The effect of anti‐seizure medications on exposure to statins: A systematic review and meta‐analysis

Objectives Antiseizure medications (ASMs) can reduce the efficacy of statin treatment, partly due to reduction in statin concentrations. In this systematic review and network meta‐analysis (NMA), we compared the effects of ASMs and the prototypical enzyme inducer rifampin on statin exposure. Methods The study was registered in PROSPERO (CRD42024622109) and followed the PRISMA 2015/2020 guidelines. Searches through January 19, 2026, were conducted in MEDLINE, EMBASE, the Cochrane Library, and the FDA database. We included prospective studies in which ASMs or rifampin were administered for ≥ 5 days. The primary endpoint was the area under the concentration‐time curve ratio (AUCR) of the statin with/without the perpetrator. Perpetrator‐statin combinations were compared pairwise using the standardized mean difference (SMD). The PKclin tool was used for assessing the bias risk. Results The NMA included six studies with 236 participants, of which four (206 participants) assessed four ASMs. The AUCR of simvastatin after exposure to 800 mg/day eslicarbazepine (mean 0.460; 90% confidence interval, 0.378–0.561) was comparable to those of the combinations 200–400 mg/day phenytoin–atorvastatin (0.463; 0.385–0.556), 600 mg/day carbamazepine–pravastatin (0.382; 0.321–0.455) or –rosuvastatin (0.388; 0.353–0.427), and 600 mg/day rifampin–rosuvastatin (0.371; 0.317–0.435), but lower than with 1200 mg/day eslicarbazepine–rosuvastatin (0.630; 0.571–0.694). Similarly, in the NMA, the effect of 800 mg/day eslicarbazepine on simvastatin did not differ from those of rifampin on pravastatin/rosuvastatin (SMD 0.08, confidence interval, −0.03 to 0.19) or phenytoin on atorvastatin (0.00; −0.14 to 0.14). Significance Despite the limited number of studies and methodological variation, our analysis demonstrates that all statins can be considerably affected by strong enzyme‐inducing ASMs. The effects of ASMs with moderate enzyme‐inducing activity on simvastatin, lovastatin, and atorvastatin are comparable to those of strong inducers on pravastatin or rosuvastatin. Careful selection of ASM‐statin combinations with appropriate monitoring can improve patient outcomes, and co‐medication reporting in clinical trials can help interpretation.