Efficacy and tolerability of Brivaracetam in people with intellectual disability compared to those without intellectual disability.

INTRODUCTION: In England, nearly a quarter of people with intellectual disability (PwID) have epilepsy. Though 70 % of PwID have pharmaco-resistant seizures only 10 % are prescribed anti-seizure medication (ASMs) licenced for pharmaco-resistance. Brivaracetam (BRV) licenced in 2016 has had nine post-marketing studies involving PwID. These studies are limited either by lack of controls or not looking at outcomes based on differing levels of ID severity. This study looks at evidence comparing effectiveness and side-effects in PwID to those without ID prescribed Brivaracetam (BRV). METHODS: Pooled case note data for patients prescribed BRV (2016-2022) at 12 UK NHS Trusts were analysed. Demographics, starting and maximum dose, side-effects, dropouts and seizure frequency between ID (mild vs. moderate-profound (M/P)) and general population for a 12-month period were compared. Descriptive analysis, Mann-Whitney, Fisher's exact and logistic regression methods were employed. RESULTS: 37 PwID (mild 17 M/P 20) were compared to 102 without ID. Mean start and maximum dose was lower for PwID than non-ID. Mean maximum dose reduced slightly with ID severity. No difference was found between ID and non-ID or between ID groups (Mild vs M/P) in BRV's efficacy i.e. >50 % seizure reduction or tolerability. Mental and behavioural side-effects were more prevalent for PwID (27.0 % ID, 17.6 % no ID) but not significantly higher (P = 0.441) or associated with ID severity (p = 0.255). CONCLUSION: This is the first study on BRV, which compares ID cohorts with differing severity and non-ID. Efficacy, tolerability and side-effects reported are similar across differing ID severity to those with no ID.

Efficacy and tolerability of levetiracetam in people with and without intellectual disabilities: A naturalistic case control study.

INTRODUCTION: People with Intellectual Disabilities (PwID) are twenty times more likely than general population to have epilepsy. Guidance for prescribing antiseizure medication (ASM) to PwID is driven by trials excluding them. Levetiracetam (LEV) is a first-line ASM in the UK. Concerns exist regarding LEV's behavioural and psychological adverse effects, particularly in PwID. There is no high-quality evidence comparing effectiveness and adverse effects in PwID to those without, prescribed LEV. METHODS: Pooled casenote data for patients prescribed LEV (2000-2020) at 18 UK NHS Trusts were analysed. Demographics, starting and maximum dose, adverse effects, dropouts and seizure frequency between ID (mild vs. moderate-profound (M/P)) and general population for a 12-month period were compared. Descriptive analysis, Mann-Whitney, Fisher's exact and logistic regression methods were employed. RESULTS: 173 PwID (mild 53 M/P 120) were compared to 200 without ID. Mean start and maximum dose were similar across all groups. PwID (Mild & M/P) were less likely to withdraw from treatment (P = 0.036). No difference was found between ID and non-ID or between ID groups (Mild vs M/P) in LEV's efficacy i.e. >50 % seizure reduction. Significant association emerged between ID severity and psychiatric adverse effects (P = 0.035). More irritability (14.2 %) and aggression (10.8 %) were reported in M/P PwID. CONCLUSION: PwID and epilepsy have high rates of premature mortality, comorbidities, treatment resistance and polypharmacy but remain poorly researched for ASM use. This is the largest studied cohort of PwID trialled on LEV compared to general population controls. Findings support prescribing of LEV for PwID as a first-line ASM.

Seizures and emergency department: characteristics and factors of repeat adult attendees.

BACKGROUND: To identify risk factors and characteristics for the repeated attendance at an emergency department (ED) following a seizure. METHODS: A retrospective cohort study was conducted using non-identifiable data of individuals attending ED at least twice between 2015 and 2018, following a seizure. Data were drawn from the patient administration system of an English rural medium-sized teaching district general hospital emergency department (ED), serving a population of 566,000 people. It was analysed for bio-psycho-social features associated with repeat attendances. RESULTS: Of 3522 seizure-related attendances in the four years, 450 people were identified to be repeaters attending on two or more occasions (range 2-12). Just over a quarter (27%) were 18-29 years old. Higher likelihood of re-attendance was associated with social deprivation and no fixed abode. Mental illness was a significant co-morbidity influencing repeat attendances. Nearly half (47%) had no recorded anti-seizure medication (ASM). Three fifth (60%) were on general medication and a quarter (25%) on psychotropics. Nearly a quarter (22%) had alcohol and recreational drug concerns. Just over a quarter (28%) had no previous epilepsy diagnosis. Nearly a fifth (n = 85, 19%) died during the study period. CONCLUSION: People who present repeatedly with seizures at ED are at significant risk of death over a four-year period and require pro-active clinical follow-up. People who are homeless or from socially deprived areas are over-represented in this group, as are those with alcohol problems, co-morbid mental health conditions and compliance issues. This suggests enhanced targeted intervention for this cohort is needed.

Eslicarbazepine acetate as a replacement for levetiracetam in people with epilepsy developing behavioral adverse events.

BACKGROUND: Psychiatric and behavioral side effects (PBSEs) are a major cause of antiepileptic drug (AED) withdrawal. Levetiracetam (LEV) is a recognized first-line AED with good seizure outcomes but recognized with PBSEs. Eslicarbazepine (ESL) is considered to function similarly to an active metabolite of the commonly used carbamazepine (CBZ). Carbamazepine is used as psychotropic medication to assist in various psychiatric illnesses such as mood disorders, aggression, and anxiety. AIM: The aim was to evaluate the psychiatric profile of ESL in people who had LEV withdrawn due to PBSEs in routine clinical practice to see if ESL can be used as a possible alternative to LEV. METHODS: A retrospective observational review was conducted in two UK epilepsy centers looking at all cases exposed to ESL since its licensing in 2010. The ESL group was all patients with treatment-resistant epilepsy who developed intolerable PBSEs to LEV, subsequently trialed on ESL. The ESL group was matched to a group who tolerated LEV without intolerable PBSEs. Psychiatric disorders were identified from case notes. The Hamilton Depression Scale (HAM-D) was used to outcome change in mood. Clinical diagnoses of a mental disorder were compared between groups using the Fisher's exact test. Group differences in HAM-D scores were assessed using the independent samples t-test (alpha=0.05). RESULTS: The total number of people with active epilepsy in the two centers was 2142 of whom 46 had been exposed to ESL. Twenty-six had previous exposure to LEV and had intolerable PBSEs who were matched to a person tolerating LEV. There was no statistical differences in the two groups for mental disorders including mood as measured by HAM-D (Chi-square test: p=0.28). CONCLUSION: The ESL was well tolerated and did not produce significant PBSEs in those who had PBSEs with LEV leading to withdrawal of the drug. Though numbers were small, the findings suggest that ESL could be a treatment option in those who develop PBSEs with LEV and possibly other AEDs.

Frequency and factors associated with emergency department attendance for people with epilepsy in a rural UK population.

Attendance at UK Emergency Departments (EDs) for people with epilepsy (PWE) following a seizure can be unnecessary and costly. The characteristics of PWE attending a UK rural district ED in a 12-month period were examined to foster better understanding of relevant psycho-social factors associated with ED use by conducting cross-sectional interviews using standardized questionnaires. Of the total participants (n=46), approximately one-third of the study cohort attended ED on three or more occasions in the 12-month study period and accounted for 65% of total ED attendances reported. Seizure frequency and lower social deprivation status were associated with increased ED attendance while factors such as knowledge of epilepsy, medication management, and stigma were not. Similarities in frequency of repeat attendees were comparable to a study in urban population but other factors varied considerable. Our findings suggest that regular ED attendees may be appropriate for specific enhanced intervention though consideration needs to be given to the fact that population characteristics may vary across regions.