Older Antiepileptic Drugs Research Articles

Incidence of Idiosyncratic Drug-Induced Liver Injury Caused by Prescription Drugs.

The incidence of drug-induced liver injury (DILI) is not known for most prescription medications. We aimed to estimate the incidence of DILI for commonly prescribed outpatient drugs. To establish a baseline estimate of DILI incidence, we used the estimated incidence (EI) of amoxicillin/clavulanate DILI from a previous population-based study in Iceland. This was combined with the multicenter prospective DILI Network (DILIN) cohort and the US population-based Medical Expenditure Panel Survey (MEPS). From 2005 to 2019, prescription drugs with at least five bona fide DILIN cases and data from at least 10 of the 15years from MEPS during that timeframe were included. The EI for 'drug A' was calculated as follows: RESULTS: In total, 30 drugs met the inclusion criteria, of which 11 were antibiotics, 4 were antiepileptic drugs (AEDs), 4 were statins, and 11 were other drug types. The highest EI was seen with azathioprine and older AEDs, with one DILI case per 349-2329 new prescriptions. The EI of antibiotics ranged greatly, with the highest risk seen for minocycline, amoxicillin/clavulanate, and nitrofurantoin (approximately 1:1000-2400 new prescriptions), and lowest risk for clindamycin, doxycycline, azithromycin, and amoxicillin (approximately 1:40,000-170,000 new prescriptions). The EI for commonly prescribed statins was approximately 1:10,000-50,000. Important medication classes with > 5 million new prescriptions from 2005 to 2019 but fewer than five DILIN cases included β-blockers, thiazide diuretics, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, selective serotonin reuptake inhibitors, and metformin, which presumably have very low DILI incidence. The highest EI was found for azathioprine, older antiepileptics, and minocycline. In contrast, many widely used drugs are rare causes of DILI. These findings may help clinicians better weigh potential benefits of medications against hepatotoxicity risk.

Trends in anti-neuropathic medications turnover in Iraq

Abstract Objectives Neuropathic pain (NP) is a type of chronic pain. Numerous diseases and/or lesions are associated with the development of NP, and diabetes mellitus is the most prevalent cause. Several classes of medications were recommended and/or approved as anti-neuropathic medications. This study aimed to examine the trends in the turnover of anti-neuropathic medications in Iraq. Methods This was a retrospective analysis of the turnover of selected anti-neuropathic medications in the Iraqi market derived from Advanced Marketing Statistics between 2017 and 2021. The sales units were converted to defined daily doses. Regression analysis and correlation analysis were used to compare the turnover of the medications. Key findings The overall volume of turnover of anti-neuropathic medications increased between 2017 and 2021. The anti-neuropathic market domination was shifted from carbamazepine to pregabalin, in which the average increase in pregabalin turnover of 60% [95% CI (confidence interval) 37.6–82.5] quarterly to achieve 42% of the market share (highest sales) by 2021. The overall expenditure on anti-neuropathic medications increased steadily over the study period. Conclusions The market of anti-neuropathic medications’ domination was shifted from the older antiepileptic drug (AED) (carbamazepine) to the newer AED (pregabalin). The availability and affordability of less expensive generic versions of these agents, together with the better safety profiles of the newer agents were the main driver for this shift. This indeed allowed Iraqi physicians to adhere to the latest international guidelines.

A Prospective Observational Study on Changing Trends of Antiepileptics Prescription Amongst Physicians in India

Epilepsy is one of the common neurological disease affecting millions of people worldwide. Multiple class of antiepileptic drugs (AEDs) are available which makes it difficult to select an appropriate drug therapy for epilepsy. With introduction of newer generation of antiepileptics, the drug Pool has become wider. Factors which determine the selection of therapy includes seizure type, adverse effect, drug-drug interaction, age, pregnancy, cost of treatment and drug compliance. Though the older generation of antiepileptics were effective in controlling seizures, we found that newer generation of antiepileptics are gaining popularity among the prescriber. Reason for this shift being, better efficacy, fewer side effect and better compliance by the patients. We completed the study with the conclusion that newer antiepileptic especially levetiracetam, are more preferred by doctors in comparison with older antiepileptic drugs for control of seizures, though previous generation of antiepileptics has still role in management of epilepsy and individualistic approach is needed in choosing appropriate antiepileptics.

Electroencephalographic Findings, Antiepileptic Drugs and Risk Factors of 433 Individuals Referred to a Tertiary Care Hospital in Ethiopia.

Little is known about the characteristics of electroencephalogram (EEG) findings in epileptic patients in Ethiopia. The objective of this study was to characterize the EEG patterns, indications, antiepileptic drugs (AEDs), and epilepsy risk factors. A retrospective observational review of EEG test records of 433 patients referred to our electrophysiology unit between July 01, 2020 and December 31, 2021. The age distribution in the study participants was right skewed unipolar age distribution for both sexes and the mean age of 33.8 (SD=15.7) years. Male accounted for 51.7%. Generalized tonic clonic seizure was the most common seizure type. The commonest indication for EEG was abnormal body movement with loss of consciousness (35.2%). Abnormal EEG findings were observed in 55.2%; more than half of them were Interictal epileptiform discharges, followed by focal/or generalized slowing. Phenobarbitone was the commonest AEDs. A quarter (20.1%) of the patients were getting a combination of two AEDs and 5.2% were on 3 different AEDs. Individuals taking the older AEDs and those on 2 or more AEDs tended to have abnormal EEG findings. A cerebrovascular disorder (27.4%) is the prevalent risk factor identified followed by brain tumor, HIV infection, and traumatic head injury respectively. High burden of abnormal EEG findings among epileptic patients referred to our unit. The proportion of abnormal EEG patterns was higher in patients taking older generation AEDs and in those on 2 or more AEDs. Stroke, brain tumor, HIV infection and traumatic head injury were the commonest identified epilepsy risk factors.

Pharmacoeconomics Aspects of Antiepileptic Drugs in Pediatric Patients with Epilepsy

Objective: This study assessed the differentiation of treatment costs with newer and older antiepileptic drugs (AEDs) through its correlation with treatment effectiveness and an adverse event (AE) in pediatric patients with epilepsy (PPE). Methods: PPE on monotherapy of AEDs for the last 6 months were screened for this study. Seizure frequency during the study was compared with that within 6 months before the study. The following parameters were also assessed: quality of life in epilepsy, Pittsburgh Sleep Quality Index, and Liverpool AEs Profile. An incremental cost-effectiveness ratio (ICER) analysis based on the costs of pharmacotherapy was also performed. Results: Out of 80 PPE, 67 completed the study, and 13 PPE were lost after failing to meet the inclusion criteria. A total of 56.71% of PPE were on newer AEDs, and 43.28% were on older AEDs. Newer and older AEDs did not differ significantly in seizure frequency reduction and quality of life parameters, although these were improved significantly during the study period. As per ICER, newer AEDs need an additional EUR 36.82 per unit reduction in seizure frequency. Conclusion: Newer AEDs have comparatively better efficacy, although not significantly better than older AEDs. However, the additional cost per unit improvement is quite high with newer AEDs, necessitating pharmacoeconomic consideration in pediatric epilepsy treatment.

A Review of the Prevalence, Etiology, Diagnosis, and Management of Pediatric Epilepsies in India

AbstractPediatric seizures are one of the most common neurological manifestations seen in pediatrics. Unravelling the etiology, timely and appropriate investigations followed by suitable therapies are essential for improving quality of life. During the pandemic, focused group discussions were conducted among 50 pediatric neurologists across five cities in India to gather insights on treatment practices in pediatric epilepsy and to optimize therapeutic strategies and alternative approaches for rational use of antiepileptic medications. These discussions were mainly aimed at reviewing current literature on prevalence, etiology, diagnosis, and management of epilepsy in children and subsequently rationalizing diagnostic and treatment approaches in routine clinical practice. Epileptic encephalopathies comprise of childhood epilepsy with progressive cerebral dysfunction. Genomics plays a vital role in identifying the underlying genetic associations, empowering precision therapy. Currently, the ketogenic diet has become a well-recognized modality for reducing severity of seizures. To overcome the high incidence of adverse effects due to older antiepileptic drugs, newer drugs are being developed to improve ease of use, diminish drug interactions, decrease adverse effects, and identify drugs with unique mechanisms of action. Common lacunae in practice include information gaps, educating parents, or caregivers about rational drug use and ensuring compliance to antiepileptic medications. This article discussed the consensus clinical viewpoint of expert clinicians, as well as insights on optimized treatment of pediatric epilepsies in both infancy and childhood. It also discusses aspects, like reducing drug burden, emerging therapies in the identification of the genetic basis of epilepsies, and targeted therapy alternatives, for pediatric populations in the Indian scenario.

Treatment Pattern of Antiepileptic Drugs in Pediatric with Epilepsy

Studying drug utilization helps to develop twin concepts for therapeutic formulation and essential drug lists. The main preference of using Antiepileptic drug (AED) therapy is that patients can be seizure-free for their lifetime. Treating children with epilepsy remains a major challenge, despite having several AEDs. Hence, we aimed to study drug utilization patterns among pediatric patients with epilepsy. This prospective study was conducted on 150 patients lesser than 18 years of age, receiving antiepileptic drugs. A specially designed case record form was used to collect the data on socioeconomic status, disease data, and treatment details. The majority of the children were females (60.6%), ages ranged from day 1 to 4 years (56.6%). About 35.33% were skilled laborers followed by 32.23% semi-skilled. Around 49.3% of patients belonged to the lower-middle-class family and 41.33% were diagnosed to have generalized tonic-clonic seizures (GTCS). The majority of the children were on monotherapy (81.33%) while 18.66% were on dual therapy or polytherapy. Regarding the usage of antiepileptic drugs, we found that 70.66% of children were on older AEDs like sodium valproate (27.33%) followed by clobazam (31.33%). Levetiracetam was the only new antiepileptic drug that was prescribed in 10% of patients. Monotherapy is considered as best modality, due to its low cost, safety profile, and lesser drug interactions. It can also improve drug treatment compliance and adherence. Along with older AEDs, there has been an increase in the utilization of newer AEDs, which help to broaden the therapeutic option towards the management of childhood epilepsy with a better safety profile.

Clinical characteristics of antiepileptic-induced liver injury in patients from the DILIN prospective study

Antiepileptic drugs (AEDs) are a common cause of drug-induced liver injury (DILI). Over the last few decades, several newer AEDs were approved for marketing in the United States, and they are increasingly prescribed for indications other than seizures. Contemporaneous data related to trends and characteristics of AED-related liver injury are sparse. We report the trends, characteristics, and outcomes of patients with AED-related DILI enrolled into the DILIN Prospective Study between 2004 and2020. Among 1,711 participants with definite, highly likely, or probable DILI, 66 (3.9%) had AED-related DILI (lamotrigine [n= 18], phenytoin [n= 16], carbamazepine [n= 11], valproate [n= 10], gabapentin [n= 4], and others [n= 7]). The frequency of AED-related liver injury significantly decreased during the study period (from 8.5% of cases during 2004-2007 to 2.6% during 2015-2020, p= 0.01). AEDs other than phenytoin were commonly prescribed for non-seizure indications. Compared to non-AEDs, patients with AED-related liver injury were younger (mean age 38.5 vs. 50.1 years-old, p <0.001) and more likely African American (27% vs. 12%, p= 0.008). DRESS was common with liver injury caused by lamotrigine, phenytoin, and carbamazepine, but not valproate or gabapentin. Liver injury severity was moderate to severe in the majority: 5 died, and 3 underwent orthotopic liver transplantation (OLT). No patient with lamotrigine-related DILI, including 13 with hepatocellular jaundice, died or needed OLT, while 3 out of 16 patients (19%) with phenytoin-related DILI either died or required OLT. The frequency of AED-related liver injury significantly decreased over the last 2 decades in our experience. AED-related liver injury has several distinctive features, including a preponderance in African American patients and those with immunoallergic skin reactions, with outcomes depending on the type of AED involved. Medications used to treat epilepsy may sometimes cause severe liver injury. However, several new medications have been approved over the last 2 decades and they may not be as toxic to the liver as older antiepileptic medications (AEDs). This study shows that overall liver injury due to AEDs is decreasing, likely due to decreasing use of older AEDs. Liver injury due to AEDs appears to be more common in African Americans and is commonly associated with allergic skin reactions.

Antiepileptic drugs lamotrigine and valproate differentially affect neuronal maturation in the developing chick embryo, yet with PAX6 as a potential common mediator

Exposing the immature nervous system to specific antiepileptic drugs (AEDs) during pregnancy is linked to neurodevelopmental disorders such as autism spectrum disorder (ASD). Newer AEDs like lamotrigine (LTG) are hailed as safer, but recent epidemiological data suggest that even LTG carries a risk, although much lower than that associated with valproic acid (VPA), an older AED, which is also known to cause morphological alterations in the developing brain. Increasing evidence highlights cerebellar abnormalities as important in ASD pathophysiology. Transcription factor PAX6 is a key activity-dependent mediator and regulates crucial processes during cerebellar development. The chicken cerebellum recapitulates important characteristics of human cerebellar development, and may thus be suitable for the assessment of interventions aiming to modify maturation and cerebellar development.In the present study, exposure of chicken on embryonic day 16 (E16) to LTG or VPA resulted in decreased cerebellar mass and level of proliferating nuclear cell antigen (PCNA) for clinically relevant concentrations of VPA. However, both AEDs reduced cerebellar protein levels of PAX6 and MMP-9 at E17. Furthermore, PAX6 immunohistochemical staining of coronal sections of chicken cerebellum showed a significant reduction in PAX6-positive cell density and changes in cerebellar cortex thickness, mostly caused by the change in IGL-layer thickness. In conclusion, prenatal exposure to LTG or VPA provoked differential maturational changes in the developing cerebellum that may reflect some of the underlying molecular mechanisms for the observed human ASD pathology after AEDs exposure during pregnancy.

A Possible Type IV Hypersensitivity Reaction to Older Antiepileptic Drugs During and After Recovery from COVID-19 Infection.

Nearly two years after the onset of the coronavirus disease 2019 (COVID-19) pandemic, healthcare workers face new and unexpected complications. Although accelerating the vaccination process in recent months has reduced the incidence and mortality of the COVID-19 infection, the general population (particularly vulnerable groups) remains at risk of new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants. Over the last two months, Iran has encountered the fifth wave of the COVID-19 pandemic, i. e., the B.1.617.2 (Delta) variant of the SARS-CoV-2, with faster infectiousness and higher severity and mortality among hospitalized patients 1. Although fever, cough, and expectoration are the most common clinical features of COVID-19, recent studies have indicated an increasing number of skin manifestation reports in the disease. Besides, there is growing evidence that underlying SARS-CoV-2 infection may increase the risk of adverse drug reactions 2. However, the enduring concern in our medical centers in recent days is a raised incidence of Stevens-Johnson syndrome (SJS) in recovered COVID-19 patients following monotherapy with older antiepileptic drugs (0.004 vs. 0.0008% - i. e., 5 times higher than the pre-COVID-19 period) 3. It is worth noting that these patients did not have any history of SJS/toxic epidermal necrolysis (TEN) or additional etiopathogenic factors, including infections, genetic factors (particularly HLA-B*1502 allele), and malignancy. Furthermore, for many years before developing the COVID-19 and recovering from it, they had been treated with the above drugs without showing any cutaneous hypersensitivity reactions. These observational findings raise two important questions: (i) Could a history of the COVID-19 infection be a potential risk factor for type IV hypersensitivity reactions to older antiepileptic drugs? (ii) If so, what are its mechanisms of action?

New antiepileptic drugs: usage, adverse effects, and interactions

Valproic acid, phenytoin, carbamazepine, primidone, and ethosuximide are older antiepileptic drugs that have long been in use. However, many new drugs have been developed, and many clinicians often find it difficult to select appropriate drugs. We reviewed the usage, adverse effects, and interactions of new antiepileptic drugs, referring to the 2018 guideline of the American Association of Neurology. Lamotrigine should be considered for monotherapy in patients with new-onset focal epilepsy. For new-onset generalized epilepsy, valproic acid is still the first-line treatment. Pregabalin and perampanel are effective as adjuvant therapy for refractory adult focal epilepsy. Lamotrigine and levetiracetam should be considered as adjuvant therapy for generalized refractory epilepsy. Lamotrigine and levetiracetam are relatively safe for use during pregnancy. Gabapentin, pregabalin, lamotrigine, topiramate, levetiracetam, zonisamide, lacosamide, perampanel, rufinamide, eslicarbazepine acetate, and clobazam all have different indications for usage and adverse effects. Treatment must be individualized by selecting appropriate drugs according to patients’ risk of complications. KEY WORDS: Anticonvulsants, Epilepsy, Adverse effects, Pharmacology

SNO and EANO practice guideline update: Anticonvulsant prophylaxis in patients with newly diagnosed brain tumors.

To update the 2000 American Academy of Neurology (AAN) practice parameter on anticonvulsant prophylaxis in patients with newly diagnosed brain tumors. Following the 2017 AAN methodologies, a systematic literature review utilizing PubMed, EMBASE Library, Cochrane, and Web of Science databases was performed. The studies were rated based on the AAN therapeutic or causation classification of evidence (class I-IV). Thirty-seven articles were selected for final analysis. There were limited high-level, class I studies and mostly class II and III studies. The AAN affirmed the value of these guidelines. In patients with newly diagnosed brain tumors who have not had a seizure, clinicians should not prescribe antiepileptic drugs (AEDs) to reduce the risk of seizures (level A). In brain tumor patients undergoing surgery, there is insufficient evidence to recommend prescribing AEDs to reduce the risk of seizures in the peri- or postoperative period (level C). There is insufficient evidence to support prescribing valproic acid or levetiracetam with the intent to prolong progression-free or overall survival (level C). Physicians may consider the use of levetiracetam over older AEDs to reduce side effects (level C). There is insufficient evidence to support using tumor location, histology, grade, molecular/imaging features when deciding whether or not to prescribe prophylactic AEDs (level U).

Antiepileptic Drugs and Thyroid Hormone Homeostasis: Literature Review and Practical Guideline

Thyroid hormones play an essential role in central nervous system development, normal physiological brain function and repairing mechanisms. On one hand, thyroid hormone alterations influence cortical excitability and on the other hand anti-epileptic drugs (AEDs) are associated with alterations in thyroid hormone metabolism. Although this interaction has long been described, and epilepsy is a common and chronic neurological disease, studies describing the interplay are often small and retrospective.We performed a systematic review of the current literature on epilepsy, AED therapy and thyroid hormone metabolism. Forty-seven studies were included.Most studies were retrospective cross-sectional studies (n=25) and investigated thyroid function alterations in patients on older AEDs such as phenobarbital, phenytoin, carbamazepine and valproic acid. Overall, almost one third of patients with epilepsy had subclinical hypothyroidism, especially patients on valproate and carbamazepine. Studies with patients receiving polytherapy are scarce, but reported a higher risk for hypothyroidism in patients with older age, female sex, longer duration of epilepsy, intractable epilepsy and polytherapy. Studies on newer AEDs are also scarce and further studies essential to improve the care for epilepsy patients.AEDs are associated with alterations in thyroid hormone metabolism. Thyroid function monitoring is indicated in patients on AEDs, especially those with refractory chronic epilepsy and those on polytherapy. We provide a practical guideline for thyroid function monitoring for the clinician taking care of patients on AEDs.

Hip Fracture Risk in Antiepileptic Drug Initiators and Non-Initiators with Alzheimer's Disease.

ObjectiveTo determine the risk of hip fracture in persons with Alzheimer´s disease (AD) who initiated antiepileptic drugs (AEDs).MethodsIn the Medication use and AD (MEDALZ) cohort of 70,719 Finnish community dwellers with clinically verified incident AD diagnosis in 2005–2011, we identified all incident users of AEDs using national Prescription register. AEDs were classified as older (valproate, carbamazepine, clonazepam, phenytoin, levetiracetam, primidone) or newer (pregabalin, gabapentin, oxcarbazepine, lamotrigine, topiramate). We matched each user to 2 non-users. Incident hip fractures until 2015 were identified from the Care register for health care. We calculated inverse probability of treatment weighted hazard ratios (HR), with 95% confidence intervals, using Cox regression.ResultsAltogether 5522 incident users were identified and matched to 11,044 non-users (in both groups, women: 65%; median age: 81 years). Altogether 53.3% of users initiated with newer AEDs (pregabalin 79.8%, gabapentin 10.2%) while 46.7% initiated with older AEDs (valproate 67.6%, carbamazepine 13.0%). Age- and sex-adjusted IR of hip fracture per 100 person-years was 1.8 (95% CI 1.6–1.9) in non-users and 2.0 (95% CI 1.8–2.2) in users. Increased risk of hip fracture was observed in users (HR 1.17, 95% CI 1.05–1.30) compared with non-users. The risk was higher for short duration of use (<14 weeks, HR 3.64, 95% CI 2.90–4.58) than for medium duration (14 to <64 weeks, HR 1.74, 95% CI 1.48–2.05) or ≥64 weeks’ use (HR 1.23, 95% CI 1.08–1.40), compared to non-users with same follow-up time. Older AEDs had HR of 1.46 (1.03–2.08) compared with newer AEDs.ConclusionOur results imply that AED use is associated with an increased risk of hip fracture in people with AD. These findings prompt careful consideration before prescribing AEDs to persons with AD. Persons with AD treated with antiepileptics should be carefully monitored due to their increased risk of falling and fractures.

Efficacy and tolerability of eslicarbazepine acetate as monotherapy in patients of newly diagnosed focal epilepsy

IntroductionEslicarbazepine Acetate, a novel anti-epileptic drug has been approved as monotherapy in focal onset seizures, with/without secondary generalization in adults. Eslicarbazepine has many advantages over older anti-epileptic drugs and is useful in patients of new onset focal epilepsy.Objectives Aim of our study was to determine the efficacy and safety of Eslicarbazepine Acetate, observe its well-tolerated use and monitor adverse effects in newly diagnosed patients of focal epilepsy.MethodsStudy was done at Department of Psychiatry, Teerthanker Mahaveer University, Moradabad. A total of 30 newly diagnosed cases of focal epilepsy between 18-60 years of age were studied for 6 months, using a Semi-structured Interview and Liverpool Adverse Events Profile.ResultsMajority of patients were males (58%), between 21-30 years. Patients with partial/focal seizures (63%) were more common than those of generalized seizures (37%). Majority of the participants had 1-2 episodes of focal seizures weekly(48%), while some had almost daily(32%). Majority were on Eslicarbazepine Acetate 800 mg in two divided doses daily (64%), while the others received 1200 mg in three divided doses(32%). The mean Liverpool Adverse Events Profile score initially was 28.34 ± 6.28 which significantly improved after 4 weeks treatment to 22.80 ± 4.35 (p &lt; 0.05). The improvement in newly diagnosed focal seizures patients was significantly more than other patients (p &lt; 0.05). No major side effects were observed.ConclusionsEslicarbazepine Acetate as a monotherapy is effective in treating focal epilepsy. Better results of this drug are found in newly diagnosed focal epilepsy patients.DisclosureNo significant relationships.

Prescription patterns of antiepileptic drugs for adult patients with newly diagnosed focal epilepsy from 2006 to 2017 in Japan

ObjectiveThis study aimed to examine prescription patterns of antiepileptic drugs (AEDs) for adult patients with newly diagnosed focal epilepsy in Japan and whether these patterns adhere to the 2010 Japanese Society of Neurology Guidelines of Epilepsy Treatment. MethodsData from the JMDC Claims Database were obtained for patients aged between 20 and 65 years with newly diagnosed focal epilepsy who were prescribed AEDs between 2006 and 2017. Available prescription information up to the patient’s first year was recorded and longitudinal descriptive statistics, Cochran Armitage Trend (CAT) tests, and annual percentage change (APC) were used to analyze AED trends and overall guideline adherence. In addition, logistic regression analyses were used to compare these results across different health facilities. ResultsA total of 6024 adult patients with newly diagnosed focal epilepsy were enrolled. The prescription of new AEDs increased significantly (CAT, p < 0.001, APC = 28.74 %) up to 36.8 % of all prescriptions in 2017 when compared to 2006. Among new AEDs, prescriptions for levetiracetam increased most rapidly and were followed by lamotrigine. In contrast, prescriptions for older AEDs, especially valproate, decreased over this same time period. The average guideline adherence rate from 2010 to 2017 was 75.3 %, and was not significantly different over time (CAT, p = 0.55). Health facilities with either more than 500 beds or between 20–499 beds had higher odds of prescribing new AEDs and improved guideline adherence when compared to facilities with 0–19 beds. ConclusionPrescription patterns of AEDs for adult patients with newly diagnosed focal epilepsy exhibited a trend from older to new AED classes between 2006 and 2017, with consistent, high guideline adherence from 2010 to 2017. Health facilities with 0–19 beds were less likely to prescribe new AEDs and completely adhere to proposed guidelines.

RTID-10. SURGEONS TRIAL OF PROPHYLAXIS FOR EPILEPSY IN SEIZURE NAÏVE PATIENTS WITH MENINGIOMA: A RANDOMIZED CONTROLLED TRIAL (STOP ‘EM)

Abstract BACKGROUND Meningioma is the commonest primary brain tumour. 70% of patients are seizure-free at presentation, but approximately 12% will have seizures within 12 months of surgery. Seizures impact quality of life. Neurosurgeons administer prophylactic anti-epileptic drugs (AED) to prevent seizures despite a lack of evidence to support this. A meta-analysis of RCTs in brain tumours suggests that older AED may prevent seizures in the first week after surgery but not thereafter. There are no studies assessing newer AEDs in the prophylactic setting. RESEARCH QUESTION In patients with meningioma who have never had a seizure and are undergoing surgical resection, does prophylactic levetiracetam reduce the risk of developing seizures? DESIGN multi-centre, double-blind RCT in 20 UK centres. 1:1 randomisation of 14 days levetiracetam 500mg bd started one day before surgery compared to placebo. PRIMARY OBJECTIVE Determine whether 2 weeks prophylactic levetiracetam reduces the risk of developing seizures within 12 months of surgery compared to placebo. ECONOMIC OBJECTIVE Estimate cost-effectiveness of prophylactic levetiracetam. SECONDARY OBJECTIVES Determine effect of prophylaxis on time to first seizure and first convulsive seizure, whether prophylaxis affects quality of life and influences return to driving, safety of prophylaxis. POPULATION seizure-naïve meningioma undergoing surgery. SAMPLE SIZE seizure rate at 12 months is 12.3%. A 50% reduction is clinically beneficial. A two-group chi-squared test with 5% two-sided significance level will have 90% power to detect the difference between a Group 1 proportion of 0.12 and a Group 2 proportion of 0.06 when the sample size in each group is 477. Allowing for 5% dropout, 1004 patients will be recruited. FUNDING NIHR (£1.64M) award June 2020. Study opens March 2021. TRANSLATIONAL RESEARCH MRI, blood and tissue will be collected to explore risk factors for seizures. CONCLUSIONS study will provide class I evidence of the role of prophylactic levetiracetam in meningioma surgery.

Antiepileptic drug use and mortality among community-dwelling persons with Alzheimer disease.

ObjectiveTo evaluate the risk of death in relation to incident antiepileptic drug (AED) use compared with nonuse in people with Alzheimer disease (AD) through the assessment in terms of duration of use, specific drugs, and main causes of death.MethodsThe MEDALZ (Medication Use and Alzheimer Disease) cohort study includes all Finnish persons who received a clinically verified AD diagnosis (n = 70,718) in 2005–2011. Incident AED users were identified with 1-year washout period. For each incident AED user (n = 5,638), 1 nonuser was matched according to sex, age, and time since AD diagnosis. Analyses were conducted with Cox proportional regression models and inverse probability of treatment weighting (IPTW).ResultsNearly 50% discontinued AEDs within 6 months. Compared with nonusers, AED users had an increased relative risk of death (IPTW hazard ratio [HR], 1.23; 95% confidence interval [CI], 1.12–1.36). This was mainly due to deaths from dementia (IPTW HR, 1.62; 95% CI, 1.42–1.86). There was no difference in cardiovascular and cerebrovascular deaths (IPTW HR, 0.98; 95% CI, 0.67–1.44). The overall mortality was highest during the first 90 days of AED use (IPTW HR, 2.40; 95% CI, 1.91–3.03). Among users of older AEDs, relative risk of death was greater compared to users of newer AEDs (IPTW HR, 1.79; 95% CI, 1.52–2.16).ConclusionIn older vulnerable patients with a cognitive disorder, careful consideration of AED initiation and close adverse events monitoring are needed.

Prescription pattern of antiepileptic drugs in a tertiary care hospital

Background: Epilepsy is a chronic neurological disorder which affects about 0.5% to 1% of the population. The older antiepileptic drugs like carbamazepine and phenytoin are the mainstay of treatment of epilepsy. With the development of newer drugs for various type of epilepsy, the prescribing pattern for epilepsy has changed over the last decade. The objective of this study was to evaluate the prescription pattern of antiepileptic drugs in outpatient department of a tertiary care health care centre in Kerala and to assess how adherent they are to the available treatment guidelines of epilepsy.Methods: Data was collected from patients attending the outpatient department of Neurology in Government Medical College, Kozhikode for 2 months from January 2018 to February 2018. A total of 442 patients were enrolled in the study and data regarding the type of epilepsy, the antiepileptic drug prescribed, and the demographic profile were recorded and analysed.Results: Among the study participants, 237 were males (53.6%) and 205 females (46.2%). The study showed that among the 442 participants enrolled, the most common type of epilepsy was focal seizures (64.5%) and the most commonly prescribed drug was carbamazepine (28%), followed by levetiracetam (22%) and valproate (20%). Majority of the patients were treated with a single drug (79.2%).Conclusions: Newer drugs have been increasingly added to the list of antiepileptic drugs, but most of them serve as adjuvant to older ones and the important drugs used as monotherapy are still the older ones.

RETRACTED: Levetiracetam inhibits THP-1 monocyte chemotaxis and adhesion via the synaptic vesicle 2A

Long-term therapy with older antiepileptic drugs (AEDs), but not levetiracetam (LEV), may increase the risk of atherosclerosis (AS), suggesting that LEV may have a potential anti-AS effect. The synaptic vesicle 2A (SV2A) is known to the specific binding site of LEV. Numerous studies have documented that SV2A is a membrane protein specifically expressed in nervous system. Interestingly, our previous research showed that SV2A also existed in human CD8+ T lymphocytes. Therefore, we hypothesized that LEV was associated with decreased risk of AS by regulating monocytes chemotaxis and adhesion. We showed that SV2A protein were detected in THP-1 human monocytic leukemia cells. LEV (300μM) inhibited the chemotaxis and adhesion of THP-1cells after transfection with plasmids expressing SV2AWT, but not SV2AR383Q which was a known functional mutation site of human SV2A. Furthermore, RT-PCR and western blot analysis demonstrated that LEV (300μM) decreased the expression level of chemokine-related receptors (CX3CL1, CCR1, CCR2, and CCR5),and reduced levels of phosphorylated AKT (p-AKT) in THP-1cells with SV2AWT expressing plasmids. Taken together, these findings indicated that LEV has an inhibitory effect on THP-1 monocyte adhesion and chemotaxis, suggesting that SV2A may serve as a novel therapeutic target to prevent AS.