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A machine learning workflow was developed to predict remission after 8\u2009weeks of pharmacotherapy (total score of \u22648 on the Montgomery \u00c5sberg Depression Rating Scale [MADRS]).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Supervised machine learning models were trained on data from BP\u2010D patients treated with olanzapine (<jats:italic>N<\/jats:italic>\u2009=\u2009168) and were externally validated on patients treated with olanzapine\/fluoxetine combination (OFC; <jats:italic>N<\/jats:italic>\u2009=\u2009131) and lamotrigine (LTG; <jats:italic>N<\/jats:italic>\u2009=\u2009126). Top predictors were used to develop a prognosis rule informing how many symptoms should change and by how much within 4\u2009weeks to increase the odds of achieving remission.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>An AUC of 0.76 (NIR:0.59; <jats:italic>p<\/jats:italic>\u2009=\u20090.17) was established to predict remission in olanzapine\u2010treated subjects. These trained models achieved AUCs of 0.70 with OFC (NIR:0.52; <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.03) and 0.73 with LTG (NIR:0.52; <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.003), demonstrating external replication of prediction performance. Week\u20104 changes in four MADRS symptoms (reported sadness, reduced sleep, reduced appetite, and concentration difficulties) were top predictors of remission. Across all pharmacotherapies, three or more of these symptoms needed to improve by \u22652 points at Week\u20104 to have a 65% chance of achieving remission at 8\u2009weeks (OR: 3.74, 95% CI: 2.45\u20135.76; <jats:italic>p<\/jats:italic>\u2009&lt;\u20099.3E\u201011).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Machine learning strategies achieved cross\u2010trial and cross\u2010drug replication in predicting remission after 8\u2009weeks of pharmacotherapy for BP\u2010D. Interpretable prognoses rules required only a limited number of depressive symptoms, providing a promising foundation for developing simple quantitative decision aids that may, in the future, serve as companions to clinical judgment at the point of care.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bdi.13506","type":"journal-article","created":{"date-parts":[[2024,10,4]],"date-time":"2024-10-04T02:35:01Z","timestamp":1728009301000},"page":"36-46","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Predicting remission after acute phase pharmacotherapy in patients with bipolar I depression: A machine learning approach with cross\u2010trial and cross\u2010drug replication"],"prefix":"10.1111","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2232-0788","authenticated-orcid":false,"given":"Jean","family":"Marrero\u2010Polanco","sequence":"first","affiliation":[{"name":"Department of Molecular Pharmacology and Experimental Therapeutics Mayo Clinic  Rochester Minnesota USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jeremiah B.","family":"Joyce","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Psychology Mayo Clinic  Rochester Minnesota USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Caroline W.","family":"Grant","sequence":"additional","affiliation":[{"name":"Department of Molecular Pharmacology and Experimental Therapeutics Mayo Clinic  Rochester Minnesota USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paul E.","family":"Croarkin","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Psychology Mayo Clinic  Rochester Minnesota USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9764-1768","authenticated-orcid":false,"given":"Arjun P.","family":"Athreya","sequence":"additional","affiliation":[{"name":"Department of Molecular Pharmacology and Experimental Therapeutics Mayo Clinic  Rochester Minnesota USA"},{"name":"Department of Psychiatry and Psychology Mayo Clinic  Rochester Minnesota USA"},{"name":"Center for Individualized Medicine Mayo Clinic  Rochester Minnesota USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5674-3079","authenticated-orcid":false,"given":"William V.","family":"Bobo","sequence":"additional","affiliation":[{"name":"Department of Behavioral Science and Social Medicine Florida State University College of Medicine  Tallahassee Florida USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2024,10,3]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1136\/gpsych-2022-100760"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40265-023-01872-x"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40345-019-0160-1"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jad.2015.05.016"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mayocp.2017.06.022"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2215-0366(23)00199-2"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.4088\/JCP.13091ip1"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1080\/17512433.2022.2112949"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neubiorev.2022.104552"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.psychres.2021.114326"},{"issue":"3","key":"e_1_2_10_12_1","first-page":"7","article-title":"Defining the clinical course of bipolar disorder: response, remission, relapse, recurrence, and roughening","volume":"40","author":"Hirschfeld RM","year":"2007","journal-title":"Psychopharmacol Bull"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.2217\/pgs-2019-0119"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1192\/bjp.bp.112.108357"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1017\/S1461145708009735"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1097\/jcp.0000000000000099"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jad.2020.11.106"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1145\/2939672.2939785"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.18637\/jss.v033.i01"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.18637\/jss.v106.i01"},{"key":"e_1_2_10_21_1","unstructured":"RStudio: Integrated Development for R. 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