
Abstract
Objective: To provide an up-to-date evaluation of valproic acid (VPA) use trends, patterns, and predictors in females of reproductive age in ambulatory care settings in the US.
Methods: A retrospective, cross-sectional study was conducted using 2017 through 2022 Medical Expenditure Panel Survey data to examine trends in VPA use. Prescription rates were calculated per 1,000 prescription events with 95% confidence intervals. VPA prescriptions were stratified by clinical indication and recipient group (females aged 12–49 years, females aged ≥50 years, and males aged 12–49 years). Multivariable logistic regression was used to identify predictors of VPA use among females aged 12–49 years and all females with comorbid bipolar disorder, headache, or seizure conditions.
Results: The cumulative total of VPA prescription events across the 2017–2022 study period was 29,754,849 (95% CI, 23,843,243–35,666,455). Of these, 5,442,682 (95% CI, 2,879,340–8,006,024) were issued to females aged 12–49 years (18.3% of all VPA prescriptions). From 2017 to 2022, VPA prescribing decreased by nearly 50% (P =.037). Most VPA prescriptions filled by females aged 12–49 years were for migraine or other headache syndromes (27.2%), followed by bipolar disorder (24.6%) and convulsions or epilepsy (20.7%). Of the estimated 153,120 females aged 12–49 years who filled a prescription for VPA between 2017–2022, 85.9% were not using contraception.
Conclusion: Approximately 1 in 5 VPA prescriptions between 2017 to 2022 were prescribed to females of reproductive age. VPA was most commonly used for the treatment of migraine or other headache syndrome, followed by bipolar disorder and convulsive disorder. Only 14.1% of females of reproductive age using VPA were also using contraception. Interventional studies aimed at reducing VPA use in females of reproductive age are needed.
J Clin Psychiatry 2026;87(1):25m16009
Author affiliations are listed at the end of this article.
Members Only Content
This full article is available exclusively to Professional tier members. Subscribe now to unlock the HTML version and gain unlimited access to our entire library plus all PDFs. If you’re already a subscriber, please log in below to continue reading.
References (42)
- Gotlib D, Ramaswamy R, Kurlander JE, et al. Valproic acid in women and girls of childbearing age. Curr Psychiatry Rep. 2017;19(9):58. PubMed CrossRef
- Tomson T, Battino D, Bromley R, et al. Executive summary: management of epilepsy in pregnancy: a report from the International League Against Epilepsy Task Force on Women and Pregnancy. Epilepsia. 2019;60(12):2343–2345. PubMed CrossRef
- Meador KJ, Baker GA, Browning N, et al. Fetal antiepileptic drug exposure and cognitive outcomes at age 6 years (NEAD study): a prospective observational study. Lancet Neurol. 2013;12(3):244–252. PubMed CrossRef
- Romoli M, Mazzocchetti P, D’Alonzo R, et al. Valproic acid and epilepsy: from molecular mechanisms to clinical evidences. Curr Neuropharmacol. 2019;17(10):926–946. PubMed CrossRef
- Food and Drug Administration. FDA Drug Safety Communication: Valproate Anti-seizure Products Contraindicated for Migraine Prevention in Pregnant Women due to Decreased IQ Scores in Exposed Children. 2013. Accessed June 23, 2025. https://www.fda.gov/drugs/drug-safety-and-availability/fda-drug-safety-communication-valproate-anti-seizure-products-contraindicated-migraine-prevention#:∼:text=%5B05%2D06%2D2013%5D,the%20prevention%20of%20migraine%20headaches
- World Health Organization. Statement on the risks associated with use of valproic acid (sodium valproate) in women and girls of childbearing potential. 2023. Accessed June 23, 2025. https://www.who.int/news/item/02-05-2023-use-of-valproic-acid-in-women-and-girls-of-childbearing-potential
- Freeman MP. Prescribing Guideline for valproic acid and women of reproductive potential: forget it exists. J Clin Psychiatry. 2022;83(6):22ed14609. PubMed CrossRef
- Yatham LN, Kennedy SH, Parikh SV, et al. Canadian Network for Mood and Anxiety Treatments (CANMAT) and International Society for Bipolar Disorders (ISBD) 2018 guidelines for the management of patients with bipolar disorder. Bipolar Disord. 2018;20(2):97–170. PubMed CrossRef
- Ghosh S, Sinha JK, Khan T, et al. Pharmacological and therapeutic approaches in the treatment of epilepsy. Biomedicines. 2021;9(5):470. PubMed CrossRef
- Vatzaki E, Straus S, Dogne JM, et al. Latest clinical recommendations on valproate use for migraine prophylaxis in women of childbearing age: overview from European Medicines Agency and European Headache Federation. J Headache Pain. 2018;19(1):68. PubMed CrossRef
- Rizvi A, Shaan F, Reyazuddin M. Valproate prescribed to reproductive-age women in ambulatory care: analysis of 2018-2019 National Ambulatory Health Care data. Prim Care Companion CNS Disord. 2023;25(4):22br03500. PubMed CrossRef
- Birnbaum AK. Are women of childbearing Age still receiving valproate? Epilepsy Curr. 2018;18(6):380–381. PubMed CrossRef
- Gaudio M, Konstantara E, Joy M, et al. Valproate prescription to women of childbearing age in English primary care: repeated cross-sectional analyses and retrospective cohort study. BMC Pregnancy Childbirth. 2022;22(1):73. PubMed CrossRef
- Andrade C, Jyothi SA, Renitha T, et al. Use of valproate in women: an audit of prescriptions to 10,001 psychiatry, neurology, and neurosurgery outpatients. J Clin Psychiatry. 2021;83(1):21m14023. PubMed CrossRef
- Clavenna A, Campi R, Putignano D, et al. Changes in antiepileptic drug prescriptions over a decade in childbearing women in Lombardy region, Italy. Br J Clin Pharmacol. 2022;88(3):1152–1158. PubMed CrossRef
- Di Vito L, Mazzoni S, Belotti LMB, et al. Impact of regulatory restrictions on the use of valproic acid in women of childbearing age: an Italian study. Epilepsia. 2023;64(4):910–918. PubMed CrossRef
- Scholz K, Köster I, Meyer I, et al. Prescribing of valproate and oral antiepileptics for women of childbearing age and during pregnancy in Germany between 2010 and 2020. Pharmacoepidemiol Drug Saf. 2023;32(11):1306–1314. PubMed CrossRef
- Ura H, Matsuoka N, Kubota K, et al. Trends in prescription of anti-seizure medications in Japan between 2018 and 2021: a retrospective study using the National Database Open Data Japan. Epilepsy Behav. 2024;159:109949. PubMed CrossRef
- Hughes JE, Buckley N, Looney Y, et al. Valproate utilisation trends among women of childbearing potential in Ireland between 2014 and 2019: a drug utilisation study using interrupted time series. Pharmacoepidemiol Drug Saf. 2022;31(6):661–669. PubMed CrossRef
- Tennant M, Frampton C, Mulder R, et al. Changes in sodium valproate dispensing in women of childbearing age with a diagnosis of borderline personality disorder in Aotearoa New Zealand. N Z Med J. 2024;137(1597):36–43. PubMed CrossRef
- Corfe-Tan J, McLay L, Mentzel C. Prescription of sodium valproate to women of childbearing potential in Southern District Mental Health Services in New Zealand. Australas Psychiatry. 2023;31(6):776–781. PubMed CrossRef
- Wójcik K, Kruk M, Koń B, et al. Treatment patterns in women of childbearing age and pregnant women with epilepsy in Poland between the years 2019 and 2022-A nationwide population-based cohort study. Seizure. 2024;115:75–80. PubMed CrossRef
- Degremont A, Kerbrat S, Balusson F, et al. Prescribing trends for valproate among pregnant women: a cross-sectional study in 2013 and 2016 using the French Health Insurance Database. Neurology. 2022;98(21):e2163–e2173. PubMed CrossRef
- Kurvits K, Laius O, Uusküla M, et al. Valproic acid prescription trends among females of childbearing age in Estonia: a 14-year nationwide prescription database study. Seizure. 2020;76:28–31. PubMed CrossRef
- Agency for Healthcare Research and Quality. MEPS HC 243 2022 Full Year Consolidated Data File. 2024. Accessed June 23, 2025. https://www.meps.ahrq.gov/data_stats/download_data/pufs/h243/h243doc.pdf
- Agency for Healthcare Research and Quality. Medical Expenditure Panel Survey, Survey Background. Accessed June 23, 2025. https://www.meps.ahrq.gov/mepsweb/about_meps/survey_back.jsp
- Agency for Healthcare Research and Quality. MEPS HC 239A: 2022 Prescribed Medicines. 2024. Accessed June 23, 2025. https://www.meps.ahrq.gov/data_stats/download_data/pufs/h239a/h239adoc.pdf
- Agency for Healthcare Research and Quality. MEPS HC 241: 2022 Medical Conditions. 2024. Accessed June 23, 2025. https://www.meps.ahrq.gov/data_stats/download_data/pufs/h241/h241doc.pdf
- Smolinski NE, Sarayani A, Thai TN, et al. Prenatal exposure to valproic acid across various indications for use. JAMA Netw Open. 2024;7(5):e2412680. PubMed CrossRef
- Valentino K, Teopiz KM, Kwan ATH, et al. Anatomical, behavioral, and cognitive teratogenicity associated with valproic acid: a systematic review. CNS Spectr. December 2024;29(6):604–610. PubMed CrossRef
- Hird MA, Sandoe CH. Migraine management in medically complex patients: a narrative review. Curr Neurol Neurosci Rep. 2024;24(9):423–438. PubMed CrossRef
- European Medicines Agency. Valproate and related substances. 2018. Accessed June 23, 2025. https://www.ema.europa.eu/en/news/new-measures-avoid-valproate-exposure-pregnancy-endorsed
- Daniels K, Abma JC. Current Contraceptive Status Among Women Aged 15–49: United States, 2017–2019. NCHS Data Brief;2020(388):1–8. PubMed
- Finer LB, Zolna MR. Declines in unintended pregnancy in the United States, 2008-2011. N Engl J Med. 2016;374(9):843–852. PubMed CrossRef
- The New York Times. Tracking the States Where Abortion Is Now Banned. 2022. Accessed June 23, 2025. https://www.nytimes.com/interactive/2022/us/abortion-laws-roe-v-wade.html
- Sarayani A, Albogami Y, Thai TN, et al. Prenatal exposure to teratogenic medications in the era of Risk Evaluation and Mitigation Strategies. Am J Obstet Gynecol. 2022;227(2):263.e1–263.e38. PubMed CrossRef
- Adedinsewo DA, Thurman DJ, Luo YH, et al. Valproate prescriptions for nonepilepsy disorders in reproductive-age women. Birth Defects Res A Clin Mol Teratol. 2013;97(6):403–408. PubMed CrossRef
- Wisner KL, Leckman-Westin E, Finnerty M, et al. Valproate prescription prevalence among women of childbearing age. Psychiatr Serv. 2011;62(2):218–220. PubMed CrossRef
- Colas S, Nishikawa T, Dresco I, et al. Effectiveness of the additional risk minimisation measures for valproate among healthcare professionals and Patients: a Cross-Sectional Survey in six European countries. Pharmacoepidemiol Drug Saf. 2024;33(11):e70046. PubMed CrossRef
- Hill CE, Lin CC, Suresh S, et al. Perceptions of reproductive risk among women with epilepsy of childbearing age. Epilepsy Behav. 2024;161:110107. PubMed CrossRef
- Riley RD, Snell KI, Ensor J, et al. Minimum sample size for developing a multivariable prediction model: PART II - binary and time-to-event outcomes. Stat Med. 2019;38(7):1276–1296. PubMed CrossRef
- Precision Standards Guidelines for Reporting MEPS-HC Descriptive Statistics. Accessed August 5, 2025. https://meps.ahrq.gov/survey_comp/precision_guidelines.shtml