Is Aripiprazole an Antipsychotic?
Yes, aripiprazole is definitively an antipsychotic medication—specifically classified as a third-generation atypical antipsychotic distinguished by its unique partial dopamine D2 receptor agonist activity. 1, 2
Classification and Mechanism
Aripiprazole represents the first "third-generation" antipsychotic, a designation that reflects its fundamentally different pharmacological mechanism compared to earlier antipsychotics. 2 Unlike first-generation antipsychotics that function purely as dopamine D2 receptor antagonists, or second-generation agents that act as serotonin-dopamine receptor antagonists, aripiprazole operates as a partial agonist at dopamine D2 and serotonin 5-HT1A receptors while antagonizing 5-HT2A receptors. 1, 3, 4
This partial agonist activity at D2 receptors is what pharmacologically separates third-generation from second-generation antipsychotics and provides the mechanistic basis for aripiprazole's efficacy in treating both positive and negative symptoms of schizophrenia. 2, 4
Clinical Indications
Aripiprazole is FDA-approved and clinically effective for:
- Schizophrenia and schizoaffective disorder in adult patients, with demonstrated efficacy in treating positive and negative symptoms 5, 3, 4
- Acute bipolar mania, with preliminary data supporting effectiveness 3, 6
- Treatment shows rapid onset of action within the first week of therapy 3, 7
Distinguishing Features from Other Antipsychotics
Aripiprazole is recommended as a first-line antipsychotic choice due to its superior metabolic side effect profile. 1 Key advantages include:
- Low risk of weight gain—a major differentiator from second-generation agents like clozapine and olanzapine 1, 4, 7
- Minimal prolactin elevation, unlike many other antipsychotics 1, 4
- Low propensity for extrapyramidal symptoms (EPS) compared to first-generation agents, though akathisia and motoric activation can occur 4, 6
- No clinically significant QTc prolongation at recommended doses 4, 8
The evidence from a large epidemiological study shows aripiprazole had one of the lowest odds ratios for ventricular arrhythmia/sudden cardiac death among antipsychotics studied (OR 0.90,95% CI 0.31-2.59). 9
Important Clinical Caveats
Aripiprazole may cause paradoxical activation or agitation in some patients due to its partial agonist properties, which is an important consideration when selecting this agent. 2 Common adverse effects include insomnia, anxiety, headache, agitation, and akathisia, though these are typically transient. 4, 7
The drug requires no dosage titration and is effective within the first few weeks of treatment at recommended doses of 10-15 mg once daily. 3, 4 However, dosage adjustment is necessary when coadministered with CYP3A4 or CYP2D6 inhibitors or inducers due to hepatic metabolism. 4
Monitoring Requirements
Before initiating aripiprazole, measure BMI, waist circumference, blood pressure, HbA1c, glucose, lipids, prolactin, liver function, electrolytes, complete blood count, and EKG. 1 Follow-up monitoring should include glucose at 4 weeks, BMI/waist/blood pressure weekly for 6 weeks, then comprehensive parameters at 3 months and annually. 1