Antiepileptic Drugs In Patients Research Articles

Comparative Efficacy of Antiepileptic Drugs in patients with Status Epilepticus admitted to the Neurocritical Care Unit (P6.070)

Comparative Efficacy of Antiepileptic Drugs in patients with Status Epilepticus admitted to the Neurocritical Care Unit (P6.070)

Adverse effects & drug load of antiepileptic drugs in patients with epilepsy: Monotherapy versus polytherapy.

Background & objectives:Although the need for a combination of antiepileptic drugs (AEDs) in the treatment of epilepsy is well justified, but an associated increase in adverse effects (AEs) lends a restriction to polytherapy. The aim of this study was to evaluate AEs and drug load (prescribed daily dose/defined daily doses) of AEDs in patients with epilepsy (PWE).Methods:Consecutive PWEs attending Epilepsy clinic in a tertiary care hospital in New Delhi, India, were enrolled in the study. Demographic variables, such as age, gender, diagnosis, age at onset of seizures, frequency of seizures, use of all AEDs and adverse event profile (AEP) score were noted. Routine laboratory tests including lipid profile, fasting blood glucose, haematological parameters and liver and kidney function tests were done.Results:A total of 697 consecutive patients were included in this study. Of them, 64.4 per cent were male; mean age was 29.6 ± 10.6 yr. Generalized seizures and focal seizures were recorded in n=386 (55.4%) and n=311 (44.6%), respectively. Monotherapy and polytherapy with two and greater than or equal to three AEDs were prescribed in 264 (37.9%), 243 (34.9%) and 190 (27.2%) patients, respectively. The average AED load, duration of treatment as well as AEP score were found to be significantly higher in combination of greater than or equal to three AEDs as compared to both monotherapy and combination of two AEDs, whereas no significant difference was observed between monotherapy and combination of two AEDs. Patients on monotherapy were in good control of seizures as compared to polytherapy. There was no significant change in biochemical parameters between the groups.Interpretation & conclusions:Polytherapy with combination of greater than or equal to three AEDs was associated with higher AEs and lower seizure control as compared to both monotherapy and combination of two AEDs. AEs did not correlate with AED load, seizure type, gender and age of the patients but were associated with both numbers of AEDs as well as seizure frequency in PWE.

The yield of non-elective inpatient video-EEG monitoring in adults.

Inpatient video-EEG monitoring (VEM) can contribute to the diagnosis and treatment in many of the monitored patients. Most admissions to VEM are elective and are scheduled ahead before the monitoring session. To retrospectively evaluate the yield of non-elective VEM sessions. We retrospectively reviewed the VEM recordings and medical records of all the patients admitted to our one-bed VEM unit from June 2007 to June 2015. A VEM session was diagnostic when a seizure, an event or previously unreported interictal epileptiform discharges were recorded. The study group included 304 adults aged 18-92years (mean 40.4±17.4years), 181 (59%) women. The diagnostic yield of non-elective and elective VEM session was similar (66 and 69%, respectively). In non-elective VEM, fewer patients had known epilepsy (p=0.0001), session duration was shorter (p=0.0001), and seizures and interictal epileptiform discharges were recorded less frequently compared to elective VEM (p=0.005 and p=0.0001, respectively). Non-elective VEM can provide useful information in patients admitted to the neurology department with recent neurological or behavioral events. A timely and correct diagnosis in these patients can potentially reduce unnecessary use of antiepileptic drugs in patients with psychogenic nonepileptic seizures and the morbidity and mortality associated with undiagnosed seizures.

Propofol versus thiopental sodium for the treatment of refractory status epilepticus.

This review is an update of a previously published review in the Cochrane Database of Systematic Reviews (Issue 6, 2015).Failure to respond to antiepileptic drugs in patients with uncontrolled seizure activity such as refractory status epilepticus (RSE) has led to the use of anaesthetic drugs. Coma is induced with anaesthetic drugs to achieve complete control of seizure activity. Thiopental sodium and propofol are popularly used for this purpose. Both agents have been found to be effective. However, there is a substantial lack of evidence as to which of the two drugs is better in terms of clinical outcomes. To compare the efficacy, adverse effects, and short- and long-term outcomes of refractory status epilepticus (RSE) treated with one of the two anaesthetic agents, thiopental sodium or propofol. We searched the Cochrane Epilepsy Group Specialized Register (16 August 2016), the Cochrane Central Register of Controlled Trials (CENTRAL) via the Cochrane Register of Studies Online (CRSO, 16 August 2016), MEDLINE (Ovid, 1946 to 16 August 2016), ClinicalTrials.gov (16 August 2016), and the South Asian Database of Controlled Clinical Trials (16 August 2016). Previously we searched IndMED, but this was not accessible at the time of the latest update. All randomised controlled trials (RCTs) or quasi-RCTs (regardless of blinding) assessing the control of RSE using either thiopental sodium or propofol in patients of any age and gender. Two review authors screened the search results and reviewed the abstracts of relevant and eligible trials before retrieving the full-text publications. One study with a total of 24 participants was available for review. This study was a small, single-blind, multicentre trial studying adults with RSE receiving either propofol or thiopental sodium for the control of seizure activity. This study was terminated early due to recruitment problems. For our primary outcome of total control of seizures after the first course of study drug, there were 6/14 patients versus 2/7 patients in the propofol and thiopental sodium groups, respectively (risk ratio (RR) 1.50, 95% confidence interval (CI) 0.40 to 5.61, low quality evidence). Mortality was seen in 3/14 patients versus 1/7 patients in the propofol and thiopental sodium groups, respectively (RR 1.50, 95% CI 0.19 to 11.93, low quality evidence). Our third primary outcome of length of ICU stay was not reported. For our secondary outcomes of adverse events, infection was seen in 7/14 patients versus 5/7 patients in the propofol and thiopental sodium groups, respectively (RR 0.70; 95% CI 0.35 to 1.41). Hypotension during administration of study drugs and requiring use of vasopressors was seen in 7/14 patients versus 4/7 patients in the propofol and thiopental sodium groups, respectively (RR 0.87; 95% CI 0.38 to 2.00). The other severe complication noted was non-fatal propofol infusion syndrome in one patient. Patients receiving thiopental sodium required more days of mechanical ventilation when compared with patients receiving propofol: (median (range) 17 days (5 to 70 days) with thiopental sodium versus four days (2 to 28 days) with propofol). At three months there was no evidence of a difference between the drugs with respect to outcome measures such as control of seizure activity and functional outcome. Since the last version of this review we have found no new studies.There is a lack of robust, randomised, controlled evidence to clarify the efficacy of propofol and thiopental sodium compared to each other in the treatment of RSE. There is a need for large RCTs for this serious condition.

An evaluation of factors affecting adherence to antiepileptic drugs in patients with epilepsy: a cross-sectional study.

Adherence to antiepileptic drug (AED) therapy is important for controlling seizures in patients with epilepsy (PWE). It is vital to identify the factors influencing adherence to AED therapy using validated tools. This study aimed to evaluate the pattern and extent of AED adherence among PWE and to identify the factors that influence adherence. This was a cross-sectional study involving PWE who had a confirmed diagnosis. Treatment adherence was assessed using the four-item Morisky Medication Adherence Scale. Univariate analysis with chi-square test was used to observe the association between different variables and AED adherence. Binary logistic regression analysis was used to identify the predictors of adherence. 451 PWE (mean age 27.3 ± 8.1 years) were enrolled in the study; 251 (55.7%) were male and 198 (43.9%) were from the lower socioeconomic class. 326 (72.3%) patients had high adherence to AED therapy, while 125 (27.7%) had low adherence. AED adherence was significantly associated with socioeconomic status (p = 0.043) and type of epilepsy (p = 0.033). However, no significant difference was observed between adherence and age, gender, marital status, epilepsy duration, number and type of AEDs, and occurrence of adverse drug reactions. Patients with focal epilepsy and those from the middle/lower-middle socioeconomic classes were less likely to be nonadherent. The primary reason for nonadherence was forgetfulness. This study found that a majority of PWE have optimal rates of AED adherence and that forgetfulness is the primary reason for nonadherence among PWE.

Rationale for mono- versus polytherapy with antiepileptic drugs for patients with epilepsy

The article considers the arguments that can provide a rationale for treatment policy in patients with epilepsy after failure of monotherapy with a first antiepileptic drug (AED). When choosing alternative monotherapy or early polytherapy with AEDs, one should consider a diversity of criteria: the mechanism of action, pharmacokinetic and pharmacodynamic properties, efficacy, and safety profile of AEDs, disease features, individual patient characteristics, and social factors. The choice of the right AED treatment policy in the early stages of the disease is important for patients because the inadequate control of seizures can result in irreversible psychosocial consequences and reduce the chance to eliminate future disabling seizures.

Clinical Profile and Changes of Serum Lipid Levels in Epileptic Patients after Cerebral Infarction

Antiepileptic drugs (AEDs) may increase development of dyslipidemia and cerebrovascular disease (CVD). We examined the clinical profile and changes of serum lipid levels after AED monotherapy in patients with poststroke epilepsy (PSE) after cerebral infarction (CI). Medical records were reviewed in consecutive 2144 CI patients. Monotherapy of valproate, carbamazepine (CBZ), phenytoin (PHT), zonisamide, levetiracetam, or lamotrigine was performed in PSE patients. Serum lipid levels were measured before and at 3 months after AED treatment. The prevalence of PSE was 7.0% in CI patients. The TOAST etiology disclosed large-artery atherosclerosis in 68 patients (45%), cardioembolism in 63 patients (42%), and undetermined cause in 19 patients (13%). CVD risk profile showed obesity of 18 patients (12%), current smoker of 30 patients (20%), hypertension of 75 patients (50%), diabetes mellitus of 32 patients (21%), dyslipidemia of 15 patients (10%), and atrial fibrillation of 63 patients (42%). CBZ or PHT administration increased serum total cholesterol (TC) and low-density lipoprotein-cholesterol (LDL-C) levels significantly compared to baseline and AED-untreated controls. Those levels were not increased significantly in other AED and control groups. Serum high-density lipoprotein-cholesterol and triglyceride levels did not differ statistically in all groups. The prevalence of post-CI epilepsy was 7.0%. The pathogenesis contributed to atherothrombosis and cardioembolism. CBZ or PHT administration increased serum TC and LDL-C significantly. Thus, we should pay more attention to serum lipid levels in patients receiving cytochrome P450 (CYP)-induced AEDs, and might considerer switching to non-CYP-induced AEDs in patients with unfavorable serum lipid changes.

The ‘Photosensitivity Model’ is (also) a model for focal (partial) seizures

The ‘Photosensitivity Model’ uses a standardized stimulation protocol of repeated intermittent photic stimulation (IPS) over a three-day period, with administration of a single dose of an investigational antiepileptic drug (AED) after a baseline IPS day in photosensitive patients, followed by a third IPS day to determine duration of effect. This ‘Photosensitivity Model’ has shown its value in the development of new AEDs. Levetiracetam (LEV), currently a first-line AED in new-onset focal epilepsies, was not effective in classical animal models, but showed dose-dependent efficacy in the human ‘Photosensitivity Model’. Nevertheless, concerns have been expressed that AEDs selectively suppressing focal seizures might not suppress generalized photoparoxysmal EEG responses (PPR), the pharmacodynamic outcome measure in the Model. Herein, the following questions have been addressed: I. Can patients with generalized epileptiform discharges, evoked by IPS, so-called PPR, have focal epilepsy (focal seizures)? II. Are the photosensitive patients with focal epilepsy, who have participated in the photosensitivity trials, non-responsive to a new AED under investigation, as compared to those with generalized epilepsies? III. Are “focal epilepsy” AEDs effective both in the ‘Photosensitivity Model’ and in real life in photosensitive patients? We performed a systematic literature review of PPR in focal seizures and focal epilepsy and we analyzed data (published and unpublished) from 20 different potential AEDs studied prospectively in the ‘Photosensitivity Model’. Finally, the PPR effects of Na+ channel-blocking AEDs (considered as the most typical AEDs for focal epilepsy) are discussed with unequivocal examples given of the focal nature of a patient’s PPR. Based on the entire data evidence, we conclude that: 1. PPRs certainly exist in focal epilepsy (17% on average); 2. Clinical signs and symptoms of PPRs can be focal and 3. PPRs can definitely be used to identify or to prove efficacy of new AEDs for patients with focal epilepsy.

Practice Current: When do you stop antiepileptic drugs in patients with genetic generalized epilepsies and in those with focal epilepsies?

More than 50 million people worldwide have epilepsy.1 About two-thirds of them are well-controlled on 1 or 2 appropriately used antiepileptic drugs (AEDs).2 One-third of patients with epilepsy remain refractory to medications, and experience seizures despite a complex regimen of multiple drugs. Some patients may be candidates for surgical interventions, either curative or palliative. Many times in clinical practice the question arises as to whether a patient is a candidate for withdrawing AEDs, either because the epilepsy is well-controlled medically or because the patient became seizure-free after surgery.

Risk Factors of Preoperative and Early Postoperative Seizures in Patients with Meningioma: A Retrospective Single-Center Cohort Study

Well-defined risk factors for the identification of patients with meningioma who might benefit from preoperative or early postoperative seizure prophylaxis are unknown. We investigated and quantified risk factors to determine individual risks of seizure occurrence in patients with meningioma. A total of 634 adult patients with meningioma were included in this retrospective cohort study. Patient gender and age, tumor location, grade and volume, usage of antiepileptic drugs (AEDs) and extent of resection were determined. Preoperative and early postoperative seizures occurred in 15% (n= 97) and 5% (n= 21) of the patients, respectively. Overall, 502 and 418 patients were eligible for multivariate logistic regression analyses of preoperative and early postoperative seizures, respectively. Male gender (odds ratio [OR], 2.06; P= 0.009), a non-skull base location (OR, 4.43; P < 0.001), and a tumor volume of >8 cm3 (OR, 3.05; P= 0.002) were associated with a higher risk of preoperative seizures and were used to stratify the patients into 3 prognostic groups. The high-risk subgroup of patients with meningioma showed a seizure rate of >40% (OR, 9.8; P< 0.001). Only a non-skull base tumor location (OR, 2.61; P= 0.046) was identified as a significant risk factor for early postoperative seizures. AEDs did not reduce early postoperative seizure occurrence. Seizure prophylaxis might be considered for patients at high risk of developing seizures who are for other reasons being considered for watchful waiting instead of resection. In contrast, our data do not provide any evidence of the efficacy of perioperative AEDs in patients with meningioma.

Cannabidiol as a new treatment for drug-resistant epilepsy in tuberous sclerosis complex.

Tuberous sclerosis complex (TSC) is an autosomal-dominant genetic disorder with highly variable expression. The most common neurologic manifestation of TSC is epilepsy, which affects approximately 85% of patients, 63% of whom develop treatment-resistant epilepsy. Herein, we evaluate the efficacy, safety, and tolerability of cannabidiol (CBD), a nonpsychoactive compound derived from the marijuana plant, as an adjunct to current antiepileptic drugs in patients with refractory seizures in the setting of TSC. Eighteen of the 56 patients who have enrolled in our current expanded-access study of cannabidiol for patients with treatment-resistant epilepsy carry a diagnosis of TSC. After an initial baseline period of 1month, patients began treatment with CBD. The initial dose of 5mg/kg/day was increased by 5mg/kg/day every week up to a maximum dose of 50mg/kg/day, if tolerated. Weekly seizure frequencies, percent change in seizure frequencies, and responder rates were calculated during the 2nd, 3rd, 6th, 9th, and 12th month of treatment with CBD. The median weekly seizure frequency during the baseline period was 22.0 (interquartile range [IQR] 14.8-57.4), which decreased to 13.3 (IQR 5.1-22.1) after 3months of treatment with cannabidiol. The median percent change in total weekly seizure frequency was -48.8% (IQR -69.1% to -11.1%) after 3months of treatment. The 50% responder rates over the course of the study were 50%, 50%, 38.9%, 50%, and 50% after 2, 3, 6, 9, and 12months of treatment with CBD, respectively. In patients taking clobazam concurrently with CBD (n=12), the responder rate after 3months of treatment was 58.3%, compared to 33.3% in patients not taking clobazam (n=6). Twelve (66.7%) of 18 patients in this study experienced at least one adverse event thought possibly related to CBD; the most common adverse events were drowsiness (n=8, 44.4%), ataxia (n=5, 27.8%), and diarrhea (n=4, 22.2%). Although double-blind, placebo-controlled trials are still necessary, these findings suggest that cannabidiol may be an effective and well-tolerated treatment option for patients with refractory seizures in TSC.

Antiepileptic Drug Removal by Continuous Renal Replacement Therapy: A Review of the Literature.

Continuous renal replacement therapy (CRRT) is used for managing acute kidney injury in critically ill patients. Removal of antiepileptic drugs (AEDs) by CRRT could be significant and may complicate patients' intensive care unit stay. The objective of the current review was to summarize the available evidence for AED removal by CRRT. An electronic literature search of PubMed (1946 to May 2016), Medline (1946 to May 2016), and Embase (1974 to May 2016) databases for studies discussing AED removal by CRRT was conducted. A total of 31 case reports discussing 32 patients were found. AEDs reported were levetiracetam (n=3), valproic acid (n=9), carbamazepine (n=10), phenytoin (n=3), phenobarbital (n=4), lacosamide (n=1), gabapentin (n=1), and topiramate (n=1). Two-thirds of the reports were about using CRRT in drug overdose and one-third was about AED removal by CRRT during therapy. Based on the current limited evidence and pharmacokinetic characteristics of AEDs, renally eliminated AEDs and/or AEDs with limited protein binding such as levetiracetam are more likely to be removed by CRRT than AEDs that are mainly metabolized and extensively protein bound such as carbamazepine. In conclusion, there is not enough evidence to provide robust dosing recommendations for AEDs in patients undergoing CRRT. Further studies are needed.

Quantifying antiepileptic drug effects using intrinsic excitability measures.

Pathologic increases in excitability levels of cortical tissue commonly underlie the initiation and spread of seizure activity in patients with epilepsy. By reducing the excitability levels in neural tissue, antiepileptic drug (AED) pharmacotherapy aims to reduce seizure severity and frequency. However, AEDs may also bring about adverse effects, which have been reported to increase with higher AED load. Measures that monitor the dose-dependent effects of AEDs on cortical tissue and quantify its excitability level are therefore of prime importance for efficient clinical care and treatment but have been difficult to identify. Here, we systematically analyze continuous multiday electrocorticography (ECoG) data from 10 patients under different levels of AED load and derive the recently proposed intrinsic excitability measures (IEMs) from different brain regions and across different frequency bands. We find that IEMs are significantly negatively correlated with AED load (prescribed daily dose/defined daily dose). Furthermore, we demonstrate that IEMs derived from different brain regions can robustly capture global changes in the degree of excitability. These results provide a step toward the ultimate goal of developing a reliable quantitative measure of central physiologic effects of AEDs in patients with epilepsy.

Seizure outcome after switching antiepileptic drugs: A matched, prospective study.

Outcomes after changing antiepileptic drugs (AEDs) have largely been studied in single cohort series. We recently reported the first study to examine this question in a controlled manner. Here we expand on these results by using a matched, prospective methodology applied to both uncontrolled and well-controlled patients taking any AED. We reviewed all outpatient notes over a 9-month period and identified patients with focal epilepsy who were on monotherapy. We classified those who switched AEDs as case patients, with those remaining on the same drug serving as controls. We matched cases with controls for seizure status (seizure-free in the preceding 6 months or not), current AED, and number of failed AEDs. We subsequently assessed outcome 6 months later. Seizure-free patients who switched drug (n = 12) had a 16.7% rate of seizure recurrence at 6 months, compared to 2.8% among controls remaining on the same drug (n = 36, p = 0.11). There was a 37% remission rate among uncontrolled patients who switched drug compared to 55.6% among controls (n = 27 per group, p = 0.18). Uncontrolled patients who had previously tried more than one AED were somewhat less likely to enter remission (p = 0.057). Neither AED mechanism of action nor change in dosage impacted outcome. Herein we provide further estimation of the modest risk (~14%) associated with switching AEDs in patients in remission compared to being maintained on the same regimen. Uncontrolled patients were no more likely to enter remission after a drug switch than they were after remaining on the same drug, suggesting that spontaneous changes in disease state, and not drug response, underlie remission in this population.

Prophylactic Use of Antiepileptic Drugs in Patients with Spontaneous Intracerebral Hemorrhage

The effect of prophylactic antiepileptic drugs (AEDs) on mortality and functional outcome in patients with intracerebral hemorrhage (ICH) is uncertain. We used data from the Virtual International Stroke Trials Archive (VISTA) to evaluate the effect of prophylactic AEDs on ICH outcome. Univariate and multivariate logistic and Cox regression models were designed to determine the impact of prophylactic AEDs on mortality and disability, defined as a modified Rankin Scale (mRS) greater than 3 at 90 days following ICH. Of the 802 patients with ICH, 81 (10%) received prophylactic AEDs. Patients who received AED prophylaxis had higher ICH volume (median 23.2 cm(3) [IQR 10.5-38.0] versus 14.3 cm(3) [IQR 7.1-27.0], P= .001) and ICH score (median 1 cm(3) [IQR 0-2] versus 1 cm(3) [IQR 0-1], P = .03). In univariate analyses, AED prophylaxis was associated with higher probability of mRS greater than 3 at 90 days (62% versus 49%, P = .03) and a trend towards increased mortality (27% versus 18%, P = .06). Although seizure did not influence ICH outcome, any AED prophylaxis and phenytoin use in particular were both associated with mRS greater than 3 at 90 days (OR 1.66 [1.04-2.66], P = .03 for any AED; OR 1.97 [1.06-3.67], P = .03 for phenytoin prophylaxis) in univariate analyses. After adjustment for components of the ICH score, none of these associations remained significant. Patients with higher ICH scores and larger hemorrhages are more likely to receive prophylactic AEDs. We found no independent effect of prophylactic AED treatment on outcome after ICH.

Predictors of Functional Outcomes and Use of Antiepileptic Drugs in Patients with Primary Acute Intracerebral Hemorrhage (P1.205)

Predictors of Functional Outcomes and Use of Antiepileptic Drugs in Patients with Primary Acute Intracerebral Hemorrhage (P1.205)

Relation of Perceived Stigma to Adverse Events of Medications in Patients with Epilepsy

Purpose. We aimed to assess the influence of adverse events (AEs) of antiepileptic drugs (AEDs) on perceived stigma of Bulgarian patients with epilepsy. Methods. Our study was based on questionnaires (Liverpool Adverse Events Profile (LAEP) and stigma scale), information from medical documentation, and an interview on clinical factors of 153 consecutive patients with epilepsy. Results. Perceived stigma was observed in 64.71% of the study participants. There was a significant association between perceived stigma and the total LAEP score (p < 0.05, F = 13.71). Patients who reported AEs had an increased risk of perceiving stigma compared to those who did not experience AEs. A significant correlation between perceived stigma and the presence of neurological and psychiatric AEs (p < 0.001, r = +0.60) and a mild correlation between perceived stigma and the presence of nonneurological AEs (p < 0.01, r = +0.20) were verified. In a multivariate regression analysis the only predictors of perceived stigma were AED polytherapy and the presence of neurological and psychiatric AEs. Conclusions. AEs of AEDs in patients with epilepsy significantly correlate with perceived stigma. Our study results will be useful in the campaign to overcome stigma predictors.

Roles of Valproic Acid in Improving Radiation Therapy for Glioblastoma: a Review of Literature Focusing on Clinical Evidence.

Glioblastoma (GBM) is the most common and aggressive type of primary brain neoplasm. The current standard therapy for GBM consists of maximal surgical resection within safe limits, followed by radiation therapy (RT) and chemotherapy with temozolomide. Despite advances in treatment, the prognosis of GBM remains poor. Epileptic seizure is one of the most common symptoms in patients with GBM. Valproic acid (VPA), a histone deacetylase inhibitor, is often used as an anti-epileptic drug in patients with brain neoplasms due to its effectiveness and low toxicity profile. Several in vivo and in vitro studies have indicated that VPA has radiosensitizing effects for gliomas and radioprotective influence on normal brain tissue or hippocampal neurons. The results of several retrospective studies have also indicated potential benefit to improve survival of patients with GBM. Moreover, the promising treatment results of a phase 2 trial of concurrent radiation therapy, temozolomide, and VPA for patients with GBM have been recently reported. The use of VPA in patients with GBM has thus recently receiving more attention. In this article, we review the role of VPA in radiation therapy for GBM, focusing on the clinical evidence.

Antiepileptic Drugs for Patients with Intracerebral Hemorrhage: A Meta-Analysis.

Whether an antiepileptic drug (AED) should be prescribed for intracerebral hemorrhage (ICH) patients is a matter in dispute, and recent studies have come up with different or even opposite views. A meta-analysis on this issue has not been performed. The goal of this meta-analysis was to study antiepileptic drugs" effects on early seizure occurrence and outcome for ICH patients. We searched the PubMed, Ovid, and Cochrane library until December 2015 to identify relevant articles. A meta-analysis was conducted to evaluate the overall effect with random-effects or fixed-effects models. Four articles consisting of one randomized controlled trial and three cohort studies met the included criteria. For the occurrence of early seizure, antiepileptic drugs showed the ability to reduce the risk, but reached no statistical significance (OR=0.71; 95% CI, 0.38-1.34; test for overall effect Z=1.06, p=0.29). No association between antiepileptic drug use and poor outcome was found (OR=1.95; 95% CI, 0.56-6.79; test for overall effect Z=1.06, P=0.29), but heterogeneity was present. Summarizing published studies, the AED use did not reduce early seizure occurrence statistically but a population with high-risk factors of early seizure is likely to benefit from AEDs. Besides, AED use was not associated with poor outcome. We suggest AED use for ICH patients with high-risk factors of seizure, but not generally.

BUDGET IMPACT ANALYSIS OF PERAMPANEL FOR ADJUNCTIVE TREATMENT IN EPILEPSY PATIENTS 12 YEARS OF AGE AND OLDER FOR PARTIAL ONSET SEIZURES WITH OR WITHOUT SECONDARY GENERALIZATION AND PRIMARY GENERALIZED TONIC-CLONIC SEIZURES IN THE RUSSIAN FEDERATION

Objectives. To assess the incremental budget impact (BI) of using of utilizing perampanel to treat partial-onset seizures (POS) and primary generalized tonic-clonic seizures (PGTCS) in patients who are 12 years of age and older in Russia. Methods. The budget impact was estimated by comparing two different scenarios: Cost of POS & PGTCS without Perampanel and Cost of POS & PGTCS with Perampanel (Perampanel Adoption). In the latter scenario, market share of perampanel was assumed to increase every year for up to five years. The model was developed from a payer perspective with a time horizon of five years. Direct costs included drugs and medical resources (hospitalization, emergency care costs, visits to physician). BI was calculated as the difference in costs between Perampanel Adoption scenario and the cost without Perampanel. Results. In Russia, approximately 125,499 patients who are at least 12 years old are treated for refractory POS & PGTCS each year. The market share of perampanel in the perampanel adoption scenario from year 1 to year 5 was 0.1%, 0.5%, 1.0%, 2.0% and 3.0%, respectively. During the same period, the adoption of perampanel is projected to increase drug costs (in millions) by RUB15.2 (1.2%), RUB76.1 (6.2%), RUB152.4 (12.3%), RUB305.4 (24.7%), and RUB459.0 (37.0%), respectively. A significant portion of the 5-year cumulative increase in drug costs (RUB 1,008 million) will be offset by a decrease in non-drug medical resources (-RUB152.7 million). The cumulative budget impact from perampanel adoption for the first five years is projected to be RUB855 million (0.7%), with an additional 231 patients gaining seizure freedom over a period of 5 years from the adoption of perampanel. Conclusion. Perampanel should be considered as an alternative alongside current antiepileptic drugs in patients with symptoms refractory to prior antiepileptic treatments.