What is the recommended dose of Aripiprazole (Abilify) for adults with schizophrenia, bipolar disorder, and major depressive disorder?

Aripiprazole Dosing Recommendations

Schizophrenia

For adults with schizophrenia, start aripiprazole at 10-15 mg once daily, which is both the starting and target dose, with a therapeutic range of 10-30 mg/day; doses above 15 mg/day have not demonstrated superior efficacy. 1

Adult Dosing

• Starting dose: 10 or 15 mg once daily, administered without regard to meals 1
• Therapeutic range: 10-30 mg/day, though doses higher than 10-15 mg/day were not more effective in systematic evaluations 1
• Dose adjustments: Should not be made before 2 weeks, as this is the time needed to achieve steady-state concentrations 1
• Time to full effect: 1-2 weeks, and sometimes up to 4 weeks may be required 2
• Maintenance dosing: Most frequently administered maintenance dose is 15 mg daily in real-world practice 3

Adolescent Dosing (13-17 years)

• Target dose: 10 mg/day 1
• Titration schedule: Start at 2 mg daily, increase to 5 mg after 2 days, then to target 10 mg after 2 additional days 1
• Higher doses: 30 mg/day was not shown to be more efficacious than 10 mg/day 1
• Dose increases: Subsequent increases should be in 5 mg increments 1

Special Considerations for Schizophrenia

• Negative symptoms: Aripiprazole is a suitable option when switching antipsychotics for persistent negative symptoms 4
• Clozapine augmentation: Aripiprazole can be used to augment clozapine when significant positive symptoms remain after adequate clozapine trial 4

Bipolar Disorder

For acute manic or mixed episodes in bipolar I disorder, aripiprazole is effective at 15-30 mg/day, with similar starting and maintenance dosing as schizophrenia. 5, 6

Dosing Parameters

• Effective range: 15-30 mg/day for manic or mixed states 6
• Starting approach: Begin at lower doses (5 mg) when adding to or switching from another antipsychotic to improve tolerability 6
• Common side effects at initiation: Akathisia and gastrointestinal complaints may emerge early but are often time-limited 6

Major Depressive Disorder (Adjunctive Treatment)

For major depressive disorder as adjunctive therapy, aripiprazole augmentation can be considered, though specific dosing should follow FDA labeling for this indication. 5

• The evidence provided focuses primarily on schizophrenia and bipolar disorder dosing
• Aripiprazole is FDA-approved for adjunctive treatment of MDD 5

Dose Adjustments for Drug Interactions and Metabolic Considerations

Critical dose reductions are required based on CYP450 enzyme interactions and genetic polymorphisms. 1

CYP2D6 Poor Metabolizers

• Administer half of usual dose 1
• If also taking strong CYP3A4 inhibitors: Administer one-quarter of usual dose 1

Drug Interactions Requiring Dose Adjustment

• Strong CYP2D6 inhibitors (quinidine, fluoxetine, paroxetine) or strong CYP3A4 inhibitors (itraconazole, clarithromycin): Administer half of usual dose 1
• Both strong CYP2D6 and CYP3A4 inhibitors: Administer one-quarter of usual dose 1
• Strong CYP3A4 inducers (carbamazepine, rifampin): Double usual dose over 1-2 weeks 1
• When inhibitors are withdrawn: Return to original dose 1
• When inducers are withdrawn: Reduce to original dose over 1-2 weeks 1

Key Clinical Pearls

Pharmacokinetic Considerations

• Half-life: Approximately 75 hours for aripiprazole and 94 hours for active metabolite dehydro-aripiprazole 7, 2
• Steady-state: Achieved by day 14, with 4-fold accumulation from day 1 to day 14 7
• Bioavailability: 87% oral bioavailability 7, 8

Tolerability Profile

• Low propensity for: Weight gain, metabolic disturbances, hyperprolactinemia, and QT prolongation 6, 7
• EPS risk: Placebo-level incidence of extrapyramidal symptoms, superior to haloperidol 7
• Most common adverse effects: Headache, anxiety, insomnia, nausea, vomiting, lightheadedness, and akathisia 7, 8

Common Pitfalls to Avoid

• Do not increase doses before 2 weeks - steady-state is not achieved until day 14 1, 7
• Do not automatically escalate above 15 mg/day - higher doses (20-30 mg) show no additional therapeutic benefit in most patients 1, 7
• Do not forget CYP450 adjustments - failure to reduce dose with inhibitors or in poor metabolizers increases adverse effect risk 1
• Consider lower starting doses (5 mg) when switching from or adding to other antipsychotics to minimize akathisia and GI symptoms 6