Major
fluvoxamine × venlafaxine
SSRI×SNRI (serotonin-norepinephrine reuptake inhibitor)
Mechanism
Fluvoxamine blocks CYP1A2 (a minor venlafaxine metabolic route). Venlafaxine plasma levels rise modestly. Plus additive serotonergic load.
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 antidepressants, allow a 1-week washout. Alternative for augmentation: mirtazapine or agomelatine.