Aripiprazole Prescribing Indications
Aripiprazole is primarily prescribed for schizophrenia, bipolar I disorder (manic and mixed episodes), and as an adjunctive treatment for major depressive disorder. 1
FDA-Approved Indications
Schizophrenia
- FDA-approved for treatment of schizophrenia in adults and adolescents (13-17 years) 1
- Effective for both acute treatment and maintenance therapy
- Dosing:
- Adults: 10-15 mg/day (starting dose often 10-15 mg)
- Adolescents: 10 mg/day (can be titrated to 30 mg if needed) 1
- Demonstrated significantly longer time to relapse compared to placebo in maintenance treatment 1
Bipolar I Disorder
- Approved for:
- Acute treatment of manic and mixed episodes (monotherapy)
- Maintenance treatment of bipolar I disorder (monotherapy)
- Adjunctive therapy with lithium or valproate for acute manic/mixed episodes 1
- Particularly effective when combined with lithium or valproate for acute mania/mixed episodes 2
- Superior to placebo in preventing relapse of both manic and depressive episodes in maintenance treatment 1
Major Depressive Disorder
- Approved as adjunctive therapy to antidepressants for major depressive disorder 3
- Three large-scale randomized controlled trials demonstrated clinically meaningful efficacy as adjunctive therapy 3
Mechanism of Action
Aripiprazole works through a unique mechanism compared to other antipsychotics:
- Partial agonist at dopamine D2 and D3 receptors 4, 5
- Partial agonist at serotonin 5-HT1A receptors 4
- Antagonist at serotonin 5-HT2A receptors 4
- This profile contributes to its efficacy for both positive and negative symptoms in schizophrenia with lower risk of extrapyramidal symptoms 4
Safety and Tolerability Profile
Aripiprazole offers several advantages in its side effect profile:
- Low propensity for weight gain compared to other atypical antipsychotics 5, 6
- Favorable metabolic profile with minimal impact on glucose and lipid levels 4, 6
- No association with hyperprolactinemia 5
- Does not significantly prolong QTc interval 4
However, important side effects to monitor include:
- Akathisia (particularly in patients with bipolar disorder and depression) 6
- Insomnia and anxiety 4
- Risk of extrapyramidal symptoms (though generally lower than with typical antipsychotics) 4
Special Considerations in Clinical Practice
Antipsychotic Polypharmacy
- Aripiprazole can be used as adjunctive therapy with other antipsychotics, particularly with clozapine 7
- The combination of clozapine with aripiprazole has shown benefits in treatment-resistant schizophrenia 7
- Adding aripiprazole to another antipsychotic may help reduce negative symptoms 7
Metabolic Monitoring
- Regular monitoring of metabolic parameters is essential:
- BMI, waist circumference, and blood pressure should be checked weekly for first 6 weeks
- All measures should be repeated after 3 months and annually thereafter 7
Dosing Considerations
- No dosage titration is necessary for most patients 4
- Lower starting doses may be appropriate when adding to or switching from another antipsychotic 5
- Effective in the first few weeks of treatment 4
Clinical Pearls
Aripiprazole's unique mechanism as a partial dopamine agonist makes it particularly useful for patients concerned about metabolic side effects.
For bipolar disorder, the combination of aripiprazole with lithium or valproate has shown superior efficacy compared to monotherapy with mood stabilizers alone.
When using as adjunctive therapy for depression, be vigilant about monitoring for akathisia, which occurs more frequently in this population than in schizophrenia.
The favorable metabolic profile makes aripiprazole a good choice for patients with or at risk for metabolic syndrome, diabetes, or cardiovascular disease.