aripiprazole

Aripiprazole belongs to the 'third-generation' or 'dopamine system stabilizer' class of antipsychotics due to its unique partial agonist activity at D2 receptors, which allows it to reduce dopaminergic activity in hyperdopaminergic states (mesolimbic pathway, treating positive symptoms) while maintaining or increasing dopaminergic tone in hypodopaminergic states (mesocortical pathway, less worsening of negative symptoms), theoretically minimizing extrapyramidal symptoms and hyperprolactinemia. Its partial agonism at 5-HT1A and antagonism at 5-HT2A contribute to improved negative symptom and mood effects, similar to other atypicals. Clinically, it is FDA-approved for schizophrenia, acute mania and maintenance in bipolar I disorder, adjunctive treatment of major depressive disorder, irritability associated with autism, and Tourette syndrome. Compared with other second-generation antipsychotics (e.g., olanzapine, risperidone), aripiprazole has a lower risk of weight gain, dyslipidemia, and metabolic syndrome, and a low propensity to cause hyperprolactinemia (may even lower prolactin due to D2 partial agonism). Common side effects include akathisia, insomnia, nausea, and headache; it has a relatively low risk of sedation and anticholinergic effects. Rare but important adverse effects shared with other antipsychotics include neuroleptic malignant syndrome and tardive dyskinesia (lower risk than typical antipsychotics). It has a long half-life (~75 hours), allowing once-daily dosing and available as a long-acting injectable (Abilify Maintena). Drug interactions: metabolized by CYP2D6 and CYP3A4; strong inhibitors or inducers of these enzymes can significantly alter aripiprazole levels. Board relevance: aripiprazole is frequently tested for its unique 'partial agonist' mechanism (distinguishing it from full D2 antagonists), its use as adjunct in depression, and its comparatively benign metabolic profile.