MajorSelective serotonin reuptake inhibitors×Selective serotonin reuptake inhibitors (SSRIs)
Updated · Methodology
Mechanism
These are two SSRIs, so serotonergic load doubles with no proven therapeutic gain. The sertraline label bars combining it with other serotonergic agents such as moclobemide precisely because of serotonin syndrome risk. A pharmacokinetic issue is added: fluoxetine inhibits CYP2D6 and its active metabolite persists for weeks, so the overlap continues long after the last capsule.
Symptoms
Agitation, tremor, sweating, dilated pupils, diarrhoea, tachycardia, muscle rigidity and fever: serotonin syndrome develops within hours. Mild forms are mistaken for anxiety or flu. At high doses QT prolongation adds to the risk.
Management
The two SSRIs are not taken together. Switching from fluoxetine to sertraline needs a washout because of the long half-life of the active metabolite; the reverse switch allows shorter gaps. If tremor, sweating and tachycardia appear after the second drug is added, stop the addition.
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
- AEMPS: Ficha técnica Sertralina Cinfa 100 mg comprimidos recubiertos con película EFG (2025)– AEMPS, CIMA, nº registro 66058, sección 4.5
- AEMPS: Ficha técnica Fluoxetina Cinfa 20 mg cápsulas duras EFG (2025)– AEMPS, CIMA, nº registro 63499, sección 4.5