Use Of Newer Antiepileptic Drugs Research Articles

FEATURES OF MODERN PHARMACOTHERAPY OF EPILEPTIC STATUS

In the presented review of the literature, the most significant problems of modern pharmacotherapy of status epilepticus are indicated. The urgency of treatment of status epilepticus is confirmed by its frequency and ineffectiveness of traditional drugs (benzodiazepines, hydantoins, barbiturates), which have a number of side effects from the cardiovascular and respiratory systems. In Russian intensive care medicine, treatment of status epilepticus is carried out in accordance with international standards and recommendations. For a number of years, the injectable form of valproate has proven its effectiveness, including in pediatric practice. In comparative studies, phenytoin, valproate and levetiracetam are safe and equally effective in treating status epilepticus. A particular difficulty in therapy is caused by benzodiapine-resistant status epilepticus and refractory, which requires consideration of the possibility of using a combination of antiepileptic drugs. The review of foreign and domestic sources presents the results of clinical studies that allow the use of new antiepileptic drugs, which can effectively stop status epilepticus already in the early stages. New antiepileptic drugs are especially relevant in the treatment of patients refractory to drug treatment. However, treatment with antiepileptic drugs does not always show its effectiveness in refractory and super-refractory status epilepticus, which requires new approaches in complex treatment. The tolerance of drugs and the frequency of side effects are important for patients, since most of them require long-term combined use. Correct selection of antiepileptic drugs increases the level of compliance. A special approach requires the treatment of status epilepticus in the context of palliative care and comorbid pathology. In the treatment and prevention of status epilepticus, surgical treatment and the use of a ketogenic diet can be considered.

Influence of new versus traditional antiepileptic drugs on course and outcome of status epilepticus

PurposeNew antiepileptic drugs (AEDs) are increasingly applied in second-line therapy of status epilepticus (SE). In our study, we analyzed the impact of the choice of second-line AEDs on the course and prognosis of SE. MethodsThis retrospective single- center study used data of an 8 year cohort of SE in adults from 2007 to 2014. Based on the year of market introduction with a cutoff at 1990, we classified AEDs as traditional or new. Prescription pattern associated differences in prognosis were measured through univariate and multivariable analysis of 3 endpoints: occurrence of refractory SE (RSE), functional outcome in survivors to discharge (good: mRS at discharge <3 or identical to admission mRS; otherwise poor), and in-hospital mortality. ResultsFrom 362 SE episodes during the study period, 222 episodes were included into the study, among those 150 episodes treated with new and 72 with traditional AEDs. Use of new AEDs increased during the study period. After adjustment for confounders, treatment with new AEDs was on the one hand associated with higher rate of RSE occurrence (OR 1.95, 95 % CI 1.05–3.62, p = 0.03), but, on the other hand, also with better functional outcome at discharge (OR 2.64, 95 % CI 1.16–6.00, p = 0.02), while it was not an independent predictor of in- hospital mortality (OR 0.88, 95 % CI 0.33–2.33, p = 0.80). ConclusionOur observation that new AEDs may be associated with a higher rate of RSE development and relatively better functional outcome when adjusted for the premorbid mRS needs confirmation in prospective studies.

Change in antiepileptic drug prescription patterns for pregnant women with epilepsy over the years: Impact on pregnancy and fetal outcomes.

AIMS AND OBJECTIVES:The objectives of the study were: (1) to determine if there is a change in pattern of antiepileptic drug (AED) prescription during pregnancy in women with epilepsy (WWE) attending a tertiary care institute in North India and (2) to determine if change in AED prescription pattern has resulted in improved fetal and maternal outcomes in WWE.PATIENTS AND METHODS:The current study was a retrospective analysis of records of WWE attending a medical and surgical disorder clinic of obstetrics and gynecology department of a tertiary care teaching hospital in North India. We retrospectively collected data of all the patients during the 5-year period from 2011 to 2015 (Group A) (n = 177) and compared it with our previously published data during the years 1987–1994 (Group B) (n = 219).RESULTS:There was significantly higher use of (i) levetiracetam (LEV) in Group A compared to Group B when women on monotherapy were compared (P<0.0001) and (ii) LEV (P<0.0001), clobazam (P<0.0001) and lamotrigine (P=0.0004) in Group A compared to Group B when women on polytherapy were compared. A significantly higher (P=0.02) number of women were using more than two antiepileptic drugs simultaneously in Group A compared to Group B. There was a significantly higher incidence (P = 0.001) of small for gestational age babies in Group A.CONCLUSION:Although there is an increase in the use of newer AEDs in WWE during pregnancy in North Indian population, it has not resulted in improved maternal and fetal outcomes. (2) to determine if change in AED prescription pattern has resulted in improved fetal and maternal outcomes in WWE.

513: Obstetric outcomes for women receiving newer generation antiepileptic drugs: retrospective cohort study using claims database

Women with epilepsy are at increased risk for adverse pregnancy outcomes. Since the 1990s, over 11 new antiepileptic drugs (AEDs) have been introduced. We aimed to describe the use of newer AEDs in pregnancy and differences in rates of obstetric outcomes. From the Truven Health MarketScan® Commercial Claims and Encounters Database (years 2011-14), we identified women who had a delivery admission, outpatient pharmacy dispenses for newer generation AEDs (Table) and an indication of epilepsy based on diagnosis codes during the 12 months prior to delivery. Obstetric outcomes included preterm birth, cesarean delivery, postpartum hemorrhage, placental abruption, hypertensive disorders of pregnancy, preterm labor, and severe maternal morbidity (SMM). We described the prevalence of the use of newer AEDs and rates of obstetric outcomes and absolute risk difference compared to women without a diagnosis of epilepsy (Table). In the cohort analyzed (n=1,028,125), the prevalence of epilepsy was 0.44% (n=4,528). Overall, 55% (n=2,508) received any of these AEDs during pregnancy, the most common of which were lamotrigine (49.8%) and levetiracetam (42.5%). Compared to the non-epileptic control group, women on AEDs showed significant increases in the absolute risk of cesarean delivery (5.0%), preeclampsia (0.7%), severe preeclampsia/eclampsia (0.9%) and SMM (1.6%). AEDs with the highest increases in absolute risk were topiramate (6.7%) for cesarean delivery, lamotrigine for pre-eclampsia (1.1%), and lacosamide for severe preeclampsia/eclampsia (8.4%) and SMM (9.3%). Of the 2,508 women, 414 (16.5%) received more than one AED during pregnancy. Compared to women receiving a single AED, those who received multiple AEDs had higher absolute risks of all outcomes except postpartum hemorrhage (Table). Compared to non-epileptic women, women on newer generation AEDs demonstrated an increased absolute risk for cesarean delivery, preeclampsia, severe preeclampsia/eclampsia and severe maternal morbidity. Women receiving multiple medications demonstrated the highest increase in absolute risk for adverse outcomes, similar to findings in older AEDs, possibly also reflecting a more complicated and difficult disease state.

The impact of old versus new antiepileptic drugs on costs and patient reported outcomes among older adults

The aim of this prospective questionnaire-based cross-sectional study was to examine whether the new generation of Antiepileptic drugs (AEDs) with higher acquisition cost generate lower adverse effects than the old AEDs among a sample of 102 Arabic-speaking older adults (60 years of age or older) with seizure disorders. The mean scores of the Arabic version of the Liverpool Adverse Events Profile (LAEP), which assessed the adverse effects of the AEDs, did not differ between patients taking the old and new generations of AEDs. Despite their 4-fold higher cost, the new generation of AEDs were not characterized by lower LAEP scores of adverse effects. However, higher LAEP scores were associated with better health literacy. In conclusion, the use of new AEDs was not associated with lower self-reported adverse effects scores among Arabic-speaking older adults with seizure disorders despite their higher acquisition costs.

Development of an algorithm to identify pregnancy episodes and related outcomes in health care claims databases: An application to antiepileptic drug use in 4.9 million pregnant women in France.

PurposeAccess to claims databases provides an opportunity to study medication use and safety during pregnancy. We developed an algorithm to identify pregnancy episodes in the French health care databases and applied it to study antiepileptic drug (AED) use during pregnancy between 2007 and 2014.MethodsThe algorithm searched the French health care databases for discharge diagnoses and medical procedures indicative of completion of a pregnancy. To differentiate claims associated with separate pregnancies, an interval of at least 28 weeks was required between 2 consecutive pregnancies resulting in a birth and 6 weeks for terminations of pregnancy. Pregnancy outcomes were categorized into live births, stillbirths, elective abortions, therapeutic abortions, spontaneous abortions, and ectopic pregnancies. Outcome dates and gestational ages were used to calculate pregnancy start dates.ResultsAccording to our algorithm, live birth was the most common pregnancy outcome (73.9%), followed by elective abortion (17.2%), spontaneous abortion (4.2%), ectopic pregnancy (1.1%), therapeutic abortion (1.0%), and stillbirth (0.4%). These results were globally consistent with French official data. Among 7 559 701 pregnancies starting between 2007 and 2014, corresponding to 4 900 139 women, 6.7 per 1000 pregnancies were exposed to an AED. The number of pregnancies exposed to older AEDs, comprising the most teratogenic AEDs, decreased throughout the study period (−69.4%), while the use of newer AEDs increased (+73.4%).ConclusionsWe have developed an algorithm that allows identification of a large number of pregnancies and all types of pregnancy outcomes. Pregnancy outcome and start dates were accurately identified, and maternal data could be linked to neonatal data.

O-31 Antiepileptic drug (aed) exposure in pregnancy and pregnancy outcome from national drug usage data

Background Antiepileptic drugs (AEDs) taken during pregnancy are known to increase the risk of fetal malfor-mations and potentially affect the neurodevelopment in children exposed. This study aimed to investigate the use of AEDs by pregnant women and women during their childbearing years in New Zealand and the association between AED use and rates of pregnancy termination, spontaneous abortion and stillbirth. Methods Retrospective population based cohort study using administrative databases in New Zealand between 2008 and 2014. Women who had been pregnant were identified by the National Minimum Dataset and were linked to the Pharmaceutical Collection to obtain infor-mation on use of AEDs. Women aged between 15 and 45 years dispensed AEDs were identified in the Pharmaceu-tical Collection. Results There was a significant increase in the number of women of child-bearing potential prescribed AEDs, from 9 women per 1000 women in 2008 to 11.4 wom-en per 1000 women in 2014. Use of the older generation AEDs declined over the time period while use of the newer generation AEDs increased. General practitioners provided 60% of the prescriptions of AEDs to women of child-bearing potential. Women who had been dis-pensed an AED had an increased rate of spontaneous abortion and pregnancy termination compared to those not dispensed an AED, 13.16 spontaneous abortions per 100 pregnancies, compared with, 8.00 per 100 pregnancies (risk ratio 1.64, 95% CI 1.50 to 1.80), and 21.29 terminations per 100 pregnancies compared with 19.50 per 100 pregnancies (risk ratio 1.09, 95% CI 1.02–1.17). Conclusion Use of newer AEDs is increasing in women of child-bearing potential in New Zealand leading to an overall increase in AED use in this group despite a fall in the use of older AEDs. AED use is this study was associat-ed with an increased risk of spontaneous abortion and increased rate of pregnancy termination.

Antiepileptic drug use in Italian children over a decade.

The aim of the study was to evaluate prescription profiles of antiepileptic drugs (AEDs) and to assess hospitalizations and specialist visits in pediatric patients with epilepsy. The data sources were administrative health databases of Italy's Lombardy Region, which collect prescriptions for drugs, diagnostic tests, specialist visits, and hospital discharge forms. All patients aged 0-16years with at least seven AED (group N03A of the International Anatomical Therapeutic Chemical Classification) prescriptions over two consecutive years between 2003 and 2010 were identified and classified as prevalent or incident cases (no prescriptions in two previous years). The first prescription to incident cases was analyzed. For each incident case, drug prescriptions, specialist visits, diagnostic tests, and hospitalizations in the 24months following the first (index) prescription were monitored. A total of 6527 incident cases (5.4/10,000 person-years, 95% CI 5.4-5.5) were identified. Valproic acid and carbamazepine were the most prescribed drugs (65.9 and 15.0%, respectively). The use of newer AEDs increased over time. In the 24-month observation period, 74% of incident cases continued the treatment with the index AED. The percentage of cases who changed therapy was higher in preschoolers (34%) and decreased with age. In all, 21% of incident cases were hospitalized for epilepsy and 86% had a specialist visit in the 24months after the first AED prescription. In conclusion, older AEDs, particularly valproic acid, remained the first therapeutic approach to pediatric epilepsy in Italy. For three quarters of cases, the initial AED treatment was likely effective and well tolerated.

Are Newer AEDs Better Than the Classic Ones in the Treatment of Status Epilepticus?

Several newer antiepileptic drugs have been increasingly used in patients with status epilepticus, especially levetiracetam and lacosamide, because of their intravenous availability. They may offer advantages in terms of tolerability; however, to date, no clear evidence suggests any advantage regarding efficacy after the use of newer antiepileptic drugs in this specific clinical setting. However, there has been a considerable revival of interest regarding some classic compounds, such as midazolam (MDZ), valproate (VPA), ketamine, or ketogenic diet. Awaiting comparative studies, which in part are ongoing, it seems reasonable, for the first choice, to rely on those agents that are best known and less expensive.

Bridging the treatment gap in epilepsy-is there an emerging trend in the use of newer antiepileptic drugs?

Bridging the treatment gap in epilepsy-is there an emerging trend in the use of newer antiepileptic drugs?

Trends in Antiepileptic Drug Prescriptions for Childhood Epilepsy at a Tertiary Children's Hospital in Korea, 2001-2012.

Longitudinal prescription patterns of antiepileptic drugs (AEDs) have not been described to date in Korea. Here we aimed to describe AED prescribing trends over a 12-year period and assess age differences in AED prescribing patterns in a pediatric epilepsy population. We retrieved and analyzed all AED prescribing and dispensing data in 2001-2012 in patients aged 0-18 years with an established diagnosis of epilepsy at the largest tertiary children's hospital in Korea. AEDs included for analysis were classified as older (i.e., carbamazepine, ethosuximide, phenobarbital, phenytoin, and valproic acid) and newer (i.e., gabapentin, lamotrigine, levetiracetam, oxcarbazepine, pregabalin, topiramate, vigabatrin, zonisamide, lacosamide, and rufinamide) on the basis of market availability before versus after 1991. A total of 5593 patients with epilepsy were prescribed an AED during the 12-year period. The proportion of newer AED prescriptions was 52.6 % in 2001 and continuously increased to 74.3 % in 2012. Oxcarbazepine was most widely used, followed by valproic acid. While carbamazepine and vigabatrin use progressively decreased over the 12-year period, those of lamotrigine and topiramate rapidly increased. Age differences in prescribing patterns were observed. Polytherapy was observed in 49.7 % of the total population, while 83.9 % of new users were prescribed monotherapy. This study provided updated information on AED prescription trends for childhood epilepsy. We found a progressive increase in the use of newer AEDs. However, valproic acid, the only prevalent older AED, continued to be widely prescribed. A high rate of polytherapy among the prescriptions overall raises some safety concerns.

Treatment Strategy for Adult Epilepsy: A Current Approach

The current treatment strategy for adult epilepsy will change significantly in the near future after monotherapy as well as adjunctive therapy using new antiepileptic drugs (AEDs), which have been approved. These new AEDs have unique mechanisms of action with or without a broad spectrum. They have advantages of fewer adverse effects, including central nervous system manifestations and teratogenicity, and fewer or no pharmacokinetic drug interactions, although they lack enhanced efficacy compared to the current AEDs. In addition, the new AEDs do not result in adverse effects associated with the long-term use of the previous AEDs, such as osteoporosis and hyperlipidemia. The use of new AEDs is particularly recommended for elderly patients and young women with epilepsy. Further, their use does not result in seizures or cause adverse effects, which is the goal of epilepsy treatment.

Pain Prevention Using Head and Neck Cancer as a Model

Pain is a common and often debilitating consequence of cancer and its treatment. Efforts to improve pain management for patients diagnosed with cancer have not resulted in widespread patient reports of acceptable management of pain. Patients and providers alike remain opiophobic due to a number of issues, resulting in suboptimal management of pain. Recent literature has revealed that it may be possible to prevent pain related to cancer and its treatment and therefore avoid or decrease the amount of opioids used to treat pain. This may result in better quality of life for patients. Several newer antiepileptic drugs (AEDs) have been found to decrease the perception of pain in a number of patient populations, including those with head and neck cancer. The side-effect profile for the newer AEDs is mild and well tolerated. Future efforts should focus on the use of newer AEDs to prevent pain in other cancer populations, with a focus on ideal dose and scheduling. Once established, recommendations regarding the prevention of pain in patients with cancer can be incorporated into national guidelines.

Old versus New: Why Do We Need New Antiepileptic Drugs?

Achieving complete seizure remission without adverse events is the goal of epilepsy treatment. Recently, many new antiepileptic drugs (AEDs) have been developed. Even though the efficacy of new AEDs is not stronger than that of old AEDs, there are advantages in using new AEDs. They have unique or different mechanisms of action that enable the creation of possible synergistic combinations. They usually exhibit fewer or no pharmacokinetic drug interactions. Furthermore, the response to AEDs varies individually. A similar efficacy does not imply a similar response from all patients. Many new AEDs have fewer adverse events, including induction of congenital malformations. Other concerns about the long-term effects of established AEDs, such as bone health and development of atherosclerosis, may be alleviated by the use of new AEDs. New AEDs are needed to achieve better care of patients with epilepsy.

Newer anti-epileptic drugs

A number of newer anti-epileptic drugs have been developed in the last few years to improve the treatment outcomes in epilepsy. In this review, we discuss the use of newer anti-epileptic drugs in children. MEDLINE search (1966-2013) was performed using terms newer anti-epileptic drugs, Oxcarbazepine, vigabatrin, topiramate, zonisamide, levetiracetam, lacosamide, rufinamide, stiripentol, retigabine, eslicarbazepine, brivaracetam, ganaxolone and perampanel for reports on use in children. Review articles, practice parameters, guidelines, systematic reviews, meta-analyses, randomized controlled trials, cohort studies, and case series were included. The main data extracted included indications, efficacy and adverse effects in children. Oxcarbazepine is established as effective initial monotherapy for children with partial-onset seizures. Vigabatrin is the drug of choice for infantile spasms associated with tuberous sclerosis. Lamotrigine, levetiracetam and lacosamide are good add-on drugs for patients with partial seizures. Lamotrigine may be considered as monotherapy in adolescent females with idiopathic generalized epilepsy. Levetiracetam is a good option as monotherapy for females with juvenile myoclonic epilepsy. Topiramate is a good add-on drug in patients with epileptic encephalopathies such as Lennox-Gastaut syndrome and myoclonic astatic epilepsy.

Antiepileptic drugs and breastfeeding

IntroductionThis review provides a synopsis for clinicians on the use of antiepileptic drugs (AEDs) in the breastfeeding mother.MethodsFor each AED, we collected all retrievable data from Hale’s “Medications and Mother Milk” (2012), from the LactMed database (2013) of the National Library of Medicine, and from a MedLine Search of relevant studies in the past 10 years.ResultsOlder AEDs, such as carbamazepine, valproic acid, phenytoin, phenobarbital, primidone are considered to have a good level of safety during lactation, due to the long term clinical experience and the consequent amount of available data from the scientific literature. On the contrary, fewer data are available on the use of new AEDs. Therefore, gabapentin, lamotrigine, oxcarbazepine, vigabatrin, tiagabine, pregabalin, leviracetam and topiramate are compatible with breastfeeding with a less documented safety profile. Ethosuximide, zonisamide and the continue use of clonazepam and diazepam are contraindicated during breastfeeding.ConclusionsAlthough the current available advice on the use of AEDs during breastfeeding, given by different accredited sources, present some contradictions, most AEDs can be considered safe according to our review.

PP178—Antiepileptic Drugs: Prescribing Patterns and Interaction Risk in General Practice

PP178—Antiepileptic Drugs: Prescribing Patterns and Interaction Risk in General Practice

Delivering quality care in epilepsy

The science of quality of care in medicine has been emerging for the past decade, but it has only recently addressed epilepsy care. Quality of care in this sense refers to implementation of policies in large populations to improve care. This can have a large impact on epilepsy patients, as much of their care is delivered by generalists who can improve their care through the explicit direct requirements of quality measures. Eight epilepsy quality performance measures were recently approved by national organizations, but only three were adopted by Medicare and only one by the National Quality Forum. The main reason for not adopting them is the lack of high-level evidence. However, there is high-level evidence for the efficacy of epilepsy surgery and use of newer antiepileptic drugs for the treatment of intractable epilepsy. Other problems are the lack of information about gaps in care and the imprecision in epilepsy diagnosis coding. Quality measurement will continue in epilepsy care, so a working knowledge of the topic is required by healthcare providers. Implementation of standardized quality measures can improve the care of people with epilepsy if the measures have demonstrated efficacy and can address gaps in care, and implementation is feasible.

Comparative safety of antiepileptic drugs during pregnancy

Editors’ Note: Drs. Maheshwari et al. and the article by Hernandez-Diaz et al. discuss questions of methodology in regards to the study “Comparative safety of antiepileptic drugs during pregnancy.” In reference to the article by Hu et al., “Plasma multianalyte profiling in mild cognitive impairment and Alzheimer disease,” in which several peripheral proteins associated with AD are proposed, Dr. Bennett cautions against false-positives and other confounding factors inherent in genome studies. Megan Alcauskas, MD, and Robert C. Griggs, MD # {#article-title-2} Due to the increased use of newer antiepileptic drugs (AEDs), we agree with Hernandez-Diaz et al. that it is vital to assess the efficacy and safety of the same drugs in the general population and in pregnant women, especially regarding teratogenicity.1 We also agree that valproic acid use is not acceptable …

Trends in the use of antiepileptic drugs among pregnant women in the US, 2001-2007: a medication exposure in pregnancy risk evaluation program study.

Little is known about the extent of antiepileptic drug (AED) use in pregnancy, particularly for newer agents. Our objective was to assess whether AED use has increased among pregnant women in the US, 2001-2007. We analysed data from the Medication Exposure in Pregnancy Risk Evaluation Program (MEPREP) database, 1 January 2001 to 31 December 2007. We identified liveborn deliveries among women, aged 15-45 years on delivery date, who were members of MEPREP health plans (n=585615 deliveries). Pregnancy exposure to AEDs, determined through outpatient pharmacy dispensing files. Older AEDs were available for clinical use before 1993; other agents were considered newer AEDs. Information on sociodemographic and medical/reproductive factors was obtained from linked birth certificate files. Maternal diagnoses were identified based on ICD-9 codes. Prevalence of AED use during pregnancy increased between 2001 (15.7 per 1000 deliveries) and 2007 (21.9 per 1000 deliveries), driven primarily by a fivefold increase in the use of newer AEDs. Thirteen per cent of AED-exposed deliveries involved a combination of two or more AEDs. Psychiatric disorders were the most prevalent diagnoses, followed by epileptic and pain disorders, among AED users regardless of AED type, year of conception or gestational period. AED use during pregnancy increased between 2001 and 2007, driven by a fivefold increase in the use of newer AEDs. Nearly one in eight AED-exposed deliveries involved the concomitant use of more than one AED. Additional investigations of the reproductive safety of newer AEDs may be needed.