Although valproate is a serious teratogen, neurologists Heather Angus-Leppan, MBBS, MD, and Rebecca Liu, PhD, both from the Epilepsy Initiative Group, Royal Free London, United Kingdom, conclude that “women should not be denied the human right to make their own decisions after fully informed discussion.” This analysis was published in the BMJ.
Despite harmful effects, banning valproate for people who may become pregnant or mandating contraception for women taking the drug can impose less effective treatment for some female patients and infringe on patient autonomy. Instead, individualized discussion with a specialist reflecting the full range of risks and benefits of valproate and its alternatives as well as ethical and practical considerations for the patient is a better regulatory practice.
There is currently no international agreement on the appropriate regulation of valproate in people who may become pregnant. Population-based monitoring of the effects of valproate regulations in women and their children, as well as further research into alternatives, is crucial, but presently lacking. For treating migraines, there are effective alternatives for treatment during pregnancy. For bipolar disorders, lithium is an acceptable alternative, but valproate use has increased. Relapse, untreated bipolar disorder during pregnancy, postpartum psychosis, and complications from withdrawal from valproate are important factors that must be considered. In treating focal epilepsy, there are alternatives more effective than valproate. However, for idiopathic epilepsies and some rare but severe childhood epilepsies, there are few alternatives and little information about their teratogenesis.
Arguments to ban valproate assume that if fully informed, women would elect not to take valproate if they could become pregnant. A ban may be considered by some to be a safer option, as it is difficult to provide information about the full risks to all valproate users. However, alternative drugs are sometimes less effective than valproate, and for some patients, valproate may be the only effective medication for life-threatening epilepsies.
Given the complexity of the issue, Dr Angus-Leppan and Dr Liu argue that the assessment of the risk-benefit analysis for valproate is individual. Adopting a practice of informed consent based on a thorough disclosure of the relevant risks and benefits can best facilitate patient safety and maternal outcomes on an individualized level.
Angus-Leppan H, Liu RSN. Weighing the risks of valproate in women who could become pregnant [published online April 18, 2018]. BMJ. doi:10.1136/bmj.k1596