aripiprazole lauroxil

General Information

Aripiprazole lauroxil (Aristada) is a long-acting injectable prodrug of aripiprazole indicated for schizophrenia.

It provides extended dosing intervals (monthly through every 2 months depending on strength). As with other depot antipsychotics, real-world benefit depends heavily on clinic workflow: reliable injection scheduling, missed-dose protocols, and clear documentation.

Compared with many SGAs, aripiprazole-class partial agonists tend to have lower prolactin burden and often lower sedation, but Akathisia/restlessness and insomnia can limit tolerability.

For interval comparisons and oral overlap options, see the LAI Navigator.

Aripiprazole lauroxil is chosen when teams want a partial-agonist option with longer intervals than monthly dosing. The long terminal half-life supports adherence but makes adverse effects slower to resolve after dose changes, so many clinics emphasize early tolerability checks during initiation.

Mechanism of Action

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

After conversion to aripiprazole, pharmacology mirrors the parent drug: dopamine D2/D3 partial agonism with serotonin 5-HT1A partial agonism and 5-HT2A antagonism.

Partial agonism can attenuate hyperdopaminergic pathways linked to positive symptoms while supporting cortical dopaminergic tone relevant to negative symptoms.

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

Metabolism and Pharmacokinetics

• Aripiprazole lauroxil is hydrolyzed after injection and converted to aripiprazole; metabolism then proceeds primarily via CYP2D6 and CYP3A4 with an active metabolite (dehydro-aripiprazole).
• Depot release produces a prolonged terminal half-life (on the order of many weeks), so changes in dose/interval and missed injections have delayed clinical effects.
• Strong CYP2D6 or CYP3A4 inhibitors can raise exposure and may require dose/interval adjustment; strong CYP3A4 inducers can substantially lower exposure and are generally avoided with depot formulations.

Dosing and Administration

• Initiation requires bridging: either a multi-week oral aripiprazole overlap or a one-day initiation strategy using Aristada Initio per label.
• Maintenance interval depends on strength (monthly, every 6 weeks, or every 2 months in labeled schedules). Injection site and technique vary by dose and product instructions.
• Missed-dose management is time- and interval-dependent; many clinics use standing protocols to decide when to administer the injection, when to restart oral supplementation, and when to reassess adherence barriers.
• When switching from another antipsychotic, cross-tapering and overlap are individualized to relapse risk, residual symptoms, and prior adverse effects.

Monitoring & Labs

• Weight/BMI and waist circumference; fasting lipids and glucose/HbA1c at baseline and periodically.
• Movement disorder monitoring (akathisia, parkinsonism, tardive dyskinesia), especially after initiation.
• Blood pressure/orthostasis when clinically indicated (older adults, dehydration, antihypertensive co-use).
• Injection site assessment and documentation (dose, site, local reactions).

Adverse Effects

Interactions

• Strong CYP2D6 inhibitors and strong CYP3A4 inhibitors can increase exposure and may require dose or interval adjustment.
• Strong CYP3A4 inducers can substantially lower exposure and are generally avoided with depot formulations.
• Additive CNS depression with alcohol, benzodiazepines, opioids, or sedative hypnotics; monitor for falls and daytime somnolence.
• Combined dopamine-blocking agents increase EPS risk; movement-disorder monitoring is often used when combinations are unavoidable.

Other Useful Information

• The practical “failure mode” is missed steps during initiation; checklists that cover oral overlap versus Initio strategies help reduce errors.
• Longer intervals can reduce visit burden but also reduce short-term steerability when adverse effects or underdosing emerge.
• During care transitions, document the next injection date and any oral overlap plan to avoid gaps in antipsychotic coverage.

References

1. Aristada (aripiprazole Lauroxil) Extended Release Injectable Suspension — Prescribing Information — DailyMed (2025)
2. Aristada Initio (aripiprazole Lauroxil) Extended Release Injectable Suspension — Prescribing Information — DailyMed (2025)
3. The American Psychiatric Association Practice Guideline for the Treatment of Patients With Schizophrenia — American Psychiatric Association (2020)
4. Consensus Guidelines for Therapeutic Drug Monitoring in Neuropsychopharmacology: Update 2017 — Pharmacopsychiatry (2018)