Secular Trends in the Use of Valproate-Containing Medicines in Women of Childbearing Age in Europe: A Multinational DARWIN EU Network Study

Secular Trends in the Use of Valproate-Containing Medicines in Women of Childbearing Age in Europe: A Multinational DARWIN EU Network Study. Bellas, L., Català, M., Burn, E., Guo, Y., Du, M., Verhamme, K., Fridgeirsson, E., Duarte-Salles, T., Kauko, T., Kronqvist, E., Brash, J. T., Seager, S., Prieto-Alhambra, D., Jödicke, A. M., & Prats-Uribe, A. Pharmacoepidemiol Drug Saf, 34(10):e70232, 2025. 1099-1557 Bellas, Lucía Orcid: 0000-0001-8255-9841 Català, Martí Burn, Edward Guo, Yuchen Du, Mike Verhamme, Katia Fridgeirsson, Egil Duarte-Salles, Talita Kauko, Tommi Kronqvist, Eeva Brash, James T Seager, Sarah Prieto-Alhambra, Daniel Jödicke, Annika M Prats-Uribe, Albert Darwin eu/ Journal Article Multicenter Study England 2025/10/16 Pharmacoepidemiol Drug Saf. 2025 Oct;34(10):e70232. doi: 10.1002/pds.70232.
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BACKGROUND: Valproate-containing medicines (VPA) are first-line treatments for epilepsy; however, they pose teratogenic risks, restricting their use in women of childbearing age. We aimed to estimate the secular trends in the use of VPA and alternative treatments in young women, and to characterise dose/strength, treatment duration, and indication in new VPA users. METHODS: We conducted a multi-national population-based cohort study using primary care records from the Netherlands, Spain, and the UK (IPCI, SIDIAP, CPRD GOLD), primary and outpatient specialist care records from Germany and Belgium (IQVIA DA Germany, IQVIA LPD Belgium), and hospital records from Finland (ACI VARHA), all mapped to the OMOP Common data model. All women present in the databases aged ≥ 12 and ≤ 55 years on the 1st of January of each year in the period 2010-2022 (or latest available), with at least 365 days of prior observation, were included. RESULTS: A total of 2 948 860 (CPRD GOLD), 718 835 (IPCI), 2 494 052 (SIDIAP), 157 361 (ACI VARHA), 218 250 (IQVIA LPD Belgium); and 5 152 752 (IQVIA DA Germany) women were included. Among those, 6416, 1241, 10 398, 1447, 945, and 4002 started treatments with VPA, respectively. Incidence and prevalence of VPA use in young women decreased between 2010 and 2021, while the prevalence of the alternative treatments pregabalin and gabapentin increased, especially in CPRD (it rises from 0.5% to 1.5%). Median age of new VPA users ranged between 40 and 43 years. Anxiety and depressive disorder were frequent comorbidities, and the use of hormonal contraceptives we were able to capture was low. Average treatment duration varied substantially across databases. CONCLUSION: Incidences and prevalence of use of VPA among young women declined since 2015. Conversely, alternative antiepileptics have increased in uptake, particularly gabapentinoids. The use of standardized federated analytics allowed for a rapid assessment of VPA utilization, supporting the regulatory agencies in their decision-making and improving patient safety across Europe.

@article{RN504,
   author = {Bellas, L. and Català, M. and Burn, E. and Guo, Y. and Du, M. and Verhamme, K. and Fridgeirsson, E. and Duarte-Salles, T. and Kauko, T. and Kronqvist, E. and Brash, J. T. and Seager, S. and Prieto-Alhambra, D. and Jödicke, A. M. and Prats-Uribe, A.},
   title = {Secular Trends in the Use of Valproate-Containing Medicines in Women of Childbearing Age in Europe: A Multinational DARWIN EU Network Study},
   journal = {Pharmacoepidemiol Drug Saf},
   volume = {34},
   number = {10},
   pages = {e70232},
   note = {1099-1557
Bellas, Lucía
Orcid: 0000-0001-8255-9841
Català, Martí
Burn, Edward
Guo, Yuchen
Du, Mike
Verhamme, Katia
Fridgeirsson, Egil
Duarte-Salles, Talita
Kauko, Tommi
Kronqvist, Eeva
Brash, James T
Seager, Sarah
Prieto-Alhambra, Daniel
Jödicke, Annika M
Prats-Uribe, Albert
Darwin eu/
Journal Article
Multicenter Study
England
2025/10/16
Pharmacoepidemiol Drug Saf. 2025 Oct;34(10):e70232. doi: 10.1002/pds.70232.},
   abstract = {BACKGROUND: Valproate-containing medicines (VPA) are first-line treatments for epilepsy; however, they pose teratogenic risks, restricting their use in women of childbearing age. We aimed to estimate the secular trends in the use of VPA and alternative treatments in young women, and to characterise dose/strength, treatment duration, and indication in new VPA users. METHODS: We conducted a multi-national population-based cohort study using primary care records from the Netherlands, Spain, and the UK (IPCI, SIDIAP, CPRD GOLD), primary and outpatient specialist care records from Germany and Belgium (IQVIA DA Germany, IQVIA LPD Belgium), and hospital records from Finland (ACI VARHA), all mapped to the OMOP Common data model. All women present in the databases aged ≥ 12 and ≤ 55 years on the 1st of January of each year in the period 2010-2022 (or latest available), with at least 365 days of prior observation, were included. RESULTS: A total of 2 948 860 (CPRD GOLD), 718 835 (IPCI), 2 494 052 (SIDIAP), 157 361 (ACI VARHA), 218 250 (IQVIA LPD Belgium); and 5 152 752 (IQVIA DA Germany) women were included. Among those, 6416, 1241, 10 398, 1447, 945, and 4002 started treatments with VPA, respectively. Incidence and prevalence of VPA use in young women decreased between 2010 and 2021, while the prevalence of the alternative treatments pregabalin and gabapentin increased, especially in CPRD (it rises from 0.5% to 1.5%). Median age of new VPA users ranged between 40 and 43 years. Anxiety and depressive disorder were frequent comorbidities, and the use of hormonal contraceptives we were able to capture was low. Average treatment duration varied substantially across databases. CONCLUSION: Incidences and prevalence of use of VPA among young women declined since 2015. Conversely, alternative antiepileptics have increased in uptake, particularly gabapentinoids. The use of standardized federated analytics allowed for a rapid assessment of VPA utilization, supporting the regulatory agencies in their decision-making and improving patient safety across Europe.},
   keywords = {Humans
Female
*Valproic Acid/administration & dosage/adverse effects
Adult
*Anticonvulsants/administration & dosage/adverse effects
Young Adult
Adolescent
Europe/epidemiology
Middle Aged
Cohort Studies
*Epilepsy/drug therapy
Databases, Factual
Child
antiepileptic drugs
drug utilization
network study
pharmacoepidemiology},
   ISSN = {1053-8569 (Print)
1053-8569},
   DOI = {10.1002/pds.70232},
   year = {2025},
   type = {Journal Article}
}

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M.","Prats-Uribe, A."],"bibdata":{"bibtype":"article","type":"Journal Article","author":[{"propositions":[],"lastnames":["Bellas"],"firstnames":["L."],"suffixes":[]},{"propositions":[],"lastnames":["Català"],"firstnames":["M."],"suffixes":[]},{"propositions":[],"lastnames":["Burn"],"firstnames":["E."],"suffixes":[]},{"propositions":[],"lastnames":["Guo"],"firstnames":["Y."],"suffixes":[]},{"propositions":[],"lastnames":["Du"],"firstnames":["M."],"suffixes":[]},{"propositions":[],"lastnames":["Verhamme"],"firstnames":["K."],"suffixes":[]},{"propositions":[],"lastnames":["Fridgeirsson"],"firstnames":["E."],"suffixes":[]},{"propositions":[],"lastnames":["Duarte-Salles"],"firstnames":["T."],"suffixes":[]},{"propositions":[],"lastnames":["Kauko"],"firstnames":["T."],"suffixes":[]},{"propositions":[],"lastnames":["Kronqvist"],"firstnames":["E."],"suffixes":[]},{"propositions":[],"lastnames":["Brash"],"firstnames":["J.","T."],"suffixes":[]},{"propositions":[],"lastnames":["Seager"],"firstnames":["S."],"suffixes":[]},{"propositions":[],"lastnames":["Prieto-Alhambra"],"firstnames":["D."],"suffixes":[]},{"propositions":[],"lastnames":["Jödicke"],"firstnames":["A.","M."],"suffixes":[]},{"propositions":[],"lastnames":["Prats-Uribe"],"firstnames":["A."],"suffixes":[]}],"title":"Secular Trends in the Use of Valproate-Containing Medicines in Women of Childbearing Age in Europe: A Multinational DARWIN EU Network Study","journal":"Pharmacoepidemiol Drug Saf","volume":"34","number":"10","pages":"e70232","note":"1099-1557 Bellas, Lucía Orcid: 0000-0001-8255-9841 Català, Martí Burn, Edward Guo, Yuchen Du, Mike Verhamme, Katia Fridgeirsson, Egil Duarte-Salles, Talita Kauko, Tommi Kronqvist, Eeva Brash, James T Seager, Sarah Prieto-Alhambra, Daniel Jödicke, Annika M Prats-Uribe, Albert Darwin eu/ Journal Article Multicenter Study England 2025/10/16 Pharmacoepidemiol Drug Saf. 2025 Oct;34(10):e70232. doi: 10.1002/pds.70232.","abstract":"BACKGROUND: Valproate-containing medicines (VPA) are first-line treatments for epilepsy; however, they pose teratogenic risks, restricting their use in women of childbearing age. We aimed to estimate the secular trends in the use of VPA and alternative treatments in young women, and to characterise dose/strength, treatment duration, and indication in new VPA users. METHODS: We conducted a multi-national population-based cohort study using primary care records from the Netherlands, Spain, and the UK (IPCI, SIDIAP, CPRD GOLD), primary and outpatient specialist care records from Germany and Belgium (IQVIA DA Germany, IQVIA LPD Belgium), and hospital records from Finland (ACI VARHA), all mapped to the OMOP Common data model. All women present in the databases aged ≥ 12 and ≤ 55 years on the 1st of January of each year in the period 2010-2022 (or latest available), with at least 365 days of prior observation, were included. RESULTS: A total of 2 948 860 (CPRD GOLD), 718 835 (IPCI), 2 494 052 (SIDIAP), 157 361 (ACI VARHA), 218 250 (IQVIA LPD Belgium); and 5 152 752 (IQVIA DA Germany) women were included. Among those, 6416, 1241, 10 398, 1447, 945, and 4002 started treatments with VPA, respectively. Incidence and prevalence of VPA use in young women decreased between 2010 and 2021, while the prevalence of the alternative treatments pregabalin and gabapentin increased, especially in CPRD (it rises from 0.5% to 1.5%). Median age of new VPA users ranged between 40 and 43 years. Anxiety and depressive disorder were frequent comorbidities, and the use of hormonal contraceptives we were able to capture was low. Average treatment duration varied substantially across databases. CONCLUSION: Incidences and prevalence of use of VPA among young women declined since 2015. Conversely, alternative antiepileptics have increased in uptake, particularly gabapentinoids. The use of standardized federated analytics allowed for a rapid assessment of VPA utilization, supporting the regulatory agencies in their decision-making and improving patient safety across Europe.","keywords":"Humans Female *Valproic Acid/administration & dosage/adverse effects Adult *Anticonvulsants/administration & dosage/adverse effects Young Adult Adolescent Europe/epidemiology Middle Aged Cohort Studies *Epilepsy/drug therapy Databases, Factual Child antiepileptic drugs drug utilization network study pharmacoepidemiology","issn":"1053-8569 (Print) 1053-8569","doi":"10.1002/pds.70232","year":"2025","bibtex":"@article{RN504,\r\n author = {Bellas, L. and Català, M. and Burn, E. and Guo, Y. and Du, M. and Verhamme, K. and Fridgeirsson, E. and Duarte-Salles, T. and Kauko, T. and Kronqvist, E. and Brash, J. T. and Seager, S. and Prieto-Alhambra, D. and Jödicke, A. M. and Prats-Uribe, A.},\r\n title = {Secular Trends in the Use of Valproate-Containing Medicines in Women of Childbearing Age in Europe: A Multinational DARWIN EU Network Study},\r\n journal = {Pharmacoepidemiol Drug Saf},\r\n volume = {34},\r\n number = {10},\r\n pages = {e70232},\r\n note = {1099-1557\r\nBellas, Lucía\r\nOrcid: 0000-0001-8255-9841\r\nCatalà, Martí\r\nBurn, Edward\r\nGuo, Yuchen\r\nDu, Mike\r\nVerhamme, Katia\r\nFridgeirsson, Egil\r\nDuarte-Salles, Talita\r\nKauko, Tommi\r\nKronqvist, Eeva\r\nBrash, James T\r\nSeager, Sarah\r\nPrieto-Alhambra, Daniel\r\nJödicke, Annika M\r\nPrats-Uribe, Albert\r\nDarwin eu/\r\nJournal Article\r\nMulticenter Study\r\nEngland\r\n2025/10/16\r\nPharmacoepidemiol Drug Saf. 2025 Oct;34(10):e70232. doi: 10.1002/pds.70232.},\r\n abstract = {BACKGROUND: Valproate-containing medicines (VPA) are first-line treatments for epilepsy; however, they pose teratogenic risks, restricting their use in women of childbearing age. We aimed to estimate the secular trends in the use of VPA and alternative treatments in young women, and to characterise dose/strength, treatment duration, and indication in new VPA users. METHODS: We conducted a multi-national population-based cohort study using primary care records from the Netherlands, Spain, and the UK (IPCI, SIDIAP, CPRD GOLD), primary and outpatient specialist care records from Germany and Belgium (IQVIA DA Germany, IQVIA LPD Belgium), and hospital records from Finland (ACI VARHA), all mapped to the OMOP Common data model. All women present in the databases aged ≥ 12 and ≤ 55 years on the 1st of January of each year in the period 2010-2022 (or latest available), with at least 365 days of prior observation, were included. RESULTS: A total of 2 948 860 (CPRD GOLD), 718 835 (IPCI), 2 494 052 (SIDIAP), 157 361 (ACI VARHA), 218 250 (IQVIA LPD Belgium); and 5 152 752 (IQVIA DA Germany) women were included. Among those, 6416, 1241, 10 398, 1447, 945, and 4002 started treatments with VPA, respectively. Incidence and prevalence of VPA use in young women decreased between 2010 and 2021, while the prevalence of the alternative treatments pregabalin and gabapentin increased, especially in CPRD (it rises from 0.5% to 1.5%). Median age of new VPA users ranged between 40 and 43 years. Anxiety and depressive disorder were frequent comorbidities, and the use of hormonal contraceptives we were able to capture was low. Average treatment duration varied substantially across databases. CONCLUSION: Incidences and prevalence of use of VPA among young women declined since 2015. Conversely, alternative antiepileptics have increased in uptake, particularly gabapentinoids. 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