Valproate Use in Men – Risk of Neurodevelopmental Disorders in Offspring

13 September, 2024

New evidence suggests that valproate use in men may increase the risk of neurodevelopmental disorders in their children, prompting precautionary advice for healthcare professionals.

Introduction

New evidence suggests a potential link between valproate use by men and an increased risk of neurodevelopmental disorders in their children. This article outlines precautionary advice for healthcare professionals, including the recommendation for male patients to use effective contraception during and after valproate treatment.

Overview

A recent study has raised concerns about the use of valproate in men, particularly around the time of conception, and the potential risk it poses for neurodevelopmental disorders in their children. This guideline update highlights key findings and provides healthcare professionals with advice on managing male patients using valproate.

Key Study Findings

A retrospective observational study from Norway, Denmark, and Sweden indicates a possible association between valproate use by men prior to conception and an increased risk of neurodevelopmental disorders in their children. The study compared outcomes for children born to men treated with valproate to those treated with lamotrigine or levetiracetam. Findings include:

  • A 4.0% to 5.6% risk of neurodevelopmental disorders in the valproate-treated group, compared to 2.3% to 3.2% in the lamotrigine/levetiracetam group.
  • A pooled adjusted hazard ratio of 1.50 (95% CI: 1.09–2.07), indicating a potential increased risk.
  • While the risk in men is lower than the 30-40% risk in women taking valproate during pregnancy, it remains significant enough to warrant caution.

This precautionary advice is based on these findings, though the causal role of valproate is not confirmed.

Advice for Healthcare Professionals

Counseling Male Patients:

    • Inform male patients who may father children of the potential risks of valproate, regardless of the indication or form (oral or intravenous).
    • Recommend the use of effective contraception during valproate treatment and for 3 months after stopping to allow for a completed sperm cycle not exposed to the drug.
    • At each treatment review, discuss family planning with male patients and, if necessary, refer them to a specialist to explore alternative treatments.

Contraception and Fertility:

      • Advise male patients and their female partners to use effective contraception, including condoms and another form of female contraception, throughout treatment and for 3 months after discontinuation.
      • Inform men not to donate sperm while on valproate or for 3 months after stopping treatment.

Managing Treatment Plans:

        • If a patient is planning to conceive, consider alternative treatments and refer them for specialist advice.
        • For female patients whose partners are on valproate, offer pre-conception counselling.

Reporting Adverse Reactions

Any suspected adverse reactions related to valproate use should be reported via the Yellow Card scheme. This includes side effects affecting fertility or neurodevelopmental outcomes in offspring. Accurate and detailed reporting, including batch numbers and medical history, is essential.

Next Steps

  • Updated guidance materials will be issued, including revised patient information leaflets and safety cards for men.
  • Manufacturers will send an updated letter to healthcare professionals in October 2024.

Conclusion

This new guidance highlights the need for caution in prescribing valproate to men planning to father children. Healthcare professionals must ensure patients are fully informed of the risks and the need for effective contraception. Further research is ongoing to clarify the potential risks, and updates will be provided as new evidence becomes available.

For more detailed information, consult the full Drug Safety Update or the Public Assessment Report.

Read More: Valproate use in men: as a precaution, men and their partners should use effective contraception