Commentary: Revised recommendation from CMD h on use of valproate in women is ethically incomplete and neglects the interests of women

As noted in the accompanying article by Tomson, et al., the Coordination Group for Mutual Recognition and Decentralised Procedures-Human (CMDh) of the European Medicines Agency (EMA) has recently strengthened warnings on the use of valproate in women and girls. The CMDh recommendations to healthcare professionals (HCPs) now include the following admonition: “For treatment of epilepsy and bipolar disorder in female patients who can have children, only prescribe valproate medicines for epilepsy and bipolar disorder if other treatments are ineffective or are not tolerated.” [emphasis added] One possible interpretation of this recommendation is that the intent of CMDh is to urge HCPs to prescribe all other possible drugs before prescribing valproate, without regard to complex clinical and psychosocial circumstances such as the type of epilepsy, patients’ goals for childbearing, and varying tolerance of individual patients to their comparative risks of mortality or severe morbidity from tonic–clonic seizures versus elevated risks of birth defects and cognitive deficits in potential babies exposed to valproate in utero. Although the goal of the CMDh recommendation to avoid birth defects in potential babies is ethically laudable, the strict recommendation as currently written fails to account for another, equally important ethical component of the decision process—the woman’s interests in preserving her health, and her potential strong preference to begin valproate immediately to avoid potentially fatal seizures by using the most effective drug for generalized idiopathic epilepsy. In this commentary, I argue that the current recommendation of the CMDh, as interpreted in the preceding text, is inappropriate for a complete ethical analysis of the complex and difficult decisions necessitated by the comparative risks in this situation because it focuses solely on the goal of protecting potential fetuses without considering the health interests, personal values, and goals of women with particular types of epilepsy. Instead, I will support a more nuanced, casuistrybased ethical argument that flexibly permits assessment, in consultation with her physicians and after a thorough informed consent process, of all the particular circumstances of each individual woman’s case and encourages weighing the interests, burdens and benefits, and personal values of both woman and potential child.