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Fluvoxamine augmentation increases serum mirtazapine concentrations three- to fourfold
A K Anttila1, L Rasanen, E V Leinonen
1Department of Psychiatry, Tampere University Hospital, Pitkäniemi, Finland. samia@koti.tpo.fi
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.
Insights
Fluvoxamine significantly increases mirtazapine levels, potentially causing adverse effects or mood changes. This drug interaction may require mirtazapine dosage adjustments for patient safety.
Area of Science:
- Pharmacology
- Clinical Pharmacy
Background:
- Mirtazapine is metabolized by cytochrome P450 isoenzymes CYP1A2, CYP2D6, and CYP3A4.
- Fluvoxamine is known to inhibit these isoenzymes.
Observation:
- A 17-year-old male experienced a threefold increase in mirtazapine concentration with added fluvoxamine, accompanied by increased anxiety.
- A 43-year-old female showed a fourfold increase in mirtazapine concentration with added fluvoxamine, alongside mood improvement.
Findings:
- This report details the first observed interaction between fluvoxamine and mirtazapine.
- Fluvoxamine likely causes clinically significant inhibition of mirtazapine metabolism.
Implications:
- Concurrent use of fluvoxamine and mirtazapine can lead to substantial increases in mirtazapine plasma concentrations.
- Clinicians should monitor patients for potential toxicity or altered therapeutic effects and consider mirtazapine dose adjustments when initiating or discontinuing fluvoxamine.