Is it okay to restart Abilify (aripiprazole) intramuscular (IM) at the same dose after being off of it for 3 months?

Restarting Aripiprazole IM After 3-Month Discontinuation

You should restart aripiprazole intramuscular (IM) at a reduced dose rather than the same dose after a 3-month discontinuation, as this duration exceeds multiple half-lives and requires re-titration to minimize adverse effects.

Pharmacokinetic Rationale for Dose Adjustment

• Aripiprazole has a mean elimination half-life of approximately 75 hours (about 3 days), and its active metabolite dehydroaripiprazole has a half-life of 94 hours 1
• After 3 months off medication, aripiprazole has been completely eliminated from the body (more than 20 half-lives have elapsed) 1
• When more than 3-4 half-lives have elapsed since the last dose, repeating loading doses or re-titration should be considered rather than resuming at the previous maintenance dose 2
• Steady-state concentrations require 14 days of dosing, and full therapeutic effect may take 1-4 weeks to achieve 1

Recommended Restart Strategy

Start with the standard initiation dose of 400 mg IM rather than a higher maintenance dose:

• The recommended starting dose for aripiprazole once-monthly (AOM) is 400 mg, which is both the initiation and maintenance dose for most patients 3
• In clinical studies, 90.1% of patients (1296/1439) initiated AOM at 400 mg and required no dose adjustment 3
• Provide concurrent oral aripiprazole 10-20 mg daily for 14 days after the first IM injection to ensure therapeutic plasma concentrations during the initial period 3, 4
• Alternatively, the newly approved two-injection start regimen (two 400 mg injections plus a single 20 mg oral dose on the same day) can be used 4

Monitoring After Restart

• Assess for clinical response within 24-48 hours after restarting therapy 5
• Monitor for adverse effects more closely during the first 2-4 weeks, as this is when therapeutic levels are being re-established 1
• If the patient previously experienced Grade 3-4 adverse events, dose reduction upon restart is recommended 2
• Regular monitoring of clinical parameters and ECG is recommended, especially with rapid titration or in patients with cardiovascular risk factors 6

Common Pitfalls to Avoid

• Do not assume all medications can restart at the previous dose—this increases toxicity risk, particularly with narrow therapeutic index drugs 2
• Ignoring the 3-month treatment gap may lead to adverse effects if maintenance dosing is resumed without re-titration 2
• Failing to provide oral supplementation during the first 14 days can result in subtherapeutic levels and symptom recurrence 3
• Not accounting for the time needed to reach steady state (14 days) and full therapeutic effect (1-4 weeks) may lead to premature dose escalation 1

Special Considerations

• If the patient was previously stable on a higher dose (e.g., 300 mg oral daily equivalent), the 400 mg IM starting dose is still appropriate, as efficacy and safety were comparable regardless of prior oral stabilization dose (10-30 mg/day) 3
• In elderly patients (>65 years) or those with hepatic/renal impairment, consider starting at a lower dose 2
• If disease symptoms have significantly worsened during the 3-month gap, restart with loading dose regimen rather than maintenance dosing 2