What are the considerations for using Abilify (aripiprazole) in a 13-year-old patient?

Aripiprazole Use in a 13-Year-Old

Aripiprazole is FDA-approved for adolescents aged 13 years and older for schizophrenia at a target dose of 10 mg/day, starting at 2 mg and titrating over several days, with doses up to 30 mg/day studied but showing no additional benefit over 10 mg/day. 1

FDA-Approved Indications and Dosing

For schizophrenia in adolescents 13-17 years:

• Start at 2 mg daily, titrate to 5 mg after 2 days, then to target dose of 10 mg after 2 additional days 1
• Subsequent dose increases should be in 5 mg increments 1
• The 30 mg/day dose was not more efficacious than 10 mg/day in clinical trials 1
• Can be administered without regard to meals 1

For bipolar disorder (manic episodes) in adolescents ≥13 years:

• Approved in the EU at 10 mg once daily for 12 weeks for moderate to severe manic episodes 2
• Efficacy demonstrated in reducing manic symptoms, though tolerability is less favorable in younger patients (10-12 years) compared to older adolescents 2

Clinical Efficacy Evidence

In the pivotal pediatric schizophrenia trial (n=302, ages 13-17):

• Both 10 mg/day and 30 mg/day doses were superior to placebo on PANSS total score 1
• The 30 mg/day dose showed no additional benefit over 10 mg/day 1
• Mean baseline PANSS scores were approximately 94, with reductions of -26.7 for 10 mg/day and -28.6 for 30 mg/day versus -21.2 for placebo 1

Aripiprazole has proven efficacy in children and adolescents for:

• Schizophrenia (FDA-approved ≥13 years) 1, 3
• Bipolar disorder (EU-approved ≥13 years) 2, 3
• Tourette's syndrome (off-label) 3
• Behavioral impairments associated with autism and intellectual disability (off-label) 3

Critical Safety Considerations

The most important adverse effects in adolescents are:

• Weight gain (more pronounced than in adults) 2, 3, 4
• Sedation/drowsiness (very common) 2, 3, 4
• Extrapyramidal symptoms including Parkinsonism (though incidence at 10 mg/day over 12 weeks was not significantly different from placebo) 2, 3, 4
• Metabolic effects (less severe than other atypical antipsychotics but still clinically significant) 3

Severe adverse events reported in children and adolescents include:

• Neuroleptic malignant syndrome 1, 4
• Chronic/extreme insomnia 4
• Suicidal thoughts or behavior (FDA black box warning for antidepressants applies) 1
• Behavioral changes and paradoxical psychoses 4
• Convulsions 4

Tolerability is worse with:

• Higher doses (30 mg/day vs 10 mg/day) 2
• Younger age (10-12 years vs ≥13 years) 2
• Multiple concurrent medications 3

Mandatory Monitoring Requirements

Before initiating aripiprazole:

• Screen for diabetes or family history of high blood sugar 1
• Assess for seizure history 1
• Check blood pressure (both low and high BP are risk factors) 1
• Evaluate for heart problems or stroke history 1
• Screen for low white blood cell count 1

During treatment:

• Monitor blood sugar at baseline and periodically during therapy 1
• Assess for extrapyramidal symptoms (stiff muscles, tremor, abnormal movements) 1, 4
• Watch for signs of neuroleptic malignant syndrome (high fever, stiff muscles, confusion, sweating, changes in pulse/heart rate/blood pressure) 1
• Monitor weight gain and metabolic parameters 3
• Assess for suicidal thoughts or behavior, especially in first few months or with dose changes 1

Current postprescription monitoring is very poor in clinical practice, despite the importance of these adverse events 3

Dosage Adjustments for Drug Interactions

Reduce aripiprazole dose to half the usual dose when coadministered with:

• Strong CYP2D6 inhibitors (quinidine, fluoxetine, paroxetine) 1
• Strong CYP3A4 inhibitors (itraconazole, clarithromycin) 1

Reduce aripiprazole dose to one-quarter the usual dose when:

• Patient is a known CYP2D6 poor metabolizer taking strong CYP3A4 inhibitors 1
• Coadministering both strong CYP2D6 and CYP3A4 inhibitors 1

Double the usual dose over 1-2 weeks when coadministered with:

• Strong CYP3A4 inducers (carbamazepine, rifampin) 1

Critical Pitfalls to Avoid

Do not use aripiprazole in patients with dementia-related psychosis (increased risk of death; not FDA-approved for this indication) 1

Do not abruptly discontinue without consulting prescriber (may cause withdrawal symptoms) 1

Avoid overheating and dehydration: limit exercise in hot weather, stay in cool places, avoid excessive sun exposure, wear light clothing, drink plenty of water 1

Do not drive or operate heavy machinery until effects are known (may cause drowsiness) 1

Watch for new or worsening symptoms requiring immediate medical attention:

• Suicidal thoughts or attempts 1
• New or worse depression or anxiety 1
• Panic attacks or severe agitation 1
• Aggressive behavior or violence 1
• Extreme increase in activity and talking (mania) 1

Off-Label Use Considerations

Off-label prescriptions account for a significant proportion of aripiprazole use worldwide in children and adolescents 3

Common off-label uses include:

• ADHD with severe conduct problems 5
• Autism spectrum disorders 4, 5
• Obsessive-compulsive disorder 4
• Tourette syndrome 4, 5

Off-label use should be limited because severe adverse events occur more frequently in multiple-prescription settings, and the benefit/risk ratio may be unfavorable 3

Practical Clinical Experience

In a Danish clinic study of 33 patients aged 9-18 years:

• Aripiprazole was effective and well-tolerated for severe conduct problems, ADHD with high restlessness, psychotic symptoms with autism, and intensive tics 5
• Doses were higher in cases of complex diagnoses and in older children (for non-complex diagnoses) 5
• Treatment effect was better in patients who did not gain weight 5
• Dosage in complex diagnoses did not depend on age but on other clinical factors 5