Mirtazapine
Regulatory sources consulted
- openfda-label-cc15149e-2921-468f-a145-513b01885a81
- AEMPS CIMA FT 86890
- ANSM BDPM RCP 69084246
- PubMed PMID:36253442 ↗
- PubMed PMID:38301258 ↗
- PubMed PMID:34986373 ↗
- PubMed PMID:36401591 ↗
- CredibleMeds.org
- OpenFDA · N06AX11
- AEMPS CIMA · nº registro 86890 ↗
- ANSM BDPM · CIS 69084246 ↗
- RxNorm rxcui 15996 ↗
- PubMed PMID:38015216 ↗
Approved indications
- Treatment of major depressive disorder (MDD) in adults.
- Management of refractory hyperemesis gravidarum (off-label use). · off-label
- Management of psychostimulant (e.g., methamphetamine) withdrawal (off-label use). · off-label
Contraindications
Absolute
- Concomitant use with monoamine oxidase inhibitors (MAOIs) or within 14 days of discontinuing an MAOI.
- Known hypersensitivity to mirtazapine or any of its excipients.
Clinical warnings
- Boxed warning · Increased risk of suicidal thoughts and behaviors in pediatric and young adult patients. Not approved for pediatric use. — FDA
- Major warning · Agranulocytosis and severe neutropenia. Monitor for fever, sore throat, or other signs of infection and obtain a complete blood count if they occur. — FDA
- Major warning · Serotonin syndrome, especially when combined with other serotonergic drugs (MAOIs, SSRIs, triptans). — FDA
Drug interactions
- HighMAO Inhibitors (e.g., Phenelzine, Linezolid)N06AF
Mechanism: Increased risk of serotonin syndrome due to additive effects on serotonin.
Recommendation: Contraindicated. Do not use concomitantly or within 14 days of discontinuing the MAOI.
FDA label
- HighCarbamazepineN03AF01
Mechanism: Potent induction of CYP3A4, which increases mirtazapine metabolism and reduces its plasma concentrations by ~60%.
Recommendation: Consider increasing the mirtazapine dose. Monitor clinical response. When carbamazepine is discontinued, a reduction in mirtazapine dose may be necessary.
FDA labelANSM RCP
- HighKetoconazoleJ02AB02
Mechanism: Potent inhibition of CYP3A4, which decreases mirtazapine metabolism and increases its Cmax by ~40% and AUC by ~50%.
Recommendation: Consider reducing the mirtazapine dose. Monitor for clinical response and adverse effects. When ketoconazole is discontinued, an increase in mirtazapine dose may be necessary.
FDA labelANSM RCP
Adverse events
Common (≥1%)
somnolence · increased appetite · weight gain · dizziness · dry mouth
Rare but serious
agranulocytosis · bone marrow aplasia · serotonin syndrome · QT prolongation · Torsades de Pointes · Stevens-Johnson syndrome · hyponatremia · seizures
Pregnancy and lactation
FDA category: C (historical)
There are no adequate studies in pregnant women. Use during pregnancy only if the potential benefit justifies the potential risk to the fetus. Caution should be exercised when administered to a nursing woman as mirtazapine is excreted in human milk.
Recent literature (PubMed)
Revisión sistemática y metaanálisis en red de 34 estudios (n=9384) que evaluaron 20 antidepresivos en la fase de mantenimiento del TDM. Mirtazapina demostró ser superior al placebo en la prevención de recaídas a los 6 meses, confirmando su eficacia en el tratamiento a largo plazo.
Revisión sobre el manejo de la hiperemesis gravídica refractaria. Se menciona explícitamente a la mirtazapina como una farmacoterapia alternativa a considerar cuando los antieméticos típicos fallan, destacando un importante uso off-label.
Metaanálisis en red de 65 estudios (N=12,415) sobre estrategias de aumento en la depresión resistente al tratamiento. Se encontró que la mirtazapina como agente de aumento tenía tasas de discontinuación significativamente más altas en comparación con el placebo, lo que sugiere problemas de tolerabilidad en este contexto.
Revisión de la evidencia para el manejo clínico de la abstinencia a psicoestimulantes. Se señala la eficacia potencial de la mirtazapina para la abstinencia de metanfetamina en las fases aguda y protraída, sugiriendo un posible uso off-label en adicciones.