{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T17:59:38Z","timestamp":1781719178282,"version":"3.54.5"},"reference-count":42,"publisher":"Public Library of Science (PLoS)","issue":"6","license":[{"start":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T00:00:00Z","timestamp":1781654400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004565","name":"Ministry of Education Brunei Darussalam","doi-asserted-by":"crossref","award":["JPLL\/A\/4:A[2021]\/J1 (123)"],"award-info":[{"award-number":["JPLL\/A\/4:A[2021]\/J1 (123)"]}],"id":[{"id":"10.13039\/501100004565","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:sec id=\"sec001\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Mood stabilisers carbamazepine, lamotrigine and valproate remain the cornerstone medication in the treatment of epilepsy, and in the management of psychiatric disorders alongside lithium. Prescribing decisions are influenced by patient\u2019s preference, clinical history, and risk. This study examines mood stabiliser initiation and prevalence prescribing trends in UK primary care (1995\u20132018), stratified by sex (male and females) and age (18\u201339, 40\u201359, 60\u201379 and 80\u201399 years), irrespective of diagnosis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec002\">\n                    <jats:title>Method<\/jats:title>\n                    <jats:p>Cohort studies using UK anonymised electronic primary care data from IQVIA Medical Research Data (IMRD) of individuals aged 18\u201399 years registered with participating General Practice.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec003\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Carbamazepine prescribing declined sharply across ages and sexes since the early 2000s. In contrast, lamotrigine prescribing increased markedly from 2005, thus becoming most initiated among individuals aged 18\u201339 years by 2018. Carbamazepine initiation predominated in individuals aged 40\u201399 years, and more so in females than males. Valproate initiation decreased throughout study period: (2018 vs 1995) adjusted Incidence Rate Ratio (aIRR) ranged from 0.12\u20130.44. However, prevalence rose in males (18\u201379 years) with adjusted Prevalence Rate Ratio (aPRR) ranged from 1.14\u20131.60, and females (40\u201379 years) at aPRR 1.12\u20131.31. By 2018, valproate was still prevalent among 18\u201339 years males (3.40\/1000 individuals [3.19\u20133.61]) compared to females (1.18\/1000 individuals [1.06\u20131.30]). Carbamazepine, lamotrigine and valproate were almost equally prescribed by 2018, while lithium the least prescribed. Mood stabiliser prescribing was higher among socioeconomically deprived individuals, both in terms of initiation and prevalence: (Townsend 5 vs Townsend 1) aIRR ranged from 1.07\u20133.26, and aPRR 1.17\u20132.90.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec004\">\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Over the study period across demographics, carbamazepine prescribing declined while lamotrigine prescribing increased substantially. By 2018, carbamazepine was mainly initiated in males and females aged 40\u201399 years and lamotrigine dominated in 18\u201339 years. Valproate initiation fell but remained prevalent in 18\u201339 years males; lithium prescribing remained low. Mood stabilisers were frequently prescribed in socioeconomically deprived individuals.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1371\/journal.pone.0351169","type":"journal-article","created":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T17:42:10Z","timestamp":1781718130000},"page":"e0351169","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Comprehensive insights into the prescribing trends of carbamazepine, lamotrigine, lithium, and valproate in the UK Primary Care from 1995 to 2018"],"prefix":"10.1371","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4538-5795","authenticated-orcid":true,"given":"Siti Watiqah","family":"Samsuddin","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan Carlos","family":"Bazo-Alvarez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricia","family":"Schartau","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irene","family":"Petersen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2026,6,17]]},"reference":[{"key":"pone.0351169.ref001","volume-title":"Making decisions using NICE guidelines","author":"National Institute for Health and Care Excellence","year":"2024"},{"key":"pone.0351169.ref002","volume-title":"Depression in adults: treatment and management","author":"National Institute for Health and Care Excellence","year":"2022"},{"issue":"1","key":"pone.0351169.ref003","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1177\/0269881119889296","article-title":"Evidence-based guidelines for the pharmacological treatment of schizophrenia: Updated recommendations from the British Association for Psychopharmacology","volume":"34","author":"TR Barnes","year":"2020","journal-title":"J Psychopharmacol"},{"key":"pone.0351169.ref004","volume-title":"Epilepsies in children, young people and adult","author":"National Institute for Health and Care Excellence","year":"2022"},{"key":"pone.0351169.ref005","volume-title":"Bipolar disorder: assessment and management","author":"National Institute for Health and Care Excellence","year":"2014"},{"issue":"1","key":"pone.0351169.ref006","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1186\/s40345-023-00322-7","article-title":"Why is lithium [not] the drug of choice for bipolar disorder? a controversy between science and clinical practice","volume":"12","author":"LV Kessing","year":"2024","journal-title":"Int J Bipolar Disord"},{"key":"pone.0351169.ref007","unstructured":"National Health Service Business Services Authority NHSBSA. 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Kaeley","year":"2019","journal-title":"J Family Med Prim Care"},{"issue":"5","key":"pone.0351169.ref028","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1111\/j.1600-0404.2005.00474.x","article-title":"Epilepsy, osteoporosis and fracture risk - a meta-analysis","volume":"112","author":"P Vestergaard","year":"2005","journal-title":"Acta Neurol Scand"},{"issue":"9","key":"pone.0351169.ref029","doi-asserted-by":"crossref","first-page":"1358","DOI":"10.1212\/01.wnl.0000180910.72487.18","article-title":"Effect of antiepileptic medication on bone mineral measures","volume":"65","author":"SJ Petty","year":"2005","journal-title":"Neurology"},{"issue":"5","key":"pone.0351169.ref030","doi-asserted-by":"crossref","first-page":"316","DOI":"10.1097\/NRL.0000000000000522","article-title":"Trends in antiseizure medication prescribing among nursing home residents with and without a seizure diagnosis","volume":"28","author":"JD 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