Dr. Marlene Freeman, Associate Director of the Center for Women’s Mental Health at Massachusetts General Hospital and Editor-in-Chief of The Journal of Clinical Psychiatry (JCP), recently shared an expert commentary highlighting new research on the reproductive risks of valproic acid.
The Major Dealbreaker: Valproic Acid
Dr. Freeman emphasizes that while a lot of psychiatric medications are well studied and frequently reasonably safe when weighing the risks of untreated psychiatric illness against medication exposure, valproic acid is a clear exception. She describes it as a “major dealbreaker” for women and girls of reproductive potential because of its well-established and severe teratogenic risks.
Valproic acid, also known as valproate or Depakote, is associated with a high risk of major congenital malformations, including neural tube defects, as well as long-term neurodevelopmental harms. These risks begin very early in pregnancy, often before a person realizes they are pregnant, so intervening after conception is an ineffective safety strategy.
Considering Reproductive Potential
“As a perinatal psychiatrist, I really want to emphasize how important it is for all prescribers who treat women of childbearing potential that pregnancies are often unplanned or mistimed,” Dr. Freeman states. Therefore, pregnancy is always a relevant clinical consideration when treating women of reproductive potential. For that reason, valproic acid should not be prescribed to anyone who could become pregnant, even if they are not planning a pregnancy.
Dr. Freeman further explains that contraceptive methods are not 100% effective, and patients should have the option to remain on a medication that keeps them well as part of their long-term treatment plan.
Regulatory Proposals: A REMS-Style Framework
A commentary by Suleiman et al. proposes that the FDA consider a Risk Evaluation and Mitigation Strategy (REMS) for valproate, similar to the system used for Accutane (isotretinoin). Such a framework could require patients to acknowledge risks, confirm they are using an effective contraception, provide documentation that they are not pregnant before starting treatment, and receive education on pregnancy prevention.
This approach aims to reduce preventable fetal exposure by adding structured safeguards.
Dr. Freeman notes that while such measures could help draw attention to the medication’s teratogenicity, she proposed that valproic acid should be “taken off the table” for anyone of reproductive potential.
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—Skye Scoggins, BS
