{
  "abstract": "Background Valproate exposure during pregnancy causes major congenital malformations in 11% and neurodevelopmental disorders in 30–40% of exposed children. Despite regulatory interventions, including the European 2018 Pregnancy Prevention Programme, pregnancy exposures continued. We evaluated the impact of a Medicines and Healthcare products Regulatory Agency National Patient Safety Alert (NPSA), which mandated two-specialist approval for valproate prescribing in patients under 55 years.Methods We conducted a population-based interrupted time series analysis using England National Health Service (NHS) prescribing data from January 2022 to April 2025. In total, we analysed 4 879 978 valproate prescriptions—both new and repeat—across ~8000 general practices. The primary outcome was monthly patients prescribed valproate. Secondary analyses examined regional variation, possible prescribing displacement to hospitals and an equivalent time series design with lamotrigine and levetiracetam as control medications to distinguish valproate-specific effects from broader trends.Results Following the NPSA alert, there was a significant decrease in people prescribed valproate in primary care in England. Compared with the preintervention trend (prescribing had been increasing by +12.6 people per month), postintervention prescribing declined by −72.6 people per month, yielding a total change in trend of −85.2 people per month (95% CI −122.9 to −47.5, p<0.001). There was no immediate step change. All seven NHS regions demonstrated significant declines. Postintervention decreases were also seen for hospital prescribing. Lamotrigine and levetiracetam showed no intervention effect.Conclusions The 2023 NPSA alert achieved valproate prescribing reductions across England through mandatory procedural requirements. The two-specialist approval proved effective where previous educational interventions failed. However, given this restricts access to a highly effective antiepileptic drug, particularly for generalised epilepsies, prospective studies evaluating seizure control outcomes following valproate withdrawal are needed to assess the impact of these regulatory restrictions.",
  "authors": [
    {
      "affiliations": [
        "Centre for Rheumatic Diseases, King’s College London, London, UK"
      ],
      "name": "James Galloway"
    },
    {
      "affiliations": [
        "The University of Manchester, Manchester, UK",
        "Northern Care Alliance NHS Foundation Trust, Salford, UK"
      ],
      "name": "Matthew Jones"
    },
    {
      "affiliations": [
        "Centre for Rheumatic Diseases, King’s College London, London, UK"
      ],
      "name": "Mark Gibson"
    },
    {
      "affiliations": [
        "Centre for Rheumatic Diseases, King’s College London, London, UK"
      ],
      "name": "Kaiyang Song"
    },
    {
      "affiliations": [
        "Centre for Rheumatic Diseases, King’s College London, London, UK"
      ],
      "name": "Katie Bechman"
    },
    {
      "affiliations": [
        "Manchester Centre for Clinical Neurosciences, Northern Care Alliance NHS Foundation Trust, Salford, UK"
      ],
      "name": "Rajiv Mohanraj"
    },
    {
      "affiliations": [
        "Department of Psychology, King’s College London, London, UK"
      ],
      "name": "Sam Norton"
    },
    {
      "affiliations": [
        "Centre for Rheumatic Diseases, King’s College London, London, UK"
      ],
      "name": "Mark D Russell"
    }
  ],
  "title": "Mandatory specialist approval requirements reduce valproate prescribing: population-based evaluation of a National Patient Safety Alert",
  "uid": "f5ed1444-2574-535c-9810-40fc0e292a9d"
}