Major
duloxetine × Tramadol
SNRI×Other opioids
Mechanism
Dual risk. Duloxetine (SNRI) raises synaptic serotonin and norepinephrine. Tramadol blocks serotonin and norepinephrine reuptake and lowers seizure threshold. Combined action amplifies serotonergic activity.
Symptoms
Serotonin syndrome: agitation, confusion, tremor, myoclonus, hyperreflexia. Autonomic features: sweating, tachycardia, hypertension, fever. First signs appear within hours of co-administration.
Management
Avoid the combination. For analgesia on duloxetine, use paracetamol, an NSAID, or morphine/oxycodone. For neuropathic pain, gabapentin or pregabalin.