Levetiracetam is usually the drug we reach for precisely because we assume it doesn’t interact with anything. That assumption is what this study puts under pressure.
Kai Michael Schubert led a target trial emulation using routine data from 165 healthcare organisations, comparing antiseizure medications in 9,529 adults with epilepsy who were also on a DOAC. Against lamotrigine or lacosamide, levetiracetam was associated with roughly double the risk of thromboembolic events (stroke, heart attack, other clots) and about a 60% higher risk of death. Strong enzyme inducers looked worse for clots too, although with less bleeding.
Put it all together and, if everyone had been on lamotrigine or lacosamide, something like 28% of the thromboembolic events in this group might have been avoided.
This is observational work, so it shows association rather than cause, and nobody should change their medication without speaking to their doctor. But it is a signal that deserves a proper look, because “levetiracetam doesn’t interact” is baked deeply into how we all prescribe.
Big congratulations to Michael, and thanks to the international team across Zurich, Liverpool, UCL, Gothenburg, Bern, Bolzano, Salzburg, Yale, and Catanzaro who made this possible. 🎉
Read the paper in JAMA Neurology: https://doi.org/10.1001/jamaneurol.2026.2712