Aripiprazole (Abilify)

Class

Second-generation (atypical) antipsychotic

Mechanism

Partial agonist at dopamine D2 and serotonin 5-HT1A receptors; antagonist at 5-HT2A receptors; exhibits dopamine system stabilization by modulating dopaminergic tone based on endogenous dopamine levels

FDA-Approved Use

Schizophrenia, bipolar I disorder (manic/mixed episodes), adjunctive treatment of major depressive disorder (MDD), irritability associated with autism spectrum disorder (ASD), Tourette’s disorder

Off-Label Use

Generalized anxiety disorder (GAD), delusional disorder, psychosis in dementia, obsessive-compulsive disorder (OCD) augmentation, post-stroke affective lability, post-stroke aggression, agitation/aggression in neurodevelopmental disabilities

Formulation

Oral tablets, orally disintegrating tablets (ODT), oral solution, long-acting injectable (Abilify Maintena, Aristada)

Titration

2–5 mg p.o. daily (for MDD augmentation); titrate every 1–2 weeks as tolerated

Dose Range

2–15 mg/day (for MDD adjunct); higher ranges (10–30 mg/day) for schizophrenia or bipolar disorder

Kinetics

Half-life ~75 hours (oral); metabolized via CYP2D6 and CYP3A4; steady state reached in ~2 weeks

Common AEs

Akathisia, insomnia, anxiety, nausea, headache, constipation

Serious/Rare AEs

Extrapyramidal symptoms (EPS), impulse control disorders, tardive dyskinesia, neuroleptic malignant syndrome (NMS), orthostatic hypotension

Monitoring

Monitor weight, lipids, glucose, and extrapyramidal symptoms (EPS) every 3–6 months; consider ECG if cardiac risk factors are present, although considered to have a favorable cardiac safety profile among second-generation antipsychotics

Black Box Warning

Increased mortality in elderly patients with dementia-related psychosis; increased risk of suicidality in children, adolescents, and young adults with MDD

Considerations

In elderly patients with dementia-related psychosis, aripiprazole is associated with an increased risk of mortality and should be used cautiously, if at all. In individuals with Parkinson’s disease (PD), aripiprazole may be used as an adjunct for depressive or psychotic symptoms, but it can worsen parkinsonian motor features and requires close monitoring. Aripiprazole may lower the seizure threshold, so caution is warranted in individuals with seizure disorders or those with a history of traumatic brain injury (TBI).