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.

Lacosamide in the general population and in people with intellectual disability: Similar responses?

PURPOSE: Epilepsy prevalence is significantly higher in people with Intellectual Disability (ID) compared to people with epilepsy (PWE) from the general population. Increased psychological and behavioural problems, healthcare costs, morbidity, mortality and treatment resistance to antiepileptic drugs (AEDs) is associated with epilepsy in ID populations. Prescribing AEDs for PWE and ID is challenging and influenced heavily by studies conducted with the general population. Our study compares Lacosamide (LCM) response for the ID population to those from the general population; using data from an UK based epilepsy database register (EP ID/PDD AED Register). METHODS: Pooled retrospective case notes data for PWE prescribed LCM at 11 UK NHS Trusts were analysed. Participants were classified as per WHO guidance into groups of moderate-profound ID, mild ID and General population. Demographics, concomitant AEDs, starting and maximum dosage, exposure length, adverse effects, dropout rates, seizure frequency were collected. Group differences were reported as odds ratios estimated from univariable logistic regression models. RESULTS: Of 232 consented participants, 156 were from the general population and 76 had ID (24 mild, 52 moderate-profound). Twelve month withdrawal rates and reasons, efficacy, side-effects, start and maximum doses were similar between the groups. Dose titration between baseline and three months was significantly slower in the ID group (p = 0.02). CONCLUSION: There were no differences for LCM outcomes between general and ID groups. Slower LCM titration in ID populations in the first 3 months was associated with higher retention and lower behavioural side effects as compared to similar European studies.