Which antipsychotic shows the greatest reduction in plasma levels when coadministered with carbamazepine?

• A. Clozapine
• B. Quetiapine
• C. Olanzapine
• D. Risperidone

Answer: (B)

Carbamazepine is a powerful hepatic enzyme inducer, especially of CYP3A4. Drugs that are substrates of CYP3A4 are metabolized faster when carbamazepine is present, leading to lower plasma levels and often reduced efficacy. Quetiapine is primarily cleared by CYP3A4, so its metabolism is most markedly increased by carbamazepine, causing a substantial drop in its plasma concentration. The other antipsychotics listed rely more on other enzymes (for example, olanzapine and clozapine involve CYP1A2 and other pathways, risperidone mainly via CYP2D6), so their levels are less dramatically affected by CYP3A4 induction. In practice, coadministration may require dose adjustments and careful monitoring of response and tolerability.