Evaluating fenfluramine hydrochloride as an oral solution for the treatment of seizures associated with Lennox-Gastaut syndrome

IntroductionLennox-Gastaut syndrome (LGS) is a severe childhood-onset developmental and epileptic encephalopathy characterised by treatment-refractory seizures, including tonic/atonic "drop" seizures, and intellectual impairment and slow spike-wave discharges on the electroencephalogram. Fenfluramine, previously prescribed as a weight-loss drug but then withdrawn, has recently been approved in the US, EU and UK for the adjunct treatment of seizures associated with LGS.Areas coveredEfficacy and safety findings from clinical trials of fenfluramine in LGS are reviewed. The evidence for adverse effects that may be of particular concern with fenfluramine, namely cardiac abnormalities and weight loss, are discussed in the context of the use of fenfluramine for the treatment of the refractory seizures in LGS.Expert opinionFenfluramine has demonstrated efficacy in reducing the frequency of seizures in LGS, notably drop seizures, in short-term and long-term clinical trials. Valvular heart disease and pulmonary hypertension have not been reported at the low doses (≤ 26 mg/day) used in these studies, however, data are limited. Due to its novel mechanism of action, fenfluramine may be of benefit in LGS which has not responded adequately to other antiseizure medications. However, none of these medications, including fenfluramine, achieves the ultimate goal of seizure freedom in most cases.<br/

The Department of Health (England) Action Plan for Improving Services for People with Epilepsy: Will It Improve Quality of Care?

Issues related to avoidable mortality in people with epilepsy have been highlighted in the National Sentinel Clinical Audit of Epilepsy-Related Death in the UK. This audit concluded that 39% of adult epilepsy-related deaths and 59% of epilepsy-related deaths in children were potentially or probably avoidable. Particular attention was drawn to the important and poorly understood condition of sudden unexplained death in epilepsy. This audit prompted a report by the Chief Medical Officer, which was followed by a document prepared by the Department of Health (England) entitled Improving Services for People with Epilepsy: Department of Health Action Plan in Response to the National Clinical Audit of Epilepsy-Related Deaths. The action plan comprises the following sections: (i) Introduction; (ii) Pathology and Post Mortem Investigations; (iii) Improving Care Management and Treatment of Epilepsy; and (iv) Information Provision. The fact that the Department of Health in England has drawn attention to these important matters is in itself worthwhile. However, the action plan does not give a firm commitment to taking the necessary steps required to rectify the shortcomings in the current services.Epilepsy, Health-policy

Antipsychotic Medication and Risk of Incident Seizure in People with Autism Spectrum Disorder: Analyses with Cohort and Within Individual Study Designs

There are many case reports of seizures apparently associated with the prescription of antipsychotics. This study aimed to examine whether there is an association between the prescription of antipsychotics and incident seizures in individuals with autism spectrum disorder using retrospective data based on patients’ chart review. A cohort study was conducted to compare the rate of incident seizure between 3923 users of antipsychotics with 10,086 users of other psychotropics. This was followed by a self-controlled case series (SCCS) analysis of 149 patients to eliminate the effect of time-invariant confounders. The results showed no evidence of increased risk of seizure after exposure to antipsychotic agents (Hazard Ratio 1.28, 95% CI 0.74–2.19) compared to other psychotropics

Prenatal exposure to antidepressants or antipsychotics and the risk of seizure in children

Perinatal mental health problems account for a substantial health burden across the world. Almost one in two women aged under 25 report some form of common mental disorders during pregnancy1. The use of psychotropic medications, especially antidepressants and antipsychotics, has doubled in the past two decades, with a disproportionate increase amongst women at childbearing age and during pregnancy

Prenatal exposure to antidepressants or antipsychotics and the risk of seizure in children

Perinatal mental health problems account for a substantial health burden across the world. Almost one in two women aged under 25 report some form of common mental disorders during pregnancy1. The use of psychotropic medications, especially antidepressants and antipsychotics, has doubled in the past two decades, with a disproportionate increase amongst women at childbearing age and during pregnancy