Major
Escitalopram × Sertraline
Selective serotonin reuptake inhibitors (SSRIs)×Selective serotonin reuptake inhibitors (SSRIs)
Mechanism
Two SSRIs simultaneously raise synaptic serotonin activity. Without added clinical benefit, additive effect raises serotonin syndrome, hyponatraemia, and GI bleeding risks.
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. If one SSRI is ineffective, switch to another after a 2-week washout (or 5 weeks after fluoxetine). In severe depression, monotherapy plus mirtazapine or psychotherapy.