Major
citalopram × Fluoxetine
SSRI (selective serotonin reuptake inhibitor)×Selective serotonin reuptake inhibitors
Mechanism
Two SSRIs simultaneously. Fluoxetine is a potent CYP2D6 inhibitor and weak CYP2C19 inhibitor, so citalopram levels may rise. Additive serotonin syndrome and QT prolongation risk.
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 citalopram, allow at least 5 weeks of washout (due to norfluoxetine). From citalopram to fluoxetine, 2 weeks suffice.