fluoxetine and risperidone

Fluoxetine is a strong inhibitor of CYP2D6, the enzyme primarily responsible for the metabolism of risperidone. This reduces the clearance of risperidone and increases its plasma concentrations. Risperidone is also metabolised by CYP3A4 to a lesser extent, but the predominant effect is CYP2D6 inhibition.

Co-administration can lead to elevated risperidone levels, increasing the risk of dose-related adverse effects such as extrapyramidal symptoms, sedation, orthostatic hypotension, and QT interval prolongation. The clinical significance is greatest when fluoxetine is started or its dose increased in a patient already stabilised on risperidone.

If co-prescription is necessary, consider reducing the risperidone dose and monitor for signs of extrapyramidal symptoms, sedation, and hypotension. Monitor blood pressure and ECG if risk factors for QT prolongation. When discontinuing fluoxetine, risperidone levels may fall, requiring dose adjustment. Consider alternative antidepressants with less CYP2D6 inhibition.

Well-established interaction based on pharmacokinetic studies and clinical case reports; consistent with known CYP2D6 inhibition. Product labelling recommends caution and dose adjustment.