Clinical experience with perampanel: focus on psychiatric adverse effects.

BACKGROUND: Perampanel (PER) is a novel antiepileptic drug that inhibits the AMPA class of glutamate receptors. It has been available in the UK since September 2012. We undertook a retrospective analysis of efficacy and tolerability of PER in 47 patients with drug-refractory epilepsy attending a regional epilepsy service in the UK. METHODS: Demographic and clinical data of patients with refractory epilepsy prescribed PER were collected by review of records. Efficacy, as measured by responder rates (>50% reduction in seizure frequency), retention rates, and adverse effects, was analyzed. RESULTS: Of the 47 patients prescribed PER, 39 (87%) had focal epilepsy, four (9%) had idiopathic generalized epilepsy, 3 (6%) had symptomatic generalized epilepsy, and 1 had unclassified epilepsy. Patients were taking a median of 2 AEDs (range: 1-5) when starting on PER. The median dose of PER was 8 mg (range: 2-12 mg). Thirteen (28%) patients were classed as responders, but no patients experienced sustained seizure freedom. Twenty-one (45%) patients had withdrawn from PER during the study period, with 16 (76%) of them withdrawing due to intolerable adverse effects, 4 due to inadequate seizure control, and 1 due to the combination of both. The most frequent adverse effects requiring withdrawal from PER were behavioral reactions including suicidal ideation (n = 2), aggressive behavior (n = 2), and both (n = 1). CONCLUSION: In our experience, PER had a retention rate of 55% and a responder rate of 28%. Psychiatric adverse effects, including suicidal ideation, were the most common reasons for withdrawal.

Audit of epilepsy healthcare provision in a large UK category B prison.

PURPOSE: We reviewed all prisoners diagnosed with epilepsy within a large UK category B prison: collecting demographic information and the prevalence and nature of their seizure disorder; and reviewed standards of their epilepsy healthcare provision. Previous work has highlighted poorer seizure control and limited access to specialist services in this patient group. METHODS: Fifty-five male prisoners with a previously established diagnosis of epilepsy were identified by the prison healthcare manager during the six-month audit period. Anonymised audit data was collected during clinical interviews undertaken by members of a regional specialist epilepsy service and recorded on a standardised proforma. Data collection occurred during six prison visits within the audit period. RESULTS: Point prevalence of epilepsy was 2%. Data suggest that demographics are complex and challenging in this patient group. We found increased rates of alcohol (40%) and drug (82%) misuse and mental health problems (85.5%). Just over one third of cases were prescribed medications with potential for misuse (diversion). Further optimization of anti-seizure medication (ASM) regimens was required in 67.3% of the study sample, with only 12.7% of cases being free of seizures for the last 12 months. Access to specialist epilepsy services was limited; only 38.2% had a specialist review in the last 12 months. Most cases (76.4%) did not recall receiving guidance on precautions that should be taken regarding duties or cell arrangements in relation to having a diagnosis of epilepsy. CONCLUSIONS: Tighter collaboration between prison healthcare and local NHS specialist services is recommended to optimise epilepsy healthcare in UK prison settings.

Effect of trained Seizure Alert Dogs on frequency of tonic-clonic seizures.

We have previously reported that dogs can be trained to recognize specific changes preceding an epileptic seizure in humans. Such dogs can provide an overt signal that acts as a useful warning to the human. Early observations suggested that seizure frequency might also be reduced. We report a prospective study of 10 consecutive referrals to our Seizure Alert Dogs service of people with tonic-clonic seizures. Seizure frequency was monitored over a 48 week period including 12 weeks baseline after entry, a 12 week training period, and 24 weeks follow up. Comparing baseline seizure frequency to the last 12 weeks of follow up, there was a 43% mean reduction in seizure frequency ( P= 0.002). Nine out of /10 subjects showed a 34% or greater reduction, 4 /10 showed a 50% or greater reduction, and only one showed no improvement. Although a significant drop in seizure frequency was seen during the first 4 weeks of training ( P= 0.0078) a further drop occurred between the first and last 4 week period of training (P = 0.038) and this final improvement was maintained for the whole 24 week follow up.

Outcome of pregnancy in women attending an outpatient epilepsy clinic: adverse features associated with higher doses of sodium valproate.

The risk of an adverse outcome to pregnancy is increased in women with epilepsy. This is partly attributable to antiepileptic drugs. Guidelines for the management of pregnancy in women with epilepsy generally advise against polytherapy but make no distinction between the risks of different drugs. Several recent studies have however shown greater risk of adverse outcome in offspring exposed to sodium valproate in utero, particularly at higher doses. The outcome of pregnancy was monitored to identify antiepileptic drug treatment associated with a poor outcome in a mainly prospective study of women attending an outpatient clinic. From January 1990 to December 1999 all 69 pregnancies in women referred to the clinic were monitored. Drug treatments and other risk factors were recorded. In each child dysmorphic features, developmental delay and structural anomalies were assessed and graded. Data were analysed for drug- and dosage-dependent differences in outcome. In each assessment area a positive association between adverse outcome and dose was found for sodium valproate but not for carbamazepine. Severe adverse outcomes were found only in children exposed to sodium valproate at maternal doses above 1000 mg per day.