Modafinil and SSRIs (General): Interaction Overview
Modafinil induces CYP3A4 and CYP2C19 liver enzymes — the same enzymes that metabolize many SSRIs (citalopram, escitalopram, sertraline).
Mechanism of Interaction
Modafinil induces CYP3A4 and CYP2C19 liver enzymes — the same enzymes that metabolize many SSRIs (citalopram, escitalopram, sertraline). CYP2C19 induction by modafinil can increase the metabolic clearance of these SSRIs, potentially reducing their effective plasma concentration by 20–50%. This could reduce antidepressant efficacy over time. The interaction is pharmacokinetic, not pharmacodynamic, meaning no serotonin syndrome risk but potential loss of SSRI effectiveness.
Recommendation
Inform your prescribing psychiatrist if using modafinil regularly alongside SSRIs. They may need to adjust your SSRI dose. Do not self-adjust SSRI dosing. Monitor for return of depressive symptoms.
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