Zhu LN, et al. – The clinicians compared the efficacy and tolerability of newer antiepileptic drugs (AEDs), like Eslicarbazepine (ESL), Lacosamide (LAC), Perampanel (PER) and Brivaracetam (BRV) with Levetiracetam (LEV) when used as add–on treatments for uncontrolled focal epilepsy. They proposed that in efficacy, ESL, LAC, and BRV were not inferior to LEV. At a high dose, ESL, LAC, and PER could have a possible worse tolerability profile compared to LEV, however, BRV possibly exhibited a similar tolerability to LEV. Newer AEDs could not exceed the LEV on efficacy and tolerability.

• For all available randomized controlled trials (RCTs) investigating the therapeutic effects of newer AEDs or LEV vs placebo, the clinicians performed an online database search on PubMed, Embase, Cochrane Online Library and Clinicaltrials.gov.
• Then, they performed indirect comparisons for clinical efficacy and tolerability at different doses between the newer AEDs and LEV using Indirect Treatment Comparison (ITC) software.

• The clinicians included 24 RCTs with a total of 8540 patients.
• At all dose level, ESL, LAC, and BRV did not show significant difference in efficacy compared to LEV.
• At the highest effective recommended dosages, PER demonstrated lower 50% response rates and seizure-free rates.
• Compared to LEV, treatment-emergent adverse events (TEAEs) and withdrawal rates because of adverse events (AEs) of LAC and PER were higher at the highest effective recommended dosages, and overall AE rates from ESL were higher than LEV.