Major
Mirtazapine × Tramadol
Other antidepressants (NaSSA)×Other opioids
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
Avoid the combination. For analgesia on mirtazapine, use paracetamol, an NSAID, or morphine/oxycodone. For neuropathic pain, gabapentin or pregabalin.