for LAI formulations (≈5% with Abilify Maintena).

Interactions

  • Strong CYP2D6 inhibitors (fluoxetine, paroxetine, quinidine) increase exposure—reduce oral dose by 50% and adjust LAI schedules per labeling.
  • Strong CYP3A4 inhibitors (ketoconazole, clarithromycin, itraconazole) increase exposure—reduce dose by 50%.
  • Strong CYP3A4 inducers (carbamazepine, rifampin, St. John’s wort) markedly reduce exposure—double oral dose or avoid; LAIs are generally contraindicated with strong inducers.
  • Additive CNS depression with alcohol, benzodiazepines, or opioids.
  • Caution with antihypertensives or α1 blockers due to orthostatic hypotension risk.
  • Monitor QTc when combining with other QT-prolonging medications, though aripiprazole itself has low QT liability.

Other Useful Information

  • Long elimination half-life supports once-daily dosing and aids adherence.
  • Smoking does not meaningfully affect levels (no CYP1A2 pathway), simplifying counseling compared with clozapine or olanzapine.
  • Short-term metabolic signal: a 7-week double-blind trial reported smaller BMI increases with aripiprazole than risperidone; decreased appetite was more common with aripiprazole, and asking about appetite early can be a practical marker.
  • Long-term switching data: an 18-month EULAST follow-up found ~4–5 kg mean weight gain after switching to aripiprazole or paliperidone and no metabolic advantage for LAIs; routine metabolic monitoring remains important.
  • Abilify Maintena requires 14-day oral supplementation after the first injection; Asimtufii combines a one-time 20 mg oral dose with the first injection.
  • Aristada uses aripiprazole lauroxil with specific initiation (Aristada Initio + oral dose or 21-day oral overlap).
  • Akathisia can emerge in the first month; beta-blockers or dose adjustments are often considered if restlessness emerges, and the contrast view can help when comparing other partial agonists.
  • Patients and caregivers should be informed about impulse-control warnings and prompt reporting of new urges.

References

  1. ABILIFY (aripiprazole) tablets and injection — Prescribing Information — DailyMed (2025)
  2. Abilify Maintena (aripiprazole) Extended Release Injectable Suspension — Prescribing Information — DailyMed (2025)
  3. Abilify Asimtufii (aripiprazole) Extended Release Injectable Suspension — Prescribing Information — DailyMed (2025)
  4. Aristada (aripiprazole Lauroxil) Extended Release Injectable Suspension — Prescribing Information — DailyMed (2025)
  5. WHO EML 2023 Aripiprazole
  6. Skyquest2022 Antipsychotic Market
  7. Aripiprazole maintenance study in recently manic bipolar I patients — Journal of Clinical Psychiatry (2006)
  8. Safety OF Once Monthly Aripiprazole Initiation IN Schizophrenia — Current Medical Research and Opinion (2013)
  9. Consensus Guidelines for Therapeutic Drug Monitoring in Neuropsychopharmacology: Update 2017 — Pharmacopsychiatry (2018)
  10. FDA NDA 021436
  11. Assessing THE Metabolic Impact OF Aripiprazole Versus Risperidone IN THE Treatment OF Schizophrenia: A Randomized Double Blind Controlled Clinical Trial — BMC Psychiatry (2025)
  12. THE Effect OF Switching Antipsychotics TO Aripiprazole Versus Paliperidone ON Weight/cardiometabolic Parameters: 18 Month Follow UP Findings From THE European Long Acting Antipsychotics IN Schizophrenia Trial (eulast) — Eur Neuropsychopharmacol (2026)
aripiprazole (ABILIFY) — PsychMed