{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T17:28:13Z","timestamp":1791048493580,"version":"4.1.0"},"reference-count":34,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,3,4]],"date-time":"2026-03-04T00:00:00Z","timestamp":1772582400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"},{"start":{"date-parts":[[2026,4,10]],"date-time":"2026-04-10T00:00:00Z","timestamp":1775779200000},"content-version":"vor","delay-in-days":37,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Med Inform Decis Mak"],"DOI":"10.1186\/s12911-026-03403-6","type":"journal-article","created":{"date-parts":[[2026,3,4]],"date-time":"2026-03-04T11:47:10Z","timestamp":1772624830000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Explainable counterfactual reasoning in depression medication selection at multi-levels (personalized and population)"],"prefix":"10.1186","volume":"26","author":[{"given":"Xinyu","family":"Qin","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark H.","family":"Chignell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandria","family":"Greifenberger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sachinthya","family":"Lokuge","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elssa","family":"Toumeh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tia","family":"Sternat","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Katzman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lu","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,3,4]]},"reference":[{"issue":"1","key":"3403_CR1","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1002\/gps.4286","volume":"31","author":"M Sinyor","year":"2016","unstructured":"Sinyor M, Tan LPL, Schaffer A, Gallagher D, Shulman K. Suicide in the oldest old: an observational study and cluster analysis. Int J Geriatric Psychiatry. 2016;31(1):33\u201340.","journal-title":"Int J Geriatric Psychiatry"},{"issue":"3","key":"3403_CR2","doi-asserted-by":"publisher","first-page":"133","DOI":"10.1159\/000506879","volume":"89","author":"D Carrozzino","year":"2020","unstructured":"Carrozzino D, Patierno C, Fava GA, Guidi J. The Hamilton rating scales for depression: a critical review of clinimetric properties of different versions. Psychotherapy Psychosomatics. 2020;89(3):133\u201350.","journal-title":"Psychotherapy Psychosomatics"},{"issue":"4","key":"3403_CR3","doi-asserted-by":"publisher","first-page":"235","DOI":"10.1139\/jpn.0241","volume":"27","author":"R McIntyre","year":"2002","unstructured":"McIntyre R, Kennedy S, Bagby RM, Bakish D. Assessing full remission. J Psychiatry Neurosci. 2002;27(4):235\u201339.","journal-title":"J Psychiatry Neurosci"},{"issue":"1","key":"3403_CR4","doi-asserted-by":"publisher","first-page":"56","DOI":"10.1136\/jnnp.23.1.56","volume":"23","author":"M Hamilton","year":"1960","unstructured":"Hamilton M. A rating scale for depression. J Neurol, Neurosurg Psychiatry. 1960;23(1):56.","journal-title":"J Neurol, Neurosurg Psychiatry"},{"issue":"4","key":"3403_CR5","doi-asserted-by":"publisher","first-page":"278","DOI":"10.1111\/j.2044-8260.1967.tb00530.x","volume":"6","author":"M Hamilton","year":"1967","unstructured":"Hamilton M. Development of a rating scale for primary depressive illness. Br J Soc Clin Psychol. 1967;6(4):278\u201396.","journal-title":"Br J Soc Clin Psychol"},{"key":"3403_CR6","doi-asserted-by":"crossref","unstructured":"Nixon N, Guo B, Garland A, Kaylor-Hughes C, Nixon E, Morriss R. The bi-factor structure of the 17-item Hamilton depression rating scale in persistent major depression; dimensional measurement of outcome. PLoS ONE. 2020;15(10):e0241370.","DOI":"10.1371\/journal.pone.0241370"},{"issue":"6","key":"3403_CR7","doi-asserted-by":"publisher","first-page":"826","DOI":"10.4088\/JCP.v68n0602","volume":"68","author":"GI Papakostas","year":"2007","unstructured":"Papakostas GI, Shelton RC, Smith J, Fava M. Augmentation of antidepressants with atypical antipsychotic medications for treatment-resistant major depressive disorder: a meta-analysis. J Clin Psychiatry. 2007;68(6):826\u201331.","journal-title":"J Clin Psychiatry"},{"issue":"9","key":"3403_CR8","doi-asserted-by":"publisher","first-page":"540","DOI":"10.1177\/0706743716659417","volume":"61","author":"SH Kennedy","year":"2016","unstructured":"Kennedy SH, Lam RW, McIntyre RS, Tourjman SV, Bhat V, Blier P, et al. Canadian network for mood and anxiety treatments (CANMAT) 2016 clinical guidelines for the management of adults with major depressive disorder: section 3. Pharmacological Treatments Can J Psychiatry. 2016;61(9):540\u201360.","journal-title":"Pharmacological Treatments Can J Psychiatry"},{"issue":"3","key":"3403_CR9","doi-asserted-by":"publisher","first-page":"234","DOI":"10.1192\/bjp.178.3.234","volume":"178","author":"ME Thase","year":"2001","unstructured":"Thase ME, Entsuah AR, Rudolph RL. Remission rates during treatment with venlafaxine or selective serotonin reuptake inhibitors. Br J Psychiatry. 2001;178(3):234\u201341.","journal-title":"Br J Psychiatry"},{"key":"3403_CR10","doi-asserted-by":"crossref","unstructured":"Shelton RC. Serotonin and norepinephrine reuptake inhibitors. Antidepressants: from biogenic amines to New mechanisms of action. 2019;145\u201380.","DOI":"10.1007\/164_2018_164"},{"key":"3403_CR11","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/1471-244X-12-143","volume":"12","author":"M Garcia-Toro","year":"2012","unstructured":"Garcia-Toro M, Medina E, Galan JL, Gonzalez MA, Maurino J. Treatment patterns in major depressive disorder after an inadequate response to first-line antidepressant treatment. BMC Psychiatry. 2012;12:1\u20136.","journal-title":"BMC Psychiatry"},{"issue":"11","key":"3403_CR12","doi-asserted-by":"publisher","first-page":"1544","DOI":"10.1001\/jamainternmed.2018.3763","volume":"178","author":"MA Gianfrancesco","year":"2018","unstructured":"Gianfrancesco MA, Tamang S, Yazdany J, Schmajuk G. Potential biases in machine learning algorithms using electronic health record data. JAMA Intern Med. 2018;178(11):1544\u201347.","journal-title":"JAMA Intern Med"},{"key":"3403_CR13","doi-asserted-by":"publisher","first-page":"82","DOI":"10.1016\/j.inffus.2019.12.012","volume":"58","author":"AB Arrieta","year":"2020","unstructured":"Arrieta AB, D\u00edaz-Rodr\u00edguez N, Del Ser J, Bennetot A, Tabik S, Barbado A, et al. Explainable artificial intelligence (XAI): concepts, taxonomies, opportunities and challenges toward responsible AI. Inf Fusion. 2020;58:82\u2013115.","journal-title":"Inf Fusion"},{"key":"3403_CR14","unstructured":"Molnar C. Interpretable machine learning: a Guide for making black box models explainable. 2022. Online book, chapter on counterfactual explanations. 2nd ed. Self-published. Available from: https:\/\/christophm.github.io\/interpretable-ml-book\/."},{"key":"3403_CR15","doi-asserted-by":"publisher","unstructured":"Holzinger A, Langs G, Denk H, Zatloukal K, M\u00fcller H. Causability and explainability of artificial intelligence in medicine. Wiley Interdiscip Rev Data Min Knowl Discov. 2019;9(4):e1312. https:\/\/doi.org\/10.1002\/widm.1312.","DOI":"10.1002\/widm.1312"},{"key":"3403_CR16","doi-asserted-by":"publisher","DOI":"10.4324\/9781315806419","volume-title":"What might have been: the social psychology of counterfactual thinking","author":"NJ Roese","year":"2014","unstructured":"Roese NJ, Olson JM. What might have been: the social psychology of counterfactual thinking. Psychology Press; 2014."},{"key":"3403_CR17","unstructured":"Hern\u00e1n MA, Robins JM. Causal inference. CRC Boca Raton, FL."},{"key":"3403_CR18","unstructured":"Kim B, Khanna R, Koyejo OO. Examples are not enough, learn to criticize! criticism for interpretability. Adv Neural Inf Process Syst. 2016;29."},{"key":"3403_CR19","first-page":"841","volume":"31","author":"S Wachter","year":"2017","unstructured":"Wachter S, Mittelstadt B, Russell C. Counterfactual explanations without opening the black box: automated decisions and the GDPR. Harv JL Tech. 2017;31:841.","journal-title":"Harv JL Tech"},{"key":"3403_CR20","doi-asserted-by":"crossref","unstructured":"Poyiadzi R, Sokol K, Santos-Rodriguez R, De Bie T, Flach P. FACE: feasible and actionable counterfactual explanations. Proceedings of the AAAI\/ACM Conference on AI, Ethics, and Society. 2020. p. 344\u201350.","DOI":"10.1145\/3375627.3375850"},{"key":"3403_CR21","doi-asserted-by":"crossref","unstructured":"Laugel T, Lesot MJ, Marsala C, Renard X, Detyniecki M. Inverse classification for comparison-based interpretability in machine learning. arXiv preprint arXiv:171208443. 2017.","DOI":"10.1007\/978-3-319-91473-2_9"},{"key":"3403_CR22","doi-asserted-by":"crossref","unstructured":"Dandl S, Molnar C, Binder M, Bischl B. Multi-objective counterfactual explanations. International Conference on Parallel Problem Solving from Nature. Springer; 2020. p. 448\u201369.","DOI":"10.1007\/978-3-030-58112-1_31"},{"key":"3403_CR23","doi-asserted-by":"crossref","unstructured":"Mothilal RK, Sharma A, Tan C. Explaining machine learning classifiers through diverse counterfactual explanations. Proceedings of the 2020 conference on fairness, accountability, and transparency. 2020. p. 607\u201317.","DOI":"10.1145\/3351095.3372850"},{"key":"3403_CR24","unstructured":"Ribera M, Lapedriza A. Can we do better explanations? A proposal of user-centered explainable AI. CEUR Workshop Proceedings. 2019."},{"key":"3403_CR25","doi-asserted-by":"crossref","unstructured":"Ribeiro MT, Singh S, Guestrin C. \u201cwhy should i trust you?\u201d Explaining the predictions of any classifier. Proceedings of the 22nd ACM SIGKDD international conference on knowledge discovery and data mining. 2016. p. 1135\u201344.","DOI":"10.1145\/2939672.2939778"},{"key":"3403_CR26","unstructured":"Lundberg SM, Lee SI. A unified approach to interpreting model predictions. Advances in neural information processing systems. 2017;30."},{"key":"3403_CR27","unstructured":"Craven M, Shavlik J. Extracting tree-structured representations of trained networks. Adv Neural Inf Process Syst. 1995;8."},{"key":"3403_CR28","doi-asserted-by":"crossref","unstructured":"Kommiya Mothilal R, Mahajan D, Tan C, Sharma A. Towards unifying feature attribution and counterfactual explanations: different means to the same end. Proceedings of the 2021 AAAI\/ACM Conference on AI, Ethics, and Society. 2021. p. 652\u201363.","DOI":"10.1145\/3461702.3462597"},{"key":"3403_CR29","doi-asserted-by":"crossref","unstructured":"Ali S, Akhlaq F, Imran AS, Kastrati Z, Daudpota SM, Moosa M. The enlightening role of explainable artificial intelligence in medical & healthcare domains: a systematic literature review. Comput Biol Med. 2023;107555.","DOI":"10.1016\/j.compbiomed.2023.107555"},{"issue":"2\u20133","key":"3403_CR30","doi-asserted-by":"publisher","first-page":"123","DOI":"10.1561\/2200000044","volume":"5","author":"A Kulesza","year":"2012","unstructured":"Kulesza A, Taskar B, et al. Determinantal point processes for machine learning. Found Trends\u00ae Mach Learn. 2012;5(2\u20133):123\u2013286.","journal-title":"Found Trends\u00ae Mach Learn"},{"issue":"10","key":"3403_CR31","doi-asserted-by":"publisher","first-page":"1702","DOI":"10.1176\/appi.ajp.159.10.1702","volume":"159","author":"ML Gilmor","year":"2002","unstructured":"Gilmor ML, Owens MJ, Nemeroff CB. Inhibition of norepinephrine uptake in patients with major depression treated with paroxetine. Am J Psychiatry. 2002;159(10):1702\u201310.","journal-title":"Am J Psychiatry"},{"issue":"13","key":"3403_CR32","doi-asserted-by":"publisher","first-page":"3201","DOI":"10.1038\/npp.2008.47","volume":"33","author":"MJ Owens","year":"2008","unstructured":"Owens MJ, Morgan WN, Plott SJ, Nemeroff CB. Estimates of serotonin and norepinephrine transporter inhibition in depressed patients treated with paroxetine or venlafaxine. Neuropsychopharmacology. 2008;33(13):3201\u201312.","journal-title":"Neuropsychopharmacology"},{"issue":"1","key":"3403_CR33","first-page":"321","volume":"16","author":"VC Nitesh","year":"2002","unstructured":"Nitesh VC. SMOTE: synthetic minority over-sampling technique. J Artif Intell Res. 2002;16(1):321.","journal-title":"J Artif Intell Res"},{"key":"3403_CR34","doi-asserted-by":"publisher","first-page":"273","DOI":"10.1016\/j.jad.2022.01.105","volume":"302","author":"J Rabinowitz","year":"2022","unstructured":"Rabinowitz J, Williams JB, Anderson A, Fu DJ, Hefting N, Kadriu B, et al. Consistency checks to improve measurement with the Hamilton rating scale for depression (HAM-D). J Affect Disord. 2022;302:273\u201379.","journal-title":"J Affect Disord"}],"container-title":["BMC Medical Informatics and Decision Making"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12911-026-03403-6","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12911-026-03403-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12911-026-03403-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,10]],"date-time":"2026-04-10T10:43:45Z","timestamp":1775817825000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1186\/s12911-026-03403-6"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,4]]},"references-count":34,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["3403"],"URL":"https:\/\/doi.org\/10.1186\/s12911-026-03403-6","relation":{},"ISSN":["1472-6947"],"issn-type":[{"value":"1472-6947","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,4]]},"assertion":[{"value":"22 August 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"16 February 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"4 March 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The data used in this analysis was anonymized data from a database of multiple clinical trials provided by a pharmaceutical company. Data were collected across sites throughout the United States and Canada in alignment with FDA and Health Canada regulations, respectively, and were monitored by the pharmaceutical company. Each original clinical trial was approved by the relevant institutional review boards or ethics committees, as disclosed in the primary disclosures of the clinical trial data on\n                      \n                      and within the text of the corresponding published papers. According to the Tri-Council Policy Statement: Ethical Conduct for Research Involving Humans, under article 2.4, \u201cREB review is not required for research that relies exclusively on secondary use of anonymous information, or anonymous human biological materials, so long as the process of data linkage or recording or dissemination of results does not generate identifiable information.\u201d The research presented in this manuscript relies on secondary use of anonymous information, as the data was originally collected for a purpose other than the current research purpose. Informed consent was obtained from each patient or their legal representative and the investigator before any study-related procedures commenced, in accordance with the requirements of the FDA, Health Canada, and other applicable regulations. The study was conducted in compliance with the principles of the Declaration of Helsinki. Clinical trial number: not applicable.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"119"}}