ABILIFY
Clinical safety rating: caution
Aripiprazole is an atypical antipsychotic indicated for schizophrenia, acute manic and mixed episodes associated with bipolar I disorder, adjunctive treatment of major depressive disorder, and irritability associated with autistic disorder. It functions as a partial agonist at dopamine D2 and serotonin 5-HT1A receptors, and as an antagonist at serotonin 5-HT2A receptors.
Partial agonist at dopamine D2 and serotonin 5-HT1A receptors; antagonist at serotonin 5-HT2A receptors.
| Metabolism | Hepatic metabolism primarily via CYP3A4 and CYP2D6; also by dehydrogenation and N-dealkylation. |
| Excretion | Renal (25% unchanged, 18% as dehydro-aripiprazole) and fecal (55% unchanged and metabolites). |
| Half-life | Aripiprazole: 75 hours; dehydro-aripiprazole: 94 hours. Steady-state reached in ~14 days. |
| Protein binding | >99% bound to albumin and alpha-1-acid glycoprotein. |
| Volume of Distribution | 4.9 L/kg (high distribution into tissues). |
| Bioavailability | Oral: 87% (tablet and solution); IM: 100%. |
| Onset of Action | Oral: 1-3 weeks for antipsychotic effect; IM: 30-90 minutes for agitation. |
| Duration of Action | Oral: 24 hours (once-daily dosing); IM: 2-6 hours for agitation (single dose). |
Schizophrenia: 10-15 mg once daily (max 30 mg). Bipolar mania: 15-30 mg once daily (as monotherapy or adjunct). Adjunctive MDD: 2-5 mg once daily, titrating to 5-10 mg. Autism irritability: 2 mg/day initially, titrated to 5-10 mg/day (max 15 mg/day).
| Dosage form | TABLET, ORALLY DISINTEGRATING |
| Renal impairment | No dosage adjustment required for renal impairment; not removed by hemodialysis. |
| Liver impairment | No specific guidelines; use caution in severe hepatic impairment (Child-Pugh class C) due to limited data. |
| Pediatric use | Schizophrenia (13-17 years): 2 mg/day, target 10-25 mg/day. Bipolar mania (10-17 years): 2 mg/day, target 10-30 mg/day. Autism irritability (6-17 years): 2 mg/day, target 5-15 mg/day. |
| Geriatric use | Initiate at lower doses (e.g., 2-5 mg/day) and titrate slowly due to increased risk of adverse effects, especially orthostatic hypotension and cognitive decline. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
There are no adequate and well-controlled studies in pregnant women. Use only if potential benefit justifies potential risk to the fetus.
| Placental transfer | Aripiprazole crosses the placenta; detectable in cord blood and amniotic fluid. |
| Breastfeeding | Aripiprazole is excreted in human breast milk; milk-to-plasma (M/P) ratio is approximately 0.5 to 1.0. Relative infant dose is estimated to be 1-3% of maternal weight-adjusted dose. Limited data; use with caution. Monitor infant for sedation, poor feeding, and abnormal movements. |
| Teratogenic Risk |
■ FDA Black Box Warning
Increased risk of death in elderly patients with dementia-related psychosis due to cerebrovascular events.
| Common Effects | Nausea, Vomiting, Constipation, Headache, Dizziness, Insomnia, Akathisia, Anxiety |
| Serious Effects | Neuroleptic malignant syndromeTardive dyskinesiaSeizuresStroke in elderly dementia patientsAcute dystonic reactions |
Known hypersensitivity to aripiprazole or any of its excipients.
| Precautions | Increased mortality in elderly dementia patients, suicidal thoughts/behaviors, neuroleptic malignant syndrome, tardive dyskinesia, metabolic changes (hyperglycemia, dyslipidemia, weight gain), orthostatic hypotension, leukopenia/neutropenia, seizures, body temperature dysregulation, dysphagia, impulse control disorders. |
| Food/Dietary |
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| Pregnancy category C. First trimester: risk of major malformations not significantly increased based on limited data; however, neurodevelopmental effects uncertain. Second and third trimesters: neonates exposed in late pregnancy are at risk for extrapyramidal symptoms (EPS) and withdrawal syndrome including agitation, hypertonia, hypotonia, tremor, somnolence, respiratory distress, feeding disorder. |
| Fetal Monitoring | Monitor for maternal weight gain, blood glucose, and lipid profile. Assess for extrapyramidal symptoms. Fetal ultrasound for growth and anomaly if indicated. Neonatal monitoring for EPS, withdrawal, and sedation for at least 48 hours after birth. |
| Fertility Effects | Aripiprazole may cause hyperprolactinemia (though less than with typical antipsychotics), which can lead to menstrual irregularities, galactorrhea, and potential reversible impairment of fertility. No long-term fertility studies in humans. |
| Grapefruit juice may increase aripiprazole exposure; avoid concurrent intake. No other significant food interactions. Alcohol can enhance CNS depression; limit or avoid. |
| Clinical Pearls | Abilify (aripiprazole) is a partial dopamine agonist, which reduces the risk of extrapyramidal symptoms and hyperprolactinemia compared to full antagonists. Monitor for akathisia, especially during dose titration. QT prolongation risk is lower than with other antipsychotics; use caution in patients with cardiac disease. Avoid use in dementia-related psychosis due to increased mortality. Therapeutic effects may take 2-4 weeks; full response often requires 6-8 weeks. |
| Patient Advice | Take exactly as prescribed; do not stop abruptly without consulting your doctor. · May cause drowsiness or dizziness; avoid driving until you know how it affects you. · Avoid alcohol and grapefruit juice as they can alter drug levels. · Report any uncontrolled muscle movements, especially in face or tongue. · Monitor weight and blood glucose regularly as it can cause metabolic changes. · If you miss a dose, take it as soon as you remember unless it's almost time for the next dose; do not double up. · Use effective contraception if of childbearing potential; discuss pregnancy plans with your doctor. |