Should we initiate Abilify (aripiprazole) at 10mg twice daily or 20mg nocte?

Aripiprazole Dosing: Once Daily Administration is Standard

Aripiprazole (Abilify) should be administered as 10-15 mg once daily, not as 10 mg twice daily. The FDA-approved dosing is explicitly once-a-day administration without regard to meals, and there is no evidence supporting or recommending twice-daily dosing for this medication 1.

FDA-Approved Dosing Regimen

• The recommended starting and target dose is 10 or 15 mg once daily for adults with schizophrenia 1.
• Aripiprazole has been systematically evaluated and shown to be effective in a dose range of 10 to 30 mg/day when administered once daily 1.
• Dosage increases should generally not be made before 2 weeks, the time needed to achieve steady-state concentrations 1.

Pharmacokinetic Rationale for Once-Daily Dosing

• The mean elimination half-life of aripiprazole is approximately 75 hours (over 3 days), with steady-state concentrations achieved by day 14 2, 3.
• The active metabolite dehydro-aripiprazole has an even longer half-life of approximately 94 hours 3.
• At least 1 to 2 weeks, and sometimes up to 4 weeks, may pass before aripiprazole reaches its full effect due to this prolonged pharmacokinetic profile 3.
• This extended half-life makes once-daily dosing both appropriate and sufficient for maintaining therapeutic drug levels 2.

Clinical Evidence Supporting Once-Daily Dosing

• Multiple randomized controlled trials have demonstrated efficacy with once-daily administration at doses of 10-30 mg/day 2.
• Short-term studies (less than 12 weeks) revealed an effective dose range of 10-20 mg/day given once daily 4.
• Long-term studies (16-52 weeks) showed efficacy at average doses between 15-28.1 mg/day administered once daily 4.
• Doses higher than 10 or 15 mg/day were not more effective than these lower doses in systematic evaluations 1.

Optimal Dosing Strategy

• Start with 10 mg once daily (or 15 mg if more rapid control is needed) 1.
• Administer at a consistent time each day without regard to meals 1.
• If inadequate response after 2 weeks at steady state, consider increasing to 15-20 mg once daily rather than splitting doses 1.
• Maximum recommended dose is 30 mg once daily, though doses above 15-25 mg/day show limited additional benefit 4.

Common Pitfall to Avoid

• Do not split aripiprazole into twice-daily dosing - this is not supported by FDA labeling, pharmacokinetic data, or clinical trial evidence 1, 2.
• The long half-life eliminates any theoretical benefit of divided dosing and may increase non-adherence due to more complex regimen 3.
• If a patient is currently on "10 mg BD" (twice daily), this represents a total daily dose of 20 mg, which should be consolidated to 20 mg once daily 1.

Dosage Adjustments

• When co-administered with strong CYP3A4 or CYP2D6 inhibitors, reduce the aripiprazole dose by half 1.
• When co-administered with strong CYP3A4 inducers, double the aripiprazole dose 1.
• In patients who are known CYP2D6 poor metabolizers, reduce the dose by half 1.