Fluvoxamine Augmentation Increases Serum Mirtazapine Concentrations Three- to Fourfold

OBJECTIVE: To report two cases of interaction between fluvoxamine and mirtazapine. CASE SUMMARY: A 17-year-old boy was treated with mirtazapine 30 mg/d. The addition of fluvoxamine 100 mg/d to the regimen caused a threefold increase in the mirtazapine concentration. This interaction was associated with increased anxiety. A second patient, a 43-year-old woman, was treated with mirtazapine 15 mg/d. There was a fourfold increase in her mirtazapine concentration and simultaneous mood improvements after augmentation with fluvoxamine 50 mg/d. DISCUSSION: This is the first report of any interaction between fluvoxamine and mirtazapine. Mirtazapine is mainly metabolized by cytochrome P450 isoenzymes CYP1A2, CYP2D6, and CYP3A4. Fluvoxamine and cimetidine Inhibit the same isoenzymes, but fluvoxamine is probably the only agent that causes a clinically significant interaction. CONCLUSIONS: Adding fluvoxamine to treatment with mirtazapine may cause a significant increase in mirtazapine concentration. This interaction may necessitate adjustment of the mirtazapine dosage.