The efficacy and safety of rufinamide in drug-resistant epilepsy: A meta-analysis of double-blind, randomized, placebo controlled trials

Objective: To evaluate the clinical efficacy and safety of rufinamide in drug-resistant epilepsy.

Methods: We searched PubMed, Web of Science and Clinical trial.org up to August 6, 2015. Study selection, extraction and risk of bias assessment were performed independently by two authors. A random or fixed-effect model was used to derive pooled effects risk ratios (RRs) and 95% confidence intervals (CIs).

Results: Five randomized controlled trials were included in the final analysis with a total of 1512 patients. Rufinamide increased the 50% (RR 1.852, 95%CI 1.446-2.372, P<0.001) and 75% (RR 8.547, 95%CI 2.534-28.832, P<0.001) responder rates but not the seizure-free rate (RR 1.740, 95%CI 0.511-5.924, P=0.376) compared to placebo. Subgroup analysis demonstrated that the effect of rufinamide may be dose-dependent and related to seizure type. Regarding safety, rufinamide increased the rate of at least one adverse event (RR 1.103, 95%CI 1.047-1.161, P<0.001) and the withdrawal rate due to adverse events (RR 2.341, 95%CI 1.556-3.522, P<0.001), but it did not increase the rate of severe adverse events (RR 1.454, 95%CI 0.945-2.241, P=0.090). Individual adverse events (headache, dizziness, fatigue, somnolence, nausea, diplopia and vomiting) were significantly higher in the rufinamide group.

Conclusions: This study confirmed significant effects of rufinamide as adjunctive treatment for drug-resistant seizures, both partial and tonic-atonic. However, rufinamide may induce more tolerable (but not severe) adverse events. Further large clinical trials to investigate the long-term efficacy and safety of rufinamide are warranted.