{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,28]],"date-time":"2026-01-28T06:07:02Z","timestamp":1769580422515,"version":"3.49.0"},"reference-count":49,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2023,9,25]],"date-time":"2023-09-25T00:00:00Z","timestamp":1695600000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100004312","name":"Eli Lilly and Company","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004312","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000025","name":"National Institute of Mental Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000025","id-type":"DOI","asserted-by":"publisher"}]},{"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":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Bipolar Disorders"],"published-print":{"date-parts":[[2024,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Few studies have systematically examined the safety and effectiveness of antidepressant versus mood stabilizer monotherapy of bipolar II depression. To date, there are no aggregated or mega\u2010analyses of prospective trials of individual participant\u2010level data (IPD) to inform future treatment guidelines on the relative safety and effectiveness of antidepressant or lithium monotherapy.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Data from a series of four independent, similarly designed trials of antidepressant or lithium monotherapy (where longitudinal IPD were available) (<jats:italic>n<\/jats:italic>\u2009=\u2009393) were aggregated into an IPD dataset (i.e., mega\u2010analysis). Hierarchical log\u2010linear growth models were used to analyze primary outcome of change over time in Hamilton Rating Scale for Depression (HRSD) scores; while secondary outcomes examined Clinical Global Impressions severity (CGI\/S) and change (CGI\/C) scores, and change over time in Young Mania Rating (YMR) scores.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Relative to lithium monotherapy, antidepressant monotherapy demonstrated significantly greater symptom reduction on HRSD scores across time (<jats:italic>b<\/jats:italic>\u2009=\u2009\u22122.33, <jats:italic>t<\/jats:italic>\u2009=\u2009\u22126.68, <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.0001), significantly greater symptom reduction on the CGI\/S across time (<jats:italic>b<\/jats:italic>\u2009=\u2009\u22120.414, <jats:italic>t<\/jats:italic>\u2009=\u2009\u22126.32, <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001), and a significant improvement in CGI\/C across time (<jats:italic>b<\/jats:italic>\u2009=\u2009\u22120.47, <jats:italic>t<\/jats:italic>\u2009=\u2009\u22127.43, <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.0001). No differences were observed in change over time for YMR scores between antidepressant and lithium monotherapy (<jats:italic>b<\/jats:italic>\u2009=\u20090.06, <jats:italic>t<\/jats:italic>\u2009=\u20090.49, <jats:italic>p<\/jats:italic>\u2009=\u20090.62).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Findings from this IPD mega\u2010analysis of bipolar II depression trials suggest a divergence from current evidence\u2010based guidelines recommending combined mood stabilizer plus antidepressant therapy. The current mega\u2010analysis suggests that antidepressant monotherapy may provide superior short\u2010term effectiveness without clinically meaningful increase in treatment\u2010emergent hypomanic symptoms compared to lithium monotherapy.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bdi.13378","type":"journal-article","created":{"date-parts":[[2023,9,26]],"date-time":"2023-09-26T02:54:36Z","timestamp":1695696876000},"page":"255-264","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Multi\u2010trial, aggregated, <scp>individual participant<\/scp> data mega\u2010analysis of short\u2010term antidepressant versus mood stabilizer monotherapy of bipolar type <scp>II<\/scp> major depressive episode"],"prefix":"10.1111","volume":"26","author":[{"given":"Jay D.","family":"Amsterdam","sequence":"first","affiliation":[{"name":"Depression Research Unit, Department of Psychiatry Perelman School of Medicine at the University of 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