Prescription Of Antiepileptic Drugs Research Articles

From Diagnosis to Treatment: A Comprehensive Review of Biomarkers and Therapeutic Advances in Parkinson’s Disease

Background Parkinson’s disease (PD) is a progressive neurodegenerative disorder characterized by the loss of dopaminergic neurons, resulting in motor symptoms. Ongoing research shows promise for long-term solutions. Summary Studies highlight the dysregulation of Syt11 and α-synuclein (α-syn) in PD. Disrupted α-syn homeostasis due to palmitoylation of Syt11 contributes to its aggregation, potentially playing a role in PD pathology. α-synuclein aggregates in stool samples show promise as an early diagnostic biomarker. Vocal impairments in PD may be linked to α-syn-induced neuropathology. Irisin, produced after exercise, promotes the degradation of pathologic α-syn. Progress has been made in identifying PD biomarkers. Retinal thinning and abnormal protein aggregates in skin biopsies provide noninvasive diagnostic indicators. Blood-based biomarkers like α-syn, DJ-1, and LRRK2 hold promise but face limitations. Artificial intelligence (AI) models enhance mitophagy, detect PD through sleep-breathing signals, and improve survival. AI analysis aids noninvasive assessment and risk prediction. Further understanding of PD involves studying pathological seeds and genetic mutations. Adenosine receptor regulation relates to early-onset PD, and specific gene mutations impact patient survival. Differentiated-induced pluripotent stem cells offer the potential for cell replacement therapy. Autoimmune features and T-cell involvement suggest intervention targets. Stem cell-based therapies and neurostimulation strategies show promise for improving motor function. Imaging reveals increased central inflammation in PD, suggesting an inflammatory role. Machine learning algorithms and home gait speed monitoring aid in diagnosis and disease progression tracking. Abnormal putamen gradients reflect dopaminergic loss and motor dysfunction. Antiepileptic drug prescriptions are associated with an increased PD risk. Personalized medicine, gut–brain axis involvement, and vestibular stimulation therapy offer potential PD treatment avenues. Genetic engineering techniques and deep brain stimulation show promise for alleviating PD symptoms. Key Message Ongoing research and technological advancements promise to improve PD screening, diagnosis, and treatment, bringing hope to affected individuals.

Prescribing of valproate and oral antiepileptics for women of childbearing age and during pregnancy in Germany between 2010 and 2020.

To examine prescriptions of valproate and oral antiepileptic drugs (OAED) in Germany irrespective of the indication in women in general and particularly in women of childbearing age (13-49 years) and during pregnancy between 2010 and 2020, that is, before, during and after the implementation of the EU risk minimization measures (RMMs). Analysis of claims data. all women continuously insured with the AOK health insurance fund in the respective observation year (2010-2020) and the previous year. OAED were identified by ATC code N03. Period of pregnancy was calculated based on birth information in claims data. (i) prevalent use of valproate/OAED: number of women with at least one prescription of valproate/OAED per year divided by all women of the study population (rate per 1000 women); (ii) percentage of OAED recipients with at least one valproate prescription during pregnancy (13-49 years) in the respective observation year. Prevalence rate/1000 women for valproate use decreased by -31.33% across all age groups (2010-2014: -7.48%; 2014-2018: -16.47%; 2018-2020: -11,17%) with a strong reduction in women 13-49 years between 2014 and 2018 (-28.74%). The rate for OAED across all age groups rose from 33.43/1000 women in 2010 to 41.03/1000 (+22,73%). Valproate use during pregnancy of women with OAED declined from 1.29% in 2010 to 0.59% in 2020 (-54,26%) (2010-2014: -5.14%; 2014-2018: -42.31%; 2018-2020: -16.69%). Even if, due to the descriptive nature of the study, no causal relationship can be postulated between the RMMs and the strong decrease in valproate prescriptions, our results are compatible with the hypothesis that the measures have improved drug therapy safety.

PRESCRIPTION PATTERN OF ANTIEPILEPTIC DRUGS IN CHILDREN WITH EPILEPSY: A CROSS-SECTIONAL STUDY

Objective: To evaluate the pattern of prescription of antiepileptic drugs (AED) in children with epilepsy attending a tertiary care hospital in North India. Methods: An observational cross-sectional study was conducted for a duration of 1 year. Data on demographic variables including age, gender, type of epilepsy, and prescription of all AEDs and their different combinations were collected from the patients of epilepsy coming to the Department of Pediatrics, Rajindra Hospital attached to Government Medical College, Patiala, Punjab, India and analyzed using WHO core prescription indicators. Results: Out of 100 prescriptions analyzed, 55% of patients were males and 45% were females. The mean age of patients was 8.65 years (±3.80). Generalized epilepsy (78%) was the most commonly diagnosed epilepsy. 92% of patients were prescribed monotherapy, while polytherapy was used in 8% of patients. Valproate was the most common drug used in monotherapy (44.56%), followed by phenytoin (21.74%) and phenobarbitone (15.22%). In polytherapy, the most common combination used was valproate with clobazam (62.5%). 96.6% of prescriptions were based on the National List of Essential Medicines (NLEM), 2022. Conclusion: Monotherapy was the preferred modality of treatment in our hospital. Conventional drugs were favored in monotherapy, while benzodiazepines and newer drugs were more commonly used as an add-on drugs in polytherapy. Valproate was the most commonly used AED in monotherapy as well as polytherapy.

Seizures and chronic kidney disease: An in-depth review

Seizures are not uncommon in patients with chronic kidney disease (CKD), with an approximate incidence of roughly 10%. There are two primary groups: Patients who develop acute provoked seizures in the setting of CKD and patients with pre-existing epilepsy who then develop CKD. The recognition of potential etiology and management of seizures in this patient population may be challenging for clinicians, particularly non-neurologists. Standard antiepileptic drug (AED) treatment is indicated for those with pre-existing epilepsy. The prescription of AED in CKD population requires careful consideration, due to potentially altered pharmacokinetics. Clinicians frequently encounter challenges in the selection, loading, titration, and maintenance of AEDs. There are few internationally recognized consensus recommendations for AED prescription in CKD and dialysis. Non-AED management aims at addressing factors that may have provoked the seizure. In this article, we provide an in-depth review of the potential etiologies and pathophysiological pathways of provoked seizures in CKD. We discuss strategies, including non-AED treatment options, which aim to prevent, and/or manage provoked seizures in the setting of CKD. We discuss the AEDs used in contemporary clinical practice and how their metabolism is affected by CKD, concurrent AED prescriptions, and dialysis.

Association between Antiepileptic Drugs and Incident Parkinson’s Disease among Patients Followed in German Primary Care Practices

The aim of this study was to analyze whether prescriptions of antiepileptic drugs (AEDs) are significantly associated with an increased incidence of Parkinson's disease (PD) in the German population. This study used data from German primary care practices found in the Disease Analyzer database (IQVIA) and included all patients aged ≥18 years who were diagnosed with PD between January 2010 and December 2021 (index date). The controls were patients without PD matched (1:1) by age, sex, and pre-diagnostic observation time in years. Associations between AED prescriptions (any AED as well as separate evaluations for carbamazepine, lamotrigine, levetiracetam, sodium valproate, gabapentin, and pregabalin) and subsequent diagnosis of PD were examined using a logistic regression model adjusted for epilepsy, restless legs syndrome, and neuropathy diagnoses. We identified 24,950 cases that were matched with 24,950 controls (mean age 75.2 years, 47.3% women). Diagnoses of epilepsy, restless legs syndrome, and neuropathy as well as AED prescription were significantly associated with an increased incidence of PD. In the multivariate analysis, incidence of PD was significantly associated with epilepsy (OR: 1.91; 95% CI: 1.69-2.15), restless legs syndrome (OR: 3.02; 95% CI: 2.73-3.34), and neuropathy (OR: 1.53; 95% CI: 1.44-1.62)), as well as the prescription of any AED (OR: 1.43; 95% CI: 1.33-1.53), sodium valproate (OR: 2.39; 95% CI: 1.84-3.11), gabapentin (OR: 1.36; 95% CI: 1.22-1.52), and pregabalin (OR: 1.28; 95% CI: 1.15-1.41). Conclusion: Prescriptions of AEDs, including sodium valproate, gabapentin, and pregabalin, were associated with an increased risk of subsequent PD, even after adjustment for underlying diagnoses. Further studies are needed to confirm the present results.

Use of Antiepileptic Drugs and Risk of Prostate Cancer: A Nationwide Case-Control Study in Prostate Cancer Data Base Sweden.

An inverse association between use of antiepileptic drugs (AEDs) and prostate cancer (PCa) has been suggested, putatively due to the histone deacetylases inhibitory (HDACi) properties of the AEDs. In a case-control study in Prostate Cancer data Base Sweden (PCBaSe), PCa cases diagnosed between 2014 and 2016 were matched to five controls by year of birth and county of residence. AED prescriptions were identified in the Prescribed Drug Registry. Odds ratios (ORs) and 95% confidence intervals for risk of PCa were estimated using multivariable conditional logistic regression, adjusted for civil status, education level, Charlson comorbidity index, number of outpatient visits, and cumulative duration of hospital stay. Dose responses in different PCa risk categories and HDACi properties of specific AED substances were further explored. 1738/31591 (5.5%) cases and 9674/156802 (6.2%) controls had been exposed to AED. Overall, users of any AED had a reduced risk of PCa as compared to nonusers (OR: 0.92; 95% CI: 0.87-0.97) which was attenuated by adjustment to healthcare utilisation. A reduced risk was also observed in all models for high-risk or metastatic PCa in AED users compared to nonusers (OR: 0.89; 95% CI: 0.81-0.97). No significant findings were observed for dose response or HDACi analyses. Our findings suggest a weak inverse association between AED use and PCa risk, which was attenuated by adjustment for healthcare utilisation. Moreover, our study showed no consistent dose-response pattern and no support for a stronger reduction related to HDAC inhibition. Further studies focusing on advanced PCa and PCa treatments are needed to better analyse the association between use of AED and risk of PCa.

Quality of epilepsy care in a rural and deprived Scottish population.

Epilepsy is among the commonest neurological disorders globally. Appropriate prescription and good adherence to anticonvulsants can achieve seizure freedom rates of 70%. Scotland is an affluent nation with free at point-of-access health care but there remain significant healthcare inequalities, particularly associated with deprivation. Anecdotally, epileptics in rural Ayrshire rarely engage with healthcare services. We describe the prevalence and management of epilepsy in a deprived and rural Scottish population. Electronic records were used to obtain the following for patients with coded diagnoses of 'Epilepsy' or 'Seizures' within a general practice list of 3500 patients: demographics; diagnosis; seizure types; date and level (primary, secondary) of last review; last seizure date; anticonvulsant prescription; adherence; and any clinic discharge due to non-attendance. 92 patients were coded as above. 56 had a current diagnosis of epilepsy (prev 16.1/100,000). 69% had good adherence. 56% had good seizure control, with adherence associated with control. Of the 68% managed by primary care, 33% were uncontrolled and 13% had had an epilepsy review in the previous year. 45% of patients referred to secondary care were discharged for non-attendance. We demonstrate a high prevalence of epilepsy, low anticonvulsant adherence and sub-optimal rates of seizure freedom. These may be linked to poor attendance at specialist clinics. Management in primary care is challenging as evidenced by low review rates and high rates of ongoing seizures. We propose that the synergistic factors of uncontrolled epilepsy, deprivation and rurality make it difficult to attend clinics, with resultant health inequalities.

Association Between Antiepileptic Drugs and Incident Parkinson Disease

Recent studies have highlighted an association between epilepsy and Parkinson disease (PD). The role of antiepileptic drugs (AEDs) has not been explored. To investigate the association between AEDs and incident PD. This nested case-control study started collecting data from the UK Biobank (UKB) in 2006, and data were extracted on June 30, 2021. Individuals with linked primary care prescription data were included. Cases were defined as individuals with a Hospital Episode Statistics (HES)-coded diagnosis of PD. Controls were matched 6:1 for age, sex, race and ethnicity, and socioeconomic status. Prescription records were searched for AEDs prescribed prior to diagnosis of PD. The UKB is a longitudinal cohort study with more than 500 000 participants; 45% of individuals in the UKB have linked primary care prescription data. Participants living in the UK aged between 40 and 69 years were recruited to the UKB between 2006 and 2010. All participants with UKB-linked primary care prescription data (n = 222 106) were eligible for enrollment in the study. Individuals with only a self-reported PD diagnosis or missing data for the matching variables were excluded. In total, 1477 individuals were excluded; 49 were excluded due to having only self-reported PD, and 1428 were excluded due to missing data. Exposure to AEDs (carbamazepine, lamotrigine, levetiracetam, and sodium valproate) was defined using routinely collected prescription data derived from primary care. Odds ratios and 95% CIs were calculated using adjusted logistic regression models for individuals prescribed AEDs before the first date of HES-coded diagnosis of PD. In this case-control study, there were 1433 individuals with an HES-coded PD diagnosis (cases) and 8598 controls in the analysis. Of the 1433 individuals, 873 (60.9%) were male, 1397 (97.5%) had their race and ethnicity recorded as White, and their median age was 71 years (IQR, 65-75 years). An association was found between AED prescriptions and incident PD (odds ratio, 1.80; 95% CI, 1.35-2.40). There was a trend for a greater number of prescription issues and multiple AEDs being associated with a greater risk of PD. This study, the first to systematically look at PD risk in individuals prescribed the most common AEDs, to our knowledge, found evidence of an association between AEDs and incident PD. With the recent literature demonstrating an association between epilepsy and PD, this study provides further insights.

Adherence to Prophylactic Anticonvulsant Guidelines for Newly Diagnosed Brain Tumor Patients: A Quality Improvement Study.

Clinical guidelines suggest that prophylactic antiepileptic drugs (AEDs) should be given to newly diagnosed seizure-naive brain tumor patients for up to 1 week after craniotomy. Yet, data suggest that prophylactic AEDs are used up to 12 months after surgery. A quality improvement project was implemented to improve adherence to evidence-based prophylactic AED guidelines. A quasi-experimental, pre- and post-test intervention design was used to assess the effect of a multiphase intervention on guideline adherence and prophylactic anticonvulsant prescription rates. The 16-week intervention consisted of provider education sessions, provider alerts, documentation templates, and a weekly audit and feedback. Participants included four providers and newly diagnosed seizure-naive brain tumor patients. Measures included guideline adherence rates and AED prescription rates extracted from chart review, and a provider attitude and knowledge survey. Analyses included descriptive statistics, Wilcoxon signed-rank tests, and Chi-square tests. Guideline adherence increased significantly (p < .01) from 4 months before implementation (15.8%) to 1 year before implementation (27.8%) and then to 93.3% after implementation. Provider knowledge showed clinically meaningful decreases in the likelihood to prescribe prophylactic AEDs (-.5 point) and increased understanding of prophylactic AED side effects (+0.5 point), although these were not statistically significant (p = .083). Finally, prophylactic AED prescription rates decreased by 2.2% (p = .119) compared with 4 months and 1 year before implementation (2.6%; p = .072). This project highlights the important role of provider education, provider alerts, a documentation template, and audit and feedback in improving guideline adherence rate. Findings suggest that the combination intervention and weekly audit and feedback strategy can improve guideline adherence to prophylactic anticonvulsant use in seizure-naive newly diagnosed brain tumor patients. By following prophylactic AED guideline recommendations, clinicians can avoid the potential side effects of anticonvulsant-induced cognitive, behavioral, and psychiatric issues that can impair patients' quality of life.

Race and the emergency department management of febrile seizures.

To determine if racial disparities exist in the management of febrile seizures in a large pediatric emergency department (ED), We performed a retrospective cross-sectional analysis of children 6 months to 6 years-old who presented to the ED with a febrile seizure over a 4-year period. Multivariate logistic regression models were built to examine the association between race and the primary outcome of neuroimaging, and secondary outcomes of hospital admission and abortive anticonvulsant prescription at ED discharge. There were 980 ED visits during the study period. Overall, 4.0% of children underwent neuroimaging and 11.1% were admitted. Of the 871 children discharged from the ED, 9.4% were prescribed an abortive anticonvulsant. There were no differences by race in neuroimaging or hospital admission. However, black children were less likely to be prescribed abortive anticonvulsants (adjusted odds ratio [aOR] 0.47; 95% confidence interval [CI]: 0.23–0.96) compared to non-black peers, when adjusting for demographic and clinical confounders. Stratification by insurance revealed that this disparity existed in Medicaid-insured patients (aOR 0.33, 95% CI: 0.14–0.78) but not in privately-insured patients. We found no racial disparities in neuroimaging or hospital admission among ED patients with febrile seizures. We did find racial disparities in our secondary outcome of abortive anticonvulsant prescription, driven primarily by individuals on Medicaid insurance. This pattern of findings may reflect the lack of standardized recommendations regarding anticonvulsant prescription, in contrast to the guidelines issued for other ED management decisions. Further investigation into the potential for treatment guidelines to reduce racial disparities is needed.

The utility of hematological indices in differentiation between general and focal onset epilepsy

Introduction and Aim: Epilepsy is one of the most common neurological disorders with mainly focal and generalized onset types. Discrimination between these types is of paramount importance because the prescription of antiepileptic drugs (AEDs) depends on such decimation. Currently this made mainly upon the medical history of the patient. The aim of the study is to evaluate the role of hematological indices in discrimination between focal and generalize onset epilepsy. Patients and Methods: This cross-sectional study included a total of 100 patients with epilepsy (mean age 21.44±10.5, range 6-52, 67 males and 33 females). Blood samples were collected for the participant and complete blood count (CBC) was performed. Furthermore, serum concentration of K+ and Na+ was determined. Results: There were 38 patients with generalized and 62 patients with focal onset epilepsy. In multivariate initial analysis, each of mean platelet volume (MPV) (odds ratio (OR)= 2.56, 95%CI=1.09-13.22, p= 0.046) and serum Na+ (OR= 3.85, 95%CI=1.13-13.19, p= 0.032) were significantly associated with generalized onset epilepsy. Furthermore, two AEDs: carbamazepine and valproic acid were also independently associated with generalized and local onset epilepsy, respectively. Conclusion: These data indicate the possible utility of MPV in the discrimination between generalized and focal onset epilepsy. However, further studies are required for more reliable conclusions.

National assessment of anti-epileptic drug exposures among pre-teens and adolescents, 2000–2020

Background and objectives Anti-epileptic drugs (AEDs) are increasingly used to treat psychiatric conditions, exposing many children to potentially harmful medications. This includes adolescents, who are at higher risk for self-harm. The purpose of this study was to describe the epidemiology of pediatric AED poisonings and assess which AEDs are associated with more severe clinical outcomes. Methods This retrospective cross-sectional analysis examined single-substance AED exposure cases in pre-teens (10–14 years) and adolescents (15–19 years) reported to the National Poison Database System (NPDS) between 2000 and 2020 (cases through 2019 were included for trend analysis due to incomplete population data). We described characteristics of ingestions by age group, including AEDs implicated. Results There were 74,818 AED exposure cases reported to the NPDS, including 25,928 (34.7%) in pre-teens and 48,890 (65.3%) in adolescents. Among adolescents, 35,570 (72.8%) exposure cases were intentional, with 27,655 (56.6%) specifically related to a suspected suicide attempt. The most common AEDs implicated in poisonings were clonazepam (19.8%), valproic acid (15.3%), and lamotrigine (13.8%). The odds of hospitalization (adjusted odds ratio [aOR] 2.0 [95% confidence interval [CI], 2.0–2.1]), intubation (aOR 2.1 [95% CI, 1.8–2.4]), seizure (aOR 1.6 [95% CI, 1.4–1.9]), and serious outcome (aOR 1.8 [95% CI, 1.7–1.9]) were higher in the adolescent group compared to the pre-teen group. Intentional ingestions increased by a yearly rate of 2.8% (95% CI, 2.3–3.2). Intentional tiagabine exposure was associated with the greatest increased odds of serious outcome (aOR 4.7 [95% CI, 3.6–6.3]). Discussion In this cross-sectional analysis of pediatric AED exposure cases reported to the NPDS, AED poisonings among pre-teens and adolescents increased significantly between 2000 and 2019. Of particular concern is the large increase in intentional exposure cases related to AEDs. With the population-adjusted rate of epilepsy diagnoses remaining relatively unchanged, these results may indicate that the rise in AED exposure cases may be related to increased prescribing of AEDs for psychiatric indications as opposed to epilepsy. Conclusions Pediatric AED poisonings reported to the NPDS are increasing, especially among adolescents engaging in intentional ingestions. These findings provide additional information for consideration in risk-benefit assessments when selecting medications for the treatment of psychiatric conditions in children.

First afebrile seizures: Clinical and radiological view with emergent testing.

The first afebrile seizures in children are an important and common reason for emergency department admissions. We aim to examine the presentation, laboratory/neurodiagnostic investigation, and emergency management of children with first afebrile seizures. The retrospective study included 333 patients aged 1 month to 18 years admitted with a first afebrile seizure to the pediatric emergency department of Prof. Dr. Cemil Taşcıoğlu City Hospital between January 2017 and January 2020. Age, gender, seizure duration and type, treatments for seizures, laboratory, neurophysiological, and radiological investigations, ward or intensive care unit hospitalizations, and antiepileptic drugs on discharge were recorded. The average age of the patients was 81.6 ± 62.9 months; 187 (56.2%) were male and 146 (43.8%) were female. Two hundred and sixty-one (78.4%) patients had only one seizure. In 45 (13.5%) of the patients, the seizure recurred in the emergency department. Hypoglycemia, hyponatremia, and hypocalcemia were detected in 13 (3.9%) patients. Patients with clinically significant cranial computed tomography results were at an increased risk for seizures lasting longer than 5 min. Patients with focal seizures had more recurrences, were given more antiepileptic drugs during the emergency, had better known etiology, more intensive care unit hospitalization, and greater post-discharge antiepileptic drug prescription. Biochemical abnormalities remain in the background in the etiology of afebrile seizures. Patients with abnormal neuroimaging on cranial tomography tended to have longer seizures. Patients with focal seizures followed a more complicated course as they had more recurrences and more hospitalization in the intensive care unit.

Telemedicine in epilepsy management during the coronavirus disease 2019 pandemic.

BackgroundTelemedicine has spread rapidly during the coronavirus disease 2019 (COVID‐19) pandemic and shown its usefulness, particularly for patients with epilepsy, compared to face‐to‐face visits. We sought to evaluate the clinical features of patients with childhood onset epilepsy associated with consultations by telephone call during the COVID‐19 pandemic.MethodsWe retrospectively investigated the medical records of patients with childhood onset epilepsy who visited an outpatient clinic in Saitama Children's Medical Center, Saitama, Japan, from 1 March 2020 to 30 September 2020. To find the clinical features of patients who utilized telemedicine consultation (by telephone call), we divided the patients into the telemedicine group and the face‐to‐face group. We then reviewed the clinical features. Telemedicine consultation was not implemented for new patients.ResultsWe enrolled 776 outpatients in total, and 294 patients (37.9%) utilized telemedicine consultations. The total number of visits was 2,299 and the total number of telemedicine consultations was 373 (16.2%). No clinical feature was associated with telemedicine consultations except for age at onset of epilepsy. The number of oral antiepileptic drugs prescriptions decreased in 23 of 776 (3.0%) of the patients who did not experience seizure deterioration, including status epilepticus, or who visited the emergency room.ConclusionTelemedicine consultations were successfully utilized for epilepsy treatment at our outpatient clinic, regardless of epilepsy type, etiology, seizure frequency, comorbidities, and patients' residential areas. Thus, telemedicine by telephone call may be a useful resource in the management of patients with childhood onset epilepsy during the pandemic.

Prescription patterns and dosages of antiepileptic drugs in prevalent patients with epilepsy in Taiwan: A nationwide retrospective cross-sectional study

ObjectiveTo evaluate the prescription patterns and prescribed daily dose (PDD)/defined daily dose (DDD) ratios of antiepileptic drugs (AEDs) in prevalent patients with epilepsy in Taiwan. Materials and methodsA nationwide retrospective cross-sectional study was conducted for prevalent patients with epilepsy in 2016 using the Taiwanese National Health Insurance Research Database. The prescription records of AEDs of all prevalent patients with epilepsy were retrieved. The mean PDDs and PDD/DDD ratios of AEDs in adult patients were obtained to evaluate dosing adequacy. A chi-square test and two-sample t test were used to analyze the differences in AED prescription patterns and dosages, respectively, among patients with different ages, sexes, comorbidities, and therapeutic approaches. ResultsA total of 118,937 prevalent patients with epilepsy were enrolled. The predominant therapeutic approach was monotherapy, especially in the elder adults, accounting for 82.9% of elder adult patients with epilepsy. The proportion of AED monotherapy was higher in patients with dementia (78.9%) and stroke (80.6%). The top three antiepileptic monotherapies were valproic acid (28.7%), levetiracetam (19.1%), and phenytoin (16.9%); however, oxcarbazepine (22.8%) was substituted for carbamazepine (3.9%) as monotherapy for patients aged 0–17 years. Among adult patients with epilepsy, the PDD/DDD ratio of each AED in monotherapy was less than 1.00. The mean PDD of each AED was higher in polytherapy than in monotherapy (p < 0.01), except for lacosamide. The mean PDDs of all evaluated AEDs in monotherapy were lower in elder adult patients than in younger adult patients, most of which reached statistical significance (p < 0.001). ConclusionsIn Taiwan, valproic acid was the most prescribed AED for prevalent patients with epilepsy. The mean PDDs of most AEDs were lower than the DDDs developed by the World Health Organization.

Characterization of pregnancies among women with epilepsy using valproate before or during pregnancy – A longitudinal claims data analysis from Germany

PurposeTo characterize pregnancies among women with epilepsy who have filled a prescription for valproate at any time before or during pregnancy and to assess other antiepileptic drug (AED) prescriptions. MethodsBased on health claims data (German Pharmacoepidemiological Research Database - GePaRD; covering ~20% of the population), we selected pregnancies beginning between 2014 and 2016 in women with at least three years of observation period before pregnancy and with at least one epilepsy diagnosis code in the year before pregnancy. Among those, we selected pregnancies with at least one valproate dispensation any time before or during pregnancy. We further described these pregnancies regarding patterns in the dispensation of valproate and other AED among the women from their first day in the database until the end of the pregnancy. ResultsAmong 2068 pregnancies fulfilling the inclusion criteria, we identified 454 pregnancies (89% ending in live births and 8% in induced abortions) in 430 women with at least one valproate dispensation before or during pregnancy. In 357 of these pregnancies (79%), valproate was only dispensed before pregnancy, while 97 pregnancies (21%) had a valproate dispensation during pregnancy and of these, 77% (N = 75) during the first trimester. The proportion with a valproate dispensation during pregnancy declined from 2014 (25%) to 2016 (19%), also concerning exposure during the first trimester (2014: 20%, 2015: 17%, 2016: 12%), while the proportion ending in an induced abortion was increasing (2014: 5%, 2015: 8%, 2016: 13%). In 48% of exposed pregnancies (N = 36), there was no other AED dispensed during the entire observation time before pregnancy. This proportion was lower for pregnancies beginning in 2016 (33%) than for those beginning in 2014 and 2015 (53% and 50%, respectively). ConclusionIn most women with epilepsy using valproate before or during pregnancy, valproate was dispensed only well before pregnancy beginning. The proportion exposed to valproate during the first trimester declined between 2014 and 2016, but the low proportion treated with alternative AED before valproate treatment suggests there is still room for improvement.

Impacts of statin and metformin on neuropathy in patients with type 2 diabetes mellitus: Korean Health Insurance data

BACKGROUNDNeuropathy is a common chronic complication in type 2 diabetes mellitus (T2DM). Statin and metformin are commonly used medications in T2DM patients, and some studies showed statin- or metformin-induced neuropathy.AIMTo evaluate the incidence of neuropathy among patients with T2DM associated with statin and metformin therapies. METHODSKorean Health Insurance Review and Assessment national patient sample data from 2016 and 2017 were used. Patients with T2DM and no complications were divided into statin/metformin/statin + metformin users and non-users. Neuropathy incidence was defined by International Statistical Classification of Diseases and Related Health Problems, 10th revision codes and concomitant prescriptions for anticonvulsants or antidepressants. Logistic regression analyses were conducted to examine the associations between statin/metformin/statin + metformin therapies and the incidence of neuropathy. Propensity score (PS) matching was performed on the basis of age, sex and comorbidities.RESULTSOverall, 34964 and 35887 patients with T2DM and no complications were included in the Korean Health Insurance Review and Assessment national patient sample datasets from 2016 and 2017, respectively. Statin therapy was associated with increased risks of neuropathy in 2016 and 2017 [PS-matched odds ratio (OR) = 1.22, 95% confidence interval (CI): 1.08-1.38; PS-matched OR = 1.17, 95%CI: 1.03-1.33, respectively]. Metformin therapy was associated with reduced risks of neuropathy in 2016 and 2017 (PS-matched OR = 0.30, 95%CI: 0.21-0.42; PS-matched OR = 0.44, 95%CI: 0.32-0.60, respectively). Combined statin + metformin therapy was not significantly associated with neuropathy in 2016 or 2017 (PS-matched OR = 0.85, 95%CI: 0.61-1.19; PS-matched OR = 0.95, 95%CI: 0.66-1.38, respectively). CONCLUSIONStatin therapy was associated with enhanced risk of new-onset neuropathy in patients with T2DM, but metformin therapy showed the opposite association.

P.020 The North American AED Pregnancy Registry: A Canadian Subgroup Analysis (1997-2019)

Background: This study aims to provide data on the care of pregnant women with epilepsy (pWWE) that is directly applicable to the Canadian context. Methods: Between 1997 and 2019, pWWE from Canada and the USA who enrolled into the North American AED Pregnancy Registry (NAARP) completed a questionnaire on their AED (anti-epileptic drug) usage. Enrollment rates to NAARP were compared between the two countries, and between the different Canadian provinces using population-based enrollment rate ratios (PERR). The AED prescription pattern among Canadian pWWE was analysed and compared with the USA. Results: During the study period, 10,215 women enrolled into NAARP : 4.1% (n=419) were Canadian, below the expected population-based contribution (PERR=0.42; p&lt;0.01). Within Canada, the three northern territories (PERR=0; p&lt;0.01), Prince-Edward Island (PERR=0; p&lt;0.01), and Quebec (PERR=0.41; p&lt;0.01) had the lowest enrollment rate ratios. Lamotrigine was the most commonly prescribed AED among canadian pWWE; they were, however, more likely to be on polytherapy (25%; p=0.13), on Carbamazepine (24%; p&lt;0.01) or valproic acid (21%; p&lt;0.01) than their American counterparts. Conclusions: Greater enrollment of Canadian women to NAARP, through enhanced clinician referrals, in particular from underrepresented provinces/territories, could lead to more accurate population-specific data and help identify gaps in the care of this vulnerable patient population.

Prescription preferences of antiepileptic drugs in brain tumor patients: An international survey among EANO members.

BackgroundThis study aimed at investigating antiepileptic drug (AED) prescription preferences in patients with brain tumor-related epilepsy (BTRE) among the European neuro-oncology community, the considerations that play a role when initiating AED treatment, the organization of care, and practices with regard to AED withdrawal.MethodsA digital survey containing 31 questions about prescription preferences of AEDs was set out among members of the European Association of Neuro-Oncology (EANO).ResultsA total of 198 respondents treating patients with BTRE participated of whom 179 completed the entire survey. Levetiracetam was the first choice in patients with BTRE for almost all respondents (90% [162/181]). Levetiracetam was considered the most effective AED in reducing seizure frequency (72% [131/181]) and having the least adverse effects (48% [87/181]). Common alternatives for levetiracetam as equivalent first choice included lacosamide (33% [59/181]), lamotrigine (22% [40/181]), and valproic acid (21% [38/181]). Most crucial factors to choose a specific AED were potential adverse effects (82% [148/181]) and interactions with antitumor treatments (76% [137/181]). In the majority of patients, neuro-oncologists were involved in the treatment of seizures (73% [132/181])). Other relevant findings were that a minority of respondents ever prescribe AEDs in brain tumor patients without epilepsy solely as prophylaxis (29% [53/181]), but a majority routinely considers complete AED withdrawal in BTRE patients who are seizure-free after antitumor treatment (79% [141/179]).ConclusionsOur results show that among European professionals treating patients with BTRE levetiracetam is considered the first choice AED, with the presumed highest efficacy and least adverse effects.

SCSS-01. ANTICONVULSANT PROPHYLAXIS IN PATIENTS WITH NEWLY DIAGNOSED BRAIN TUMORS: DOES IT PREVENT FIRST SEIZURES, DOES IT IMPROVE SURVIVAL, AND DO WE BELIEVE THE DATA?

Abstract BACKGROUND Despite an American Academy of Neurology Practice Guideline and ASCO/SNO endorsement against the routine use of anticonvulsant prophylaxis in patients with primary and metastatic brain tumors, there remains widespread variation in practice and several unanswered questions. METHODS Exhaustive evidence-based literature searches were conducted, and patient-level data from randomized controlled trials (RCTs) were analyzed to answer three questions: does anticonvulsant prophylaxis reduce the risk of first seizures in patients with primary and metastatic brain tumors; does prophylaxis improve one-year overall survival in patients with primary and metastatic brain tumors; and what effect have practice guidelines had on practice patterns. RESULTS Five RCTs (n=441 patients) addressed anticonvulsant prophylaxis in patients with brain tumors. Overall, anticonvulsant prophylaxis did not reduce the risk of a first seizure in patients with any brain tumor (RR= 0.95 [0.58-1.55], p= 0.85, anticonvulsant prophylaxis vs. placebo), brain metastasis (RR = 0.96 [0.73-1.25], p=0.77, 5 RCTs) or primary brain tumors (RR= 1.03 [0.19-5.72], p=0.97, 4 RCTs). Eleven RCTs of anticonvulsant prophylaxis (n=3767 patients with CNS tumors) provided data for survival analysis and demonstrated a lower RR of death at one year compared to those who did not receive prophylaxis (0.88 [0.81-0.94] p = 0.0006). Physician-reported practice of prescribing anticonvulsant prophylaxis diminished only negligibly after initial guideline publication (54.9% [1 study] vs. 51.6%, [3 studies] p&amp;lt;0.014). CONCLUSION Prophylactic anticonvulsants in patients without a history of seizures does not reduce the risk of first seizures in patients with primary or metastatic brain tumors. Despite this, anticonvulsant prophylaxis provides a small survival benefit at one year, although, this finding may be driven by confounded studies. Rates of anticonvulsant prophylaxis prescription have decreased only minimally and remain very high despite strong evidence against this practice and guideline publication. Evidence-based medicine requires additional mechanisms for encouraging practice change.