Evaluating the use of sodium valproate and other anti-seizure medication in nationwide linked electronic health records in England and Wales

, ed. (2024) Evaluating the use of sodium valproate and other anti-seizure medication in nationwide linked electronic health records in England and Wales. BMJ Medicine. ISSN 2754-0413 (In Press)

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Abstract

Objective: Sodium valproate is an evidence-based treatment for idiopathic generalised epilepsy (IGE), and is also used for bipolar affective disorder. Sodium valproate is known to have teratogenic effects and has been subject to regulatory changes. Key policy statements in 2018 aimed at women of childbearing potential and introducing the pregnancy prevention programme (PPP) were followed by the onset of the Covid-19 pandemic. We investigated the use of sodium valproate in England and Wales during the period 2019 to 2023, including by women during pregnancy, comparing with other anti-seizure medications (ASMs) in comprehensive national level electronic health records. Methods and Analysis: Prevalent (current) and incident (new) uses of sodium valproate and other ASMs before and during the Covid-19 pandemic (January 2019 - December 2023) were identified using NHS England’s Secure Data Environment and the SAIL Databank, covering the whole population of England and Wales respectively. Use was stratified by age-bands and sex. Annual rates were calculated for 2019-2022. Rates of dispense by Local Authority District (LAD) per 10,000 women of child-bearing potential (CBP; aged 15-49 years) were also calculated. We assessed pregnancy rates per 1000 women aged 15-49 dispensed ASMs and examined the timing and dose of sodium valproate dispensed during pregnancy. Rates of disease indication (epilepsy, bipolar affective disorder) per 1000 women dispensed sodium valproate were calculated. We investigated trends in epilepsy-related deaths between 2015 to 2022 using time series analysis. Results: Use of sodium valproate in women of CBP decreased whilst use of most other ASMs increased between 2019 and 2023. New initiation of sodium valproate per 100,000 women fell from 7 to 5 in women aged 15-19, 11 to 7 in women aged 20-29 and 14 to 7 in women aged 30-39 between 2019 and 2022. Incident use also declined in men of the same age but remained at much higher levels (from 53 to 43 in men aged 15-19, 59 to 47 in men aged 20-29 and 57 to 42 in men aged 30-39 per 100,000 men). Pregnancy rates fell from 6.0 to 5.2 per 1000 women of CBP dispensed sodium valproate over the same period. The number of pregnant women with evidence of a sodium valproate dispense during the pregnancy period fell from 140 in 2019 to 85 in 2023. Epilepsy was the most common indication, followed by bipolar affective disorder (751 and 193 per 1,000 women of CBP dispensed sodium valproate respectively in 2023). There was no clear evidence that epilepsy-related deaths increased in women aged 15-49 during 2015-2022; but there was some evidence for a slight increase in men aged 15-49 during the later period between April 2018 and December 2022. Conclusion: Using comprehensive national records, we have tracked changes in the prescribing of ASMs in response to regulatory actions. We demonstrated that rates of use of sodium valproate by women, including during pregnancy, fell before and continued to slowly decline during the Covid-19 pandemic. Incident use also declined in men but remained at much higher levels than in women. This approach linking national dispensing data to health records at the individual level facilitates the possibility of monitoring changes to medicines affected by regulatory changes, including in specific population groups such as pregnant women, and their potential impact on health outcomes.

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