Cannabidiol is efficacious as an adjunctive treatment in children with epilepsy associated with Dravet and Lennox-Gastaut syndromes. As its role is currently adjunctive, we reviewed the interactions of cannabidiol with other antiseizure medications (ASMs). Methods: A search of Cochrane, Pubmed and Embase databases from January 2015 to April 2020 was performed. All original research papers discussing interactions between cannabidiol and ASMs were included. Bibliographies of review articles were searched to identify further papers. Adverse events and side effects were excluded. Results: Cannabidiol interacts with ASMs through both pharmacokinetic and pharmacodynamic mechanisms. Thirty studies were identified (eighteen observational cohort studies, two randomised-control trials, three case reports/series, three animal studies, two briefing reports, an analysis of cohort data and a clinical trial simulation). There is potential for pharmacokinetic interactions between CBD and brivaracetam, clobazam, eslicarbazepine, lacosamide, gabapentin, oxcarbazepine, phenobarbital, potassium bromide, pregabalin, rufinamide, sirolimus/everolimus, stiripentol, tiagabine, topiramate and zonisamide. Pharmacodynamic interactions were identified for clobazam, valproate and levetiracetam. An animal study identified that the brain concentration of ASMs may be altered while the serum concentration remains the same. Conclusion: Pharmacokinetic and pharmacodynamic interactions exist between cannabidiol and ASMs. The cytochrome p450 system in particular has been implicated in pharmacokinetic interactions, although not exclusively. The existing literature is limited for some ASMs by studies having relatively small cohorts. As increasing numbers of patients use cannabidiol, specialists need to monitor closely for interactions clinically and with blood levels when required.
We found little evidence of the utility of the NAPI as a measure of short-term neurobehavioural function or for predicting neurodevelopmental outcomes in very preterm infants. It may have greater predictive power when used serially to detect delayed neurobehavioural maturation.
Children and adolescents treated with antiepileptic drugs are known to have problems with bone metabolism, bone mineral density loss, and 2–3 times the fracture risk of healthy controls. We reviewed the literature regarding bone mineral density in children with epilepsy and vitamin D therapy in children treated with anti-epileptic drugs. Studies of bone mineral density markers in children with epilepsy have mostly found little significant difference in bone mineral density markers in children with epilepsy. They have been limited by small sample size and many of the studies have not corrected for confounding factors such as comorbidities, mobility, nutrition, and obesity. Studies of vitamin D therapy in children with epilepsy have shown little evidence of effect and have been similarly limited by lack of stratification with regard to confounding factors. There is a need for larger studies, using clinically significant outcomes such as fractures, including at risk populations such as symptomatic generalised epilepsy, impaired mobility, and polytherapy. At the present time in the absence of good evidence to the contrary, there remains concern that children with epilepsy are at risk of poor bone health and that vitamin D therapy may be beneficial. As low-dose vitamin D supplementation (400 IU per day) is now recommended for healthy children and it is biologically feasible that children with epilepsy may be at higher risk of clinically significant deficiency, it is important that neurologists ensure that low-dose vitamin D supplementation should be prescribed and compliance followed up in children with epilepsy.
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