What is the recommended dose of Abilify (aripiprazole) Long-Acting Injectable (LAI) for a patient?

Aripiprazole LAI Dosing Recommendations

The recommended starting and maintenance dose for Aripiprazole Long-Acting Injectable (LAI) is 400 mg administered intramuscularly once monthly (every 4 weeks), with 14 days of concurrent oral aripiprazole (10-20 mg/day) after the first injection. 1, 2

Standard Dosing Regimen

Initial Dose

• 400 mg intramuscularly is both the starting and maintenance dose for most patients with schizophrenia 1, 2
• This dose achieves plasma concentrations consistent with therapeutic levels observed with oral aripiprazole 10-30 mg/day 2
• Across clinical studies, 90.1% (1296/1439) of patients initiated on 400 mg required no dose adjustment 2

Oral Supplementation Requirements

• Administer 14 days of oral aripiprazole (10-15 mg/day) after the first LAI injection to ensure therapeutic plasma levels during the initial period 2
• Median aripiprazole plasma concentrations reach therapeutic levels within 7 days, but the 14-day overlap accounts for interpatient variability 2
• After 4 weeks, mean plasma concentrations (93-112 ng/mL) fall within the established therapeutic window of 94.0-534.0 ng/mL 2

Alternative Dosing Intervals

Beyond the standard monthly regimen, additional FDA-approved options include:

• 662 mg every 4 weeks 1
• 882 mg every 6 weeks 1
• 1064 mg every 8 weeks 1

These extended-interval regimens were established through pharmacokinetic bridging studies and offer flexibility for tailoring treatment to individual patient needs 1.

Two-Injection Start (TIS) Alternative

A newer initiation strategy involves two 400 mg injections with only a single 20 mg oral aripiprazole dose, which may offer pharmacokinetic advantages over the traditional one-injection start 3:

• The TIS regimen maintains serum levels of the active moiety (aripiprazole + dehydroaripiprazole) within the therapeutic window 3
• The traditional one-injection start (OIS) with 14 days oral supplementation showed peaks above the therapeutic window, potentially exposing patients to toxicity 3
• Both regimens demonstrated comparable efficacy and tolerability in patients with and without substance use disorders 3

Switching from Other Antipsychotics

When transitioning from other oral antipsychotics to aripiprazole LAI:

• Cross-titrate over >1 to 4 weeks by tapering the prior antipsychotic while titrating oral aripiprazole to 10-30 mg/day 2
• This gradual approach results in lower discontinuation rates due to adverse events (2.7%) compared to rapid switches ≤1 week (10.4%) 2
• After stabilization on oral aripiprazole, initiate LAI 400 mg with 14 days of continued oral coverage 2

Time to Full Effect

• Steady-state plasma concentrations are attained within 14 days for both aripiprazole and its active metabolite dehydroaripiprazole 4
• Full therapeutic effect may require 1-2 weeks, and sometimes up to 4 weeks after achieving steady state 4
• Dosage increases should not be made before 2 weeks of continuous therapy 4

Special Populations

Substance Use Disorders

• The standard 400 mg every 4 weeks dose (used in 77.5% of patients) demonstrated efficacy in patients with schizophrenia and co-occurring substance use disorders 5
• After 6 months, significant improvements were observed in psychopathological symptoms (>30% reduction in CGI scores) and daily functioning 5

Efficacy Across Dose Ranges

• Efficacy and safety were comparable regardless of whether patients were previously stabilized on oral aripiprazole 10 mg or 30 mg daily 2
• This supports 400 mg LAI as appropriate across the therapeutic spectrum without requiring dose adjustments based on prior oral doses 2

Safety Profile

• Aripiprazole LAI is generally well tolerated with an adverse event profile consistent with oral aripiprazole, except for injection-site reactions 1
• The drug exhibits low propensity for metabolic disturbances compared to other atypical antipsychotics 1
• Discontinuation rates due to lack of efficacy across clinical studies ranged from only 2.3%-10.0% 2