Major
Bupropion × Haloperidol
Other antidepressants (NDRI)×First-generation antipsychotics. Butyrophenone derivatives
Mechanism
Haloperidol is a CYP2D6 substrate; bupropion is a potent CYP2D6 inhibitor. Haloperidol plasma levels rise 2- to 3-fold. Risk of extrapyramidal symptoms and QT prolongation emerges. Both drugs also lower the seizure threshold.
Symptoms
Extrapyramidal symptoms (tremor, rigidity, akathisia), QT prolongation on ECG, seizures. Older patients: fall risk.
Management
Avoid the combination. Alternative antipsychotics without CYP2D6 dependence: olanzapine or aripiprazole. Alternative antidepressants without CYP2D6 inhibition: sertraline or escitalopram.
Check the full regimen, not just this pair
Opens the checker with these two drugs prefilled. Add the rest of the regimen and recompute additive risks.