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Mandatory specialist approval requirements reduce valproate prescribing: population-based evaluation of a National

James Galloway1, Matthew Jones2,3, Mark Gibson4

  • 1Centre for Rheumatic Diseases, King's College London, London, UK james.galloway@kcl.ac.uk.

BMJ Quality & Safety
|November 25, 2025
PubMed

Insights

A UK safety alert significantly reduced valproate prescribing by mandating two-specialist approval. This intervention proved more effective than prior educational efforts in lowering valproate use among women of childbearing age.

Area of Science:

  • Neurology
  • Pharmacovigilance
  • Public Health

Background:

  • Valproate medication during pregnancy is linked to major congenital malformations (11%) and neurodevelopmental disorders (30-40%).
  • Despite regulatory actions like the European 2018 Pregnancy Prevention Programme, in-utero valproate exposures persisted.
  • A UK Medicines and Healthcare products Regulatory Agency (MHRA) National Patient Safety Alert (NPSA) mandated two-specialist approval for valproate prescriptions in patients under 55.

Purpose of the Study:

  • To evaluate the impact of the MHRA NPSA alert on valproate prescribing patterns in England.
  • To assess the effectiveness of mandatory two-specialist approval compared to previous interventions.

Main Methods:

  • Population-based interrupted time series analysis of NHS prescribing data (January 2022–April 2025).
  • Analysis of 4,879,978 valproate prescriptions across approximately 8000 general practices.
  • Secondary analyses included regional variations, hospital prescribing displacement, and control medications (lamotrigine, levetiracetam).

Main Results:

  • The NPSA alert led to a significant decrease in primary care valproate prescribing.
  • Post-intervention, monthly prescribing declined by 72.6 people, a total trend change of -85.2 people/month (p<0.001), contrasting with a pre-intervention increase of 12.6 people/month.
  • Significant declines were observed across all seven NHS regions and in hospital prescribing; control medications showed no intervention effect.

Conclusions:

  • The 2023 NPSA alert successfully reduced valproate prescribing through mandatory procedural requirements.
  • The two-specialist approval system demonstrated effectiveness where educational interventions had previously failed.
  • Further prospective studies are needed to evaluate seizure control outcomes and the impact of these restrictions on patients with epilepsy, particularly generalized epilepsies.
Abstract

Keywords:
Clinical practice guidelinesGeneral practiceHealth policyImplementation scienceMedication safety

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