Major
duloxetine × Fluoxetine
SNRI×Selective serotonin reuptake inhibitors
Mechanism
Fluoxetine is a potent CYP2D6 inhibitor; duloxetine is minorly metabolised by CYP2D6. Additive serotonergic load with dual SSRI/SNRI dosing.
Symptoms
Serotonin syndrome: agitation, confusion, tremor, myoclonus, hyperreflexia. Autonomic features: sweating, tachycardia, hypertension, fever. First signs appear within hours of co-administration.
Management
The combination is not prescribed. When switching from fluoxetine to duloxetine, allow a 5-week washout (due to norfluoxetine); from duloxetine to fluoxetine, 1 week.
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.