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Aripiprazole

Aripiprazole

Abilify Abilify Maintena Aristada Abilify Mycite Abilify Asimtufii

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Updated: December 06, 2025

Overview

Aripiprazole is an atypical antipsychotic medication primarily used to treat schizophrenia, bipolar disorder, and as an adjunct treatment for major depressive disorder. It was first approved by the FDA in 2002 and is notable for its unique mechanism of action as a partial dopamine agonist. Unlike typical antipsychotics, aripiprazole acts as a dopamine-serotonin system stabilizer, providing effective symptom control with a generally favorable side effect profile. It is also used off-label for other psychiatric conditions and has multiple formulations including oral tablets, orally disintegrating tablets, solution, and long-acting injectables.

Drug Class

Second-generation (atypical) antipsychotic Dopamine-serotonin system stabilizer Therapeutic category: Psychotherapeutic agent

Mechanism of Action

Aripiprazole exerts its effects through: • Partial agonism at dopamine D2 and serotonin 5-HT1A receptors • Antagonism at serotonin 5-HT2A receptors • Partial agonism at dopamine D3 receptors • Moderate affinity for histamine H1 and α1-adrenergic receptors This unique profile helps modulate dopamine and serotonin activity in mesolimbic and mesocortical pathways while minimizing extrapyramidal symptoms.

Pharmacokinetics

Absorption: Well-absorbed orally (87% bioavailability), peak plasma concentrations in 3-5 hours. Food delays absorption but doesn't affect overall bioavailability. Distribution: Extensive tissue distribution (Vd 4.9 L/kg), 99% protein bound primarily to albumin Metabolism: Primarily hepatic via CYP3A4 and CYP2D6 to active metabolite dehydro-aripiprazole Excretion: Approximately 55% fecal and 25% renal excretion Half-life: 75 hours (aripiprazole), 94 hours (active metabolite)

Pharmacodynamics

Produces: • Stabilization of dopamine activity in key brain pathways • Modulation of serotonin transmission • Reduction in positive and negative symptoms of schizophrenia • Mood stabilization in bipolar disorder • Minimal anticholinergic effects compared to other antipsychotics

Indications

• Schizophrenia: Treatment of acute episodes and maintenance therapy in adults and adolescents (13-17 years) • Bipolar I Disorder: Acute treatment of manic/mixed episodes and maintenance therapy as monotherapy or adjunct • Adjunctive Treatment: For major depressive disorder (MDD) when inadequate response to antidepressants • Irritability: Associated with autistic disorder in pediatric patients (6-17 years) • Tourette's Disorder: Treatment of tics in pediatric patients (6-18 years)

Contraindications

Absolute: • Hypersensitivity to aripiprazole Relative: • Dementia-related psychosis (increased mortality risk) • History of seizures or conditions lowering seizure threshold • Cardiovascular disease or hypotension • Parkinson's disease/Lewy body dementia

Dosage & Administration

Schizophrenia (oral): Initial: 10-15 mg once daily Maintenance: 10-30 mg daily Bipolar Mania: Monotherapy: 15 mg once daily (range 10-30 mg) Adjunct: 10-15 mg once daily MDD Adjunct: Initial: 2-5 mg daily, titrate to 5-15 mg daily Autism-Related Irritability: 2-15 mg daily based on weight Long-Acting Injections: Abilify Maintena: 400 mg monthly Aristada: 441-1064 mg monthly/6 weeks

Special Populations

Pediatric: Weight-based dosing required, increased susceptibility to EPS Geriatric: Lower initial doses recommended, increased mortality risk in dementia Renal impairment: No dose adjustment needed Hepatic impairment: Maximum dose 15 mg daily for severe impairment

Adverse Effects

Common (>10%): • Headache • Anxiety/agitation • Insomnia • Nausea/vomiting • Constipation • Akathisia Serious (<1%): • Neuroleptic malignant syndrome (NMS) • Tardive dyskinesia • Seizures • Orthostatic hypotension • Hyperglycemia/diabetes • Suicidal ideation (in young adults)

Drug Interactions

• CYP2D6 inhibitors (fluoxetine, paroxetine): May increase aripiprazole levels • CYP3A4 inducers (carbamazepine): May decrease efficacy • Antihypertensives: May potentiate hypotension • CNS depressants: Enhanced sedative effects • Serotonergic drugs: Increased risk of serotonin syndrome

Warnings & Precautions

• Black Box Warning: Increased mortality in elderly patients with dementia-related psychosis • Risk of suicidal thoughts/behaviors in young adults • Potential for metabolic changes (weight gain, dyslipidemia, hyperglycemia) • Orthostatic hypotension risk • Cognitive/motor impairment warnings • Discontinuation syndrome with abrupt cessation

Pregnancy & Lactation

Pregnancy: Category C - Risk cannot be ruled out. Neonates exposed during 3rd trimester may develop withdrawal symptoms or EPS. Lactation: Excreted in breast milk. Consider risk-benefit ratio. Monitor infants for sedation, poor feeding, or developmental milestones.

Monitoring Parameters

• Weight/BMI at baseline and regularly • Fasting blood glucose and lipid profile • EPS symptoms (akathisia, dystonia, parkinsonism) • Mental status/suicidal ideation • Blood pressure (especially orthostatic changes) • CBC in patients with pre-existing low WBC

Patient Counseling

• Take consistently with or without food • Do not stop abruptly - taper under medical supervision • Report any unusual movements or restlessness • Monitor for signs of hyperglycemia (thirst, urination) • Caution with alcohol and other CNS depressants • Rise slowly to prevent dizziness • Notify provider if pregnant or planning pregnancy

Storage & Stability

Store at 20-25°C (68-77°F) Protect from light and moisture Oral solution stable for 6 months after opening Unopened vials: Follow expiration date

Clinical Pearls

• Start low and go slow to minimize akathisia risk • Consider prophylactic benztropine in high-risk patients • Metabolic monitoring should be ongoing, not just at initiation • Long-acting injections require 14-day oral overlap • Partial agonism may cause initial activation before therapeutic effect • Particularly effective for negative symptoms in schizophrenia

References

• Aripiprazole (Abilify) Package Insert. Otsuka Pharmaceutical Co., Ltd. 2023 • Stahl SM. Stahl's Essential Psychopharmacology. 5th ed. Cambridge University Press; 2021 • Kane JM, et al. Efficacy and safety of aripiprazole in the treatment of schizophrenia. J Clin Psychiatry. 2002;63 Suppl 4:3-11 • FDA Drug Safety Communication: Antipsychotic drug labels updated on use during pregnancy. 2021