A system requiring sign off from two specialists to prescribe sodium valproate in patients under 55 years has had a significant impact on use of the drug, a study has found.
The stricter approval process introduced in 2023 led to a large drop in the number of women being prescribed the anti-seizure drug which can cause birth defects when taken in pregnancy.
Before the rule came in, prescriptions for valproate were increasing by about 13 people a month, despite advice cautioning on its use and the pregnancy prevention programme which required an annual risk assessment.
NHS prescribing data from January 2022 to April 2025 of more than 4.8 million valproate prescriptions across 8,000 general practices and found showed that after the mandatory two signatures rule, prescriptions fell by 72 people per month.
Valproate in pregnancy can cause serious birth defects in around one in nine babies and early childhood developmental problems in up to four in ten children.
The mandatory approval process brought in by the Medicines and Healthcare products Regulatory Agency (MHRA) applies to all patients under 55 years regardless of sex and both specialists need to agree there is no suitable alternative.
For females under 55 years already established on valproate, the new rules meant that two specialists must independently review and document that no other effective treatment exists or that reproductive risks do not apply.
In 2024, the MHRA warned that men taking valproate and their partners should use effective contraception, because of a small increased risk of harm to children if the drug is used by a father at conception.
Healthcare professionals were told to inform male patients about this ‘newly identified risk’ at their next routine treatment review and discuss how it impacts their current treatment and other options available.
Writing in BMJ Quality and Safety, researchers from King’s College London said the figures showed 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 figures showed that the drop in prescribing was not sudden, but that valproate use steadily declined over time.
Hospital prescriptions also fell, the researchers added and the number of prescriptions for epilepsy medications lamotrigine and levetiracetam showed no change, suggesting the decline could be attributed to the rule change.
Lead author Professor James Galloway, professor of rheumatology at King’s College London, 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.’
He added they were now looking to apply lessons from the valproate story ‘to inform similar safety challenges in our own field, demonstrating how shared learning across specialities can improve care quality throughout the NHS’.
More 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, he said.
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