Outcomes of Sustained-Release Formulation of Valproate and Topiramate Monotherapy in Patients with Epilepsy: A Multi-Centre, Cohort Study

Abstract

BackgroundNew-generation antiepileptic drugs (AEDs) tend to replace traditional AEDs as the first-line choice for epilepsy. However, whether this change results in better outcome, especially in China, remains unknown.Methodology/Principal FindingsTwo broad spectrum AEDs, the traditional drug of sustained-release formulation of valproate (SRVPA) and the new-generation drug of topiramate, were compared in patients with epilepsy as monotherapy in this multi-centre, observational cohort study from 2000 to 2011. The primary outcome was time to treatment failure. The secondary outcomes included time to first seizure, time to 12-month remission, and time to 24-month remission. Drug tolerability was assessed. Cox proportional hazard models (95% confidence interval [CI]) were used to analyse the relative risks expressed as hazard ratios (HR).Of the 1008 recruited patients, 519 received SRVPA and 489 received topiramate. SRVPA was better than topiramate (28.3% vs. 41.5%; HR = 0.62, [95% CI 0.49–0.77]; p<0.0001) in primary outcome, and in time to first seizure (56.1% vs. 69.3%; HR = 0.73, [95% CI 0.62–0.86]; p = 0.0002). No significant difference was observed between two groups in time to 12-month remission (52.6% vs. 42.5%; HR = 1.01, [95% CI 0.84–1.23]; p = 0.88) and time to 24-month remission (34.7% vs. 25.2%; HR = 1.11, [95% CI 0.88–1.42]; p = 0.38). 36 patients (6.9%) in SRVPA group and 37 patients (7.6%) in topiramate group presented treatment failure associated with intolerable adverse events, there was no significant difference between the two groups (p = 0.70).ConclusionsThe SRVPA is more suitable than topiramate for Chinese epileptic patients, and our results support the viewpoint that traditional AEDs should be the first-line choice for epilepsy rather than new-generation AEDs.

Substitution has better efficacy than add-on therapy for patients with focal epilepsy after their first antiepileptic drug treatments fail

“…The proportion of patients whose treatments failed due to lack of efficacy to those their treatments failed due to adverse effect was 4.5:1. This is consistent with a multi-center long-term retrospective study in China [23]. Along with the increase of treatment methods, the incidence of intolerant adverse effect had a downturn trend.…”

“…Real-world evidence can supplement the content of RCT and has the most promising effectiveness among different treatment strategies [21]. More and more researchers propose that well-designed long-term clinical trials with head-to-head comparisons are required [22][23][24][25]. The American Academy of Neurology and International League Against Epilepsy Commission has recommended more meaningful long-term comparative trials representative of real-world clinical practices [26,27].…”

“…Seizure: European Journal of Epilepsy 64 (2019) [23][24][25][26][27][28] duration (HR 0.997 [95%CI: 0.996-0.999], p = 0.001), seizure frequency one year before medication (HR 0.587 [0.458-0.752], p = 0.000), and the maximal dose (PDD/DDD ratio) (HR1 0.831 [1.074-3.120], p = 0.026). Unbalanced factors, including age of initial drug use, history of taking AED irregularly, and the longest preintervention interseizure interval, were adjusted.…”

Interference of TRPV1 function altered the susceptibility of PTZ-induced seizures

“…Epilepsy is characterized by the imbalance between excitation and inhibition of central nervous system (CNS) (Engel, 1996 ; Stafstrom, 2003 ), affecting 1–3% of the worldwide population (Bhalla et al, 2012 ). Current prescribed anti-epileptic drugs (AED) are not effective in all individuals with epilepsy (Fu et al, 2009 ; Hu et al, 2012 ), thus it is necessary to find novel therapeutic targets for epilepsy. Previous studies have showed that ion channels play pivotal roles in epilepsy, and most of them have focused on the selective ion channels such as sodium and potassium channels (Armijo et al, 2005 ; Lerche et al, 2013 ).…”

Piperine exerts anti-seizure effects via the TRPV1 receptor in mice

“…Anti-epileptic drugs provide control of seizures in most patients with epilepsy. Nonetheless, current anti-epileptic drugs are only effective in 60-70% of individuals and many drugs can produce numerous unwanted side effects in patients (Hu et al, 2012). For these reasons, novel drugs to treat epilepsy are highly necessary.…”