Are anti-epileptic drugs associated with immune dysfunction? A large data-linkage nested case-control study

<h3>Background</h3> Some anti-epileptic drugs (AEDs) have been associated with immune dysfunction. We aimed to investigate whether AEDs were associated with increased risk of: (1) leukopenia; (2) infection. <h3>Methods</h3> Routinely-collected healthcare datasets from North-East Scotland (2009–2021) for GP prescribing, haematology laboratories, and hospital discharge coding were linked in the Grampian Data Safe Haven. Each case (individual prescribed AEDs) was matched to four controls (without AED prescription) with the same sex, age (+/- 1 year) and Charlson Comorbidity Index. We used logistic regression adjusted for matching variables to assess association between specific AEDs and number of antibiotic prescriptions; and between any AED and hospital infection episodes. <h3>Results</h3> We linked data on 32480 cases (on any AED) and 129920 controls. Carbamazepine, lamotrigine and valproate were associated with neutropenia (OR[95%CI]: 4.12[3.47–4.9], 4.72[3.83–5.81], 5.07[4.32–5.96], respectively) and lymphopenia (2.75[2.48–3.05], 2.85[2.51- 3.23], 2.27[2.04–2.52], respectively). AEDs were associated linearly with more antibiotic prescriptions per year, with valproate having the strongest association (&gt;4 vs 0 antibiotics/year OR[95%CI]: 2.18[1.88–2.53]). AED use was associated with more frequent hospital infection episodes (2.11[2.01–2.2]). <h3>Conclusion</h3> AEDs are associated with leukopenia and higher infection risk. Further work should clarify causation, but the role of AEDs should be considered in those with frequent or unusual infections.