Antiepileptic drug monotherapy for epilepsy in the elderly: A systematic review and network meta‐analysis

Abstract

Objective: To estimate the comparative efficacy and safety of antiepileptic drugs (AEDs) in the elderly with new-onset epilepsy. Methods: We searched electronic databases for randomized controlled trials (RCTs) of monotherapy AEDs to treat epilepsy in elderly. The following outcomes were analyzed: seizure freedom and withdrawal from the study for any cause at 6 and 12 months; withdrawal from the study for any adverse event (AE) at 12 months; and occurrence of any AE at 12 months. Effect sizes were estimated by network metaanalyses within a frequentist framework. The hierarchy of competing interventions was established using the surface under the cumulative ranking curve (SUCRA) and mean ranks. Results: Five RCTs (1425 patients) were included. Included AEDs were carbamazepine immediate-and controlled-release (CBZ-IR, CBZ-CR), gabapentin (GBP), lacosamide (LCM), lamotrigine (LTG), levetiracetam (LEV), phenytoin (PHT), and valproic acid (VPA). At the pairwise and network meta-analyses, there were no differences in any of the comparison according to 6-and 12-month seizure freedom.The treatment with CBZ-IR and CBZ-CR was associated with a higher risk of withdrawal than LTG, LEV, or VPA, and CBZ-IR had the overall highest probability of discontinuation across all AEDs. According to SUCRA, the following had the greatest likelihood ranking best for seizure freedom at 6 and 12 months: LCM, LTG, and LEV. CBZ-CR and CBZ-IR had the highest probabilities of being worst for the 12-month retention. CBZ-IR, CBZ-CR, and GBP had the highest probabilities of withdrawal from the study for AEs, , and VPA had the highest probability of being the best-tolerated option. Significance: Although no significant difference in efficacy was found across treatments, LCM, LTG, and LEV had the highest probability of ranking best for achieving seizure freedom. CBZ-IR and CBZ-CR showed a poor tolerability profile, leading to higher withdrawal rates compared to LEV and VPA. K E Y W O R D Selderly, epilepsy, monotherapy, network meta-analysis, randomized-controlled trials 2246 | LATTANZI eT AL.

Pharmacotherapeutic considerations for late-onset epilepsy

“…Conversely, this meta-analysis confirmed that carbamazepine (especially the immediate-release formulation) was associated with a higher risk of discontinuation [15]. Similar results were found in a network meta-analysis of RCTs of ASMs used to treat post-stroke epilepsy: lamotrigine and levetiracetam were better tolerated than controlled-release carbamazepine, with no differences in seizure freedom between these three drugs (probably because of the small sample size) [16].…”

Evidence‐based anti‐seizure monotherapy in newly diagnosed epilepsy: A new approach

“…Carbamazepine was not recommended due to the risk of drug interactions with other concomitant treatments, and gabapentin was not recommended due to level A evidence derived from a single study with possible methodological flaws 25 . Instead, lamotrigine and levetiracetam became the first choice for the elderly in the updated Swedish MPA practice guidelines, concordant with a recently published systematic review that found high probability of seizure freedom for lamotrigine and levetiracetam, and a poor tolerability for carbamazepine, in the elderly with new onset epilepsy 26 …”

Current role of carbamazepine and oxcarbazepine in the management of epilepsy

“…A systematic review and network meta-analysis of AEDs in the elderly showed no significant difference in efficacy across treatments, but CBZ had a poor tolerability profile, leading to higher withdrawal rates compared with levetiracetam and valproate [113]. OXC, with its low potential for enzyme induction, appears to be safe to use in elderly patients with evidence indicating that its tolerability in this age group is similar to that of younger adult patients [111,114].…”