Major
Sertraline × Tramadol
Selective serotonin reuptake inhibitors (SSRIs)×Other opioids
Mechanism
Sertraline (SSRI) raises synaptic serotonin; tramadol blocks serotonin and norepinephrine reuptake. Combined action amplifies serotonergic transmission. Sertraline also blocks CYP2D6 (less than fluoxetine) – the tramadol activation route.
Symptoms
Serotonin syndrome: agitation, confusion, tremor, myoclonus, hyperreflexia, dilated pupils. Autonomic features: sweating, tachycardia, hypertension, fever. First signs appear within hours of co-administration.
Management
Avoid the combination. For analgesia on sertraline, use paracetamol, an NSAID, or morphine/oxycodone. For chronic analgesic needs, gabapentin or pregabalin for neuropathic pain.
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.