Antiepileptic Drug Monotherapy Research Articles

Patterns of antiepileptic drugs use in epileptic pediatric patients in Jordan

Objectives:To determine prescribing patterns of antiepileptic drugs (AEDs) in pediatric patients with confirmed diagnosis of epilepsy, and to provide knowledge of general practice of physicians.Methods:The study was a multi-center cross-sectional observational study, in specialized clinics for management of epilepsy in north, central and south Jordan. This study was conducted from January 2014 to July 2014. These were 3 from university tertiary care hospitals and 4 from governmental tertiary care hospitals.Results:A total of 694 pediatric patients were included. Monotherapy AED use had the highest frequency 465 (67.0%), followed by dual therapy 162 (23.3%). The frequency of monotherapy in university hospitals was lower than governmental hospitals (p<0.05); however, Polytherapy was more frequent in younger children. Two old AEDs were most frequently prescribed as a monotherapy; Valproic acid 235 (50.5%) and carbamazepine 155 (33.3%). The most common combination in dual therapy was valproic acid with carbamazepine 28 (17.3%). The second most common combinations were carbamazepine with levetiracetam 21 (13.0%) or valproic acid with levetiracetam 20 (12.3%).Conclusion:Older AED remain first line drugs for use in both monotherapy and combination therapy for epileptic disorders. Polytherapy is associated with younger kids and being treated in a university hospital.

Antiepileptic drug combinations not involving valproate and the risk of fetal malformations.

To investigate the relationship between antiepileptic drug (AED) polytherapy in pregnant women and the risk of fetal malformations as prescribing practice changed, with valproate being used less often and at lower doses. Specifically, the risks associated with two of the most common AEDs included in polytherapy over recent years, levetiracetam and topiramate, were examined. An observational cohort study in which malformation rates were analyzed in 1,461 pregnancies exposed to AED monotherapy, and in 484 exposed to antiepileptic drug combinations, from the Australian Register of Antiepileptic Drugs in Pregnancy over a 15-year period (1999-2014). Fetal malformation rates had fallen over time in monotherapy pregnancies, but increased in polytherapy pregnancies, despite decreasing use and lower dosages of valproate. The rise in polytherapy malformation rates began around 2005 when levetiracetam and topiramate use began to increase. Excluding pregnancies involving valproate exposure, malformation rates were higher in the remaining polytherapy pregnancies as compared with the monotherapy ones (6.90% vs. 3.64%; odds ratio [OR] 1.96, 95% confidence interval [CI] 1.14-3.39). Malformation rates were similar in polytherapy pregnancies whether or not levetiracetam was included (7.14% vs. 8.38%), but were higher in polytherapy pregnancies involving topiramate (14.94% vs. 6.55%: OR 2.507, 95% CI 1.23-5.10). Logistic regression showed that topiramate in polytherapy had a positive dose relationship with teratogenicity risk (p = 0.025). The malformation risk associated with AED polytherapy depends on the specific drugs involved. Topiramate, when used as part of AED polytherapy that did not include valproate, was associated with a dose-related increased risk of fetal malformations.

Open Label Trial of Add on Lacosamide Versus High Dose Levetiracetam Monotherapy in Patients With Breakthrough Seizures.

In patients who do not achieve seizure freedom on low-dose first-line monotherapy antiepileptic drug (AED), the current practice is to increase the AED to higher doses. For patients who fail low dose levetiracetam (LEV), a reasonable alternative to increasing dosage may be the addition of a low-dose adjunctive AED. In this open-label, pilot trial, low-dose lacosamide (200 mg/d) was added to adult patients with breakthrough seizures on low-dose monotherapy LEV (≤1500 mg/d). Comparison was made with a retrospective historical control cohort in whom the dose of LEV was raised after a breakthrough seizure. The main objectives were to determine efficacy effect size and tolerability. Twenty patients were recruited in the prospective polytherapy cohort, of whom 19 received at least 1 dose of adjunctive AED; the monotherapy cohort consisted of 36 patients. Six-month seizure freedom was achieved in 9 of 19 patients in the polytherapy cohort and in 15 of 36 patients in the monotherapy cohort (hazard ratio for seizure occurrence for polytherapy relative to monotherapy was 0.76; 95% confidence interval, 0.35-1.65; P = 0.49). There were treatment emergent adverse effects in 11 patients (61.1%) in the polytherapy cohort and 26 (72.2%) in the monotherapy cohort. Greater number of patients in the monotherapy cohort experienced irritability/depression (33.3% vs 5.6%, P < 0.05). Low-dose polytherapy with LEV and lacosamide was well tolerated and efficacious. Further studies are needed to determine whether this is a reasonable alternative to high-dose LEV monotherapy.

Prescription patterns of antiepileptic drugs in young women: development of a tool to distinguish between epilepsy and psychiatric disorders.

Antiepileptic drugs (AEDs) are also prescribed for therapeutic indications other than epilepsy (EPI), namely, psychiatric disorders (PSY). Our aim was to develop an algorithm able to distinguish between EPI and PSY among childbearing age women based on differences in AED exposure in these patient groups. Two groups of women (18-45 years) with EPI or PSY treated with AEDs in the first semester of 2010 or 2011 were extracted from paper or electronic medical charts of specialized centers. Through the prescription database of Bologna Local Health Authority (Italy), AEDs, treatment schedule and co-treatments were collected for each patient. A prescription-based hierarchical classification system was developed. The algorithm obtained was subsequently validated on internal and external data. Eighty-one EPI and 94 PSY subjects were recruited. AED monotherapy was the most common choice in both groups (69% EPI vs 79% PSY). Some AEDs were used only in EPI, others exclusively in PSY. Co-treatments with antipsychotics (6% vs 67%), lithium (0% vs 9%), and antidepressants (7% vs 70%) were fewer in EPI than in PSY. The hierarchical classification system identified antipsychotics, SSRIs (Selective Serotonin Reuptake Inhibitors), and number of AEDs as variables to discriminate EPI and PSY, with an overall error rate estimate of 9.7% (95%CI: 5.3% to 14.1%). Among the differences between EPI and PSY, prescription data alone allowed an algorithm to be developed to diagnose each childbearing age woman receiving AEDs. This approach will be useful to stratify patients for risk estimates of AED-treated patients based on administrative databases. Copyright © 2016 John Wiley & Sons, Ltd.

Antiepileptic Drugs

Treatment of epilepsy starts with antiepileptic drug (AED) monotherapy. Knowledge of the spectrum of efficacy, clinical pharmacology, and modes of use for individual AEDs is essential for optimal treatment for epilepsy. This article addresses AEDs individually, focusing on key pharmacokinetic characteristics, indications, and modes of use. Older-generation AEDs are effective but have tolerability and pharmacokinetic disadvantages. Several newer-generation AEDs have undergone comparative trials demonstrating efficacy equal to and tolerability at least equal to or better than older AEDs as first-line therapy. The list includes lamotrigine, oxcarbazepine, levetiracetam, topiramate, and, more recently, zonisamide. Pregabalin was found to be less effective than lamotrigine. Lacosamide, pregabalin, and eslicarbazepine have undergone successful trials of conversion to monotherapy. Other newer-generation AEDs with a variety of mechanisms of action are suitable for adjunctive therapy. Rational AED combinations should avoid AEDs with unfavorable pharmacokinetic interactions or pharmacodynamic interactions related to mechanism of action. Knowledge of AED pharmacokinetics, efficacy, and tolerability profiles facilitates the choice of appropriate AED therapy for patients with epilepsy.

Rapid versus slow withdrawal of antiepileptic monotherapy in 2-year seizure-free adult patients with epilepsy (RASLOW) study: a pragmatic multicentre, prospective, randomized, controlled study.

Antiepileptic drug withdrawal may be an option for patients who have been seizure free for some years. The best withdrawal rate is questionable; in particular, it is unknown whether "rapid" withdrawal is associated with a higher risk of relapse as compared to "slow" withdrawal. We aim to establish if a slow or a rapid withdrawal schedule of antiepileptic monotherapy influences relapse rate in adult patients with focal or generalized epilepsy who have been seizure free for at least 2years. This multicentre, prospective, randomized controlled study will enroll adult patients with focal or generalized epilepsy, who are seizure free on monotherapy. Patients will be randomized to a slow (160days) or a rapid (60days) schedule. Follow-up will last 1year after randomization. The primary endpoint is the time to seizure relapse; secondary endpoints are compliance to the assigned schedule, occurrence of status epilepticus, of seizure-related injuries and mortality. A sample size of 350 patients has been planned. Univariate and multivariate analysis by Kaplan-Meier curves and Cox regression (primary endpoint) and by logistic regression (secondary endpoint) will be performed. The present study should contribute to better define the best withdrawal period for AED treatment in adult patients with epilepsy.

Comparison of body composition in persons with epilepsy on conventional & new antiepileptic drugs.

Background & objectives:Certain antiepileptic drugs (AEDs) such as valproic acid (VPA) are known to affect body weight, and lipid profile. However, evidences regarding effects of AEDs on the body composition are deficient. This cross-sectional study compared the body composition and lipid profile among patients with epilepsy on newer and conventional AEDs.Methods:The patients with epilepsy (n=109) on treatment with conventional and newer AEDs (levetiracetam, lamotrigine and clobazam) for > 6 months were enrolled. Of these, 70 were on monotherapy: levetiracetam (n=12), VPA (n=16), carbamazepine (n=20) and phenytoin (n=22) and the remaining on polytherapy. Their body composition [body fat mass, lean dry mass (LDM), total body water (TBW), intracellular water (ICW), extracellular water (ECW) and basal metabolic rate (BMR) was estimated and biochemical parameters were assessed.Results:Levetiracetam group had no significant difference with VPA, carbamazepine, phenytoin and control groups, except low LDM (17.8±2.4) than VPA groups (20.2±2.7, P<0.05). In comparison with control, AEDs monotherapy groups had no significant difference, except higher LDM and ECW in VPA group. Among groups based on conventional and newer AEDs, there was no significant difference in body composition parameters except for higher LDM (as % of BW) in conventional AEDs only treated group than control (P<0.01).Interpretation & conclusions:The alterations observed in body composition with valproic acid in contrast to other AEDs like levetiracetam, carbamazepine and phenytoin could affect treatment response in epilepsy especially in subjects with already altered body composition status like obese and thin frail patients, which needs to be established by prospective studies (CTRI/2013/05/003701).

Favorable change of lipid profile after carbamazepine withdrawal.

Patients treated with carbamazepine (CBZ) have increased serum levels of total cholesterol (TC), high-density lipoproteins (HDL), and low-density lipoproteins (LDL). We aimed to investigate whether these changes of serum lipids are reversible after CBZ withdrawal. We used a prospective, randomized double-blinded design. A total of 160 patients who had been seizure free on anti-epileptic drug monotherapy for more than 2years were included and randomized to withdrawal or not. The intervention was completed by 150 (80 females, 53%) patients. Serum samples from before and 4months after completed withdrawal or no withdrawal were obtained from 130 patients (63 females, 48%). Of these, 84 were treated with CBZ, 28 with valproate, nine with phenytoin, four with phenobarbital, and five with lamotrigine. Of the patients who had been treated with CBZ, 47 were randomized to the withdrawal group, and 37 were randomized to the non-withdrawal group. Among the CBZ-treated patients, a significant decrease in serum levels of TC, LDL, and apolipoprotein B (ApoB) were found in the withdrawal group compared with the non-withdrawal group. Mean differences in change were as follows: TC 0.68mmol/l (P=0.005, CL - 1.15 to -0.21); LDL - 0.67mmol/l (P=0.001, CL - 1.03 to -0.29); ApoB - 0.13g/l (P=0.02, CL - 0.23 to -0.03). No significant changes in HDL, apolipoprotein A, and C-reactive protein were detected. Our results indicate that CBZ may have unfavorable effects on serum levels of TC, LDL, and ApoB. However, these changes seem to be reversible even after years of treatment.

Long-term Effectiveness of Antiepileptic Drug Monotherapy in Partial Epileptic Patients: A 7-year Study in an Epilepsy Center in China.

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.

PO67LEVETIRACETAM MAY BE INDEPENDENTLY ASSOCIATED WITH HIGHER FATIGUE IN ADULT GLIOMA OUTPATIENTS

INTRODUCTION: The widely used antiepileptic drug (AED) Levetiracetam has previously been associated with behavioural changes. We hypothesised that patients taking Levetiracetam would experience higher levels of fatigue than patients on other AEDs. METHOD: Secondary analysis of a prospective observational study. Clinically stable adult outpatients with cerebral glioma completed a Visual Analogue Scale for fatigue (range 0-100mm, called ‘high' if >60mm). AED prescription was prospectively recorded. RESULTS: N = 166 patients consented to participate in the parent study (61% male; mean age 49yrs; 70% high-grade glioma). Fatigue was commonly reported (high in 43%; 95%CI 35-50%). AEDs were prescribed singly or multiply to most patients (n = 113). Levetiracetam (LEV) was the most frequent AED monotherapy. With clinical and statistical significance, patients on LEV monotherapy reported higher fatigue (n = 33, mean = 57mm, SD 5.2, 95%CI 46-67mm) than those on monotherapy with any other AED (n = 50, mean = 43mm, SD 3.9, 95%CI 35-50mm, t-test p < 0.0001). Surprisingly, this association was independent of functional status (ANCOVA p = 0.04, LR p < 0.0001, R2 = 27.7). Patients on LEV were more than twice as likely to report high fatigue as patients on other AEDs (OR 2.7 [1.1-6.2]). We observed similar findings with polytherapy involving LEV. CONCLUSION: Therapy-related side effects reduce quality of life and treatment compliance while increasing healthcare costs. Our data suggest that fatigue may be more common with Levetiracetam therapy specifically. Specialist review of AED medication may benefit some glioma patients with severe or persistent fatigue. Explanatory biological mechanisms of LEV-specific fatigue could be experimentally pursued.

Brand name to generic substitution of antiepileptic drugs does not lead to seizure-related hospitalization: a population-based case-crossover study.

There is still controversy on brand-to-generic (B-G) antiepileptic drugs (AEDs) substitution. To assess association between B-G AED substitution and seizure-related hospitalization, we designed a case crossover using the French National Health Insurance Database. We identified a cohort of adult patients who filled a prescription in 2009-2011 for AEDs with at least one brand name and one generic form. The outcome date was defined as the date of hospitalization, coded G40.x or G41.x, with a G40/G41 hospitalization-free period of at least 1 year. Patients with a medical history of cancer and women who gave birth in 2009-2011 were excluded. We required individuals to have regular dispensations of AEDs within the year preceding the outcome date. Free patients were defined as patients who had only brand name dispensations before the control period. Eight thousand three hundred seventy nine patients (mean age ± standard deviation, 52.7 ± 18.8 years; sex ratio male/female, 1.27) were analyzed. Discordant pairs were 491 with B-G substitution in the control period only and 478 with B-G substitution in the case period only; odds ratio (95% confidence interval) 0.97 (0.86-1.10). No statistically significant interaction was detected among the four prespecified subgroup analyses (gender, age strata, free or non-free, and strict AED monotherapy or not). Controlling for non-seizure-related hospitalizations made no material difference. Sensitivity analyses yielded similar results. Brand-to-generic AED substitution was not associated with an elevated risk of seizure-related hospitalization.

Generic versus branded antiepileptic drug monotherapy for epilepsy

Generic versus branded antiepileptic drug monotherapy for epilepsy

Driven to Tears: Epilepsy Specialists and the Automobile.

Introduction I like to tell my residents and fellows that one of the benefits of working in the field of epilepsy is that you’re rarely ever wrong: ask four different attending physicians the same question and you’re likely to get four different answers; so whatever you propose to do for a patient, there’s probably someone who will back you up. I could scarcely come up with a better illustration of my aphorism than the results of a recent Quantitative Practical Use-Driven Learning Survey in epilepsy (Q-PULSE) regarding driving. We asked respondents their practice vis-a-vis driving in four different situations: 1) a patient on a monotherapy regimen who is tapering off the sole antiepileptic drug (AED), 2) a patient on a polytherapy regimen who is tapering off one of two AEDs, 3) a patient who is switching from one monotherapy AED to another. and 4) a patient who has psychogenic seizures. Driven to Tears: Epilepsy Specialists and the Automobile

Spotlight on the August 18 Issue

#### Notable in Neurology This issue features articles discussing inspiratory and expiratory muscle training in subacute stroke and the effect of clopidogrel plus aspirin on functional outcome after TIA or minor stroke. Another article focuses on retinal pathology in Susac syndrome and its detection by spectral-domain optical coherence tomography. ### Antiepileptic drugs and intrauterine death: A prospective observational study from EURAP![Graphic][1]</img> The authors found no difference in risk of intrauterine death in pregnant women with epilepsy exposed to antiepileptic drug monotherapy. The most important … [1]: /embed/inline-graphic-1.gif

Etiologic features and utilization of antiepileptic drugs in people with chronic epilepsy in China: Report from the Epilepsy Cohort of Huashan Hospital (ECoH)

PurposeChronic epilepsy is estimated to affect more than 2 million people in China. However, data of its clinical characteristics was rarely reported in China. In the present study, we summarized the etiologic features and utilization patterns of antiepileptic drugs (AEDs) in people with chronic epilepsy in a tertiary medical center in China. MethodsWe prospectively recruited people with chronic epilepsy treated at the Epilepsy Outpatient Clinic of Huashan Hospital during October 2009 to August 2013. Demographic data, clinical characteristics, AED treatment, epilepsy-associated risk factors and medical history, and results of supplementary examinations of each participant were collected retrospectively via an interviewer-administered questionnaire and confirmed by the medical records. ResultsAmong 554 people with chronic epilepsy, 58.0% of them were male, 66.8% had focal seizure, and 29.2% had symptomatic cause. Developmental anomalies of cerebral structure (16.7%) and cerebral trauma (16.7%) shared the leading cause of symptomatic epilepsy among children with epilepsy. While cerebral trauma (29.1%) and cerebrovascular disorder (36.4%) were the most common causes in groups of adults and elderly. Fifty percent of participants were taking AED monotherapy. Proportions of people with idiopathic, cryptogenic and symptomatic epilepsy treated by multitherapy were 35%, 46% and 45.6%, respectively. Valproic acid (VPA) was the most frequently utilized AED as monotherapy (32.7%) and within multitherapy (62.5%). SignificanceThis hospital-based study reported that etiologic features were diverse in different age groups of people with chronic epilepsy. VPA was widely utilized to treat chronic epilepsy in mainland China.

Antiepileptic drugs and intrauterine death

To compare the risk of spontaneous abortions and stillbirth associated with maternal use of different antiepileptic drugs (AEDs). The EURAP registry is an observational international cohort study primarily designed to determine the risk of major congenital malformations (MCMs) after prenatal AED exposure. Using EURAP data, we prospectively monitored pregnancies exposed to the 6 most common AED monotherapies and to polytherapy. Intrauterine death (spontaneous abortion and stillbirth combined) was the primary endpoint. Of 7,055 pregnancies exposed to monotherapy with lamotrigine (n = 1,910), carbamazepine (n = 1,713), valproic acid (n = 1,171), levetiracetam (n = 324), oxcarbazepine (n = 262), or phenobarbital (n = 260), and to polytherapy (n = 1,415), 632 ended in intrauterine deaths (592 spontaneous abortions and 40 stillbirths). Rates of intrauterine death were similar across the different monotherapies (8.2%; 95% confidence interval [CI] 7.5%-8.9%), higher with polytherapy (12.1%; 95% CI 10.5%-13.9%), but showed no relationship with AED dose in monotherapy at conception. Multivariable analysis including 11 covariates in addition to the different AED exposures showed that the risk was greater with polytherapy vs monotherapy (risk ratio [RR] 1.38; 95% CI 1.14-1.66), parental history of MCMs (RR 1.92; 1.20-3.07), maternal age (RR 1.06; 1.04-1.07), and number of previous intrauterine deaths (RR 1.09; 1.00-1.19). The risk was greater with early enrollment and decreased with later gestational week at enrollment (RR 0.84; 0.82-0.86). The most important risk factors for intrauterine death in pregnancies of women with epilepsy include maternal exposure to AED polytherapy and the presence of MCMs in at least one of the parents.

Efficacy and safety of ezogabine/retigabine as adjunctive therapy to specified single antiepileptic medications in an open-label study of adults with partial-onset seizures

PurposeTo assess efficacy/tolerability of ezogabine (EZG)/retigabine (RTG) in combination with specified monotherapy antiepileptic drug (AED) treatments in adults with uncontrolled partial-onset seizures using a flexible dosing regimen. MethodsNCT01227902 was an open-label, uncontrolled study of flexibly dosed EZG/RTG. Adults with partial-onset seizures must have been taking either carbamazepine/oxcarbazepine (CBZ/OXC), lamotrigine (LTG), levetiracetam (LEV), or valproic acid (VPA). The study comprised a screening/baseline phase, a 4-week titration phase (initiation on 150mg/day [50mg three times daily (TID)] with weekly increases of 150mg/day [50mg TID] over 4 weeks to 600mg/day), and a flexible dose evaluation (FDE) phase (optional weekly dose changes of 50–150mg/day, to an optimal daily dosage [300–1200mg/day]). The primary efficacy endpoint was percentage of patients experiencing a ≥50% reduction from baseline in partial seizure frequency (responder rate) during the treatment phase (titration and FDE phases). Safety and tolerability were also assessed. ResultsPatients (N=203) were enrolled and received ≥1 dose of EZG/RTG. The dose of EZG/RTG prescribed most frequently during the treatment phase was 600mg/day for all AED groups. Responder rates during the treatment phase were: 40.0% (CBZ/OXC), 32.0% (LTG), 50.0% (LEV), and 56.9% (VPA). Treatment-emergent adverse events occurred in 82% (CBZ/OXC), 76% (LTG), 73% (LEV), and 67% (VPA) of patients; most were of mild-to-moderate intensity. ConclusionsEZG/RTG was effective as adjunctive therapy to CBZ/OXC, LTG, LEV, and VPA, using a flexible dosing regimen, in adults with partial-onset seizures; safety and tolerability were consistent with that previously observed.

Changes in the anti-oxidant system in adult epilepsy patients receiving anti-epileptic drugs

Anti-epileptic drugs (AEDs) have been widely used in patients with epilepsy. This study evaluated the adverse effects of two commonly prescribed AED monotherapies, carbamazepine (CBZ) and valproic acid (VPA). The aim of this study was to evaluate the influence of these anti-epileptic drugs on paraoxonase-1 (PON-1), glutathione S-transferase (GST) and acetyl cholinesterase (AChE) activities in the serum of adult patients with epilepsy. Of the 56 epileptic adults, 28 were given valproate, and the remaining 28 were given carbamazepine. Glutathione (GSH) levels in epilepsy patients receiving anti-epileptic drug treatment were insignificantly higher compared with controls. GST activity in epilepsy patients receiving anti-epileptic drug treatment was insignificantly lower compared with controls. PON1 and AChE activity in epilepsy patients receiving anti-epileptic drug treatment was significantly lower compared with controls. PON1 and AChE activities in the serum of patients treated with carbamazepine monotherapy were lower than in patients treated with valproic acid monotherapy.

Effects of antiepileptic drug monotherapy on one-carbon metabolism and DNA methylation in patients with epilepsy.

PurposeThe aim of this study was to compare the serum levels of one-carbon metabolism (OCM) nutrients (e.g., folate, homocysteine and vitamin B12) and peripheral blood DNA methylation in epileptic patients under treatment with antiepileptic drugs (AEDs) and in healthy controls.MethodsIn this cross-sectional study, 60 patients with epilepsy who were receiving valproate (VPA) (n = 30) or lamotrigine (LTG) (n = 30) monotherapy were enrolled. Thirty age and sex matched healthy subjects served as the controls. Serum concentrations of OCM nutrients and peripheral blood DNA methylation status were measured.ResultsCompared to the control group, the VPA group had higher serum levels of homocysteine (p<0.05). No difference in homocysteine concentration was observed in the LTG group. Patients receiving VPA or LTG had significantly lower serum folate levels in comparison with controls (p<0.001). The level of methylation of long interspersed nucleotide element-1 (LINE-1) in peripheral blood was not significantly different between the AED monotherapy group and healthy controls. A difference in the methylation levels of methylenetetrahydrofolate reductase (MTHFR) amplicon was observed between AED-treated patients with epilepsy and controls (p<0.01). A positive correlation between serum folate levels and peripheral blood MTHFR amplicon methylation status was also observed (r = 0.25, p = 0.023).ConclusionOur findings suggest that the effects of AED monotherapy on OCM may induce specific regions of DNA hypomethylation.

Antiepileptic drug prescribing patterns in Iraq and Afghanistan war veterans with epilepsy

ObjectiveWe examined patterns of antiepileptic drug (AED) use in a cohort of Iraq/Afghanistan war veterans (IAVs) who were previously identified as having epilepsy. We hypothesized that clinicians would be more likely to prescribe newer AEDs and would select specific AEDs to treat seizures based on patient characteristics including gender and comorbidities. MethodsFrom the cohort of IAVs previously identified with epilepsy between fiscal years 2009 and 2010, we selected those who received AEDs from the Veterans Health Administration in FY2010. Regimens were classified as monotherapy or polytherapy, and specific AED use was examine overall and by gender. Multivariable logistic regression examined associations of age; gender; race/ethnicity; medical, psychiatric, and neurological comorbidities; and receipt of neurology specialty care associated with the six most commonly used AEDs. ResultsAmong 256,284 IAVs, 2123 met inclusion criteria (mean age: 33years; 89% men). Seventy-two percent (n=1526) received monotherapy, most commonly valproate (N=425) and levetiracetam (n=347). Sixty-one percent of those on monotherapy received a newer AED (levetiracetam, topiramate, lamotrigine, zonisamide, oxcarbazepine). Although fewer women than men received valproate, nearly 90% (N=45) were of reproductive age (≤45years). Antiepileptic drug prescribing patterns were associated with posttraumatic stress disorder, bipolar disorder, cerebrovascular disease, dementia/cognitive impairment, headache, and receipt of neurological specialty care (all p<0.01). SignificanceIn this cohort of veterans with epilepsy, most received AED monotherapy and newer AEDs. Prescribing patterns were different for men and women. The patterns observed between AEDs and neurological/psychiatric comorbidities suggest that clinicians are practicing rational prescribing.