Major
Bupropion × Fluoxetine
Other antidepressants (NDRI)×Selective serotonin reuptake inhibitors
Mechanism
Fluoxetine is a potent CYP2D6 inhibitor. Levels of bupropion's active metabolite (hydroxybupropion) rise. Both drugs lower the seizure threshold.
Symptoms
Seizures (generalised tonic-clonic or focal), agitation, tremor, insomnia. Patients with prior epilepsy or eating disorders are at particular risk.
Management
The combination is possible for augmentation with careful monitoring. Keep doses low: fluoxetine 20 mg, bupropion 300 mg/day. Avoid with prior epilepsy or eating disorders.