Aripiprazole exerts its therapeutic effects through its action on multiple neurotransmitter systems in the brain. Its key mechanisms include:

1. Dopamine Partial Agonism:
   • Aripiprazole acts as a partial agonist at dopamine D2 and D3 receptors. This means it stabilizes dopamine activity by acting as an agonist in areas with low dopamine levels (improving negative symptoms) and as an antagonist in areas with high dopamine levels (reducing positive symptoms).
   • This unique action contributes to its efficacy in treating schizophrenia and bipolar disorder with a lower risk of extrapyramidal side effects (EPS) and hyperprolactinemia.
2. Serotonin Receptor Modulation:
   • Aripiprazole is a partial agonist at serotonin 5-HT1A receptors, which may contribute to its antidepressant and anxiolytic effects.
   • It is an antagonist at serotonin 5-HT2A receptors, which helps improve negative symptoms and reduce the risk of EPS.
3. Other Receptor Interactions:
   • Aripiprazole has affinity for adrenergic α1 and histamine H1 receptors, which contributes to its side effect profile (e.g., sedation, orthostatic hypotension).
4. Stabilization of Neurotransmitter Systems:
   • By modulating dopamine and serotonin activity, aripiprazole helps stabilize mood and reduce psychotic symptoms.

Aripiprazole is approved for a variety of clinical conditions, including:

1. Schizophrenia:
   • Treatment of acute and chronic schizophrenia in adults and adolescents aged 13–17 years.
2. Bipolar Disorder:
   • Management of acute manic or mixed episodes in adults and pediatric patients aged 10–17 years.
   • Maintenance treatment to prevent recurrence of manic or depressive episodes.
3. Adjunctive Therapy for Major Depressive Disorder (MDD):
   • Used in combination with antidepressants for adults with MDD who have not responded adequately to antidepressant therapy alone.
4. Irritability Associated with Autism Spectrum Disorder (ASD):
   • Treatment of irritability, aggression, and self-injurious behavior in pediatric patients aged 6–17 years.
5. Other Uses:
   • Off-label use for borderline personality disorder, Tourette’s syndrome, and agitation in dementia (with caution).

The dosage of aripiprazole varies depending on the indication, patient age, and clinical response. The following dosing guidelines are based on the British National Formulary (BNF) and clinical pharmacology references:

1. Schizophrenia:
   • Adults: Start with 10–15 mg once daily, increasing to a target dose of 10–30 mg daily.
   • Adolescents (13–17 years): Start with 2 mg daily, increasing to 10 mg daily over two weeks.
2. Bipolar Disorder:
   • Adults: Start with 15 mg once daily, increasing to a target dose of 15–30 mg daily.
   • Pediatric Patients (10–17 years): Start with 2 mg daily, increasing to 10 mg daily over two weeks.
3. Adjunctive Therapy for MDD:
   • Adults: Start with 2–5 mg once daily, increasing to a target dose of 5–15 mg daily.
4. Irritability Associated with ASD:
   • Pediatric Patients (6–17 years): Start with 2 mg daily, increasing to 5–15 mg daily over two weeks.

Important Considerations:

• Aripiprazole is available in oral tablets, orally disintegrating tablets, and long-acting injectable (LAI) formulations.
• Dose adjustments may be necessary for patients with hepatic or renal impairment.
• Regular monitoring of weight, blood glucose, and lipid levels is recommended due to the risk of metabolic side effects.

Aripiprazole is generally well-tolerated, but it is associated with a range of side effects, some of which can be serious. Common side effects include:

1. Central Nervous System:
   • Dizziness, headache, insomnia, and akathisia (restlessness).
2. Gastrointestinal:
   • Nausea, vomiting, and constipation.
3. Metabolic Effects:
   • Weight gain, hyperglycemia, and dyslipidemia, which increase the risk of metabolic syndrome and type 2 diabetes.
4. Endocrine:
   • Minimal risk of hyperprolactinemia compared to other antipsychotics.
5. Other:
   • Fatigue, blurred vision, and orthostatic hypotension.

Serious Side Effects:

• Neuroleptic Malignant Syndrome (NMS): A rare but life-threatening condition characterized by fever, muscle rigidity, and autonomic instability.
• Tardive Dyskinesia: A potentially irreversible movement disorder associated with long-term use of antipsychotics.
• Increased Mortality in Elderly Patients with Dementia: Aripiprazole is associated with an increased risk of stroke and death in elderly patients with dementia-related psychosis.

Aripiprazole requires careful monitoring and adherence to specific precautions to ensure patient safety:

1. Metabolic Monitoring:
   • Regular monitoring of weight, blood glucose, and lipid levels is essential to detect and manage metabolic side effects.
2. Pregnancy and Lactation:
   • Aripiprazole should be used during pregnancy only if the potential benefits outweigh the risks. It is excreted in breast milk, so breastfeeding is generally not recommended.
3. Elderly Patients:
   • Lower doses may be required due to increased sensitivity to side effects, particularly sedation and orthostatic hypotension.
4. Cardiovascular Risk:
   • Use with caution in patients with a history of cardiovascular disease or risk factors for QT prolongation.
5. Suicidal Risk:
   • Monitor for worsening depression or suicidal thoughts, particularly in patients with mood disorders.

Aripiprazole has a moderate potential for drug interactions due to its metabolism via cytochrome P450 enzymes (primarily CYP2D6 and CYP3A4). Key interactions include:

1. CYP2D6 Inhibitors:
   • Fluoxetine and paroxetine can increase aripiprazole levels, increasing the risk of side effects.
2. CYP3A4 Inhibitors:
   • Ketoconazole and clarithromycin can increase aripiprazole levels.
3. CYP3A4 Inducers:
   • Carbamazepine and rifampin can decrease aripiprazole levels, reducing its efficacy.
4. Central Nervous System Depressants:
   • Alcohol, benzodiazepines, and opioids can enhance sedation and respiratory depression.
5. Other Interactions:
   • Antihypertensives: Aripiprazole may enhance the hypotensive effects of antihypertensive medications.

Aripiprazole is the generic name for this medication. It is marketed under various brand names, depending on the country and manufacturer. Some examples include:

• Abilify (a well-known brand in the United States and other regions).
• Aripiprex.
• Aristada (long-acting injectable formulation).
• Aripiprazole Accord.