MajorTricyclic antidepressants (TCA)×Selective serotonin reuptake inhibitors (SSRIs)
Updated · Methodology
Mechanism
Dual risk. Sertraline blocks CYP2D6 – the amitriptyline metabolic route – and amitriptyline plasma levels rise 2- to 4-fold. Both drugs are also serotonergic.
Symptoms
Serotonin syndrome (agitation, tremor, tachycardia). Amitriptyline anticholinergic effects (dry mouth, constipation, confusion in older patients). QT prolongation.
Management
If combined for augmentation, halve amitriptyline and check ECG at 2 weeks. Alternative: mirtazapine or agomelatine (no CYP2D6 dependence).
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.
Summary of a multi-drug list →
Medicine list: everything you take in one place →
Sources
- FDA: Amitriptyline HCl tablets prescribing information (2014)– ; DailyMed setid 4e520c63-1cf6-40f6-a51c-3f9b0e181342
- FDA: Zoloft (sertraline) drug interactions section (2017)– ; DailyMed setid fda754f6-d0f3-4dce-a17a-927d64f912f7
- AEMPS: Ficha técnica: Amitriptilina (nº registro 89862), sección 4.5 (2026)– AEMPS, CIMA, nº registro 89862, revisión 05/2026, sección 4.5
- AEMPS: Ficha técnica: Sertralina (nº registro 66057), sección 4.4 (2025)– AEMPS, CIMA, nº registro 66057, revisión 08/2025, sección 4.4