Major
duloxetine × Mirtazapine
SNRI×Other antidepressants (NaSSA)
Mechanism
Mirtazapine + SNRI – augmentation in resistant depression ('California rocket fuel'). Serotonin syndrome is rare but possible at high doses.
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 possible for augmentation. Keep doses low: mirtazapine 15–30 mg, duloxetine 30–60 mg/day. Monitor blood pressure, pulse, and mental status in the early weeks.