Major
Amitriptyline × fluvoxamine
Tricyclic antidepressants (TCA)×SSRI
Mechanism
Fluvoxamine blocks CYP1A2 and CYP2C19 – the main amitriptyline demethylation routes. TCA plasma levels rise 2- to 4-fold. Plus serotonin syndrome risk.
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. Alternative antidepressants if fluvoxamine fails: sertraline or escitalopram (no CYP1A2 effect). For neuropathic pain, replace amitriptyline with gabapentin or pregabalin.
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.