A comparative study on the efficacy of different combinational anti-seizure medication therapies following valproate monotherapy failure

Effects of treatment with clinically relevant valproate, carbamazepine, oxcarbazepine, topiramate, lamotrigine and levetiracetam on ovarian folliculogenesis in young rats

ObjectiveTo compare medication adherence and healthcare utilization among patients who were treated with anti-seizure medications (ASMs) as first add-on to monotherapy for epilepsy using the national health insurance claims data. MethodsA retrospective observational cohort study was conducted using the Korean National Health Insurance claims data. Patients who received ASM as first add-on to monotherapy during January 2017 to February 2018 were included. The selected patients were followed up for 12 months to evaluate persistence, adherence, and healthcare resource utilization. ResultsIn total, 4277 patients who received ASM as first add-on to monotherapy for epilepsy were enrolled. The mean treatment duration of add-on ASM was 296.6 ± 108.6 days during the 1-year follow-up period and 64.3% of the total population were persistent on the add-on ASM at 365 days from the index date. The mean medication possession ratio (MPR) was 90.3 ± 23.7 and the proportion of adherent patients with ≥80% MPR was 79.3%. Lamotrigine (LTG), levetiracetam (LEV), oxcarbazepine (OXC), and perampanel (PER) groups showed significantly higher persistence and adherence than carbamazepine (CBZ), topiramate (TPM), and valproate (VAL) groups during the 1-year follow-up period. Significant differences in length of stays, total hospitalization cost, outpatient visit cost, and emergency cost were shown between ASM groups and LTG, LEV, OXC, and PER showed relatively low utilization and cost. ConclusionsBetter adherence was observed in LTG, LEV, OXC, and PER groups than in CBZ, TPM, and VAL groups. Healthcare utilization and related costs showed significant difference between ASM groups.

Objective To prepare expert consensus opinion in treatment of epilepsy in China.Methods To sent an anonymous questionnaire on the treatment of adolescent and adult epilepsy syndromes to a group of hospital neurologists in the field of epilepsy. The questions were formatted to simulate real-world clinical situations in the treatment of symptomatic localization related epilepsy (SLRE), idiopathic generalized epilepsy (IGE), and treatment in special patient populations and patients with comorbidity. The experts were asked to rate treatment options based on a modified RAND 9-point scale (with 9 most appropriate and 1 least appropriate). Statistical analysis of data was performed as defined by the expert consensus method. The results were used to develop user-friendly recommendations concerning overall treatment strategies and choice of specific medications. Results Of the 50 experts to whom the survey was sent, 49 (98%) responded. Of the respondents, 11 (22.4%) were female and 38 (77.6%) male. Their mean age was 53.9 years, with a mean of 17.9 years in practice. The median number of patients seen per month was 100 ( range, 20 to 800 ). For initial monotherapy of IGE ( generalized tonic-clonic ( GTC ),absence, and myoclonic seizures), valproate was rated as treatment of choice. Treatment options were rated for 3 types of SLRE: simple partial seizures ( SPS), complex partial seizures ( CPS ) , and secondarily generalized tonic-clonic seizures (SGTC). In SLRE-SPS and SLRE-CPS, carbamazepine and oxcarbazepine were treatments of choice, with lamotrigine, topiramate and levetiracetam as second line agents. In SLRESGTC, carbamazepine, lamotrigine and oxcarbazepine were treatments of choice, while lamotrigine,topiramate, levetiracetam and valproate were also usually appropriate. Valproate was selected as treatment of choice when combined with other AEDs in IGE. For SLRE, combination/add-on therapy of carbamazepine ( oxcarbazcpine ) + topiramate, carbamazepine ( oxcarbazepine ) + levetiracetam, carbamazepine (oxcarbazepine) +valproate, valproate + lamotrigine were considered as treatment of choice. For women who are pregnant or trying to conceive, lamotrigine was treatment of choice for both idiopathic generalized epilepsy (IGE) and symptomatic localization related epilepsy (SLRE). For patients with school-age,lamotrigine was treatment of choice for IGE, with oxcarbazepine and lamotrigine for SLRE. In people with both epilepsy syndromes who have depression, valproate and lamotrigine were treatment of choice for IGE; in SIRE, lamotrigine, oxcarbazepine and carbamazepine were treatment of choice. In persons with epilepsy and hepatitis B, whether liver function was normal or not, topiramate and levetiracetam were treatment of choice for IGE; in SLRE with normal liver function, oxcarbazepine was treatment of choice, while topiramate and levetiracetam were selected for SLRE with liver function impairment. Valproate and levetiracetam were treatment of choice for seizures in the emergency department. Conclusions The expert consensus method concisely summarizes expert opinion, and this opinion may be helpful in situations in which the medical literature is scant or lacking. Key words: Epilepsy; Drug therapy; Questionnaires

An increasing number of antiseizure medications (ASMs) are approved for monotherapy for focal epilepsy, but direct comparisons of the lifetime cost-effectiveness of all existing treatment strategies are lacking. This study aims to compare the cost-effectiveness of new ASMs and traditional ASMs as first-line monotherapy for newly diagnosed focal epilepsy. We used a Markov model to evaluate the lifetime cost-effectiveness of 10 ASMs in the treatment of focal epilepsy, with lacosamide (LCM) as a control, from the perspective of society in the United States. Effectiveness, cost data, and health state utilities were obtained from published literature. The cycle of the model is 6 months. Willingness to pay was defined as $150 000 per quality-adjusted life year (QALY). One-way and probabilistic sensitivity analyses were conducted to evaluate parameter uncertainty, and several scenario analyses were also conducted. The base case analysis showed that carbamazepine (CBZ) was the least costly ASM and more effective than valproic acid (VPA), levetiracetam (LEV), gabapentin (GBP), topiramate (TPM), and lamotrigine (LTG) from an American social perspective. In contrast, oxcarbazepine (OXC), phenytoin (PHT), phenobarbitone (PHB), LCM, and zonisamide (ZNS) were more effective than CBZ, with incremental cost-effectiveness ratios of $334 703.50, $325 610.99, $3 037 148.62, $1 178 954.91, and $108 153 360.85/QALY, respectively. The traditional ASMs were ranked as CBZ, PHT, VPA, and PHB; the new ASMs were ranked as OXC, LEV, LCM, LTG, TPM, GBP, and ZNS. When generic drugs are used, PHT, OXC, and CBZ remain the three most cost-effective options. In terms of cost-effectiveness, CBZ monotherapy is the best option for newly diagnosed focal epilepsy, followed by OXC, PHT, VPA, LEV, PHB, LCM, LTG, TPM, GBP, and ZNS. Most traditional ASMs are more cost-effective than new ASMs; OXC is an exception.

Effects of valproic acid, levetiracetam, carbamazepine, lamotrigine, and topiramate on LIF, E-cadherin, and FOXO1 mediator molecules in rat embryo implantation.

Issues in the Treatment of Epilepsy

PP14.7 – 2997: Screening osteoporosis in patients with antiepileptic drug using urine N-telopeptide of collagen type I

Background:It is important to choose an appropriate antiepileptic drug (AED) to manage partial epilepsy. Traditional AEDs, such as carbamazepine (CBZ) and valproate (VPA), have been proven to have good therapeutic effects. However, in recent years, a variety of new AEDs have increasingly been used as first-line treatments for partial epilepsy. As the studies regarding the effectiveness of new drugs and comparisons between new AEDs and traditional AEDs are few, it is determined that these are areas in need of further research. Accordingly, this study investigated the long-term effectiveness of six AEDs used as monotherapy in patients with partial epilepsy.Methods:This is a retrospective, long-term observational study. Patients with partial epilepsy who received monotherapy with one of six AEDs, namely, CBZ, VPA, topiramate (TPM), oxcarbazepine (OXC), lamotrigine (LTG), or levetiracetam (LEV), were identified and followed up from May 2007 to October 2014, and time to first seizure after treatment, 12-month remission rate, retention rate, reasons for treatment discontinuation, and adverse effects were evaluated.Results:A total of 789 patients were enrolled. The median time of follow-up was 56.95 months. CBZ exhibited the best time to first seizure, with a median time to first seizure of 36.06 months (95% confidential interval: 30.64–44.07). CBZ exhibited the highest 12-month remission rate (85.55%), which was significantly higher than those of TPM (69.38%, P = 0.006), LTG (70.79%, P = 0.001), LEV (72.54%, P = 0.005), and VPA (73.33%, P = 0.002). CBZ, OXC, and LEV had the best retention rate, followed by LTG, TPM, and VPA. Overall, adverse effects occurred in 45.87% of patients, and the most common adverse effects were memory problems (8.09%), rashes (7.76%), abnormal hepatic function (6.24%), and drowsiness (6.24%).Conclusion:This study demonstrated that CBZ, OXC, and LEV are relatively effective in managing focal epilepsy as measured by time to first seizure, 12-month remission rate, and retention rate.

Antiepileptic Drugs: All Ages

Sleep in patients with epilepsy.

Impact of mood stabilizers and antiepileptic drugs on cytokine production in-vitro

ObjectiveTo evaluate and compare long-term effectiveness of five antiepileptic drugs (AEDs) for monotherapy of adult patients with focal epilepsy in routine clinical practice.MethodsAdult patients with focal epilepsy, who were prescribed with carbamazepine (CBZ), valproate (VPA), lamotrigine (LTG), topiramate (TPM), or oxcarbazepine (OXC) as monotherapy, during the period from January 2004 to June 2012 registered in Wenzhou Epilepsy Follow Up Registry Database (WEFURD), were included in the study. Prospective long-term follow-up was conducted until June 2013. The endpoints were time to treatment failure, time to seizure remission, and time to first seizure.ResultsThis study included 654 patients: CBZ (n=125), VPA (n=151), LTG (n=135), TPM (n=76), and OXC (n=167). The retention rates of CBZ, VPA, LTG, TPM, and OXC at the third year were 36.1%, 32.4%, 57.6%, 37.9%, and 41.8%, respectively. For time to treatment failure, LTG was significantly better than CBZ and VPA (LTG vs. CBZ, hazard ratio, [HR] 0.80 [95% confidence interval: 0.67-0.96], LTG vs. VPA, 0.53 [0.37-0.74]); TPM was worse than LTG (TPM vs. LTG, 1.77 [1.15-2.74]), and OXC was better than VPA (0.86 [0.78-0.96]). After initial target doses, the seizure remission rates of CBZ, VPA, LTG, TPM, and OXC were 63.0%, 77.0%, 83.6%, 67.9%, and 75.3%, respectively. LTG was significantly better than CBZ (1.44 [1.15-1.82]) and OXC (LTG vs. OXC, 0.76 [0.63-0.93]); OXC was less effective than LTG in preventing the first seizure (1.20 [1.02-1.40]).ConclusionLTG was the best, OXC was better than VPA only, while VPA was the worst. The others were equivalent for comparisons between five AEDs regarding the long-term treatment outcomes of monotherapy for adult patients with focal epilepsy in a clinical practice. For selecting AEDs for these patients among the first-line drugs, LTG is an appropriate first choice; others are reservation in the first-line but VPA is not.

To determine rates of cross-sensitivity of rash among commonly used antiepileptic drugs (AEDs) in patients with epilepsy. The incidence of AED-related rash was determined in 1875 outpatients (> or =12 years), taking carbamazepine (CBZ), clobazam (CLB), felbamate (FBM), gabapentin (GBP), levetiracetam (LEV), lamotrigine (LTG), oxcarbazepine (OXC), phenobarbital (PB), phenytoin (PHT), primidone (PRM), tiagabine (TGB), topiramate (TPM), vigabatrin (VGB), valproic acid (VPA), or zonisamide (ZNS). We compared rates of rash for each AED in patients with vs those without a rash to 1) another specific AED; 2) any other AED; 3) any two other AEDs; and 4) any non-epilepsy medication. A total of 14.3% (269/1,875) of patients had a rash attributed to at least one AED; 2.8% had a rash to two or more AEDs. Of patients who had a rash to CBZ and were also prescribed PHT (n = 59), 57.6% had a rash to PHT (abbreviated as CBZ --> PHT: 57.6%); of patients who had a rash to PHT and were also prescribed CBZ (n = 81), rate of rash was 42% (i.e., PHT --> CBZ: 42%). Other results: CBZ --> LTG: 20% (n = 50); LTG --> CBZ: 26.3% (n = 38); CBZ --> OXC: 33% (n = 15); OXC --> CBZ: 71.4% (n = 7); CBZ --> PB: 26.7% (n = 30); PB --> CBZ: 66.7% (n = 12); LTG --> PHT: 38.9% (n = 36); PHT --> LTG: 18.9% (n = 74); PB --> PHT: 53.3% (n = 15); PHT --> PB: 19.5% (n = 41); OXC --> LTG: 37.5% (n = 8); LTG --> OXC: 20% (n = 15). There was evidence of specific cross-sensitivity between CBZ and PHT, and between CBZ and PB. Cross-sensitivity rates between certain antiepileptic drugs (AEDs) are high, especially when involving carbamazepine and phenytoin. Specific cross-sensitivity rates provided here may be useful for AED selection and counseling in individual patients.

Objective To understand the incidences of adverse reactions on cognition, language, and bone metabolism related to 8 commonly used antiepileptic drugs in China using SIDER database. Methods The integrated incidences of adverse reactions on cognition, language, and bone metabolism related to 8 commonly used antiepileptic drugs (carbamazepine, oxcarbazepine, valproate, clonazepam, lamotrigine, levetiracetam, topiramate, and zonisamide) marketed in China was searched in the SIDER database. Results The main drugs that affected cognition were topiramate and valproate. The incidences of memory impairment caused by topiramate and abnormal thinking related to valproate were 1.2%-10.8% and 6.0%, respectively. Topiramate was the main drug that affected language. The incidences of dysarthria and speech disorder caused by topiramate were 1.6%-6.2% and 1.0%-16.8%, respectively. The main antiepileptic drugs that affected bone metabolism were carbamazepine, oxcarbazepine, and valproate. But there was no incidence information because of the limited small amount of literature reports after marketing. Conclusions The results of data analysis in this database indicate that different antiepileptic drugs have different effects on cognitive function, language function and bone metabolism, and the frequency of adverse reactions is different. The clinical use of antiepileptic drugs needs to weigh the advantages and disadvantages according to the specific situation of patients. Key words: Drug-related side effects and adverse reactions; Epilepsy; Anticonvulsants; Cognition; Language; Osteoporosis; Fractures, bone

Balancing foetal disadvantage and seizure freedom in women capable of pregnancy - the Australian pregnancy register experience.