Major
Escitalopram × Fluoxetine
Selective serotonin reuptake inhibitors (SSRIs)×Selective serotonin reuptake inhibitors
Mechanism
Two SSRIs simultaneously raise synaptic serotonin activity. Fluoxetine's active metabolite (norfluoxetine) persists in plasma for up to 5 weeks, so serotonin syndrome risk outlasts fluoxetine discontinuation.
Symptoms
Serotonin syndrome: agitation, confusion, tremor, myoclonus, hyperreflexia, dilated pupils. 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 escitalopram, allow at least a 5-week washout. From escitalopram to fluoxetine, 2 weeks suffice.