Abilify Tapering Guide
aripiprazole
Boxed Warning
Increased mortality in elderly patients with dementia-related psychosis. Suicidality risk in children, adolescents, and young adults (for MDD adjunct indication).
Overview
Aripiprazole is an atypical antipsychotic with a unique mechanism as a partial agonist at dopamine D2 receptors. It is approved for schizophrenia, bipolar I disorder, adjunctive treatment of MDD, irritability in autism, and Tourette disorder.
2mg, 5mg, 10mg, 15mg, 20mg, 30mg
Tablets: 2mg, 5mg, 10mg, 15mg, 20mg, 30mg; Orally disintegrating tablets: 10mg, 15mg; Oral solution: 1mg/mL; Intramuscular injection: 9.75mg/1.3mL; Extended-release injection (Abilify Maintena): 300mg, 400mg
Category C (risk cannot be ruled out)
Mechanism of Action
Partial agonist at dopamine D2 and serotonin 5-HT1A receptors, and antagonist at serotonin 5-HT2A receptors. This unique "dopamine stabilizer" profile means it can act as a functional antagonist in hyperdopaminergic states and a functional agonist in hypodopaminergic states.
Taper Notes
Long parent half-life (75–94 hours) with active metabolite dehydro-aripiprazole (~94 hours) provides intrinsic kinetic buffering. Oral solution (1 mg/mL) supports fine titration. Often used adjunctively at low doses; akathisia is the most common dose-limiting effect throughout the dose range.
Maudsley Deprescribing Guidance
Long active-moiety half-life buffers each dose reduction. Oral solution (1 mg/mL) supports proportional reductions. Reduce gradually despite favorable kinetics — delayed pharmacodynamic effects are common.
Common Withdrawal Symptoms
Interactions & Safety
Drug Interactions
- CYP2D6 inhibitors (fluoxetine, paroxetine) increase aripiprazole levels — reduce aripiprazole dose by 50%
- CYP3A4 inhibitors (ketoconazole, itraconazole) increase aripiprazole levels — reduce dose by 50%
- CYP3A4 inducers (carbamazepine, rifampin) decrease aripiprazole levels — double dose when co-administered
Food Interactions
- Food does not affect absorption
- Avoid alcohol (additive CNS depression)
Contraindications
- Known hypersensitivity to aripiprazole
Toxicity
Akathisia is the most common dose-limiting side effect. Less metabolic burden than other atypicals (lower weight gain, lipid changes). Compulsive behaviors (gambling, eating, shopping) reported. NMS and tardive dyskinesia rare.
Pharmacokinetics
ADME Profile
Well absorbed after oral administration. Bioavailability ~87%. Tmax 3–5 hours. Food does not significantly affect absorption.
~4.9 L/kg
Hepatic via CYP3A4 and CYP2D6 to the active metabolite dehydro-aripiprazole, which has similar D2 receptor affinity. Dehydro-aripiprazole represents ~40% of parent drug AUC in plasma.
Fecal (~55%) and renal (~25%). Less than 1% excreted unchanged in urine.
>99% (primarily albumin)
~3.5 mL/min/kg
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