Introduction
Aripiprazole (marketed as Abilify) is an atypical antipsychotic medication approved by the FDA in 2002. It represents a unique class of psychotropic agents known as dopamine partial agonists, distinguishing it from other antipsychotics. Abilify is widely used across multiple psychiatric conditions in both adult and pediatric populations, offering a favorable metabolic side effect profile compared to many other antipsychotics.
Mechanism of Action
Aripiprazole functions as a partial agonist at dopamine D2 and serotonin 5-HT1A receptors, and as an antagonist at serotonin 5-HT2A receptors. This unique mechanism provides:
- Moderate affinity for dopamine D2 receptors with intrinsic activity lower than dopamine itself
- High affinity for serotonin 5-HT2A receptors with antagonistic properties
- Moderate affinity for serotonin 5-HT1A, 5-HT2C, and 5-HT7 receptors
- Moderate affinity for alpha-1 adrenergic receptors and histamine H1 receptors
- Minimal affinity for muscarinic cholinergic receptors
This pharmacological profile allows aripiprazole to modulate dopaminergic and serotonergic neurotransmission without complete receptor blockade, resulting in its "dopamine system stabilizer" characterization.
Indications
FDA-approved indications:- Schizophrenia (adults and adolescents 13-17 years)
- Bipolar I disorder (acute manic/mixed episodes and maintenance in adults and children 10-17 years)
- Adjunctive treatment of major depressive disorder (adults)
- Irritability associated with autistic disorder (children 6-17 years)
- Tourette's disorder (children 6-18 years)
- Treatment of agitation in dementia (with caution)
- Borderline personality disorder
- Treatment-resistant depression
Dosage and Administration
Oral formulations:- Tablets: 2 mg, 5 mg, 10 mg, 15 mg, 20 mg, 30 mg
- Orally disintegrating tablets: 10 mg, 15 mg
- Oral solution: 1 mg/mL
- Schizophrenia: 10-15 mg once daily
- Bipolar mania: 15-30 mg once daily
- Adjunctive MDD: 2-5 mg once daily
- Titration: May increase at intervals of no less than 2 weeks
- Hepatic impairment: No dosage adjustment required
- Renal impairment: No dosage adjustment required
- Elderly: Consider lower starting doses (particularly with dementia-related psychosis)
- CYP2D6 poor metabolizers: Reduce dose by 50%
- When used with strong CYP3A4 inhibitors: Reduce dose by 50%
- When used with strong CYP2D6 inhibitors: Reduce dose by 50%
- May be taken with or without food
- Oral solution: Use calibrated measuring device
- Store at room temperature (15-30°C)
Pharmacokinetics
Absorption: Well-absorbed with peak plasma concentrations achieved within 3-5 hours. Bioavailability is 87%. Food does not affect absorption. Distribution: Extensive tissue distribution with volume of distribution of 4.9 L/kg. Highly protein-bound (≥99%) primarily to albumin. Metabolism: Primarily metabolized by hepatic cytochrome P450 enzymes CYP3A4 and CYP2D6 via dehydrogenation, hydroxylation, and N-dealkylation. The active metabolite is dehydro-aripiprazole. Elimination: Mean elimination half-life is approximately 75 hours (aripiprazole) and 94 hours (dehydro-aripiprazole). Excretion primarily via feces (55%) and urine (25%).Contraindications
- Hypersensitivity to aripiprazole or any component of the formulation
- History of neuroleptic malignant syndrome (NMS)
- Dementia-related psychosis in elderly patients (increased mortality risk)
- Concomitant use with strong CYP3A4 inducers (reduces aripiprazole levels)
Warnings and Precautions
Boxed Warning:- Increased mortality in elderly patients with dementia-related psychosis
- Cerebrovascular adverse events in elderly patients with dementia
- Neuroleptic malignant syndrome (NMS)
- Tardive dyskinesia
- Metabolic changes (hyperglycemia, dyslipidemia, weight gain)
- Orthostatic hypotension
- Leukopenia, neutropenia, agranulocytosis
- Seizures
- Cognitive and motor impairment
- Dysphagia and esophageal dysmotility
- Suicide risk in depression and psychiatric disorders
- Pathological gambling and other compulsive behaviors
Drug Interactions
Significant interactions:- Strong CYP3A4 inhibitors (ketoconazole, itraconazole): Increase aripiprazole exposure → reduce aripiprazole dose by 50%
- Strong CYP2D6 inhibitors (quinidine, fluoxetine, paroxetine): Increase aripiprazole exposure → reduce aripiprazole dose by 50%
- Strong CYP3A4 inducers (carbamazepine, rifampin): Decrease aripiprazole exposure → double aripiprazole dose
- Antihypertensive agents: Enhanced hypotensive effects
- CNS depressants: Additive sedative effects
Adverse Effects
Common (≥10%):- Headache (27%)
- Anxiety (15%)
- Insomnia (18%)
- Nausea (15%)
- Vomiting (12%)
- Constipation (11%)
- Akathisia (13%)
- Sedation (8-12%)
- Neuroleptic malignant syndrome
- Tardive dyskinesia
- Hyperglycemia and diabetes mellitus
- Seizures
- Orthostatic hypotension
- Suicidal ideation
- Compulsive behaviors (gambling, shopping, eating)
Monitoring Parameters
Baseline assessment:- Complete medical and psychiatric history
- Physical examination with weight, height, BMI
- Vital signs (blood pressure, pulse)
- Fasting blood glucose/HbA1c
- Lipid profile
- CBC with differential
- Liver function tests
- Assessment for movement disorders (AIMS scale)
- Weight and BMI at 4, 8, and 12 weeks, then quarterly
- Blood pressure and pulse regularly
- Fasting glucose at 12 weeks, then annually
- Lipid profile at 12 weeks, then annually
- Monitoring for extrapyramidal symptoms
- Assessment for emerging compulsive behaviors
- Mental status and suicide risk assessment
- Treatment response and side effect evaluation
Patient Education
Key points for patients and caregivers:- Take medication exactly as prescribed; do not stop abruptly
- May take several weeks to achieve full therapeutic effect
- Report any unusual movements, muscle stiffness, or fever immediately
- Monitor for changes in mood, behavior, or suicidal thoughts
- Be aware of potential for compulsive behaviors (gambling, shopping, binge eating)
- Rise slowly from sitting/lying position to prevent dizziness
- Avoid alcohol and other CNS depressants
- Use caution when driving or operating machinery until effects are known
- Inform all healthcare providers about aripiprazole use
- Store medication safely away from children and pets
- Keep follow-up appointments for monitoring
- Report any pregnancy or planning pregnancy to healthcare provider
References
1. FDA Prescribing Information: Aripiprazole (Abilify). Revised 2023. 2. Kane JM, et al. Efficacy and safety of aripiprazole and haloperidol versus placebo in patients with schizophrenia and schizoaffective disorder. J Clin Psychiatry. 2002;63(9):763-771. 3. Marcus RN, et al. Aripiprazole in the treatment of irritability in pediatric patients with autistic disorder. Pediatrics. 2009;124(6):1533-1540. 4. Berman RM, et al. The efficacy and safety of aripiprazole as adjunctive therapy in major depressive disorder. J Clin Psychopharmacol. 2007;27(2):156-165. 5. Stahl SM. Dopamine system stabilizers: aripiprazole. In: Stahl's Essential Psychopharmacology. 4th ed. Cambridge University Press; 2013. 6. Marder SR, et al. Aripiprazole in the treatment of schizophrenia: safety and tolerability in short-term, placebo-controlled trials. Schizophr Res. 2003;61(2-3):123-136. 7. American Psychiatric Association. Practice Guideline for the Treatment of Patients with Schizophrenia. 3rd ed. 2020.
This monograph is for educational purposes only and does not replace professional medical advice. Always consult with a qualified healthcare provider for medication decisions.