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Review
. 2022 Dec;7(4):556-569.
doi: 10.1002/epi4.12644. Epub 2022 Aug 30.

Anti-seizure efficacy and retention rate of carbamazepine is highly variable in randomized controlled trials: A meta-analysis

Karmele Olaciregui-Dague  1 , Leonie Weinhold  2 , Christian Hoppe  1 , Matthias Schmid  2 , Rainer Surges  1
Affiliations
Review

Anti-seizure efficacy and retention rate of carbamazepine is highly variable in randomized controlled trials: A meta-analysis

Karmele Olaciregui-Dague et al. Epilepsia Open. 2022 Dec.

Abstract

We sought to assess the anti-seizure efficacy of carbamazepine (CBZ) and retention rate (RR) in randomized, controlled trials (RCTs) in epilepsy. Our analysis was carried out according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Inclusion criteria were monotherapy of CBZ in adequate dosage for epilepsy treatment and RCT duration of ≥3 months. Outcome measures were seizure freedom rate (SFR) and RR. Random-effects meta-analyses were performed to allow for comparison with other anti-seizure medications (ASMs). Thirty RCTs of 734 were included. SFR at last follow-up ranged from 11% at 36 months to 85% at 3 months. The aggregated SFR at 6 months was 58% (CI 49-66%) and 48% (CI 40-57%) at 12 months. The 6-month SFR among blinded studies was 55% (CI 43-66%), compared with 61% (CI 50-71%) in unblinded studies. The 12-month SFR was not significantly linked to the age of study participants. RR varied from 36% at 24 months to 81% at 6 months. When adjusting for blinding, the aggregated 6-month RR in blinded studies was 59% (CI 52-66%) vs 76% (CI 71-81%) in unblinded studies. The point estimates of SFR of all RCTs showed an upward time trend, with an increase of approximately 15% between the years 1981 and 2018. In conclusion, the SFR and RR of CBZ were highly variable in RCTs and especially affected by study duration and blinding. These results underscore the impact of the design of RCTs investigating ASM and may challenge the wide use of CBZ as a comparator.

Keywords: antiepileptic drug; antiseizure medication; clinical trial; focal epilepsy; monotherapy; study design.

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Conflict of interest statement

KOD has received speaker fees from Eisai, unrelated to this work. RS has received fees as speaker or for serving on the advisory board from Angelini, Arvelle, Bial, Desitin, Eisai, Janssen‐Cilag GmbH, LivaNova, Novartis, Precisis GmbH, UCB Pharma, UnEEG and Zogenix. These activities were not related to the content of this manuscript. C. Hoppe received software license fees and honoraria from Eisai Inc. unrelated to this work. The remaining authors have no conflicts of interest.

Figures

FIGURE 1
FIGURE 1
Flow diagram (adapted from PRISMA guidelines 25 )
FIGURE 2
FIGURE 2
Distribution of included RCTs by RR and publication year, including trend line A, and distribution of included RCTs by SFR and publication year, including trend line B
FIGURE 3
FIGURE 3
Risk of bias, summarized as RoB 2.0 assessment of all included RCTs
FIGURE 4
FIGURE 4
Distribution of reported SFR across included RCTs. Studies that reported 12‐month SFR are printed bold. The studies from de Silva et al. (1996) and Marson et al. (2007) reported 12‐month SFR and SFR at additional time points (36 and 24 months, respectively),
FIGURE 5
FIGURE 5
Distribution of reported RR in included RCTs
See this image and copyright information in PMC

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