{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T07:16:25Z","timestamp":1791357385611,"version":"4.3.1"},"reference-count":29,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2014,7,24]],"date-time":"2014-07-24T00:00:00Z","timestamp":1406160000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/3.0\/"}],"funder":[{"DOI":"10.13039\/100005632","name":"Forest Laboratories","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100005632","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003358","name":"Gedeon Richter","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003358","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Bipolar Disorders"],"published-print":{"date-parts":[[2015,2]]},"abstract":"<jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>\n                      Cariprazine, an orally active and potent dopamine D\n                      <jats:sub>3<\/jats:sub>\n                      and D\n                      <jats:sub>2<\/jats:sub>\n                      receptor partial agonist with preferential binding to D\n                      <jats:sub>3<\/jats:sub>\n                      receptors, is being developed for the treatment of schizophrenia and bipolar mania. This Phase\n                      <jats:styled-content style=\"fixed-case\">II<\/jats:styled-content>\n                      trial evaluated the efficacy, safety, and tolerability of cariprazine versus placebo in the treatment of acute manic or mixed episodes associated with bipolar I disorder.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      This was a multinational, randomized, double\u2010blind, placebo\u2010controlled, flexible\u2010dose study of cariprazine 3\u201312\u00a0mg\/day in patients with acute manic or mixed episodes associated with bipolar I disorder. Following washout, patients received three weeks of double\u2010blind treatment. The primary and secondary efficacy parameters were change from baseline to Week 3 in Young Mania Rating Scale (\n                      <jats:styled-content style=\"fixed-case\">YMRS<\/jats:styled-content>\n                      ) and Clinical Global Impressions\u2013Severity (\n                      <jats:styled-content style=\"fixed-case\">CGI<\/jats:styled-content>\n                      \u2010S) scores, respectively.\n                      <jats:italic>Post\u2010hoc<\/jats:italic>\n                      analysis evaluated changes on\n                      <jats:styled-content style=\"fixed-case\">YMRS<\/jats:styled-content>\n                      single items.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      In each group, 118 patients received double\u2010blind treatment; 61.9% of placebo and 63.6% of cariprazine patients completed the study. The overall mean daily dose of cariprazine was 8.8\u00a0mg\/day. At Week 3, cariprazine significantly reduced\n                      <jats:styled-content style=\"fixed-case\">YMRS<\/jats:styled-content>\n                      and\n                      <jats:styled-content style=\"fixed-case\">CGI<\/jats:styled-content>\n                      \u2010S scores versus placebo, with least square mean differences of \u22126.1 (p\u00a0&lt;\u00a00.001) and \u22120.6 (p\u00a0&lt;\u00a00.001), respectively. On each\n                      <jats:styled-content style=\"fixed-case\">YMRS<\/jats:styled-content>\n                      item, change from baseline to Week 3 was significantly greater for cariprazine versus placebo (all, p\u00a0&lt;\u00a00.05). A significantly greater percentage of cariprazine patients than placebo patients met\n                      <jats:styled-content style=\"fixed-case\">YMRS<\/jats:styled-content>\n                      response (48% versus 25%; p\u00a0&lt;\u00a00.001) and remission (42% versus 23%; p\u00a0=\u00a00.002) criteria at Week 3. Adverse events (\n                      <jats:styled-content style=\"fixed-case\">AE<\/jats:styled-content>\n                      s) led to discontinuation of 12 (10%) placebo and 17 (14%) cariprazine patients. The most common\n                      <jats:styled-content style=\"fixed-case\">AE<\/jats:styled-content>\n                      s (&gt; 10% for cariprazine) were extrapyramidal disorder, headache, akathisia, constipation, nausea, and dyspepsia. Changes in metabolic parameters were similar between groups, with the exception of fasting glucose; increases in glucose were significantly greater for cariprazine versus placebo (p\u00a0&lt;\u00a00.05). Based on Barnes Akathisia Rating Scale and Simpson\u2013Angus Scale scores, more cariprazine than placebo patients experienced treatment\u2010emergent akathisia (cariprazine: 22%; placebo: 6%) or extrapyramidal symptoms (parkinsonism) (cariprazine: 16%; placebo: 1%).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Cariprazine demonstrated superior efficacy versus placebo and was generally well tolerated in patients experiencing acute manic or mixed episodes associated with bipolar I disorder.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/bdi.12238","type":"journal-article","created":{"date-parts":[[2014,7,24]],"date-time":"2014-07-24T01:27:38Z","timestamp":1406165258000},"page":"63-75","source":"Crossref","is-referenced-by-count":109,"title":["The efficacy and tolerability of cariprazine in acute mania associated with bipolar I disorder: a phase II trial"],"prefix":"10.1111","volume":"17","author":[{"given":"Suresh","family":"Durgam","sequence":"first","affiliation":[{"name":"Clinical Development Forest Research Institute Jersey City NJ"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anju","family":"Starace","sequence":"additional","affiliation":[{"name":"Clinical Development Forest Research Institute Jersey City NJ"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dayong","family":"Li","sequence":"additional","affiliation":[{"name":"Biostatistics Forest Research Institute Jersey City NJ"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raffaele","family":"Migliore","sequence":"additional","affiliation":[{"name":"Clinical Development Forest Research Institute Jersey City NJ"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adam","family":"Ruth","sequence":"additional","affiliation":[{"name":"Prescott Medical Communications Group Chicago IL USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gy\u00f6rgy","family":"N\u00e9meth","sequence":"additional","affiliation":[{"name":"Medical Division Gedeon Richter Plc Budapest Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Istv\u00e1n","family":"Laszlovszky","sequence":"additional","affiliation":[{"name":"Medical Division Gedeon Richter Plc Budapest Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2014,7,24]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.4088\/JCP.v63n0910"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1192\/bjp.bp.105.020321"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1001\/archpsyc.65.4.386"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.109.160432"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0920-9964(12)70588-1"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1755-5949.2010.00222.x"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12272-010-1005-8"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-642-25758-2_7"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00210-008-0311-x"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00210-008-0308-5"},{"issue":"1","key":"e_1_2_7_12_1","first-page":"304","article-title":"Cariprazine (RGH\u2010188), a potential antipsychotic with dopamine D3\/D2 functional antagonist properties, attenuates manic\u2010like behaviors in animal models","volume":"10","author":"Adham N","year":"2009","journal-title":"World J Biol Psychiatry"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuint.2011.07.002"},{"issue":"1","key":"e_1_2_7_14_1","first-page":"S84","article-title":"Cariprazine exhibits dopamine D3 receptor\u2010dependent antidepressant\u2010like activity in the chronic unpredictable stress model of anhedonia","volume":"38","author":"Duman RS","year":"2012","journal-title":"Neuropsychopharmacology"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00213-012-2896-5"},{"key":"e_1_2_7_16_1","first-page":"218","volume-title":"The Clinician Global Severity and Impression Scales. 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