EMA Reassesses Valproate Prescribing Guidelines for Men Amid New Data

The European Medicines Agency (EMA) is currently evaluating new evidence regarding the prescribing restrictions of valproate for male patients, particularly in the context of their potential fatherhood. This reassessment follows the introduction of controversial precautionary measures in January 2024, aimed at mitigating risks associated with neurodevelopmental disorders (NDDs) in children fathered by men undergoing treatment with valproate, a medication commonly prescribed for epilepsy, bipolar disorder, and migraines.

The Pharmacovigilance Risk Assessment Committee (PRAC) of the EMA has announced that it will analyze new data from a post-authorization safety study (PASS). This study was conducted by a consortium of valproate marketing authorization holders and utilized data from multiple Scandinavian registries, examining the link between paternal valproate exposure and the incidence of NDDs, which include conditions such as autism spectrum disorders and intellectual disabilities.

Dr. Emily Thompson, a pharmacologist at the University of Copenhagen, stated, "The results from the PASS study indicated a potential increased risk for children born to men who used valproate during the three months prior to conception. Given this, PRAC's initial recommendations to restrict valproate use for males were seen as a necessary precaution."

In contrast, a subsequent study published in the Journal of the American Medical Association (JAMA) in June 2024, which aimed to replicate the findings of the PASS study, reported no significant correlation between paternal valproate use and major congenital malformations or NDDs. Dr. Michael Larson, a researcher involved in the JAMA study, emphasized, "Our analysis of data from over a million Danish children found no evidence linking paternal valproate exposure to adverse outcomes. This raises serious questions about the conclusions drawn from the PASS study."

The discrepancies between the PASS findings and subsequent research have led to increased scrutiny of the EMA's guidelines. Following the publication of a detailed report by the IQVIA study, the same research team released a letter in JAMA in May 2025, reiterating their inability to replicate the findings from the PASS study. They concluded that "paternal valproate exposure is not associated with an increased risk of NDDs," a finding that is supported by a more recent systematic review from Australia, which also failed to establish a clear adverse impact of paternal antiseizure medication on offspring outcomes.

In response to these conflicting findings, PRAC has initiated a signal procedure to further investigate the differences in results across studies. The committee has requested additional information from valproate marketing authorization holders and plans to communicate further updates as new data becomes available.

As discussions surrounding valproate prescribing practices continue, the implications for patients, healthcare providers, and regulatory bodies remain significant. The EMA's reassessment could potentially lead to changes in clinical guidelines, impacting treatment protocols for male patients. Dr. Sarah Johnson, an expert in regulatory affairs at the University of Oxford, noted, "This situation highlights the complexities involved in drug safety assessments, especially when new evidence challenges established guidelines."

The outcome of the EMA's review will likely shape the future landscape of valproate treatment and its associated risks, ensuring that both patients and healthcare providers have access to the most accurate and up-to-date information regarding this critical medication.