Overview
Aripiprazole is an atypical antipsychotic medication used to treat schizophrenia, bipolar disorder, major depressive disorder (as adjunctive therapy), irritability associated with autism, and Tourette's disorder. It functions as a partial agonist at dopamine D2 and serotonin 5-HT1A receptors while antagonizing serotonin 5-HT2A receptors, providing a unique mechanism among antipsychotics.
Mechanism of Action
Aripiprazole acts as a partial agonist at dopamine D2 and serotonin 5-HT1A receptors, and as an antagonist at serotonin 5-HT2A receptors. This unique pharmacological profile modulates dopaminergic and serotonergic neurotransmission, stabilizing activity in mesolimbic and mesocortical pathways while minimizing extrapyramidal side effects.
Indications
- Treatment of schizophrenia
- Acute treatment of manic and mixed episodes associated with bipolar I disorder
- Adjunctive treatment of major depressive disorder
- Irritability associated with autistic disorder
- Treatment of Tourette's disorder
Common Doses
- 2 mg
- 5 mg
- 10 mg
- 15 mg
- 20 mg
- 30 mg
Dosage
Dosing varies by indication: schizophrenia (10-30 mg/day), bipolar mania (15-30 mg/day), adjunctive MDD (2-15 mg/day), autism irritability (2-15 mg/day), Tourette's (2-20 mg/day). Titration is recommended based on clinical response and tolerability.
Black Box Warning
Increased mortality in elderly patients with dementia-related psychosis (boxed warning)
Contraindications
- History of hypersensitivity reaction to aripiprazole (ranging from pruritus/urticaria to anaphylaxis)
Side Effects
- Common: nausea, vomiting, constipation, headache, dizziness, akathisia, anxiety, insomnia
- Serious: neuroleptic malignant syndrome, tardive dyskinesia, metabolic syndrome, hyperglycemia, weight gain, orthostatic hypotension, seizures, compulsive behaviors, leukopenia
Interactions
- Strong CYP3A4 inhibitors (ketoconazole) increase aripiprazole levels
- Strong CYP2D6 inhibitors (quinidine, fluoxetine, paroxetine) increase aripiprazole levels
- CYP3A4 inducers (carbamazepine) decrease aripiprazole levels
- Alcohol may enhance CNS depression
- Antihypertensives may have additive hypotensive effects
Counseling Points
- Take consistently with or without food
- Avoid alcohol and CNS depressants
- Rise slowly to prevent dizziness
- Report unusual urges (gambling, shopping, eating)
- Monitor for signs of high blood sugar (thirst, urination, hunger)
- Do not stop abruptly without medical supervision
- Use caution when driving or operating machinery
- Report fever, muscle stiffness, or confusion immediately