Abilify (Aripiprazole): Uses and Dosing Recommendations
Aripiprazole (Abilify) is FDA-approved for schizophrenia, bipolar disorder, major depressive disorder (as adjunctive therapy), and irritability associated with autism, with specific dosing regimens for each indication.
Approved Indications
Schizophrenia
Adults:
- Starting/target dose: 10-15 mg once daily 1
- Effective dose range: 10-30 mg/day
- No additional benefit observed above 10-15 mg/day
- Dosage increases should not be made before 2 weeks (time needed to achieve steady state)
Adolescents (13-17 years):
- Target dose: 10 mg/day
- Starting dose: 2 mg/day, titrated to 5 mg after 2 days, then to 10 mg after 2 additional days
- Subsequent increases in 5 mg increments
- 30 mg/day not shown to be more effective than 10 mg/day 1
Bipolar I Disorder
- Acute Mania/Mixed Episodes:
Major Depressive Disorder
- Adjunctive Therapy:
- Used when antidepressant monotherapy is insufficient
- FDA-approved as an adjunctive treatment to antidepressants 5
- Demonstrated clinically meaningful efficacy in three 6-week randomized controlled trials
Irritability Associated with Autism
- Approved for irritability associated with autism 5
Dosing Considerations
Special Populations
- CYP2D6 Poor Metabolizers:
- Administer half of usual dose
- If also taking strong CYP3A4 inhibitors, administer quarter of usual dose 1
Drug Interactions
- Strong CYP2D6 inhibitors (e.g., fluoxetine, paroxetine) or CYP3A4 inhibitors (e.g., clarithromycin):
- Administer half of usual dose
- Both strong CYP2D6 and CYP3A4 inhibitors:
- Administer quarter of usual dose
- Strong CYP3A4 inducers (e.g., carbamazepine):
- Double usual dose over 1-2 weeks 1
Formulation Considerations
- Oral solution can substitute for tablets on a mg-per-mg basis up to 25 mg
- Patients receiving 30 mg tablets should receive 25 mg of solution 1
Pharmacological Profile
- Unique mechanism as a partial agonist at dopamine D2 and serotonin 5-HT1A receptors, and antagonist at 5-HT2A receptors 6
- This "functional selectivity" contributes to its efficacy and favorable side effect profile
- Rapid absorption with mean time to peak plasma concentration of 3 hours
- Long elimination half-life of approximately 75 hours 7
Efficacy Profile
- Effective for positive and negative symptoms of schizophrenia
- Onset of action within 1-2 weeks for schizophrenia 6
- Maintained efficacy for up to 52 weeks in long-term studies 7
- May improve cognitive function in schizophrenia patients 7
- Effective for manic and mixed episodes in bipolar disorder 2
Tolerability Advantages
- Low propensity for weight gain and metabolic disturbances
- No association with hyperprolactinemia
- Low risk for QT interval prolongation
- Placebo-level incidence of extrapyramidal symptoms (EPS) in most studies 2, 7
- When combined with other antipsychotics, aripiprazole may help reduce negative symptoms 4
Common Side Effects
- Most frequent adverse events: insomnia, anxiety, headache, akathisia
- Higher incidence of akathisia in depression studies compared to schizophrenia studies 5
- Gastrointestinal complaints may occur at treatment initiation but are often time-limited 2
Intramuscular Formulation
- Available for acute management of agitation in schizophrenia and bipolar disorder
- Effective and generally well-tolerated for acute agitation
- Low risk for EPS, cardiac effects, and metabolic disturbances 8
Clinical Pearls
- No dosage titration necessary for most adult patients
- Can be administered without regard to meals
- When switching from other antipsychotics, gradual discontinuation of the previous agent is recommended for most patients 1
- When adding to or switching from another antipsychotic, lower starting doses may improve tolerability 2
- In bipolar disorder, can be safely combined with mood stabilizers like lithium or valproate 3
By understanding the approved indications, dosing considerations, and unique pharmacological profile of aripiprazole, clinicians can optimize its use to improve outcomes in patients with various psychiatric disorders.