Major
Fluoxetine × venlafaxine
Selective serotonin reuptake inhibitors×SNRI (serotonin-norepinephrine reuptake inhibitor)
Mechanism
SSRI + SNRI – serotonin syndrome. Fluoxetine is also a potent CYP2D6 inhibitor and raises venlafaxine levels.
Symptoms
Serotonin syndrome: agitation, confusion, tremor, myoclonus, hyperreflexia. Autonomic features: sweating, tachycardia, fever.
Management
The combination is not prescribed. When switching from fluoxetine to venlafaxine, allow at least 5 weeks of washout (due to norfluoxetine). From venlafaxine 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.