{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,10]],"date-time":"2026-04-10T20:08:15Z","timestamp":1775851695743,"version":"3.50.1"},"reference-count":35,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2024,4,12]],"date-time":"2024-04-12T00:00:00Z","timestamp":1712880000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100006483","name":"AbbVie","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100006483","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Bipolar Disorders"],"published-print":{"date-parts":[[2024,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Introduction<\/jats:title><jats:p>Cariprazine treats acute manic and depressive episodes in bipolar I disorder (BP\u2010I), but its efficacy in preventing relapse of mood episode remains unknown.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>In this phase 3b, double\u2010blind, placebo\u2010controlled study, patients with BP\u2010I with acute manic or depressive episodes (each with\/without mixed features), were treated with cariprazine 3.0\u2009mg\/day during a 16\u2010week open\u2010label treatment period; those who achieved stable remission within 8\u2009weeks and remained stable for at least another 8\u2009weeks were randomized to receive cariprazine 1.5 or 3.0\u2009mg per day or placebo in the double\u2010blind treatment period for up to 39\u2009weeks. The primary efficacy endpoint was time to relapse of any mood episode. Adverse events (AEs) were assessed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Patients (440\/896) enrolled in the open\u2010label treatment period achieved stability criteria and were randomized to receive cariprazine 3.0\u2009mg\/day (<jats:italic>n<\/jats:italic>\u2009=\u2009148), cariprazine 1.5\u2009mg\/day (<jats:italic>n<\/jats:italic>\u2009=\u2009147), or placebo (<jats:italic>n<\/jats:italic>\u2009=\u2009145) in the double\u2010blind treatment period. Relapse rates were 17.9%, 16.8%, and 19.7% in the cariprazine 3.0\u2009mg\/day, cariprazine 1.5\u2009mg\/day, and placebo groups, respectively. Neither dose of cariprazine was more effective than placebo on the primary outcome (3.0\u2009mg\/day: HR\u2009=\u20090.89, [95% CI: 0.5, 1.5]; 1.5\u2009mg\/day: HR\u2009=\u20090.83, 95% CI [0.5, 1.4]). The most frequently reported AEs (\u22655%) were akathisia, headache, insomnia, and nausea in the open\u2010label treatment period and increased weight and insomnia in the double\u2010blind treatment period. In the open\u2010label and double\u2010blind treatment periods, 7.5% and 1.6% of patients experienced an AE leading to discontinuation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Cariprazine was not superior to placebo in the prevention of relapses in this study. Relapse rates were unusually low in the placebo group. Cariprazine was well\u2010tolerated.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bdi.13421","type":"journal-article","created":{"date-parts":[[2024,4,13]],"date-time":"2024-04-13T02:40:21Z","timestamp":1712976021000},"page":"442-453","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Cariprazine as a maintenance therapy in the prevention of mood episodes in adults with bipolar I disorder"],"prefix":"10.1111","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4733-2523","authenticated-orcid":false,"given":"Roger S.","family":"McIntyre","sequence":"first","affiliation":[{"name":"University of Toronto  Toronto Ontario Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bethany","family":"Davis","sequence":"additional","affiliation":[{"name":"Accelerated Enrollment Solutions  Atlanta Georgia USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jane","family":"Rodgers","sequence":"additional","affiliation":[{"name":"AbbVie Inc.  North Chicago Illinois USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ludmyla","family":"Rekeda","sequence":"additional","affiliation":[{"name":"AbbVie Inc.  Florham Park New Jersey USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Julie","family":"Adams","sequence":"additional","affiliation":[{"name":"AbbVie Inc.  North Chicago Illinois USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7405-0954","authenticated-orcid":false,"given":"Lakshmi N.","family":"Yatham","sequence":"additional","affiliation":[{"name":"Department of Psychiatry Institute of Mental Health, University of British Columbia  Vancouver Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2024,4,12]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1023\/a:1004632206684"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1177\/2045125318769235"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1001\/archpsyc.59.6.530"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1001\/archpsyc.60.3.261"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.1986.03370220100035"},{"issue":"5","key":"e_1_2_9_7_1","first-page":"5","article-title":"The impact of bipolar depression","volume":"66","author":"Post RM","year":"2005","journal-title":"J Clin Psychiatry"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.4088\/jcp.v64n0610"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1520-6394(1997)5:2<73::AID-DA3>3.0.CO;2-6"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.4088\/jcp.v63n0910"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.4088\/jcp.v64n0412"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.4088\/jcp.v65n1109"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0165-1781(97)00109-1"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.4088\/jcp.v64n0503"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1034\/j.1600-0447.2001.00059.x"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0140-6736(20)31544-0"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1111\/acps.12003"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40345-022-00264-6"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/0165-0327(94)00091-m"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-244x-8-65"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1176\/appi.ajp.2017.16040419"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.4088\/jcp.16m11201"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopsych.2010.01.015"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1001\/archpsyc.57.5.481"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.4088\/jcp.11m06878"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1001\/archpsyc.60.4.392"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1517\/17425255.2013.759211"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.4088\/jcp.14m09081"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1111\/bdi.12238"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jad.2014.11.018"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1176\/appi.ajp.2015.15020164"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1176\/appi.ajp.2018.18070824"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1111\/bdi.12852"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.euroneuro.2017.06.013"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1176\/appi.ajp.2008.08020189"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1001\/archpsyc.1993.01820180046005"}],"container-title":["Bipolar Disorders"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/bdi.13421","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,8,26]],"date-time":"2024-08-26T03:45:08Z","timestamp":1724643908000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/bdi.13421"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,4,12]]},"references-count":35,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2024,8]]}},"alternative-id":["10.1111\/bdi.13421"],"URL":"https:\/\/doi.org\/10.1111\/bdi.13421","archive":["Portico"],"relation":{},"ISSN":["1398-5647","1399-5618"],"issn-type":[{"value":"1398-5647","type":"print"},{"value":"1399-5618","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,4,12]]},"assertion":[{"value":"2024-04-12","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}