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.

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.

Evaluating the impact of a UK recovery college on mental well-being: pre- and post-intervention study.

BACKGROUND: Recovery colleges provide personalised educational mental health support for people who self-refer. The research evidence supporting them is growing, with key components and the positive experiences of attendees reported. However, the quantitative outcome evidence and impact on economic outcomes is limited. AIMS: To evaluate the impact of attending a UK recovery college for students who receive a full educational intervention. METHOD: This is a pre- and post-intervention study, with predominantly quantitative methods. Participants recruited over an 18-month period (01.2020-07.2021) completed self-reported well-being (Short Warwick-Edinburgh Mental Wellbeing Scale (SWEMWBS)) and recovery (Process of Recovery (QPR)) surveys, and provided details and evidence of employment and educational status. Descriptive statistics for baseline data and Shapiro-Wilk, Wilcoxon signed-rank and paired t-tests were used to compare pre- and post-intervention scores, with Hedges' g-statistic as a measure of effect size. Medical records were reviewed and a brief qualitative assessment of changes reported by students was conducted. RESULTS: Of 101 student research participants, 84 completed the intervention. Well-being (mean SWEMWBS scores 17.3 and 21.9; n = 80) and recovery (mean QPR scores 27.2 and 38.8; n = 75) improved significantly (P < 0.001; Hedges' g of 1.08 and 1.03). The number of economically inactive students reduced from 53 (69%) to 19 (24.4%). No research participants were referred for specialist mental health support while students. 'Within-self' and 'practical' changes were described by students following the intervention. CONCLUSIONS: Findings detail the largest self-reported pre-post data-set for students attending a recovery college, and the first data detailing outcomes of remote delivery of a recovery college.

A pragmatic randomized controlled exploratory trial of the effectiveness of Eye Movement Desensitization and Reprocessing therapy for psychotic disorder.

BACKGROUND: People with severe mental illness are often excluded from trials related to Eye Movement Desensitization and Reprocessing (EMDR) therapy. Principal concerns are that they may not tolerate treatment, might risk relapse or that psychotic symptoms may worsen. There is however building evidence of a traumatogenic etiology of psychotic disorder that may benefit therapeutically from EMDR. However, EMDR in this role is done mainly in specialist tertiary settings. AIM: To conduct a randomized exploratory trial of prospective treatment of EMDR for people with psychotic disorder and a history of trauma in an adult community mental health service. METHODS: A randomized exploratory trial with a controlled pilot design was employed to conduct a prospective treatment and six-month follow-up study with an interim 10-week analysis in a rural county in the UK (population 538,000). We recruited participants with psychotic disorder who had a reported history of trauma and were interested in receiving trauma therapy. They were then randomized to either receive EMDR or treatment as usual (TAU). The primary instrument used was the Impact of Events Scale (IES) with secondary instruments of Positive and Negative Symptoms of Psychotic Disorder (PANSS), PTSD Checklist (PCL-C), and subjective Quality of Life (MANSA). RESULTS: IES scores showed significant improvements in the EMDR group (n = 24, age 42.0 SD (14.5), 42% male) compared to the TAU group (n = 12, age 34.4 SD (11.3), 50% male) at 10 weeks and at six months (p < 0.05). There were significant improvements in PCL-C and PANSS negative symptoms scores associated with treatment (p < 0.05). All other scales showed positive trends. CONCLUSIONS: This study demonstrates that EMDR can reduce the impact of traumatic events for patients with a psychotic disorder in a clinical setting in the UK. The improvements in psychotic disorder persisted for six months after treatment. TRIAL REGISTRATION: ISRCTN43816889.

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.

Status of primary and secondary mental healthcare of people with severe mental illness: an epidemiological study from the UK PARTNERS2 programme.

BACKGROUND: There is global interest in the reconfiguration of community mental health services, including primary care, to improve clinical and cost effectiveness. AIMS: This study seeks to describe patterns of service use, continuity of care, health risks, physical healthcare monitoring and the balance between primary and secondary mental healthcare for people with severe mental illness in receipt of secondary mental healthcare in the UK. METHOD: We conducted an epidemiological medical records review in three UK sites. We identified 297 cases randomly selected from the three participating mental health services. Data were manually extracted from electronic patient medical records from both secondary and primary care, for a 2-year period (2012-2014). Continuous data were summarised by mean and s.d. or median and interquartile range (IQR). Categorical data were summarised as percentages. RESULTS: The majority of care was from secondary care practitioners: of the 18 210 direct contacts recorded, 76% were from secondary care (median, 36.5; IQR, 14-68) and 24% were from primary care (median, 10; IQR, 5-20). There was evidence of poor longitudinal continuity: in primary care, 31% of people had poor longitudinal continuity (Modified Modified Continuity Index ≤0.5), and 43% had a single named care coordinator in secondary care services over the 2 years. CONCLUSIONS: The study indicates scope for improvement in supporting mental health service delivery in primary care. Greater knowledge of how care is organised presents an opportunity to ensure some rebalancing of the care that all people with severe mental illness receive, when they need it. A future publication will examine differences between the three sites that participated in this study.

Eslicarbazepine acetate response in intellectual disability population versus general population.

BACKGROUND: A quarter of people with intellectual disability (ID) have epilepsy, compared to approximately one in a hundred across the general population. Evidence for the safe and effective prescribing of antiepileptic drugs (AEDs) for those with ID is, however, limited. AIMS OF STUDY: This study seeks to strengthen the research evidence around Eslicarbazepine Acetate (ESL), a new AED, by comparing response of individuals with ID to those from the general population who do not have ID. METHODS: A single data set was created through retrospective data collection from English and Welsh NHS Trusts. The UK-based Epilepsy Database Research Register (Ep-ID) data collection and analysis method were used. RESULTS: Data were collected for 93 people (36 ID and 57 'no ID'). Seizure improvement of '>50%' was higher at 12 months for 'no ID' participants (56%), compared to ID participants (35%). Retention rates were slightly higher for those with ID (56% compared to 53%). Neither difference was significant. CONCLUSIONS: Tolerance and Efficacy for ID and 'no ID' people in our data set were similar. Seizure improvement and retention rates were slightly lower than that found in other European data sets, but findings strengthen the evidence for the use of ESL in the ID population.

European perspective of perampanel response in people with Intellectual Disability.

BACKGROUND: Epilepsy prevalence is over 20% for those with ID. It is difficult to diagnose and treat and more likely to be treatment resistant. The evidence informing prescribing is sparse, particularly for new drugs such as perampanel (PMP). AIMS OF THE STUDY: This study seeks to strengthen the research evidence regarding PMP for people with ID by pooling information from two isolated and separately conducted studies: the UK-based Epilepsy Database Register (Ep-ID) and the data from the Kempenhaeghe clinic in the Netherlands. METHODS: A single data set of comparable data was created and analysed under agreement and supervision of a UK statistician. RESULTS: Seizure reduction within twelve months was evident in 62% of Dutch and 47% of UK patients. Retention rates were higher for those in the UK (P = .01) and for patients with moderate to profound ID, whilst side effects were more prominent in the Dutch cohort. CONCLUSIONS: Comparable rates of seizure reduction are in line with estimates for non-ID patients, adding to the evidence suggesting that PMP has a similar impact on those with ID. Taking a European perspective and sharing data across centres can help strengthen the evidence for prescribing antiepileptic drugs in the ID population.

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.

Carers' and service users' experiences of early intervention in psychosis services: implications for care partnerships.

AIM: To explore carers' and service users' experiences of UK Early Intervention Services following referral for first-episode psychosis. METHODS: Thirty-two semi-structured interviews (16 interviews with service users and 16 corresponding interviews with their carers) were completed and analysed. RESULTS: Carers spoke retrospectively and prospectively by framing their accounts into the periods before and since their engagement with Early Intervention Services. Desperation was evident as emotive experiences were recalled prior to referral. Relief then emerged as carers described support and engagement with key workers. Hope and optimism for the service user's prognosis and life trajectory were also expressed.Service users described similar positive experiences of Early Intervention Services and the support and insight they had gained through their relationships with key workers. They were however less focused on accounts of desperation and relief and more immersed in their current understanding and attempts to normalize their experiences of first-episode psychosis. Prognosis and future trajectories were only discussed tentatively. CONCLUSION: Communication and 'partnerships' with service users and carers are essential for effective service engagement, delivery of care and the reduction in relapse following first-episode psychosis. This study highlights how key workers from Early Intervention Services are appropriately valued and situated to develop such relationships. Findings also reveal that service users' and carers' focus and expectations of recovery vary during the early stages of engagement with services. How key workers manage awareness and communication around such differing expectations is a crucial consideration for maintaining the 'partnerships' necessary for effective service provision.