Major
Amitriptyline × Escitalopram
Tricyclic antidepressants (TCA)×Selective serotonin reuptake inhibitors (SSRIs)
Mechanism
Both drugs raise serotonergic transmission and prolong QT. Combined action carries serotonin syndrome and torsades de pointes risks. Escitalopram weakly blocks CYP2D6 and amitriptyline levels rise modestly.
Symptoms
Serotonin syndrome (agitation, tremor, tachycardia). QT prolongation on ECG. Amitriptyline anticholinergic effects (dry mouth, constipation, confusion in older patients).
Management
Avoid the combination. Alternative antidepressants if escitalopram fails: mirtazapine or agomelatine. If amitriptyline fails for neuropathic pain: 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.