Aripiprazole Dosing for Schizophrenia and Bipolar Disorder
Recommended Starting and Target Doses
For schizophrenia in adults, start aripiprazole at 10-15 mg once daily without titration, as this is the FDA-approved target dose range that has been systematically shown to be effective. 1
Schizophrenia Dosing
Adults:
- Starting dose: 10 or 15 mg once daily 1
- Can be taken without regard to meals 1
- No titration required—the starting dose is the target dose 1, 2
- Effective dose range: 10-30 mg/day, though doses above 15 mg/day have not demonstrated superior efficacy 1, 3
- Do not increase dosage before 2 weeks, the time needed to reach steady-state 1
Adolescents (13-17 years):
- Target dose: 10 mg once daily 1
- Start at 2 mg/day, titrate to 5 mg after 2 days, then to 10 mg after 2 additional days 1
- Subsequent increases in 5 mg increments if needed 1
- The 30 mg/day dose showed no additional benefit over 10 mg/day 1
Bipolar Disorder Dosing
Acute Mania:
- Effective dose range: 15-30 mg/day 4, 5
- For adolescents with moderate to severe manic episodes: 10 mg once daily for 12 weeks 5
Critical Dose Adjustments
Reduce dose by 50% in the following situations: 1
- Known CYP2D6 poor metabolizers 1
- Concurrent strong CYP2D6 inhibitors (quinidine, fluoxetine, paroxetine) 1
- Concurrent strong CYP3A4 inhibitors (itraconazole, clarithromycin) 1
Reduce dose to 25% of usual dose when: 1
- CYP2D6 poor metabolizers taking strong CYP3A4 inhibitors 1
- Concurrent strong CYP2D6 AND CYP3A4 inhibitors 1
Double the usual dose over 1-2 weeks when: 1
- Taking strong CYP3A4 inducers (carbamazepine, rifampin) 1
- Return to original dose over 1-2 weeks after inducer is discontinued 1
Special Population Considerations
Elderly and hepatically impaired patients:
- Start at lower doses, consider 5 mg daily 6
- The American Geriatrics Society recommends dose reduction in elderly patients 7
Poor CYP2D6 metabolizers:
Optimal Dosing Based on Clinical Evidence
The literature reveals a dose-response relationship that varies by target symptom 3:
- For acute agitation: 1-15 mg may be effective 3
- For core psychotic symptoms: 10-25 mg/day is optimal 3
- Doses below 10 mg/day lack significant efficacy for schizophrenia symptoms (except agitation) 3
- Doses above 25 mg/day lack evidence-based support for additional benefit 3
Key Clinical Pearls
Steady-state pharmacokinetics: Aripiprazole accumulates significantly over 14 days, with 4-fold higher plasma concentrations at steady-state compared to day 1, due to its 75-hour elimination half-life 2. This explains why dose increases should not occur before 2 weeks 1.
No additional benefit at higher doses: Multiple trials demonstrate that 20-30 mg/day doses provide no superior efficacy compared to 10-15 mg/day for schizophrenia 1, 2, 3. The FDA label explicitly states that "doses higher than 10 or 15 mg/day were not more effective" 1.
Tolerability considerations: Lower doses (10 mg/day) show better tolerability than higher doses (30 mg/day), particularly regarding extrapyramidal symptoms and dropout rates 5. Evening dosing may reduce daytime sedation 7.