HMN 2025: How Stricter approval process reduces prescribing of anti-seizure drug that can cause birth defects

The introduction of a stricter approval process for prescribing an anti-seizure drug that can cause birth defects when taken during pregnancy has been effective at reducing the number of prescriptions issued for the drug, according to new research.

The study, led by King’s College London suggests that making it mandatory for doctors to follow a stricter approval process for prescriptions can help to protect patients, where previous education efforts have failed. The findings were published in BMJ Quality & Safety.

Valproate is a prescription medication used to treat epilepsy and bipolar disorder and, in some cases, migraines. If taken during pregnancy, it can cause serious birth defects (in around 1 in 9 babies) and early childhood developmental problems (in up to 4 in 10 children) that can have lifelong impacts.

Despite the risks, exposure to valproate during pregnancy has continued, highlighting gaps between evidence and clinical practice. Over the last decade, several regulatory processes have been put in place to reduce valproate exposure during pregnancy—including warnings accompanied by educational materials and a pregnancy prevention program. However, safety reviews suggested that the regulations had little impact on prescribing practices.

In response, stricter prescribing requirements for valproate were introduced in 2023, mandating that the drug must not be prescribed to patients under 55 years of age unless two specialists independently confirm that there are no other suitable treatment options.

To look at the impact of the 2023 policy, the researchers looked at England NHS prescribing data from January 2022 to April 2025. They analyzed more than 4.8 million valproate prescriptions across 8,000 general practices.

Their analyses revealed that, after the new rule was introduced, the number of women being prescribed valproate dropped significantly. Before the rule, prescriptions were increasing by about 13 people per month. After the rule, prescriptions decreased by 72 people per month—a change of 85 people per month. There was no sudden drop immediately after the rule came in, but prescriptions steadily declined over time. Hospital prescriptions also fell. The number of prescriptions for two similar medicines used to treat epilepsy (lamotrigine and levetiracetam) showed no change, suggesting the decline was specifically due to the new valproate rules.

Professor James Galloway, Professor of Rheumatology at King’s College London and lead author of the paper said, “Our research demonstrates how regulatory policy can effectively change NHS prescribing practice to protect patients when education alone fails. Using publicly available data, we’ve shown that mandatory specialist approval successfully reduced harmful valproate prescribing to women of childbearing age—providing evidence how stricter safeguards can work.”

“This study exemplifies how big data can answer vital patient safety questions and showcases excellent cross-specialty collaboration, with rheumatologists, epidemiologists, statisticians, and neurologists working together. Importantly, my team in rheumatology is now looking to apply lessons from the valproate story to inform similar safety challenges in our own field, demonstrating how shared learning across specialties can improve care quality throughout the NHS.”

Dr. Matthew Jones, Consultant Neurologist and Honorary Senior Lecturer at Manchester Center for Clinical Neurosciences, Northern Care Alliance NHS Foundation Trust and co-author of the paper said, “Using valproate wisely and safely is a critical issue for neurologists in the UK. Accessing large scale data sets to better understand prescribing habits is an important step toward this goal.”

The researchers say that further research is now needed to understand whether these restrictions might have unintended consequences for managing epilepsy, particularly for people whose seizures are well controlled by the medication.

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