aripiprazole (Asimtufii)

General Information

Abilify Asimtufii is a long-acting injectable aripiprazole formulation designed for dosing every 2 months (q8wk).

It is used for schizophrenia and for maintenance monotherapy treatment of bipolar I disorder. It is often selected when adherence challenges or frequent relapse make a scheduled injection visit preferable to daily pills.

Aripiprazole is a D2/D3 partial agonist antipsychotic with a comparatively lower prolactin burden than many SGAs, but Akathisia/restlessness and insomnia can limit tolerability.

Label describes sustained plasma concentrations over 2 months with a broad Tmax range and a mean apparent terminal half-life after a single dose of ~21 days.

For interval comparisons across depot options, see the LAI Navigator and the compare view.

Asimtufii extends aripiprazole depot dosing to a q8-week schedule. It can reduce visit burden but also slows "steerability" when adverse effects or underdosing emerge. Practical constraints include initiation logistics (oral overlap vs 1-day regimen), missed-dose protocols, and early identification of akathisia/activation symptoms.

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 can attenuate hyperdopaminergic pathways linked to positive symptoms while supporting cortical dopaminergic tone relevant to negative symptoms. Serotonin 5-HT1A partial agonism and 5-HT2A antagonism contribute to mood-stabilizing effects.

• Strong partial agonist at dopamine D2 and D3 receptors.
• 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 is metabolized primarily via CYP2D6 and CYP3A4 and shares the active metabolite dehydro-aripiprazole with oral formulations.
• Asimtufii delivers aripiprazole over a 2-month period with sustained plasma concentrations and a broad Tmax range after gluteal injection(s).
• Strong inhibitors of CYP2D6 or CYP3A4 can raise exposure and may require dose or interval adjustment; strong CYP3A4 inducers can lower exposure and are generally avoided with long-acting formulations.

Dosing and Administration

• Establish oral tolerability before depot initiation when feasible. Initiation options include a 14-day oral overlap regimen after the first injection or a 1-day initiation regimen that uses Abilify Maintena plus a single oral dose (label-based).
• Maintenance dosing is every 2 months; dose selection is individualized to response, tolerability, and interaction profile.
• Missed-dose management is time-sensitive; many clinics use standing protocols that specify when to administer the injection and when to re-start oral supplementation.
• Switching from another antipsychotic requires individualized cross-tapering based on relapse risk, residual symptoms, prior adverse effects, and injection readiness.

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 and dose adjustments.
• Blood pressure/orthostasis when clinically indicated (older adults, dehydration, antihypertensive co-use).
• Injection site assessment and documentation (site rotation, local reactions).

Adverse Effects

Interactions

• Strong CYP2D6 inhibitors (e.g., fluoxetine, paroxetine) and strong CYP3A4 inhibitors (e.g., ketoconazole) can increase exposure and may require dose or interval adjustment.
• Strong CYP3A4 inducers (e.g., carbamazepine, rifampin) can substantially lower exposure and are generally avoided with depot formulations.
• Additive CNS depression with alcohol, benzodiazepines, opioids, or sedative hypnotics; monitor falls risk and daytime functioning.
• Combined dopamine-blocking agents increase EPS risk; consider movement-disorder monitoring when combinations are unavoidable.

Other Useful Information

• Depot outcomes are strongly influenced by clinic workflow: reminders, reliable injection scheduling, and clear documentation of last injection date and site.
• Because washout is slow, tolerability planning typically emphasizes early recognition of akathisia and timely management rather than waiting for spontaneous resolution.
• During care transitions, document the next injection date and any oral overlap plan to avoid gaps in antipsychotic coverage.

References

1. Abilify Asimtufii (aripiprazole) Extended Release Injectable Suspension — Prescribing Information — DailyMed (2025)
2. Abilify Maintena (aripiprazole) 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. The CANMAT and ISBD Guidelines for the Management of Patients With Bipolar Disorder: 2021 Update — Bipolar Disorders (2021)Guidelinebipolarclinical
5. Consensus Guidelines for Therapeutic Drug Monitoring in Neuropsychopharmacology: Update 2017 — Pharmacopsychiatry (2018)