MajorOther antidepressants (NaSSA)×Other opioids
Updated · Methodology
Mechanism
Tramadol is a serotonergic opioid; mirtazapine raises serotonergic transmission via α2-blockade. Additive serotonin syndrome risk.
Symptoms
Serotonin syndrome: agitation, confusion, tremor, myoclonus, hyperreflexia. Autonomic features: sweating, tachycardia, fever.
Management
If a patient taking mirtazapine needs tramadol, start with a low dose and keep the course short. Mirtazapine increases the sedative effect of opioids (mirtazapine SmPC), and the tramadol SmPC requires the lowest effective dose and shortest duration with CNS depressants. At the start and after each dose increase, watch for signs of serotonin syndrome and excessive drowsiness. Stop tramadol if serotonin syndrome is suspected. Both drugs lower the seizure threshold. In epilepsy, use tramadol only when it cannot be avoided; it is contraindicated in uncontrolled epilepsy (tramadol SmPC).
Check the full regimen, not just this pair
Opens the checker with these two drugs prefilled. Add the rest of the regimen and recompute additive risks.
Summary of a multi-drug list →
Medicine list: everything you take in one place →
Sources
- FDA: Tramadol hydrochloride tablets prescribing information (Amneal) (2026)– FDA label, DailyMed setid 8ec4e4e5-a56e-4198-8428-6b770b9bf27d, sections 5.9, 5.10, 7
- FDA: Remeron/RemeronSolTab (mirtazapine) prescribing information (2025)– FDA, DailyMed, Remeron/RemeronSolTab, Organon LLC, setid 98ad1917-a094-44f5-a28f-a64a8cfcd887, revisión 08/2025, secciones 4, 5.3 y 7
- AEMPS: Ficha técnica de Adolonta Retard 100 mg comprimidos de liberación prolongada (tramadol) (2025)– AEMPS CIMA, nregistro 61784, secciones 4.3, 4.4, 4.5
- AEMPS: Ficha técnica de Mirtazapina Cinfa 15 mg comprimidos (2021)– AEMPS CIMA, nregistro 86890, secciones 4.4, 4.5