Valuable insight from Steve Tomlin – FRPharmS FFRPS FRCPCH (Hon)
Director of the Children’s Medicines Research & Innovation Centre – CMRIC
Associate Chief Pharmacist – Research and Innovation, Great Ormond Street Hospital
Approximately 103,600 children and young people live with epilepsy in the UK, and it affects around 1 in 200 school-age children, [Young Epilepsy, 2024]. Although up to 80% of affected children could have their seizures well controlled, (usually by anti-seizure medications), [Tittensor, 2018], only 50% are seizure-free, [Moran, 2004]. This highlights the challenges of effective epilepsy management.
Epilepsy carries a significant physical and emotional burden for both the child and their parents / care-givers, which may be compounded if the child also has a learning disability. It is recognised that the prevalence of epilepsy increases with the escalating severity of intellectual disabilities; and research suggests that up to 35% of children with a mild to severe learning disability also have epilepsy, [Robertson, 2015]. Cognitive difficulties may appear at or before the onset of seizures, [Fastenau, 2009]; and there is evidence that comorbidities such as behavioural problems, learning difficulties and psychiatric manifestations have major effects on the cognitive development of children with epilepsy, [Wilmshurst, 2014].
Childhood epilepsies present treatment challenges unique to this age group; including developmental, cognitive, and behavioural comorbidities, [Wilmshurst, 2014]. The effect of seizures on the developing brain underpin the therapeutic need to prevent their occurrence, whilst avoiding adverse effects from interventions, [Wilmshurst, 2014].
After a first seizure, the chances of a second one range from 30% to 55%; and after a second unprovoked seizure, the chances of a third are 80% to 90% within 2 years if treatment is not initiated, [Glauser, 2013].
Interventions to prevent recurrence of seizures usually involve anti-seizure medications (ASMs). The type of seizure, the patient’s age, comorbidities and concomitant medication should be taken into account, [BNF, 2024]. Once an ASM is prescribed, the aim is to achieve complete seizure control with a single drug, without causing side effects. Also to use the most appropriate formulation which ensures the child can take and absorb the medication, [Appleton, 2005].
When choosing an anti-seizure medication, the dosage frequency may be determined by the plasma-drug half-life, and should be kept as low as possible to encourage adherence with the prescribed regimen, [BNF, 2024]. Careful adjustment of doses is necessary, starting with low doses and increasing gradually until seizures are controlled or there are significant adverse effects,[BNF, 2024]. If side effects occur before seizure control is reached, monotherapy with an alternative drug should be prescribed, [BNF]. The change from one ASM to another needs to be undertaken slowly, [BNF, 2024].
Combination therapy with two or more anti-seizure medications may be necessary, but increases the risk of adverse effects, drug interactions and reduced compliance with treatment, [BNF, 2024]. Dose-dependent side effects are most common during the first four to eight weeks as the ASM is titrated to its initial target dose, [Glauser, 2013]. To decrease the risk, dosages are slowly increased, particularly for children, where dosage is based on mg/kg body weight.
Nonadherence to prescribed medication is an issue of considerable concern. One study found that fifty-eight percent of children with newly diagnosed epilepsy, demonstrated persistent nonadherence during the first six months of treatment, [Modi, 2011]. Socioeconomic status was the only significant predictor of nonadherence and the authors suggest this could help identify patients at highest risk, so additional support can be provided, [Modi, 2011].
Paediatric dosing schedules are often complicated for parents to follow, particularly when their child is first diagnosed with epilepsy. Dose titration is slow and regimes can be variable from week to week, potentially leading to errors and non-intentional non-adherence. Wherever possible dosing should be as simple as possible to follow; this will ensure a child with epilepsy has the best chance of a life free from seizures.
This article was supported by Desitin Pharma Ltd. These are the views of the author and Desitin Pharma Ltd had no participation or influence into its content.
References
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