Aripiprazole Tablets – Treatment for Schizophrenia and Bipolar I Disorder

Aripiprazole tablets are an atypical antipsychotic medication approved for treating several mental health conditions in both adults and pediatric patients. It is primarily used for schizophrenia, acute manic or mixed episodes of Bipolar I Disorder, irritability associated with autistic disorder in children, and Tourette’s disorder. This oral medication is available in multiple strengths and is taken once daily without regard to meals.

Aripiprazole tablets are approved for the treatment of:

• Schizophrenia in adults and adolescents (ages 13 to 17 years).
• Acute treatment of manic and mixed episodes associated with Bipolar I Disorder in adults and pediatric patients (ages 10 to 17 years), either as monotherapy or adjunctive therapy with lithium or valproate.
• Irritability associated with autistic disorder in children and adolescents (ages 6 to 17 years).
• Tourette’s disorder in pediatric patients (ages 6 to 18 years).

Aripiprazole

Aripiprazole is categorized as an atypical antipsychotic, which works by modulating neurotransmitter activity in the brain. It acts partly as a dopamine receptor partial agonist and serotonin receptor modulator to help balance these brain chemicals, which are involved in mood, behavior, and perception.

General Administration

Administer aripiprazole once daily by mouth without regard to meals.

Adults

• Schizophrenia: Start at 10 or 15 mg/day; target dose is 10 to 15 mg/day; doses up to 30 mg/day have been evaluated but showed no additional benefit over 10-15 mg/day. Increase dose no sooner than every 2 weeks.
• Bipolar I Disorder (Manic or Mixed Episodes): Monotherapy starting dose 15 mg/day; adjunctive therapy starting dose 10 to 15 mg/day; target dose 15 mg/day; dose can be increased up to 30 mg/day based on response.

Adolescents and Pediatric Patients

• Schizophrenia (13-17 years): Initiate at 2 mg/day, increasing to 5 mg after 2 days, then to 10 mg after 2 more days. Target dose is 10 mg/day; doses up to 30 mg/day were not more effective.
• Bipolar I Disorder (10-17 years): Start at 2 mg/day, increase to 5 mg after 2 days, then target 10 mg/day. Adjunctive therapy with lithium or valproate uses the same regimen.
• Irritability associated with autistic disorder (6-17 years): Start at 2 mg/day, increase to 5 mg/day, then if needed, to 10 or 15 mg/day with no more than 5 mg increments at intervals of at least one week. Recommended dose range is 5 to 15 mg/day.
• Tourette’s Disorder (6-18 years): For patients <50 kg: start 2 mg/day, target 5 mg/day after 2 days, increase to 10 mg/day if needed with weekly increments. For patients ≥50 kg: start 2 mg/day for 2 days, then 5 mg/day for 5 days, target 10 mg/day by Day 8; dose may be increased up to 20 mg/day with weekly increments.

Dosage Adjustments Based on Metabolism and Drug Interactions

• For known CYP2D6 poor metabolizers, reduce dose by half.
• For patients taking strong CYP2D6 inhibitors or strong CYP3A4 inhibitors, reduce dose by half.
• If both strong CYP2D6 and CYP3A4 inhibitors are coadministered, reduce dose to one-quarter of usual.
• When taking strong CYP3A4 inducers, double the dose over 1 to 2 weeks.
• When interacting drugs are discontinued, adjust aripiprazole dose back to original levels over 1 to 2 weeks.
• For patients on multiple inhibitors of CYP2D6 and CYP3A4, consider starting at 25% of the usual dose and adjust based on clinical response.

Aripiprazole is contraindicated in patients with a known hypersensitivity to aripiprazole. Hypersensitivity reactions have ranged from rash, itching to anaphylaxis.

Increased Mortality in Elderly with Dementia-Related Psychosis

Aripiprazole is not approved for the treatment of dementia-related psychosis. Elderly patients with dementia-related psychosis treated with antipsychotics have an increased risk of death, including from cerebrovascular events such as stroke or transient ischemic attack.

Suicidal Thoughts and Behaviors

Antidepressants may increase the risk of suicidal thoughts and behavior in children, adolescents, and young adults up to age 24 during short-term use. Patients starting antidepressant therapy should be closely monitored for worsening depression, suicidal ideation, or unusual behavior changes.

Other Key Warnings

• Neuroleptic Malignant Syndrome (NMS): A potentially life-threatening condition requiring immediate discontinuation and monitoring.
• Tardive Dyskinesia: May occur; discontinue if clinically appropriate.
• Metabolic Changes: Can cause hyperglycemia, diabetes mellitus, dyslipidemia, and weight gain; monitor glucose, lipids, and weight regularly.
• Pathological Gambling and Compulsive Behaviors: May develop; consider dose reduction or stopping the drug.
• Orthostatic Hypotension: Monitor blood pressure and heart rate especially in patients with cardiovascular risk.
• Blood Dyscrasias: Leukopenia, neutropenia, and agranulocytosis have been reported; monitor CBC in patients with history of low white blood cell counts.
• Seizures: Use cautiously in patients with seizure history or conditions lowering seizure threshold.
• Cognitive and Motor Impairment: Use caution when operating machinery.
• Suicide Risk: Patients with schizophrenia and bipolar disorder have inherent suicide risk; high-risk patients require careful supervision.

Common Adverse Reactions in Elderly with Dementia Related Psychosis

• Lethargy: 5% with aripiprazole vs. 2% placebo
• Somnolence/Sedation: 8% vs. 3%
• Urinary Incontinence: 5% vs. 1%
• Excessive Salivation: 4% vs. 0%
• Lightheadedness: 4% vs. 1%

Aripiprazole metabolism is affected by CYP2D6 and CYP3A4 enzyme inhibitors and inducers:

• CYP2D6 poor metabolizers or those taking CYP2D6 inhibitors should have dose reduced by half.
• Co-administration with strong CYP3A4 inhibitors requires halving the dose.
• Concurrent use of strong CYP2D6 and CYP3A4 inhibitors requires dose reduction to one-quarter.
• Strong CYP3A4 inducers require doubling the aripiprazole dose gradually over 1 to 2 weeks.

Dose should be returned to original levels when interacting agents are withdrawn.