Abstract
To the Editor,
We have read with great concern the recent article by Amanat et al. (1) in your journal Cephalalgia, describing a randomised trial with potential impact on guiding clinicians in their choice of treatment for young patients with migraine.
Valproate is not licensed for the treatment of migraine in the UK and although the authors referred to some of the drug’s potential adverse effects, important safety information is missing from the paper.
Valproate is associated with a significant risk of birth defects (around 10%) and persistent neurodevelopmental disorders (30–40%) in children exposed in utero. Following a large-scale review, in March 2018 the European member states endorsed a strengthened regulatory position on valproate medicines (2,3).
In Europe, the regulatory position is that valproate should not be used in girls or women unless other treatments are ineffective or not tolerated. Furthermore, use of valproate is contraindicated in all indications, including migraine, in any girl or woman of childbearing potential unless she has a pregnancy prevention programme (PPP) in place. Use of valproate for migraine or bipolar disorder is contraindicated in pregnancy.
Despite the above measures, this study recruited both male and female patients and valproate was used as a first line therapeutic option (80% of patients were naïve to migraine preventive treatment). Eligible patients were aged 6–17 years and pregnancy was an exclusion criterion but the rationale for this exclusion is not stated. There is no mention of whether girls and their carers were informed about the risks of valproate treatment, if the risk of pregnancy (at inclusion or in the near future) was assessed in individual girls and whether the need to implement the PPP was considered.
We disagree with the concluding statement in the article, which gives reassurance that valproate is safe for children and adolescents and especially not for the long-term treatment recommended. Valproate is not safe for girls due to the teratogenic risks and developmental impact mentioned above. Clinical guidance on valproate use published in the UK in 2019 (4) recommends that valproate treatment should not be commenced even in prepubertal girls given the potential for future pregnancy.
Any perceived or real benefit from valproate in the prophylaxis of migraine in girls and women of childbearing potential is being offset by the increased risks to their future offspring.
Footnotes
Declaration of conflicting interests
The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
Funding
The authors received no financial support for the research, authorship, and/or publication of this article.