{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,9]],"date-time":"2026-05-09T04:11:35Z","timestamp":1778299895274,"version":"3.51.4"},"reference-count":17,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2019,4,26]],"date-time":"2019-04-26T00:00:00Z","timestamp":1556236800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"name":"Health and Labor Sciences Research Grants","award":["H29-Seishin-Ippan-001"],"award-info":[{"award-number":["H29-Seishin-Ippan-001"]}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Neuropsychopharm Rep"],"published-print":{"date-parts":[[2019,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Aim<\/jats:title><jats:p>Whether patients with adult bipolar disorder (<jats:styled-content style=\"fixed-case\">BD<\/jats:styled-content>) who have been clinically stabilized with lithium or lamotrigine should continue this medication is not established fully. This systematic review and meta\u2010analysis evaluated the efficacy and safety of lithium and lamotrigine for maintenance treatment in clinically stable patients with adult <jats:styled-content style=\"fixed-case\">BD<\/jats:styled-content>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>This meta\u2010analysis included only double\u2010blind, randomized, placebo\u2010controlled trials with an enrichment design that selected patients who responded acutely to lithium or lamotrigine. Reports prior to November 15, 2018, were retrieved from the PubMed\/Cochrane Library\/Embase. The primary outcome was the relapse rate due to any mood episode at the study endpoint. Other outcomes were relapse rates due to a manic\/hypomanic\/mixed episode or depression at the study endpoint, discontinuation rate, death, and death by suicide. Risk ratios (RRs) (95% confidence intervals) were calculated. When the random\u2010effects model showed significant differences between groups, the number\u2010needed\u2010to\u2010treat (<jats:styled-content style=\"fixed-case\">NNT<\/jats:styled-content>) was estimated.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The search retrieved two studies regarding lithium (N\u00a0=\u00a0218) and four evaluating lamotrigine (N\u00a0=\u00a0706). Both drugs were superior to placebo for reducing the relapse rate due to any mood episode [lithium: <jats:styled-content style=\"fixed-case\">RR<\/jats:styled-content>\u00a0=\u00a00.52 (0.41\u20100.66), <jats:italic>P\u00a0<\/jats:italic>&lt;<jats:italic>\u00a0<\/jats:italic>0.00001, <jats:italic>I<\/jats:italic><jats:sup>2<\/jats:sup>\u00a0=\u00a00%, <jats:styled-content style=\"fixed-case\">NNT<\/jats:styled-content> = 2.3 (1.6\u20104.2); lamotrigine: <jats:styled-content style=\"fixed-case\">RR<\/jats:styled-content> = 0.81 (0.70\u20100.93), <jats:italic>P\u00a0<\/jats:italic>=<jats:italic>\u00a0<\/jats:italic>0.004, <jats:italic>I<\/jats:italic><jats:sup>2<\/jats:sup>\u00a0=\u00a00%, <jats:styled-content style=\"fixed-case\">NNT<\/jats:styled-content>\u00a0=\u00a08.3 (5.0\u201025.0)] and all\u2010cause discontinuation. There were no significant differences in other outcomes between lithium or lamotrigine and the placebo groups.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Both drugs showed benefit for preventing relapse in clinically stable patients with adult <jats:styled-content style=\"fixed-case\">BD<\/jats:styled-content>. However, the number of studies and patients in this analysis was small.<\/jats:p><\/jats:sec>","DOI":"10.1002\/npr2.12056","type":"journal-article","created":{"date-parts":[[2019,4,27]],"date-time":"2019-04-27T04:28:15Z","timestamp":1556339295000},"page":"241-246","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Efficacy and safety of lithium and lamotrigine for the maintenance treatment of clinically stable patients with bipolar disorder: A systematic review and meta\u2010analysis of double\u2010blind, randomized, placebo\u2010controlled trials with an enrichment design"],"prefix":"10.1002","volume":"39","author":[{"given":"Kazuto","family":"Oya","sequence":"first","affiliation":[{"name":"Department of Psychiatry Fujita Health University School of Medicine Toyoake Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kenji","family":"Sakuma","sequence":"additional","affiliation":[{"name":"Department of Psychiatry Fujita Health University School of Medicine Toyoake Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Satoru","family":"Esumi","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Okayama University Hospital Okayama Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yasuhiko","family":"Hashimoto","sequence":"additional","affiliation":[{"name":"Faculty of Clinical Pharmacy Kobe Gakuin University Kobe Hyogo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masakazu","family":"Hatano","sequence":"additional","affiliation":[{"name":"Department of Psychiatry Fujita Health University School of Medicine Toyoake Japan"},{"name":"Department of Clinical Pharmacy Fujita Health University School of Medicine Toyoake Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuki","family":"Matsuda","sequence":"additional","affiliation":[{"name":"Department of Psychiatry Jikei University School of Medicine Minato Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuki","family":"Matsui","sequence":"additional","affiliation":[{"name":"Department of Psychiatry Jindai Hospital Toyota Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nobumi","family":"Miyake","sequence":"additional","affiliation":[{"name":"Department of Neuropsychiatry St. Marianna University School of Medicine Kawasaki Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ikuo","family":"Nomura","sequence":"additional","affiliation":[{"name":"Department of Psychiatry Fujita Health University School of Medicine Toyoake Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Makoto","family":"Okuya","sequence":"additional","affiliation":[{"name":"Department of Psychiatry Fujita Health University School of Medicine Toyoake Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nakao","family":"Iwata","sequence":"additional","affiliation":[{"name":"Department of Psychiatry Fujita Health University School of Medicine Toyoake Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masaki","family":"Kato","sequence":"additional","affiliation":[{"name":"Department of Neuropsychiatry Kansai Medical University Moriguchi Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ryota","family":"Hashimoto","sequence":"additional","affiliation":[{"name":"Department of Pathology of Mental Diseases National Institute of Mental Health National Center of Neurology and Psychiatry Kodaira Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kazuo","family":"Mishima","sequence":"additional","affiliation":[{"name":"Department of Neuropsychiatry Akita University Graduate School of Medicine Akita Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Norio","family":"Watanabe","sequence":"additional","affiliation":[{"name":"Department of Clinical Epidemiology\/Health Promotion and Human Behavior Graduate School of Medicine\/School of Public Health Kyoto University Kyoto Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9237-2236","authenticated-orcid":false,"given":"Taro","family":"Kishi","sequence":"additional","affiliation":[{"name":"Department of Psychiatry Fujita Health University School of Medicine Toyoake Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2019,4,26]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"crossref","unstructured":"DSM\u20135.Diagnostic and Statistical Manual of Mental Disorders. 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