{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T16:28:54Z","timestamp":1787502534402,"version":"build-2736575974"},"reference-count":43,"publisher":"PeerJ","license":[{"start":{"date-parts":[[2024,10,14]],"date-time":"2024-10-14T00:00:00Z","timestamp":1728864000000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"crossref","award":["211085\/Z\/18\/Z"],"award-info":[{"award-number":["211085\/Z\/18\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100014013","name":"UK Research and Innovation","doi-asserted-by":"crossref","award":["MR\/V023373\/1"],"award-info":[{"award-number":["MR\/V023373\/1"]}],"id":[{"id":"10.13039\/100014013","id-type":"DOI","asserted-by":"crossref"}]},{"name":"University College London Hospitals NIHR Biomedical Research Centre"},{"name":"NIHR North Thames Applied Research Collaboration"},{"name":"UK Research and Innovation Medical Research Council","award":["MR\/W014386\/1"],"award-info":[{"award-number":["MR\/W014386\/1"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Optimising maintenance drug treatment selection for people with bipolar disorder is challenging. There is some evidence that clinical and demographic features may predict response to lithium. However, attempts to personalise treatment choice have been limited.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Method<\/jats:title>\n                    <jats:p>We aimed to determine if machine learning methods applied to electronic health records could predict differential response to lithium or olanzapine. From electronic United Kingdom primary care records, we extracted a cohort of individuals prescribed either lithium (19,106 individuals) or olanzapine (12,412) monotherapy. Machine learning models were used to predict successful monotherapy maintenance treatment, using 113 clinical and demographic variables, 8,017 (41.96%) lithium responders and 3,831 (30.87%) olanzapine responders.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>We found a quantitative structural difference in that lithium maintenance responders were weakly predictable in our holdout sample, consisting of the 5% of patients with the most recent exposure. Age at first diagnosis, age at first treatment and the time between these were the most important variables in all models.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>\n                      Even if we failed to predict successful monotherapy olanzapine treatment, and so to definitively separate lithium\n                      <jats:italic>vs<\/jats:italic>\n                      . olanzapine responders, the characterization of the two groups may be used for classification by proxy. This can, in turn, be useful for establishing maintenance therapy. The further exploration of machine learning methods on EHR data for drug treatment selection could in the future play a role for clinical decision support. Signals in the data encourage further experiments with larger datasets to definitively separate lithium\n                      <jats:italic>vs<\/jats:italic>\n                      . olanzapine responders.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.7717\/peerj.17841","type":"journal-article","created":{"date-parts":[[2024,10,14]],"date-time":"2024-10-14T05:49:31Z","timestamp":1728884971000},"page":"e17841","source":"Crossref","is-referenced-by-count":6,"title":["Predicting maintenance lithium response for bipolar disorder from electronic health records\u2014a retrospective study"],"prefix":"10.7717","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2286-3862","authenticated-orcid":true,"given":"Joseph F.","family":"Hayes","sequence":"first","affiliation":[{"name":"Department of Psychiatry, University College London, University of London, London, United Kingdom"},{"name":"Camden and Islington NHS foundation Trust, London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7866-143X","authenticated-orcid":true,"given":"Fehmi","family":"Ben Abdesslem","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, University College London, University of London, London, United Kingdom"},{"name":"Research Institutes of Sweden (RISE), Stockholm, Sweden"},{"name":"Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra","family":"Eloranta","sequence":"additional","affiliation":[{"name":"Division of Clinical Epidemiology, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David P. J.","family":"Osborn","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, University College London, University of London, London, United Kingdom"},{"name":"Camden and Islington NHS foundation Trust, London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7949-1815","authenticated-orcid":true,"given":"Magnus","family":"Boman","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, University College London, University of London, London, United Kingdom"},{"name":"Division of Clinical Epidemiology, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden"},{"name":"MedTechLabs, BioClinicum, Karolinska University Hospital, Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"4443","published-online":{"date-parts":[[2024,10,14]]},"reference":[{"key":"10.7717\/peerj.17841\/ref-1","first-page":"420","article-title":"On the surprising behavior of distance metric in high-dimensional space","volume-title":"Database Theory \u2014 ICDT 2001, Number 1973 in Lecture Notes in Computer Science","author":"Aggarwal","year":"2001"},{"key":"10.7717\/peerj.17841\/ref-2","doi-asserted-by":"publisher","first-page":"S94","DOI":"10.1016\/j.euroneuro.2004.03.006","article-title":"The phenotypic spectra of bipolar disorder","volume":"14","author":"Alda","year":"2004","journal-title":"European Neuropsychopharmacology"},{"issue":"3","key":"10.7717\/peerj.17841\/ref-3","doi-asserted-by":"publisher","first-page":"319","DOI":"10.1002\/wps.20462","article-title":"Who are excellent lithium responders and why do they matter?","volume":"16","author":"Alda","year":"2017","journal-title":"World Psychiatry"},{"issue":"1","key":"10.7717\/peerj.17841\/ref-4","doi-asserted-by":"publisher","first-page":"79","DOI":"10.1177\/0269881119885918","article-title":"Effects of long-term antipsychotics treatment on body weight: a population-based cohort study","volume":"34","author":"Bazo-Alvarez","year":"2020","journal-title":"Journal of Psychopharmacology"},{"issue":"6","key":"10.7717\/peerj.17841\/ref-5","doi-asserted-by":"publisher","first-page":"e804","DOI":"10.7717\/peerj-cs.804","article-title":"Comparing supervised and unsupervised approaches to multimodal emotion recognition","volume":"7","author":"Carbonell","year":"2021","journal-title":"PeerJ Computer Science"},{"key":"10.7717\/peerj.17841\/ref-6","doi-asserted-by":"publisher","first-page":"219","DOI":"10.1192\/bjp.2022.28","article-title":"Using polygenic scores and clinical data for bipolar disorder patient stratification and lithium response prediction: machine learning approach","volume":"220","author":"Cearns","year":"2022","journal-title":"The British Journal of Psychiatry"},{"issue":"2","key":"10.7717\/peerj.17841\/ref-7","doi-asserted-by":"publisher","first-page":"154","DOI":"10.1002\/wps.20882","article-title":"The promise of machine learning in predicting treatment outcomes in psychiatry","volume":"20","author":"Chekroud","year":"2021","journal-title":"World Psychiatry"},{"issue":"4","key":"10.7717\/peerj.17841\/ref-8","doi-asserted-by":"publisher","first-page":"334","DOI":"10.1111\/bdi.12895","article-title":"Will machine learning applied to neuroimaging in bipolar disorder help the clinician? a critical review and methodological suggestions","volume":"22","author":"Claude","year":"2020","journal-title":"Bipolar Disorders"},{"issue":"1\u20133","key":"10.7717\/peerj.17841\/ref-9","doi-asserted-by":"publisher","first-page":"185","DOI":"10.1016\/j.jad.2007.03.003","article-title":"Prophylactic treatment response in bipolar disorder: results of a naturalistic observation study","volume":"104","author":"Garnham","year":"2007","journal-title":"Journal of Affective Disorders"},{"issue":"9712","key":"10.7717\/peerj.17841\/ref-10","doi-asserted-by":"publisher","first-page":"385","DOI":"10.1016\/S0140-6736(09)61828-6","article-title":"Lithium plus valproate combination therapy versus monotherapy for relapse prevention in bipolar i disorder (balance): a randomised open-label trial","volume":"375","author":"Geddes","year":"2009","journal-title":"The Lancet"},{"issue":"6","key":"10.7717\/peerj.17841\/ref-11","doi-asserted-by":"publisher","first-page":"495","DOI":"10.1177\/0269881116636545","article-title":"Evidence-based guidelines for treating bipolar disorder: revised third edition recommendations from the British Association for Psychopharmacology","volume":"30","author":"Goodwin","year":"2016","journal-title":"Journal of Psychopharmacology"},{"issue":"3","key":"10.7717\/peerj.17841\/ref-12","doi-asserted-by":"publisher","first-page":"544","DOI":"10.1038\/s41380-019-0634-7","article-title":"The genetics of bipolar disorder","volume":"25","author":"Gordovez","year":"2020","journal-title":"Molecular Psychiatry"},{"key":"10.7717\/peerj.17841\/ref-13","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s40345-020-00203-3","article-title":"Socio-demographic and clinical predictors of outcome to long-term treatment with lithium in bipolar disorders: a systematic review of the contemporary literature and recommendations from the isbd\/igsli task force on treatment with lithium","volume":"8","author":"Grillault Laroche","year":"2020","journal-title":"International Journal of Bipolar Disorders"},{"issue":"10","key":"10.7717\/peerj.17841\/ref-14","doi-asserted-by":"publisher","first-page":"942","DOI":"10.4088\/jcp.v63n1013","article-title":"Is response to prophylactic lithium a familial trait?","volume":"63","author":"Grof","year":"2002","journal-title":"Journal of Clinical Psychiatry"},{"issue":"12","key":"10.7717\/peerj.17841\/ref-15","doi-asserted-by":"publisher","first-page":"e82365","DOI":"10.1371\/journal.pone.0082365","article-title":"Recording of severe mental illness in united kingdom primary care, 2000\u20132010","volume":"8","author":"Hardoon","year":"2013","journal-title":"PLOS ONE"},{"issue":"6","key":"10.7717\/peerj.17841\/ref-16","doi-asserted-by":"publisher","first-page":"630","DOI":"10.1001\/jamapsychiatry.2016.0432","article-title":"Self-harm, unintentional injury, and suicide in bipolar disorder during maintenance mood stabilizer treatment: a UK population-based electronic health records study","volume":"73","author":"Hayes","year":"2016","journal-title":"JAMA Psychiatry"},{"issue":"3","key":"10.7717\/peerj.17841\/ref-17","doi-asserted-by":"publisher","first-page":"827","DOI":"10.1093\/ije\/dyv098","article-title":"Data resource profile: clinical practice research datalink (CPRD)","volume":"44","author":"Herrett","year":"2015","journal-title":"International Journal of Epidemiology"},{"issue":"6","key":"10.7717\/peerj.17841\/ref-18","doi-asserted-by":"publisher","first-page":"1233","DOI":"10.1002\/cpt.1982","article-title":"Mood-stabilizing antiepileptic treatment response in bipolar disorder: a genome-wide association study","volume":"108","author":"Ho","year":"2020","journal-title":"Clinical Pharmacology & Therapeutics"},{"issue":"2","key":"10.7717\/peerj.17841\/ref-19","doi-asserted-by":"publisher","first-page":"94","DOI":"10.1111\/acps.13062","article-title":"A systematic review and meta-analysis of clinical predictors of lithium response in bipolar disorder","volume":"140","author":"Hui","year":"2019","journal-title":"Acta Psychiatrica Scandinavica"},{"issue":"5","key":"10.7717\/peerj.17841\/ref-20","doi-asserted-by":"publisher","first-page":"517","DOI":"10.1016\/j.jclinepi.2007.10.011","article-title":"Maximization of the sum of sensitivity and specificity as a diagnostic cutpoint criterion","volume":"61","author":"Kaivanto","year":"2008","journal-title":"Journal of Clinical Epidemiology"},{"issue":"5","key":"10.7717\/peerj.17841\/ref-21","doi-asserted-by":"publisher","first-page":"428","DOI":"10.1111\/bdi.12752","article-title":"Predictive modeling for response to lithium and quetiapine in bipolar disorder","volume":"21","author":"Kim","year":"2019","journal-title":"Bipolar Disorders"},{"issue":"4","key":"10.7717\/peerj.17841\/ref-22","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1371\/journal.pmed.1003976","article-title":"Clustering of physical health multimorbidity in people with severe mental illness: An accumulated prevalence analysis of united kingdom primary care data","volume":"19","author":"Launders","year":"2022a","journal-title":"PLOS Medicine"},{"issue":"9","key":"10.7717\/peerj.17841\/ref-23","doi-asserted-by":"publisher","first-page":"725","DOI":"10.1016\/S2215-0366(22)00225-5","article-title":"The temporal relationship between severe mental illness diagnosis and chronic physical comorbidity: a UK primary care cohort study of disease burden over 10 years","volume":"9","author":"Launders","year":"2022b","journal-title":"The Lancet Psychiatry"},{"key":"10.7717\/peerj.17841\/ref-24","doi-asserted-by":"publisher","DOI":"10.48550\/arXiv.1802.03426","article-title":"UMAP: uniform manifold approximation and projection for dimension reduction","author":"McInnes","year":"2018"},{"key":"10.7717\/peerj.17841\/ref-25","article-title":"Bipolar disorder: the NICE guideline on the assessment and management of bipolar disorder in adults, children and young people in primary and secondary care","author":"National Collaborating Centre for Mental Health","year":"2014"},{"issue":"6895","key":"10.7717\/peerj.17841\/ref-26","doi-asserted-by":"publisher","first-page":"32","DOI":"10.1136\/bmj.307.6895.32","article-title":"Accuracy of diagnosis of psychosis on general practice computer system","volume":"307","author":"Nazareth","year":"1993","journal-title":"British Medical Journal"},{"issue":"11","key":"10.7717\/peerj.17841\/ref-27","doi-asserted-by":"publisher","first-page":"1588","DOI":"10.1002\/pds.5318","article-title":"Bipolar disorder prevalence and psychotropic medication utilisation in hong kong and the united kingdom","volume":"30","author":"Ng","year":"2021","journal-title":"Pharmacoepidemiology and Drug Safety"},{"issue":"2","key":"10.7717\/peerj.17841\/ref-28","doi-asserted-by":"publisher","first-page":"131","DOI":"10.1111\/acps.13122","article-title":"Prediction of lithium response using clinical data","volume":"141","author":"Nunes","year":"2020a","journal-title":"Acta Psychiatrica Scandinavica"},{"issue":"1","key":"10.7717\/peerj.17841\/ref-29","doi-asserted-by":"publisher","first-page":"e0225353","DOI":"10.1371\/journal.pone.0225353","article-title":"Asymmetrical reliability of the alda score favours a dichotomous representation of lithium responsiveness","volume":"15","author":"Nunes","year":"2020b","journal-title":"PLOS ONE"},{"key":"10.7717\/peerj.17841\/ref-30","doi-asserted-by":"publisher","first-page":"322","DOI":"10.1186\/s12888-018-1895-4","article-title":"Reasons for lithium discontinuation in men and women with bipolar disorder: a retrospective cohort study","volume":"18","author":"\u00d6hlund","year":"2018","journal-title":"BMC Psychiatry"},{"issue":"2","key":"10.7717\/peerj.17841\/ref-31","doi-asserted-by":"publisher","first-page":"e36","DOI":"10.1192\/bjo.2021.1082","article-title":"Genomic and neuroimaging approaches to bipolar disorder","volume":"8","author":"Oraki Kohshour","year":"2021","journal-title":"BJPsych Open"},{"issue":"Suppl 2","key":"10.7717\/peerj.17841\/ref-32","doi-asserted-by":"publisher","first-page":"136786","DOI":"10.1016\/j.neulet.2022.136786","article-title":"Lithium response in bipolar disorder: genetics, genomics, and beyond","volume":"785","author":"Papiol","year":"2022","journal-title":"Neuroscience Letters"},{"issue":"2","key":"10.7717\/peerj.17841\/ref-33","doi-asserted-by":"publisher","first-page":"148","DOI":"10.1002\/pds.4372","article-title":"Methods for time-varying exposure related problems in pharmacoepidemiology: an overview","volume":"27","author":"Pazzagli","year":"2018","journal-title":"Pharmacoepidemiology and Drug Safety"},{"issue":"1","key":"10.7717\/peerj.17841\/ref-34","doi-asserted-by":"publisher","first-page":"18","DOI":"10.1192\/bjp.185.1.18","article-title":"Predictors of antipsychotic treatment response in patients with first-episode schizophrenia, schizoaffective and schizophreniform disorders","volume":"185","author":"Perkins","year":"2004","journal-title":"The British Journal of Psychiatry"},{"issue":"3","key":"10.7717\/peerj.17841\/ref-35","doi-asserted-by":"publisher","first-page":"255","DOI":"10.1111\/bdi.12829","article-title":"An examination of the quality and performance of the Alda scale for classifying lithium response phenotypes","volume":"22","author":"Scott","year":"2020","journal-title":"Bipolar Disorders"},{"issue":"10","key":"10.7717\/peerj.17841\/ref-36","doi-asserted-by":"publisher","first-page":"e006556","DOI":"10.1161\/CIRCOUTCOMES.120.006556","article-title":"Recommendations for reporting machine learning analyses in clinical research","volume":"13","author":"Stevens","year":"2020","journal-title":"Circulation: Cardiovascular Quality and Outcomes"},{"key":"10.7717\/peerj.17841\/ref-37","first-page":"14266","article-title":"Transfer learning via L1 regularization","volume-title":"Advances in Neural Information Processing Systems","volume":"33","author":"Takada","year":"2020"},{"issue":"7","key":"10.7717\/peerj.17841\/ref-38","doi-asserted-by":"publisher","first-page":"1281","DOI":"10.1176\/appi.ajp.162.7.1281","article-title":"Olanzapine versus lithium in the maintenance treatment of bipolar disorder: a 12-month, randomized, double-blind, controlled clinical trial","volume":"162","author":"Tohen","year":"2005","journal-title":"American Journal of Psychiatry"},{"issue":"1","key":"10.7717\/peerj.17841\/ref-39","doi-asserted-by":"publisher","first-page":"16","DOI":"10.1186\/s40345-019-0151-2","article-title":"Clinical use of lithium salts: guide for users and prescribers","volume":"7","author":"Tondo","year":"2019","journal-title":"International Journal of Bipolar Disorders"},{"issue":"1","key":"10.7717\/peerj.17841\/ref-40","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1001\/jamapsychiatry.2015.2622","article-title":"Why psychiatry needs data science and data science needs psychiatry: connecting with technology","volume":"73","author":"Torous","year":"2016","journal-title":"JAMA Psychiatry"},{"key":"10.7717\/peerj.17841\/ref-41","doi-asserted-by":"publisher","first-page":"377","DOI":"10.3389\/fpsyt.2020.00377","article-title":"Lithium treatment over the lifespan in bipolar disorders","volume":"11","author":"Volkmann","year":"2020","journal-title":"Frontiers in Psychiatry"},{"issue":"6","key":"10.7717\/peerj.17841\/ref-42","doi-asserted-by":"publisher","first-page":"1740g","DOI":"10.1093\/ije\/dyz034","article-title":"Data resource profile: clinical practice research Datalink (CPRD) Aurum","volume":"48","author":"Wolf","year":"2019","journal-title":"International Journal of Epidemiology"},{"issue":"2","key":"10.7717\/peerj.17841\/ref-43","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1111\/bdi.12609","article-title":"Canadian network for mood and anxiety treatments (CANMAT) and international society for bipolar disorders (ISBD) 2018 guidelines for the management of patients with bipolar disorder","volume":"20","author":"Yatham","year":"2018","journal-title":"Bipolar Disorders"}],"container-title":["PeerJ"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/peerj.com\/articles\/17841.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/peerj.com\/articles\/17841.xml","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/peerj.com\/articles\/17841.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/peerj.com\/articles\/17841.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,10,14]],"date-time":"2024-10-14T05:49:45Z","timestamp":1728884985000},"score":1,"resource":{"primary":{"URL":"https:\/\/peerj.com\/articles\/17841"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,10,14]]},"references-count":43,"alternative-id":["10.7717\/peerj.17841"],"URL":"https:\/\/doi.org\/10.7717\/peerj.17841","archive":["CLOCKSS","LOCKSS","Portico"],"relation":{},"ISSN":["2167-8359"],"issn-type":[{"value":"2167-8359","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,10,14]]},"article-number":"e17841"}}