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.