The efficacy and safety of retigabine and other adjunctive treatments for refractory partial epilepsy: a systematic review and indirect comparison.

Retigabine (RTG) is now approved in Europe and the US for the adjunctive treatment of partial-onset seizures in adults with epilepsy. To support submissions to EU reimbursement authorities, we explored its efficacy and tolerability relative to selected antiepileptic drugs (AEDs). A systematic review was conducted to identify placebo-controlled trials of RTG and selected AEDs approved for use in a similar position in the management pathway of partial epilepsy (eslicarbazepine acetate [ESL], lacosamide [LCM], pregabalin [PGB], tiagabine [TGB] and zonisamide [ZNS]). Using conventional and network meta-analyses as appropriate, we report efficacy and tolerability outcomes for each AED versus placebo and the performance of RTG relative to other AEDs. Twenty studies met the inclusion criteria: three each for RTG, ESL, LCM, TGB and ZNS; five for PGB. Comparisons comprised 1-5 studies per AED. In the network meta-analysis, RTG was not found to be different from the other AEDs for responder rate (maintenance period), seizure freedom (maintenance period and double-blind period), withdrawals due to adverse events, and incidences of ataxia, dizziness, fatigue and nausea. Differences between RTG and other AEDs were found for a few comparisons, which did not reveal any trends: RTG was associated with a lower responder rate than PGB during the double-blind period, higher withdrawal rate due to any reason than ESL and a higher incidence of somnolence than TGB. Findings suggest that the risk/benefit for RTG is similar to that for comparator AEDs. However, results should be interpreted in the context of the limitations of the analyses.