{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,9]],"date-time":"2026-04-09T16:57:27Z","timestamp":1775753847513,"version":"3.50.1"},"reference-count":26,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2014,8,11]],"date-time":"2014-08-11T00:00:00Z","timestamp":1407715200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100003554","name":"Lundbeckfonden","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003554","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmacoepidemiology and Drug"],"published-print":{"date-parts":[[2015,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Animal studies have suggested that drugs inhibiting the enzyme histone deacetylase might have a beneficial effect on multiple sclerosis (MS). Valproic acid (VPA), an anti\u2010epileptic drug, is the only widely used human drug with a histone deacetylase inhibitory effect.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objective<\/jats:title><jats:p>The objective of this paper is to examine if VPA use is associated with a reduced risk of MS.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We conducted a propensity score\u2010matched cohort study in the period 1997\u20132011 linking nationwide register data on filled VPA prescriptions, MS cases, and several covariates. The VPA users were matched on propensity scores in a 1:4 ratio with non\u2010users of VPA. Incidence rates of MS were compared among VPA users and non\u2010users of VPA using Cox regression to estimate hazard ratios (<jats:italic>HR<\/jats:italic>s).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Among 16\u2009028 ever\u2010users of VPA and 54\u2009172 non\u2010users, 18 and 26 cases of MS were identified, respectively. Neither current VPA users nor recent users of VPA, who had ceased VPA treatment within the last year, were at a reduced risk of MS compared with non\u2010users of VPA (<jats:italic>HR<\/jats:italic>\u2009=\u20091.30 (95% confidence interval, 0.44\u20133.80), <jats:italic>n<\/jats:italic>\u2009=\u20094, and <jats:italic>HR<\/jats:italic>\u2009=\u20091.22 (0.28\u20135.32), <jats:italic>n<\/jats:italic>\u2009=\u20092, respectively). Similarly, in an intention\u2010to\u2010treat analysis, ever\u2010users of VPA were not at reduced risk of MS (<jats:italic>HR<\/jats:italic>\u2009=\u20092.41 (1.32\u20134.43), <jats:italic>n<\/jats:italic>\u2009=\u200918).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>In the first human study addressing a possible beneficial effect of VPA use on the risk of MS, we found no support for a protective effect. However, given the wide confidence intervals, only large effects can be ruled out with sufficient certainty. Copyright \u00a9 2014 John Wiley &amp; Sons, Ltd.<\/jats:p><\/jats:sec>","DOI":"10.1002\/pds.3692","type":"journal-article","created":{"date-parts":[[2014,8,11]],"date-time":"2014-08-11T10:03:30Z","timestamp":1407751410000},"page":"262-268","source":"Crossref","is-referenced-by-count":13,"title":["The use of valproic acid and multiple sclerosis"],"prefix":"10.1002","volume":"24","author":[{"given":"Nete Munk","family":"Nielsen","sequence":"first","affiliation":[{"name":"Department of Epidemiology Research Statens Serum Institut  Copenhagen Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Henrik","family":"Svanstr\u00f6m","sequence":"additional","affiliation":[{"name":"Department of Epidemiology Research Statens Serum Institut  Copenhagen Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Egon","family":"Stenager","sequence":"additional","affiliation":[{"name":"Rigshospitalet The Danish Multiple Sclerosis Registry  Copenhagen Denmark"},{"name":"Institute of Regional Health Research University of Southern Denmark  Odense Denmark"},{"name":"Department of Neurology Multiple Sclerosis Clinic of Southern Jutland (S\u00f8nderborg, Vejle, Esbjerg)  S\u00f8nderborg Denmark"},{"name":"National Institute of Public Health University of Southern Denmark  Copenhagen Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Melinda","family":"Magyari","sequence":"additional","affiliation":[{"name":"Department of Neurology, Neuroscience Centre, Rigshospitalet Danish Multiple Sclerosis Research Centre  Copenhagen Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nils","family":"Koch\u2010Henriksen","sequence":"additional","affiliation":[{"name":"Rigshospitalet The Danish Multiple Sclerosis Registry  Copenhagen Denmark"},{"name":"University of Aarhus Department of Clinical Epidemiology, Clinical Institute  Aarhus Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bj\u00f6rn","family":"Pasternak","sequence":"additional","affiliation":[{"name":"Department of Epidemiology Research Statens Serum Institut  Copenhagen Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anders","family":"Hviid","sequence":"additional","affiliation":[{"name":"Department of Epidemiology Research Statens Serum Institut  Copenhagen Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2014,8,11]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM200009283431307"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0404.2008.01026.x"},{"key":"e_1_2_9_4_1","first-page":"435","article-title":"Pharmacodynamic properties of N\u2010dipropylacetic acid","volume":"18","author":"Meunier H","year":"1963","journal-title":"Therapie"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2710.2005.00671.x"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.4161\/epi.1.2.2678"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tips.2009.07.002"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.2119\/molmed.2011.00077"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.cdd.4401769"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.170.7.3874"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jneuroim.2005.02.022"},{"issue":"1","key":"e_1_2_9_12_1","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1159\/000352021","article-title":"Valproic acid attenuates disease symptoms and increases endogenous myelin repair by recruiting neural stem cells and oligodendrocyte progenitors in experimental autoimmune encephalomyelitis","volume":"13","author":"Pazhoohan S","year":"2014","journal-title":"Neurodegener Dis"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn.2172"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1177\/1403494810387965"},{"issue":"4","key":"e_1_2_9_15_1","first-page":"445","article-title":"The Danish prescription registries","volume":"44","author":"Gaist D","year":"1997","journal-title":"Dan Med Bull"},{"issue":"2","key":"e_1_2_9_16_1","first-page":"91","article-title":"The Danish Multiple Sclerosis Registry. 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