Retention of perampanel in adults with pharmacoresistant epilepsy at a single tertiary care center.

RATIONALE: Observational data on antiepileptic drugs (AEDs) inform about their use in clinical practice. We describe our clinical experience with perampanel (PER) in a large UK tertiary epilepsy center. METHODS: Adults initiated on PER between October 2012 and March 2015 were followed until they discontinued PER or 10 September 2016. Data on epilepsy syndrome, duration, seizure types, concomitant and previous AED use, PER dosing, efficacy and side effects were recorded. Efficacy was categorized as temporary or ongoing (at last follow-up) seizure freedom, ≥50% seizure reduction, or other benefit (e.g. No convulsions or daytime seizures). These categories were mutually exclusive except for people with temporary seizure freedom. RESULTS: 391 received a PER prescription, five of whom never took it. No follow-up data were available for ten. 83% had focal epilepsy. People were prescribed PER in addition to 1-7 (Interquartile range [IQR] 2, 2, 3) AEDs and had previously used up to 18 (IQR 5, 7, 10) AEDs. Total exposure was 639patient/years. Retention rates were 60.4% at one year, 48.3% at two years, and 42.7% at three years. 19 (5%) people reported seizure free periods lasting at least six months. A ≥50% reduction in seizures lasting at least six months was reported by 76 people (20%), and marked improvement for ≥6months was seen in 52 (14%). Five (1%) were taken off other AEDs and continued on PER monotherapy for 4-27months. Seizures were aggravated in 57 (15%). Somatic side effects were reported by 197 (52%), mostly CNS. Mood changes, irritability or challenging behavior were reported by 137 (36%). PER was discontinued by 211 (56%) due to adverse effects (39%), inefficacy (26%), or both (35%). No idiosyncratic adverse events were seen. CONCLUSION: PER resulted in some benefit in 40% of those exposed. Adverse effects on mental health and on balance were common and should be discussed with people before initiating PER.

Perampanel in the general population and in people with intellectual disability: Differing responses.

PURPOSE: There is a shortfall of suitably powered studies to provide evidence for safe prescribing of AEDs to people with Intellectual Disability (ID). We report clinically useful information on differences in response to Perampanel (PER) adjunctive treatment for refractory epilepsy between ID sub-groups and general population from the UK Ep-ID Research Register. METHOD: Pooled retrospective case notes data of consented people with epilepsy (PWE) prescribed PER from 6 UK centres was 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 type and frequency were collected. Group differences were reported as odds ratios estimated from univariable logistic regression models. RESULTS: Of the 144 PWE (General population 71, Mild ID 48, Moderate to profound ID 48) examined the association between withdrawal and ID type was marginally statistically significant (p=0.07). Moderate to profound ID PWE were less likely to come off PER compared to mild ID (OR=0.19, CI=0.04-0.92, p=0.04). Differences in mental health side effects by groups was marginally statistically significant (p=0.06). Over 50% seizure improvement was seen in 11% of General population, 24% mild ID and 26% Moderate to profound ID. CONCLUSIONS: PER seems safe in PWE with ID. It is better tolerated by PWE with Moderate to profound ID than PWE with higher functioning. Caution is advised when history of mental health problems is present. The standardised approach of the Ep-ID register UK used confirms that responses to AEDs by different ID groups vary between themselves and General population.