Usage
Aripiprazole is prescribed for the treatment of various mental health conditions, including:
- Schizophrenia: A chronic brain disorder affecting a person’s ability to think, feel, and behave clearly.
- Bipolar I Disorder: A mental illness that causes unusual shifts in mood, energy, activity levels, concentration, and the ability to carry out day-to-day tasks. Aripiprazole is used to treat manic or mixed episodes associated with this disorder.
- Major Depressive Disorder: A common and serious medical illness that negatively affects how you feel, the way you think and how you act. Aripiprazole is used as an adjunct to antidepressant therapy in adults.
- Irritability Associated with Autistic Disorder in Children: Aripiprazole can help manage irritability symptoms such as temper tantrums, aggression, and self-injurious behavior.
- Tourette’s Disorder in Children: A disorder that involves repetitive movements or unwanted sounds (tics) that can’t be easily controlled.
Pharmacological Classification: Aripiprazole is classified as an atypical antipsychotic.
Mechanism of Action: Aripiprazole acts as a partial agonist at dopamine D2 and serotonin 5-HT1A receptors and an antagonist at serotonin 5-HT2A receptors. This unique mechanism of action is thought to stabilize dopamine and serotonin neurotransmission in the brain, thereby reducing the symptoms of psychosis and mood instability.
Alternate Names
Aripiprazole is the generic name.
Brand Names: Abilify, Abilify Maintena, Abilify Discmelt®, Abilify MyCite®.
How It Works
Pharmacodynamics: Aripiprazole’s therapeutic effects are believed to be mediated through its partial agonistic activity at dopamine D2 and serotonin 5-HT1A receptors and antagonistic activity at serotonin 5-HT2A receptors. This combination of actions helps to regulate dopamine and serotonin neurotransmission, which are often dysregulated in conditions like schizophrenia and bipolar disorder.
Pharmacokinetics:
- Absorption: Aripiprazole is well-absorbed orally, reaching peak plasma concentrations within 3-5 hours.
- Metabolism: Aripiprazole is extensively metabolized in the liver, primarily by CYP3A4 and CYP2D6 enzymes, to active and inactive metabolites.
- Elimination: Aripiprazole and its metabolites are eliminated primarily through renal (27%) and hepatic (60%) routes, with a half-life of approximately 75 hours.
Mode of Action: Aripiprazole binds to and modulates the activity of dopamine D2, serotonin 5-HT1A, and serotonin 5-HT2A receptors in the brain. In regions with excessive dopamine activity, it acts as an antagonist, blocking the effects of dopamine. Conversely, in regions with low dopamine activity, it acts as an agonist, stimulating dopamine receptors. This “stabilizing” effect on dopamine neurotransmission helps alleviate symptoms of psychosis and mood disorders.
Receptor Binding/Enzyme Inhibition/Neurotransmitter Modulation: Aripiprazole primarily interacts with dopamine D2, serotonin 5-HT1A, and serotonin 5-HT2A receptors as a partial agonist or antagonist. It is metabolized by CYP3A4 and CYP2D6 enzymes.
Elimination Pathways: Aripiprazole and its metabolites are excreted through both renal and hepatic pathways. Metabolism occurs mainly through CYP3A4 and CYP2D6 enzymes.
Dosage
Standard Dosage
Adults:
- Schizophrenia: Initial dose is 10-15 mg once daily, with a maximum dose of 30 mg/day.
- Bipolar Mania: Initial dose is 15 mg once daily, with a maximum dose of 30 mg/day. May be used as monotherapy or as adjunct to lithium or valproate.
- Major Depressive Disorder (adjunct): Initial dose is 2-5 mg once daily, with a maximum dose of 15 mg/day.
- Irritability Associated with Autistic Disorder: 5-15 mg/day.
Children (6-17 years):
- Irritability Associated with Autistic Disorder: Initial dose of 2 mg/day, titrated to 5-15 mg/day.
- Tourette’s Disorder: Dosing based on weight (see below).
- Schizophrenia: Initial dose of 2 mg/day, titrated to 10 mg/day. Maximum dose of 30 mg/day.
- Bipolar Mania: Initial dose of 2 mg/day, titrated to 10 mg/day. Maximum dose of 30 mg/day.
Special Cases:
- Elderly Patients: Lower initial doses may be necessary.
- Patients with Renal Impairment: Dosage adjustments may be required depending on the degree of impairment.
- Patients with Hepatic Dysfunction: Dosage adjustments may be required, especially in severe hepatic impairment.
- Patients with Comorbid Conditions: Careful consideration and dose adjustments may be necessary based on the specific comorbid condition.
Tourette’s Disorder Dosage in Children
- 6 to 18 years and <50 kg: 2 mg once daily initially. Increase to 5 mg/day, then up to a maximum of 10 mg/day as needed, at intervals of no less than 1 week.
- 6 to 18 years and ≥50 kg: 2 mg once daily initially. Increase to 5 mg/day for 5 days, then to 10 mg/day. The dose can be increased up to 20 mg/day, with dose adjustments in increments of 5 mg/day at intervals of no less than 1 week.
Clinical Use Cases
Aripiprazole is primarily used for long-term management of chronic mental health conditions. Its use in acute settings such as intubation, surgical procedures, mechanical ventilation, ICU, or emergency situations (status epilepticus, cardiac arrest) is generally not indicated. Short-acting intramuscular injections may be used to manage acute agitation or psychosis in patients already receiving aripiprazole.
Dosage Adjustments
Dose modifications should be based on patient-specific factors, including renal/hepatic function, metabolic disorders, concomitant medications (especially CYP3A4 and CYP2D6 inhibitors or inducers), and individual patient response and tolerability.
Side Effects
Common Side Effects
- Headache
- Nausea
- Vomiting
- Insomnia
- Akathisia (restlessness)
- Anxiety
- Dizziness
- Constipation
- Weight gain
Rare but Serious Side Effects
- Neuroleptic malignant syndrome (NMS)
- Tardive dyskinesia
- Severe allergic reactions (anaphylaxis)
- Suicidal thoughts or behavior
Long-Term Effects
- Weight gain
- Metabolic changes (dyslipidemia, diabetes)
- Tardive dyskinesia (with long-term use)
Adverse Drug Reactions (ADR)
Any of the rare but serious side effects listed above would be considered clinically significant ADRs requiring immediate intervention.
Contraindications
- Known hypersensitivity to aripiprazole
Drug Interactions
- CYP3A4 and CYP2D6 Inhibitors/Inducers: Concomitant use of strong CYP3A4 or CYP2D6 inhibitors may require aripiprazole dose reduction. CYP3A4 inducers may require aripiprazole dose increase.
- Medications that Prolong the QT Interval: Use with caution.
- Central Nervous System Depressants: Additive sedative effects may occur.
- Alcohol: Avoid use with aripiprazole.
Pregnancy and Breastfeeding
- Pregnancy Safety Category: C. Aripiprazole should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
- Breastfeeding: Aripiprazole is excreted in breast milk. The decision to breastfeed while taking aripiprazole should be made in consultation with a healthcare professional, weighing the risks and benefits.
Drug Profile Summary
- Mechanism of Action: Partial agonist at dopamine D2 and serotonin 5-HT1A receptors and an antagonist at serotonin 5-HT2A receptors.
- Side Effects: Headache, nausea, vomiting, insomnia, akathisia, anxiety, dizziness, constipation, weight gain. Rare but serious: NMS, tardive dyskinesia, anaphylaxis.
- Contraindications: Hypersensitivity to aripiprazole.
- Drug Interactions: CYP3A4/2D6 inhibitors/inducers, QT-prolonging agents, CNS depressants.
- Pregnancy & Breastfeeding: Use with caution; weigh risks and benefits.
- Dosage: Varies depending on indication and patient factors; generally 10-15 mg/day for adults.
- Monitoring Parameters: Weight, metabolic parameters (glucose, lipids), extrapyramidal symptoms (EPS), suicidality.
Popular Combinations
Aripiprazole may be combined with other medications, such as antidepressants (for major depressive disorder) or mood stabilizers (for bipolar disorder), to achieve optimal therapeutic effect. The specific combinations and dosages should be determined based on individual patient needs and clinical guidelines.
Precautions
- General Precautions: Monitor for suicidal thoughts, NMS, TD, metabolic changes, and EPS.
- Specific Populations: Carefully consider risks and benefits in pregnant/breastfeeding women, children, and the elderly.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Aripiprazole?
A: The recommended dosage varies depending on the condition being treated and the patient’s age and other individual factors. For adults with schizophrenia or bipolar mania, it’s typically 10-15 mg once daily, up to a maximum of 30 mg/day. For major depressive disorder (as adjunct therapy) the dose is 2-5 mg/day up to 15 mg/day. Pediatric dosing and dosing for other indications should be determined on a case-by-case basis in consultation with clinical guidelines.
Q2: How should Aripiprazole be administered?
A: Aripiprazole is available in oral tablets, orally disintegrating tablets, oral solution and intramuscular injection. Oral formulations can be taken with or without food. The intramuscular injection is administered by a healthcare professional.
Q3: What are the common side effects of Aripiprazole?
A: Common side effects include headache, nausea, vomiting, insomnia, akathisia, anxiety, dizziness, constipation and weight gain.
Q4: What are the serious side effects of Aripiprazole?
A: Neuroleptic malignant syndrome, tardive dyskinesia, and severe allergic reactions are rare but potentially serious side effects. Patients should be advised to seek immediate medical attention if they experience these.
Q5: What are the contraindications for Aripiprazole?
A: The primary contraindication is a known hypersensitivity to aripiprazole.
Q6: Does Aripiprazole interact with other medications?
A: Yes, Aripiprazole can interact with several medications, including CYP3A4 and CYP2D6 inhibitors and inducers, other medications that prolong the QT interval and CNS depressants.
Q7: Can Aripiprazole be used during pregnancy and breastfeeding?
A: Aripiprazole should be used during pregnancy only if the potential benefit outweighs the potential risk to the fetus. It is excreted in breast milk, and the decision to breastfeed while taking aripiprazole should be made carefully in consultation with a healthcare professional.
Q8: What monitoring parameters are important for patients taking Aripiprazole?
A: Monitor weight, metabolic parameters (blood glucose and lipids), extrapyramidal symptoms (EPS), and suicidality. Regular follow-up is crucial to assess treatment efficacy and manage potential side effects.
Q9: How long does it take for Aripiprazole to start working?
A: Some patients may experience improvement in symptoms within a few days, while others may take several weeks to see noticeable benefits.
Q10: What should patients do if they miss a dose of Aripiprazole?
A: If a dose is missed, patients should take it as soon as they remember, unless it is close to the time for the next dose. They should not double the dose to catch up.
