fluvoxamine × Mirtazapine

Serotonergic load from combining two drugs with different mechanisms. Fluvoxamine also blocks CYP1A2 (a minor mirtazapine metabolic route); mirtazapine levels may rise.

Serotonin syndrome: agitation, confusion, tremor, myoclonus, hyperreflexia. Autonomic features: sweating, tachycardia, fever.

The combination is used for augmentation in resistant depression ('California rocket fuel'). Keep doses low: mirtazapine 15–30 mg, fluvoxamine 100 mg/day. Monitor mental status in the early weeks.