{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,1]],"date-time":"2026-03-01T19:07:57Z","timestamp":1772392077253,"version":"3.50.1"},"reference-count":33,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2017,6,12]],"date-time":"2017-06-12T00:00:00Z","timestamp":1497225600000},"content-version":"vor","delay-in-days":11,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100007123","name":"Stanley Medical Research Institute","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007123","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Bipolar Disorders"],"published-print":{"date-parts":[[2017,6]]},"abstract":"<jats:sec><jats:title>Objectives<\/jats:title><jats:p>Mood stabilizers administered for bipolar disorder during pregnancy, such as valproic acid, can increase the risk of congenital anomalies in offspring. Valnoctamide is a valproic acid derivative associated with a decreased risk for congenital abnormalities in animals. The present study evaluated the efficacy and safety of valnoctamide monotherapy, compared to placebo, in the treatment of patients in an acute manic episode.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A 3\u2010week, double\u2010blind, randomized, placebo\u2010 and risperidone\u2010controlled, parallel group trial was conducted on 173 patients in an acute manic episode. Patients were randomized to receive valnoctamide 1500\u00a0mg\/d (n=71), risperidone 6\u00a0mg\/d (n=32), or matching placebo (n=70). The primary outcome measure was the change in Young Mania Rating Scale (YMRS) scores.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Valnoctamide did not differ significantly from placebo on any of the study endpoints (<jats:styled-content style=\"fixed-case\">YMRS<\/jats:styled-content>,<jats:styled-content style=\"fixed-case\"> Positive and Negative Syndrome Scale<\/jats:styled-content>, and <jats:styled-content style=\"fixed-case\">the Clinical Global Impression Scale for Bipolar Disorder [CGI<\/jats:styled-content>\u2010BP] scales; all <jats:italic>P<\/jats:italic>&gt;.60). Mixed models for repeated measures showed that risperidone produced significantly more improvement than placebo in the overall bipolar disorder <jats:styled-content style=\"fixed-case\">CGI\u2010BP<\/jats:styled-content> severity scale (<jats:italic>P<\/jats:italic>=.036), and the <jats:styled-content style=\"fixed-case\">CGI\u2010BP<\/jats:styled-content> severity scale for mania (<jats:italic>P<\/jats:italic>=.021). The Kaplan\u2010Meier survival curve revealed higher all\u2010cause discontinuation rates (mainly due to lack of efficacy) in the valnoctamide group compared to the other study groups (<jats:italic>P<\/jats:italic>=.026). Patients with higher valnoctamide plasma levels had a numerically higher <jats:styled-content style=\"fixed-case\">YMRS<\/jats:styled-content> response, but this was not statistically significant.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Valnoctamide was well tolerated at 1500\u00a0mg\/d but lacked efficacy in the treatment of symptoms in patients with acute mania. Possible differences between the biological mechanisms of action of valproic acid and valnoctamide are discussed.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bdi.12506","type":"journal-article","created":{"date-parts":[[2017,6,12]],"date-time":"2017-06-12T12:09:01Z","timestamp":1497269341000},"page":"285-294","source":"Crossref","is-referenced-by-count":7,"title":["A randomized, double\u2010blind, placebo\u2010 and risperidone\u2010controlled study on valnoctamide for acute mania"],"prefix":"10.1111","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3638-0271","authenticated-orcid":false,"given":"Mark","family":"Weiser","sequence":"first","affiliation":[{"name":"Division of Psychiatry Chaim Sheba Medical Center  Tel HaShomer Israel"},{"name":"Sackler School of Medicine Tel Aviv University  Tel Aviv Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Linda","family":"Levi","sequence":"additional","affiliation":[{"name":"Division of Psychiatry Chaim Sheba Medical Center  Tel HaShomer Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5544-0420","authenticated-orcid":false,"given":"Stephen Z","family":"Levine","sequence":"additional","affiliation":[{"name":"Department of Community Mental Health Faculty of Social Welfare and Health Sciences University of Haifa  Haifa Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Meir","family":"Bialer","sequence":"additional","affiliation":[{"name":"School of Pharmacy Institute for Drug Research Faculty of Medicine The Hebrew University of Jerusalem  Jerusalem Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tawfeeq","family":"Shekh\u2010Ahmad","sequence":"additional","affiliation":[{"name":"School of Pharmacy Institute for Drug Research Faculty of Medicine The Hebrew University of Jerusalem  Jerusalem Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Valentin","family":"Matei","sequence":"additional","affiliation":[{"name":"Spitalul Clinic de Psihiatrie Obregia  Bucarest Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexandru","family":"Tiugan","sequence":"additional","affiliation":[{"name":"Sp. 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