Abstracts

Rationale: Elderly age group has the highest incidence of new onset seizures. This group also has a different pharmacokinetics and pharmacodynamics, making it difficult to extrapolate data from the adult antiepileptic drug (AED) clinical studies. Specifically, head to head efficacy and tolerability data on newer anti-epilepsy drugs in this population is needed. Most of the clinical trials have involved comparison with carbamazepine (CBZ) which is not an ideal AED in this population given long-term side effects and medication interaction. A 2013 International League Against Epilepsy (ILAE) evidence review of AEDs in elderly gave Level A recommendation to only Gabapentin (GBP) and Lamotrigine (LTG). Since then, clinical trials have shown comparable efficacy and better tolerability of Levetiracetam (LEV) and Lacosamide (LCS) versus CBZ. In another study, LEV had similar efficacy and tolerability to LTG. Given the paucity of clinical trials in this age group, we aimed to conduct a network meta-analysis to evaluate the tolerability and efficacy of mixed treatments for the treatment of newly diagnosed epilepsy in the elderly. This type of analysis would allow comparison of two AEDs that have not been studied against each other directly.  Methods: We searched PubMed and Cochrane databases to identify randomized, double-blind, controlled trials conducted between 2000 and 2016, that compared anti-epileptic drugs (AEDs) in elderly patients with epilepsy. Study outcomes included retention rate (a measure of both efficacy and tolerability), and seizure freedom at 6 months. Heterogeneity across enrolled studies was assessed using Cochran Q and I2 statistics. A network meta-analysis was conducted using a frequentist method in R software to combine both direct and indirect evidence. Random- or fixed-effect models were used to combine evidence according to the degree of heterogeneity.  Results: We included 7 relevant trials comparing 6 AEDs – CBZ, GBP, LCS, LEV, LTG, and VPA (Valproic Acid). Data were analyzed for 1763 elderly patients with newly diagnosed epilepsy, of whom, 632 were treated with CBZ, 548 with LTG, 274 with LEV, 195 with GBP, 62 with LCS and 52 with VPA. Results from our network meta-analysis indicated that with CBZ as the reference, LEV (Odds ratio, OR: 2.58, Confidence Interval, CI: 1.77-3.71), GBP (OR: 1.69, CI: 1.17-2.45), LTG (OR: 2.33, CI: 1.80-3.02) and VPA (OR: 2.42, CI: 1.13-5.22) had a better result with respect to completion of the study at 6 months. No statistically significant difference was observed amongst the rest of AEDs with respect to retention rates. As compared to CBZ, seizure freedom at 6 months was higher with LEV (OR: 1.68, CI: 1.18-2.40) and LTG (OR: 1.35, CI: 1.03-1.75), but no significant difference was observed amongst the rest of AEDs with respect to seizure freedom. Conclusions: Prior controlled trials have shown better tolerability and comparable efficacy of CBZ, LEV, LTG, LCS and GBP in the elderly. Based on our network meta-analysis, CBZ has both a low tolerability and efficacy when compared with LEV, LTG, VPA, and GBP in this population. Also, compared to CBZ, LEV and LTG may lead to more seizure freedom at 6 months in this population.Limitations of the study include only a 6-month duration for analysis, a variable definition of elderly in different trials (60 versus 65 years of age), different dosages of AEDs in different studies, and a low number of patients in VPA and LCS group.LEV and LTG are better than CBZ in both efficacy and tolerability at 6 months in elderly with seizures. Further controlled head to head trials are required to confirm these findings.   Funding: None