Indications and prescribing patterns of antiseizure medications in children in New Zealand.

AIM: To determine indications and prescribing patterns for antiseizure medications (ASMs) in children by age, sex, and socioeconomic status. METHOD: This retrospective study searched the New Zealand database of ASM prescriptions dispensed to individuals aged 18 years or under during 2015 in three regions of New Zealand (48% paediatric population). Medical records were reviewed by a paediatric neurologist for indication. ASMs were grouped into old or new (1993 onwards). RESULTS: In total, 2594 children (0 to 18 years, mean age 11 years 2 months, median 12 years; 51% male) were dispensed 3557 ASMs for seizures (76%), pain (6%), headache (5%), mental health (3%), and movement disorders (2%). After 10 years of age, lamotrigine was more likely and valproate less likely to be prescribed in females than males. No sex difference was observed for valproate prescriptions for non-seizure indications. Topiramate prescriptions increased in adolescent females. Prescriptions for non-seizure indications increased from 7% in children aged 6 years or under to 31% in 16- to 18-year-olds. The proportion of children receiving a new ASM compared to an old ASM was greater in children from higher than lower socioeconomic areas. INTERPRETATION: Our results highlight a need for focused ASM teratogenicity messaging to clinicians prescribing ASMs for non-seizure indications. In addition, to improve equity of epilepsy care, it is critical for health policies to consider socioeconomic factors that impact on ASM prescribing.

Epidemiology of Treated Epilepsy in New Zealand Children: A Focus on Ethnicity.

BACKGROUND AND OBJECTIVES: To determine the period prevalence and incidence of treated epilepsy in a New Zealand pediatric cohort with a focus on ethnicity and socioeconomic status. METHODS: This was a retrospective cohort study. The New Zealand Pharmaceutical Collection database was searched for individuals ≤18 years of age dispensed an antiseizure medication (ASM) in 2015 from areas capturing 48% of the New Zealand pediatric population. Medical records of identified cases were reviewed to ascertain the indication for the ASM prescription. Population data were derived from the New Zealand 2013 Census. RESULTS: A total of 3,557 ASMs were prescribed during 2015 in 2,594 children, of whom 1,717 (66%) children had epilepsy. An indication for prescription was ascertained for 3,332/3,557 (94%) ASMs. The period prevalence of treated epilepsy was 3.4 per 1,000 children. Children in the most deprived areas had 1.9 times the rate of treated epilepsy (95% confidence interval [CI] 1.6-2.2) as those from the least deprived areas. Prevalence was similar for most ethnic groups (European/other: 3.7, 95% CI 3.4-3.9; Pacific Peoples: 3.6, 95% CI 3.2-4.1; Maori: 3.4, 95% CI 3.1-3.8) apart from Asians, who had a lower prevalence of 2.3 per 1,000 (95% CI 2.0-2.6). However, when adjusted for socioeconomic deprivation, the prevalence of epilepsy was highest in European and similar in Maori, Pacific, and Asian children. DISCUSSION: This is the largest pediatric epidemiology epilepsy study where diagnosis of epilepsy was confirmed by case review. This is the first study to provide epidemiologic information for pediatric epilepsy in Maori and Pacific children.

Safety and Tolerability of Transdermal Cannabidiol Gel in Children With Developmental and Epileptic Encephalopathies: A Nonrandomized Controlled Trial.

Importance: Developmental and epileptic encephalopathies (DEEs) are the most severe group of drug-resistant epilepsies. Alternatives to oral therapies are urgently needed to reduce seizures and improve developmental outcomes and comorbidities in this medically complex population. Objective: To assess the safety and tolerability of cannabidiol (CBD) transdermal gel in children with DEEs and to evaluate seizure frequency, sleep, and quality of life. Design, Setting, and Participants: This nonrandomized controlled trial was conducted in 2 centers in Australia and New Zealand from April 2018 to July 2019. Children and adolescents aged 3 to 18 years with DEEs who were receiving a stable regimen of 1 to 4 antiseizure medications were eligible for this study. After 1-month baseline and titration periods, patients entered a 5.5-month flexible-dosing maintenance period for a total of 6.5 months of treatment. Data were analyzed throughout the 6.5-month treatment period. Interventions: Twice-daily applications of CBD transdermal gel at doses of 125 to 500 mg for 6.5 months. Main Outcomes and Measures: Safety and tolerability assessments included adverse events (AEs) and examination of skin. The outcome for seizures was the median percentage change from baseline in monthly (28-day) seizure frequency of focal impaired awareness seizures (FIAS) and tonic-clonic seizures (TCS) over 6.5 months. Results: Of 48 patients (mean [SD] age, 10.5 [3.8] years; 26 [54%] boys), 29 (60%) had at least 1 treatment-related AE over 6.5 months; 44 of 46 treatment-related AEs (96%) were mild or moderate. Treatment-related AEs that occurred in at least 5% of patients were application-site dryness, application-site pain, and somnolence (each reported by 4 patients [8%]). The only treatment-related gastrointestinal AE was diarrhea, reported in a single patient. CBD treatment was associated with reductions in FIAS and TCS frequency. Analysis of the 33 patients with FIAS and TCS showed a median (interquartile range) monthly reduction in seizures of 58% (-5.3% to 81.8%) at 5 months and 43.5% (-23.8% to 57.5%) over the entire 6.5-month study period. Parents and caregivers noted improvements in social or interpersonal engagement and irritability (33 of 43 [77%] participants); alertness, energy, and sleep (23 of 43 [53%]); and cognition or concentration (20 of 43 [47%]). Conclusions and Relevance: In this study, CBD transdermal gel was safe, well tolerated, and was associated with reductions in FIAS and TCS frequency and disease burden. Trial Registration: ClinicalTrials.gov Identifier: ACTRN12618000516280.

Efficacy of cannabinoids in paediatric epilepsy.

There are hundreds of compounds found in the marijuana plant, each contributing differently to the antiepileptic and psychiatric effects. Cannabidiol (CBD) has the most evidence of antiepileptic efficacy and does not have the psychoactive effects of ∆9 -tetrahydrocannabinol. CBD does not act via cannabinoid receptors and its antiepileptic mechanism of action is unknown. Despite considerable community interest in the use of CBD for paediatric epilepsy, there has been little evidence for its use apart from anecdotal reports, until the last year. Three randomized, placebo-controlled, double-blind trials in Dravet syndrome and Lennox-Gastaut syndrome found that CBD produced a 38% to 41% median reduction in all seizures compared to 13% to 19% on placebo. Similarly, CBD resulted in a 39% to 46% responder rate (50% convulsive or drop-seizure reduction) compared to 14% to 27% on placebo. CBD was well tolerated; however, sedation, diarrhoea, and decreased appetite were frequent. CBD shows similar efficacy to established antiepileptic drugs. WHAT THIS PAPER ADDS: Cannabidiol (CBD) shows similar efficacy in the severe paediatric epilepsies to other antiepileptic drugs. Careful down-titration of benzodiazepines is essential to minimize sedation with adjunctive CBD.