MajorOther antidepressants (NDRI)×Selective serotonin reuptake inhibitors
Updated · Methodology
Mechanism
Bupropion and its metabolite hydroxybupropion inhibit CYP2D6, which metabolises fluoxetine, so fluoxetine exposure can rise. Bupropion itself is not a CYP2D6 substrate: hydroxybupropion is formed by CYP2B6. Both drugs lower the seizure threshold, and together they can cause serotonin syndrome.
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 used to augment antidepressant response, but bupropion is contraindicated in patients with a seizure history, bulimia or anorexia nervosa per the label. Start bupropion at a low dose and titrate gradually. Start fluoxetine at the low end of its dose range when bupropion is already on board, and if bupropion is added to fluoxetine, consider reducing the fluoxetine dose. When bupropion is prescribed for smoking cessation in a patient taking an antidepressant, the label advises a maximum of 150 mg a day. Watch for agitation, tremor, myoclonus and fever during the first weeks and after dose increases.
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.
Summary of a multi-drug list →
Medicine list: everything you take in one place →
Sources
- FDA: Wellbutrin (bupropion hydrochloride) prescribing information (2017)– ; DailyMed setid cbc8c074-f080-4489-a5ae-207b5fadeba3
- AEMPS: Ficha técnica Zyntabac 150 mg comprimidos de liberación prolongada (bupropión) (2024)– AEMPS, CIMA, nº registro 63265, revisión 03/2024, sección 4.4
- AEMPS: Ficha técnica Elontril 150 mg comprimidos de liberación modificada (bupropión) (2024)– AEMPS, CIMA, nº registro 68615, revisión 06/2024, secciones 4.3, 4.4 y 4.5
- FDA: Wellbutrin XL (bupropion hydrochloride extended-release) – Prescribing Information (2026)– FDA, DailyMed SPL, Bausch Health US, разделы 7.2, 7.3 и 12.3
- AEMPS: Ficha técnica Prozac 20 mg cápsulas duras (fluoxetina) (2020)– AEMPS, CIMA, nº registro 57954, revisión 12/2020, sección 4.5