Search

Background: Convulsive status epilepticus is the most severe form of epilepsy and requires urgent treatment. We synthesised the current evidence on first-line treatments for controlling seizures in adults with convulsive status epilepticus before, or at, arrival at hospital. Methods: We conducted a systematic review of randomised controlled trials (RCTs) assessing antiepileptic drugs offered to adults as first-line treatments. Major electronic databases were searched. Results: Four RCTs (1234 adults) were included. None were conducted in the UK and none assessed the use of buccal or intranasal midazolam. Both intravenous lorazepam and intravenous diazepam administered by paramedics were more effective than placebo and, notably, intramuscular midazolam was non-inferior to intravenous lorazepam. Overall, median time to seizure cessation from drug administration varied from 2 to 15 min. Rates of respiratory depression among participants receiving active treatments ranged from 6.4 to 10.6%. Mortality ranged from 2 to 7.6% in active treatment groups and 6.2 to 15.5% in control groups. Conclusions: Intravenous and intramuscular benzodiazepines are safe and effective in this clinical context. Further research is needed to establish the most clinically and cost-effective first-line treatment and preferable mode of administration. Head-to-head trials comparing buccal versus intranasal midazolam versus rectal diazepam would provide useful information to inform the management of the first stage of convulsive status epilepticus in adults, especially when intravenous or intramuscular access is not feasible. Approaches to improve adherence to clinical guidelines on the use of currently available benzodiazepines for the first-line treatment of convulsive status epilepticus should also be considered. [ABSTRACT FROM AUTHOR]

The widening range of treatment options for epilepsy, and their potential outcomes, mean decisions about treatment for people with epilepsy (PWE) are often complex. While antiepileptic drugs (AEDs) represent the mainstay of treatment, other potential nondrug interventions are gaining in importance. These treatments all have the potential for harming those using them, as well as bringing benefits. This study examined the views and experiences of PWE about a range of treatment options. We used both qualitative and quantitative approaches — a series of depth-narrative interviews, followed by a large-scale survey. Treatment options and healthcare priorities deemed important by at least 10% of interview participants were then addressed as a series of statements in the follow-on survey questionnaire. Quantitative responses supported healthcare priorities identified through the qualitative interviews. The key goal of treatment among study participants was to be able to live 'a normal life'. Important physical, psychological, and life benefits of treatment were identified — most being the direct consequence of improved seizure control. One psychological benefit, reduced worry, was also identified as an important treatment goal. All participants viewed AEDs as appropriate first-line treatment; and since adverse effects of AEDs had implications for individual levels of daily function and wellbeing, their appropriate management was considered important. In contrast, surgery was almost always regarded as the treatment of last resort. Despite lack of research evidence supporting their use, participants were interested in complementary therapies as adjunctive treatment and a means of coping with having epilepsy, with yoga and meditation of particular interest. An important finding was the desire for targeted services to help with memory problems, as was the call to increase availability of psychological/counseling services. Our findings emphasize the importance of providing treatment responsive to the life context of individual patients. They highlight not only the level of demand for specific treatment options, but also the need for high-quality evidence to support future investment in their provision. • We explored UK patient preferences for treatment of epilepsy. • Our study involved a qualitative component, followed by a large-scale survey. • Participants had clearly-formed views and preferences for care, reflecting their personal characteristics and life contexts. • Practitioners need to be mindful of these in discussions about care. • Patients deserve access to high-quality evidence about effectiveness of different treatments. [ABSTRACT FROM AUTHOR]

Abstract The Neurodevelopmental Effects of Antiepileptic Drugs (NEAD) Study was a prospective observational multicenter study in the USA and UK, which enrolled pregnant women with epilepsy on antiepileptic drug (AED) monotherapy from 1999 to 2004. The study aimed to determine if differential long-term neurodevelopmental effects exist across four commonly used AEDs (carbamazepine, lamotrigine, phenytoin, and valproate). In this report, we examine fetal AED exposure effects on learning and memory functions in 221 six-year-old children (including four sets of twins) whose mothers took one of these AEDs during pregnancy. Their performance was compared with that of a national sample of normally developing six year olds from the standardization sample of the Children's Memory Scale (CMS). The major results of this study indicate that the mean performance levels of children exposed to valproate were significantly below that of the children in the normal comparison group across all seven of the CMS Indexes. With one exception, this finding held up at the subtest level as well. These findings taken together with nonsignificant verbal and nonverbal forgetting scores appear to indicate that, as a group, children exposed to valproate experienced significant difficulty in their ability to process, encode, and learn both auditory/verbal as well as visual/nonverbal material. In addition, they exhibited significant difficulty holding and manipulating information in immediate auditory working memory. However, once the information was learned and stored, the valproate-exposed children appeared to be able to retrieve the information they did learn at normal levels. Finally, the processing, working memory, and learning deficits demonstrated by the valproate-exposed children are dose-related. In contrast to valproate, the findings pertaining to the children exposed to carbamazepine, lamotrigine, and phenytoin in monotherapy are less clear. Therefore, further research will be required to delineate the potential risks to learning and memory functions in children exposed to carbamazepine, lamotrigine, and phenytoin in monotherapy during pregnancy. Additional research employing larger prospective studies will be required to confirm the long-term cognitive and behavioral risks to children of mothers who are prescribed these four AEDs during pregnancy as well as to delineate any potential risks of newer AEDs and to understand the underlying mechanisms of adverse AED effects on the immature brain. Highlights • Fetal valproate exposure is associated with difficulty with learning and working memory. • Valproate-exposed children retrieve learned information at normal levels. • Learning and memory deficits associated with fetal valproate exposure are dose-related. • Risks to learning and memory from fetal exposure to other antiepileptic drugs are unclear. [ABSTRACT FROM AUTHOR]

Background: The aim was to analyze safety data associated with the maternal use of antiepileptic drugs in pregnancy and to assess the risk of cleft lip and/or palate (CL/P) as an outcome in the neonate. A parallel objective was to assess the completeness of the safety information concerning pregnancy exposures in the Summary of Product Characteristics (SmPCs) and the Patient Information (PI) in the USA and the UK. Methods: We analyzed individual case safety reports of CL/P associated with antiepileptic drugs in the FDA Adverse Event Reporting System. For the antiepileptic drugs with signals (EB05 ≥ 2), we reviewed Drug Analysis Prints for CL/P cases in the UK Medicines and Healthcare products Regulatory Agency (MHRA). We performed descriptive analyses of relevant SmPCs and PIs in the UK and the USA using a checklist of recommendations collected from the literature. Results: In total 817 CL/P reports were identified for 12 antiepileptic drugs in the FDA Adverse Event Reporting System. Ten of the 12 antiepileptic drugs were associated with 156 CL/P cases in the MHRA Sentinel. Safety information concerning pregnancy was found to be more comprehensive in UK SmPCs than in the US equivalents. Conclusions: There is statistical disproportionality in individual case safety reports indicative of an increased risk of CL/P with 12 antiepileptic drugs studied. More studies are required to explore the association between in utero exposure to antiepileptic drugs and the risk of CL/P. There are inconsistencies between the UK and US safety labels. CL/P associated with antiepileptic drugs is an important topic and requires providing inclusive, unbiased, up-to-date information to prescribers and women of childbearing age. [ABSTRACT FROM AUTHOR]

Epilepsy affects around 1 in 100 people and every year around 2500 women with epilepsy become pregnant. Although most will have an uneventful pregnancy, pregnancy for women with epilepsy carries additional risks to their wellbeing and that of their developing fetus and their infant. For some women, these risks include worsening symptoms of epilepsy, increased mortality risks and less effective treatment of other conditions and comorbidities like depression. For the developing fetus and infant, exposure to antiepileptic drugs can affect organogenesis and later development. This article highlights essential knowledge about this condition in pregnancy and considers how midwives can contribute to working collaboratively in ways that optimise pregnancy outcomes for these women. [ABSTRACT FROM AUTHOR]

Purpose Perampanel (PER) was first licensed in the United Kingdom in 2012 for the adjunctive treatment of focal seizures with or without secondary generalization in adults and children over 12 years of age. It has recently also been approved for use as add-on therapy for patients with primary generalized tonic–clonic seizures. This prospective audit reports preliminary outcomes with adjunctive PER in patients with focal-onset seizures in everyday clinical practice using a standard design. Methods To date, 54 patients (38 males, 16 females; 21–65 years, median: 48 years) have completed the study. The median monthly seizure frequency was 4 (range: 1–60). At baseline, patients were taking a median of 2 other antiepileptic drugs (range: 1–4 drugs), with their seizures having previously failed to improve on a median of 3 schedules (range: 1–15 schedules). After 12 weeks of stable dosing, PER was added, aiming at a target range of 6–12 mg/daily. Review took place every 6–8 weeks until one of 4 endpoints was reached: seizure freedom for ≥ 6 months on a given PER dose, ≥ 50% (responder) or < 50% (marginal effect) seizure reduction over 6 months, compared with the prospective baseline, on the highest tolerated PER dose, or withdrawal of PER due to a lack of efficacy or side effects. Results Three (5.6%) patients have remained seizure-free, with 8 (14.8%) demonstrating a ≥ 50% response and a further 17 (31.5%) reporting a marginal effect. Of the 26 (48.1%) dropping out of PER treatment, 21 (38.9%) did so because of side effects. The commonest problems were nausea, vomiting, ataxia, dizziness, and sedation. Overall, 6 (11%) patients developed neuropsychiatric problems, with 3 reporting irritability and/or aggression. Two patients had substantial weight gain, and another patient suffered recurrent falls. Treatment with enzyme-inducing AEDs had no effect on PER dosing in patients responding to PER or withdrawing due to side effects. Significance These data support the value of adjunctive PER in some patients with pharmacoresistant epilepsy in everyday clinical practice. [ABSTRACT FROM AUTHOR]

Abstract: Background and objective: Current evidence indicates long-term use of antiepileptic drugs (AEDs) is associated with impaired childhood bone health. The objective of this study was to ascertain the current clinical practice of paediatric neurologists managing children with epilepsy on long-term (>2 years) AED therapy, particularly against the UK Medicines and Healthcare products Regulatory Agency (MHRA) current recommendation of vitamin D supplementation in patients on long-term AEDs at-risk of impaired bone health. Methods: An internet-based survey of UK paediatric neurologists who routinely see children with epilepsy (n = 95) covered clinicians’ epilepsy case-load and reflection on their current clinical practice with estimation of the frequency with which they considered various bone health issues. Responses were graded as ‘frequent’(≥50%), ‘sometimes’(25%–50%) and ‘infrequent’(<25%). Results: Overall response rate was 72/95 (76%). 3% frequently recommend prophylactic calcium and vitamin D supplementation, 6% frequently perform bone screening investigations, 7% frequently give bone health advice and 10% frequently enquire about skeletal risk factors. Clinical practices were not associated with epilepsy caseload (p-values 0.44–1). 84% infrequently performed bone health screening investigations. 54% of respondents indicated that, if performed, 100% would undertake bone profile, 64% 25(OH) Vitamin D, 18% PTH, 49% dual energy X-ray absorptiometry (DEXA) scan and 13% bone X-ray. Conclusions: The majority of paediatric neurologists do not routinely consider bone health related issues in children on long-term AEDs. Greater emphasis should be placed on vitamin D supplementation in these children. [Copyright &y& Elsevier]

Abstract: Research on antiepileptic drug (AED) teratogenesis has demonstrated an increased risk for valproate. The impact of these findings on current AED prescribing patterns for women of childbearing age with epilepsy is uncertain. The Neurodevelopmental Effects of Antiepileptic Drugs (NEAD) Study is an ongoing prospective multicenter observational investigation that enrolled pregnant women with epilepsy on the most common AED monotherapies from October 1999 to February 2004 (carbamazepine, lamotrigine, valproate, and phenytoin). A 2007 survey of AED use in women of childbearing age at eight NEAD centers found a total of 932 women of childbearing age with epilepsy (6% taking no AED, 53% monotherapy, 41% polytherapy). The most common monotherapies were lamotrigine or levetiracetam. Since 2004, prescriptions of carbamazepine, phenytoin, and valproate have decreased, whereas those for levetiracetam have increased. Except for the top two AED monotherapies, there were marked differences in other monotherapies and in polytherapies between U.S. and UK centers. Future investigations are needed to examine reasons for drug choice. [Copyright &y& Elsevier]

Purpose: To assess the association between exposure to antiepileptic drugs (AEDs) and the occurrence of aplastic anemia. Methods: A retrospective case–control study was conducted using data from the U.K. General Practitioners Research Database (GPRD). Cases were defined as patients diagnosed with aplastic anemia. For each case, up to three control patients were matched on age, sex, and medical practice. Cases and controls were compared with respect to AED use. The effects of duration of AED use were assessed. Characteristics of individual cases with AED use were reviewed. Results: The study population comprised 173 cases and 497 controls. AED use was more prevalent among cases (9.2%) than among controls (0.8%). After adjustment for confounders, the use of AEDs was significantly associated with aplastic anemia (adjusted odds ratio (OR), 9.5; 95% confidence interval (CI), 3.0–39.7). The most frequently used AEDs were carbamazepine (CBZ), valproic acid (VPA), and phenytoin. The 16 exposed cases were heterogeneous with respect to patient and exposure characteristics: the age of these patients varied from 1 to 92 years, and the duration of AED use varied from 17 days to 6.8 years. Conclusions: This study indicates that use of AEDs, in particular CBZ and VPA, is associated with a ninefold increased risk of aplastic anemia. Physicians should be alert to the possibility of AED-associated aplastic anemia. [ABSTRACT FROM AUTHOR]

The incidence and prevalence of epilepsy increase substantially with old age. Despite this, the investigation and management of this patient population remains a grey area. Four hundred and eleven (53%) consultant geriatricians responded to a questionnaire exploring their approach to seizures in the elderly in order to establish an overview of current clinical practice. Between one and five patients presenting with seizures, predominantly aged between 75-85 years, were reviewed monthly. Seventy per cent of geriatricians undertook to investigate the patients themselves with biochemical and haematological profiles performed by most. Electroencephalography and computerized tomographic scanning were routinely requested by a quarter of responders. Only 58% would themselves initiate therapy with antiepileptic drugs, with 16% of consultants starting treatment following the first seizure, 59% after a second and 5% after a third. Phenytoin was first choice for generalized tonic-clonic seizures with carbamazepine preferred for partial seizures. If good control was not obtained, 67% would substitute another first line drug, while 27% would add in a second. Less than 3% would use the new anticonvulsants lamotrigine or vigabatrin. Sixty per cent monitored anticonvulsant concentrations in patients with poor control or suspected toxicity. A wide variability was seen in the current approach to seizures in the elderly, which reflects a lack of established practice. Epilepsy clinics for the elderly would encourage structured research into the many unanswered questions affecting the care of older people with seizures. [ABSTRACT FROM AUTHOR]

Purpose: To study patterns of antiepileptic drugs (AED) prescribing, particularly valproate, during pregnancy over a 10-year period in the UK, Italy, and France., Methods: Data on pregnancies conceived after 1 January 2007 with outcomes before 31 December 2016 were extracted from four European electronic health care databases (380 499 in the United Kingdom (UK), 66 681 in France, and 649 918 in Italy [355 767 in Emilia Romagna and 294 151 in Tuscany]). Prevalence of AEDs with an ATC code starting N03A and clobazam (N05BA09) were stratified by country and calendar year., Results: AED prescribing during pregnancy varied from 3.0 (2.8-3.1) per 1000 pregnancies in Emilia Romagna to 7.8 (7.5-8.0) in the UK, 5.9 (5.6-6.1) in Tuscany, and 6.3 (5.7-6.9) in France. Lamotrigine was commonly prescribed in all regions with a third of women exposed to an AED during pregnancy taking lamotrigine in the UK and France. Valproate was prescribed to 28.6% of AED exposed pregnant women in Tuscany, 21.6% in France, 16.7% in Emilia Romagna, and 11.9% in the UK. Over the study period, the prevalence of AED prescribing increased in the UK mainly due to increases in pregabalin and gabapentin, declined in France mainly related to decreases in clonazepam, and remained constant in Italy. Valproate prescriptions declined to a prevalence <1 per 1000 pregnancies in 2015 to 2016 in the UK, France, and Emilia Romagna., Conclusions: Variations in AED prescribing during pregnancy indicate the potential for further reductions, particularly of valproate. Increases in pregabalin/gabapentin prescribing, for which risks are not well known, are a cause for concern., (© 2019 John Wiley & Sons, Ltd.)

Objective: Small prospective studies have identified that children exposed to valproate in utero have poorer scores on cognitive testing. We wanted to identify whether children exposed to antiepileptic drugs (AEDs) in utero have poorer school performance., Methods: We used anonymised, linked, routinely collected healthcare records to identify children born to mothers with epilepsy. We linked these children to their national attainment Key Stage 1 (KS1) tests in mathematics, language and science at the age of 7 and compared them with matched children born to mothers without epilepsy, and with the national KS1 results. We used the core subject indicator (CSI) as an outcome measure (the proportion of children achieving a minimum standard in all subjects) and the results in individual subjects., Results: We identified 440 children born to mothers with epilepsy with available KS1 results. Compared with a matched control group, fewer children with mothers being prescribed sodium valproate during pregnancy achieved the national minimum standard in CSI (-12.7% less than the control group), mathematics (-12.1%), language (-10.4%) and in science (-12.2%). Even fewer children with mothers being prescribed multiple AEDs during pregnancy achieved a national minimum standard: CSI (by -20.7% less than the control group), mathematics (-21.9%), language (-19.3%) and science (-19.4%). We did not observe any significant difference in children whose mothers were prescribed carbamazepine or were not taking an AED when compared with the control group., Conclusions: In utero exposure to AEDs in combination, or sodium valproate alone, is associated with a significant decrease in attainment in national educational tests for 7-year-old children compared with both a matched control group and the all-Wales national average. These results give further support to the cognitive and developmental effects of in utero exposure to sodium valproate as well as multiple AEDs, which should be balanced against the need for effective seizure control for women during pregnancy., Competing Interests: Competing interests: WOP is supported by Health and Social Care Research Wales in the form of a WCAT clinical lectureship. RHT is supported by Health and Social Care Research Wales in the form of a WCAT clinical lectureship; receives/has received research support from Epilepsy Research UK, Action Medical Research, Epilepsy Action and the Dravet Society; is an associate editor of Practical Neurology and web editor of Seizure ; and has received honoraria from Eisai, Sanofi and UCB. The authors confirm that they have read the Journal’s position on issues involved in ethical publication and affirm that this report is consistent with those guidelines., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Objective: To compare patient characteristics and treatment patterns among clobazam (CLB) and clonazepam (CZP)-treated patients with epilepsy in a longitudinal primary care database., Methods: In this pharmacoepidemiological study, real-life usage data from the Clinical Practice Research Database (CPRD) were evaluated. The CPRD collects data from approximately 690 primary care practices throughout the UK. Data included were from patients with ≥1 incident CLB or CZP prescription from 1995 to 2011 and were present in the database for ≥182 days prior to the index date (date patient was first prescribed CLB or CZP within the study period)., Results: Of 21,099 patients who met inclusion criteria, 18.4% were receiving CLB and 81.6% were receiving CZP. More patients used CLB for epilepsy than CZP (76.1% vs 8.7%). CLB-treated adults (≤18years) were younger than those treated with CZP (41.0 vs 48.2 years; p<0.001), while CLB-treated children (≤18 years) were older than those treated with CZP (8.8 vs 7.3 years, p<0.001). The median CLB dosage did not change from baseline to last follow-up, while median CZP dosage increased 25% in adults and 50% in children. Median treatment duration, as well as retention rate up to 10 years, was similar between CLB and CZP in each age group., Conclusions: Among adult and pediatric patients in the UK, CLB is more often prescribed for epilepsy than CZP. The median CLB dosage used by both adults and children remained stable over the 16-year study period, while the median CZP dosage increased in both adults and children., (Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.)