{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T03:43:40Z","timestamp":1790739820157,"version":"4.1.0"},"reference-count":69,"publisher":"Public Library of Science (PLoS)","issue":"1","license":[{"start":{"date-parts":[[2021,1,20]],"date-time":"2021-01-20T00:00:00Z","timestamp":1611100800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:sec id=\"sec001\">\n<jats:title>Purpose<\/jats:title>\n<jats:p>Treatment-resistant depression (TRD) is associated with a poor quality of life and high economic burden. This observational retrospective epidemiological study aimed to estimate the proportion of patients with TRD within a cohort of patients with major depressive disorder (MDD) in Hungary and examine the mortality and comorbidities of patients with and without TRD.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec002\">\n<jats:title>Patients and methods<\/jats:title>\n<jats:p>This study included patients with MDD who experienced onset of a new depressive episode between 01 January 2009 and 31 August 2015, using data from a nationwide, longitudinal database.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec003\">\n<jats:title>Results<\/jats:title>\n<jats:p>Overall, 99,531 patients were included in the MDD cohort, of which 8,268 (8.3%) also met the criteria for TRD. The overall survival of non-TRD patients was longer than in TRD patients; the risk of mortality for TRD patients was significantly higher than of non-TRD patients (HR [CI] 1.381 [1.212\u20131.571]; p&lt;0.001). Patients with TRD had a significantly higher probability of having \u201cNeurotic, stress-related and somatoform disorders\u02ee, autoimmune conditions, cardio- or cerebrovascular diseases, thyroid gland diseases and self-harming behaviour not resulting in death than non-TRD patients (for all comparisons, p values were less than 0.005).<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec004\">\n<jats:title>Discussion<\/jats:title>\n<jats:p>To our best knowledge, this is the first study to assess the frequency of TRD in Hungary. In a cohort of Hungarian MDD patients, we have found that the proportion of TRD (~8.3%) is comparable to those reported in previous studies with similar methodology from other countries. The majority of our other main findings (e.g. more frequent self-harming behaviour, increased risk of \u201cNeurotic, stress-related and somatoform disorders\u02ee and higher overall mortality in TRD subjects) are also in line with previous results from other countries. Taking the substantial proportion of patients with TRD into consideration, a more comprehensive and targeted treatment strategy would be required for these individuals.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pone.0245510","type":"journal-article","created":{"date-parts":[[2021,1,20]],"date-time":"2021-01-20T19:33:30Z","timestamp":1611171210000},"page":"e0245510","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":36,"title":["Clinical characteristics of treatment-resistant depression in adults in Hungary: Real-world evidence from a 7-year-long retrospective data analysis"],"prefix":"10.1371","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3847-0553","authenticated-orcid":true,"given":"P\u00e9ter","family":"D\u00f6me","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6149-5364","authenticated-orcid":true,"given":"P\u00e9ter","family":"Kunovszki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P\u00e9ter","family":"Tak\u00e1cs","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L\u00e1szl\u00f3","family":"Feh\u00e9r","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tam\u00e1s","family":"Bal\u00e1zs","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K\u00e1roly","family":"Dede","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9708-4356","authenticated-orcid":true,"given":"Siobh\u00e1n","family":"Mulhern-Haughey","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S\u00e9bastien","family":"Barbreau","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zolt\u00e1n","family":"Rihmer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2021,1,20]]},"reference":[{"key":"pone.0245510.ref001","first-page":"1614","volume-title":"Kaplan & Sadock\u2019s Comprehensive Textbook of Psychiatry","author":"K Merikangas","year":"2017","edition":"1"},{"issue":"1","key":"pone.0245510.ref002","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1080\/13651501.2016.1248852","article-title":"Evidence-based pharmacotherapy of treatment-resistant unipolar depression","volume":"21","author":"M Dold","year":"2017","journal-title":"Int J Psychiatry Clin Pract"},{"key":"pone.0245510.ref003","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1016\/j.jpsychires.2019.08.002","article-title":"Changes in the global burden of depression from 1990 to 2017: Findings from the Global Burden of Disease study","volume":"126","author":"Q Liu","year":"2020","journal-title":"J Psychiatr Res"},{"issue":"10161","key":"pone.0245510.ref004","doi-asserted-by":"crossref","first-page":"2299","DOI":"10.1016\/S0140-6736(18)31948-2","article-title":"Depression","volume":"392","author":"GS Malhi","year":"2018","journal-title":"Lancet"},{"key":"pone.0245510.ref005","volume-title":"Depression and Other Common Mental Disorders: Global Health Estimates","author":"World Health Organization","year":"2017"},{"issue":"22","key":"pone.0245510.ref006","first-page":"908","article-title":"Cancer and depression: a concise review","volume":"161","author":"A Szelei","year":"2020","journal-title":"Orv Hetil"},{"issue":"1","key":"pone.0245510.ref007","first-page":"17","article-title":"Prevalence of mood and anxiety disorders in the Hungarian adult population","volume":"141","author":"E Szadoczky","year":"2000","journal-title":"Orv Hetil"},{"issue":"1","key":"pone.0245510.ref008","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1111\/acps.12959","article-title":"Clinical factors predicting treatment resistant depression: affirmative results from the European multicenter study","volume":"139","author":"A Kautzky","year":"2019","journal-title":"Acta Psychiatr Scand"},{"issue":"10053","key":"pone.0245510.ref009","doi-asserted-by":"crossref","first-page":"1603","DOI":"10.1016\/S0140-6736(16)31460-X","article-title":"Global, regional, and national disability-adjusted life-years (DALYs) for 315 diseases and injuries and healthy life expectancy (HALE), 1990\u20132015: a systematic analysis for the Global Burden of Disease Study 2015","volume":"388","author":"GBD DALYs H Collaborators","year":"2016","journal-title":"Lancet"},{"key":"pone.0245510.ref010","unstructured":"World Health Organization. The global burden of disease: 2004 update. 2008. https:\/\/www.who.int\/healthinfo\/global_burden_disease\/GBD_report_2004update_full.pdf."},{"key":"pone.0245510.ref011","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1080\/13811118.2019.1691692","article-title":"Risk factors for suicide and suicide attempts among patients with treatment-resistant depression: nested case-control study","author":"J Reutfors","year":"2019","journal-title":"Arch Suicide Res"},{"issue":"3","key":"pone.0245510.ref012","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1002\/da.22705","article-title":"Finding treatment-resistant depression in real-world data: How a data-driven approach compares with expert-based heuristics","volume":"35","author":"MS Cepeda","year":"2018","journal-title":"Depress Anxiety"},{"key":"pone.0245510.ref013","doi-asserted-by":"crossref","first-page":"674","DOI":"10.1016\/j.jad.2018.06.030","article-title":"Mortality in treatment-resistant unipolar depression: A register-based cohort study in Sweden","volume":"238","author":"J Reutfors","year":"2018","journal-title":"J Affect Disord"},{"key":"pone.0245510.ref014","unstructured":"Thase M CK. Unipolar depression in adults: Choosing treatment for resistant depression. 2019 [cited 2020 18\/03\/2020]. https:\/\/www.uptodate.com\/contents\/unipolar-depression-in-adults-choosing-treatment-for-resistant-depression."},{"key":"pone.0245510.ref015","first-page":"1","volume-title":"Treatment-resistant Depression","author":"D Souery","year":"2013"},{"key":"pone.0245510.ref016","unstructured":"European Medicines Agency. Clinical investigation of medicinal products in the treatment of depression; EMA\/CHMP\/185423\/2010 Rev. 2. 30 May 2013. https:\/\/www.ema.europa.eu\/en\/clinical-investigation-medicinal-products-treatment-depression."},{"issue":"4","key":"pone.0245510.ref017","doi-asserted-by":"crossref","first-page":"512","DOI":"10.1016\/j.clinthera.2012.09.001","article-title":"The economic burden of treatment-resistant depression","volume":"35","author":"N Olchanski","year":"2013","journal-title":"Clin Ther"},{"key":"pone.0245510.ref018","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1016\/j.jad.2018.06.045","article-title":"The burden of treatment-resistant depression: A systematic review of the economic and quality of life literature","volume":"242","author":"KM Johnston","year":"2019","journal-title":"J Affect Disord"},{"issue":"3","key":"pone.0245510.ref019","doi-asserted-by":"crossref","first-page":"273","DOI":"10.24869\/psyd.2018.273","article-title":"Challenges of Treatment-resistant Depression","volume":"30","author":"JP Pandarakalam","year":"2018","journal-title":"Psychiatr Danub"},{"issue":"Suppl 8","key":"pone.0245510.ref020","first-page":"17","article-title":"Prevalence and management of treatment-resistant depression","volume":"68","author":"CB Nemeroff","year":"2007","journal-title":"J Clin Psychiatry"},{"issue":"1","key":"pone.0245510.ref021","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1186\/s12888-019-2222-4","article-title":"The humanistic and economic burden of treatment-resistant depression in Europe: a cross-sectional study","volume":"19","author":"DH Jaffe","year":"2019","journal-title":"BMC Psychiatry"},{"key":"pone.0245510.ref022","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1016\/j.jad.2015.12.067","article-title":"Mortality and life expectancy in persons with severe unipolar depression","volume":"193","author":"TM Laursen","year":"2016","journal-title":"J Affect Disord"},{"issue":"5","key":"pone.0245510.ref023","doi-asserted-by":"crossref","first-page":"e19590","DOI":"10.1371\/journal.pone.0019590","article-title":"Life expectancy at birth for people with serious mental illness and other major disorders from a secondary mental health care case register in London","volume":"6","author":"CK Chang","year":"2011","journal-title":"PLoS One"},{"issue":"1","key":"pone.0245510.ref024","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1186\/s12916-018-1101-z","article-title":"The association of depression and all-cause and cause-specific mortality: an umbrella review of systematic reviews and meta-analyses","volume":"16","author":"MO Machado","year":"2018","journal-title":"BMC Med"},{"key":"pone.0245510.ref025","doi-asserted-by":"crossref","first-page":"109887","DOI":"10.1016\/j.jpsychores.2019.109887","article-title":"Non-melancholic depressive symptoms increase risk for incident cardiovascular disease: A prospective study in a primary care population at risk for cardiovascular disease and type 2 diabetes","volume":"129","author":"AT Rantanen","year":"2020","journal-title":"J Psychosom Res"},{"issue":"7","key":"pone.0245510.ref026","doi-asserted-by":"crossref","first-page":"1305","DOI":"10.1007\/s00125-020-05131-6","article-title":"Major depressive disorder and cardiometabolic diseases: a bidirectional Mendelian randomisation study","volume":"63","author":"B Tang","year":"2020","journal-title":"Diabetologia"},{"issue":"12","key":"pone.0245510.ref027","doi-asserted-by":"crossref","first-page":"e1916591","DOI":"10.1001\/jamanetworkopen.2019.16591","article-title":"Association of Depressive Symptoms With Incident Cardiovascular Diseases in Middle-Aged and Older Chinese Adults","volume":"2","author":"H Li","year":"2019","journal-title":"JAMA Netw Open"},{"key":"pone.0245510.ref028","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1186\/s12991-019-0248-0","article-title":"All-cause mortality in patients with treatment-resistant depression: a cohort study in the US population","volume":"18","author":"G Li","year":"2019","journal-title":"Ann Gen Psychiatry"},{"issue":"7","key":"pone.0245510.ref029","doi-asserted-by":"crossref","first-page":"825","DOI":"10.1016\/j.euroneuro.2019.06.001","article-title":"Patterns of response to antidepressants in major depressive disorder: Drug resistance or worsening of depression are associated with a bipolar diathesis","volume":"29","author":"G Perugi","year":"2019","journal-title":"Eur Neuropsychopharmacol"},{"key":"pone.0245510.ref030","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.jpsychires.2018.12.006","article-title":"Sub-threshold bipolar disorder in medication-free young subjects with major depression: Clinical characteristics and antidepressant treatment response","volume":"110","author":"P Koirala","year":"2019","journal-title":"J Psychiatr Res"},{"issue":"7","key":"pone.0245510.ref031","doi-asserted-by":"crossref","first-page":"598","DOI":"10.1176\/appi.ajp.2017.17080949","article-title":"Antidepressant-resistant depression in patients with comorbid subclinical hypothyroidism or high-normal TSH levels","volume":"175","author":"BM Cohen","year":"2018","journal-title":"Am J Psychiatry"},{"key":"pone.0245510.ref032","first-page":"906462","article-title":"Antidepressant-resistant depression and antidepressant-associated suicidal behaviour: the role of underlying bipolarity","volume":"2011","author":"Z Rihmer","year":"2011","journal-title":"Depress Res Treat"},{"key":"pone.0245510.ref033","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1111\/j.1479-8301.2002.tb00079.x","article-title":"An overview of the management of treatment resistant depression in late life","volume":"2","author":"CH Ng","year":"2002","journal-title":"Psychogeriatrics"},{"key":"pone.0245510.ref034","doi-asserted-by":"crossref","first-page":"369","DOI":"10.2147\/PPA.S29716","article-title":"Treatment-resistant depression: therapeutic trends, challenges, and future directions","volume":"6","author":"KS Al-Harbi","year":"2012","journal-title":"Patient Prefer Adherence"},{"issue":"Suppl 16","key":"pone.0245510.ref035","first-page":"18","article-title":"Clinical features of treatment-resistant depression","volume":"62","author":"SG Kornstein","year":"2001","journal-title":"J Clin Psychiatry"},{"issue":"2","key":"pone.0245510.ref036","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1093\/ijnp\/pyy024","article-title":"The Genetics of Treatment-Resistant Depression: A Critical Review and Future Perspectives","volume":"22","author":"C Fabbri","year":"2019","journal-title":"Int J Neuropsychopharmacol"},{"issue":"6","key":"pone.0245510.ref037","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1080\/15622975.2019.1635270","article-title":"Results of the European Group for the Study of Resistant Depression (GSRD)\u2014basis for further research and clinical practice","volume":"20","author":"L Bartova","year":"2019","journal-title":"World J Biol Psychiatry"},{"issue":"6","key":"pone.0245510.ref038","doi-asserted-by":"crossref","first-page":"752","DOI":"10.1016\/j.euroneuro.2018.03.011","article-title":"Comorbid thyroid disease in patients with major depressive disorder\u2014results from the European Group for the Study of Resistant Depression (GSRD)","volume":"28","author":"G Fugger","year":"2018","journal-title":"Eur Neuropsychopharmacol"},{"issue":"1","key":"pone.0245510.ref039","doi-asserted-by":"crossref","first-page":"57","DOI":"10.3949\/ccjm.75.1.57","article-title":"The STAR*D study: treating depression in the real world","volume":"75","author":"BN Gaynes","year":"2008","journal-title":"Cleve Clin J Med"},{"key":"pone.0245510.ref040","doi-asserted-by":"crossref","first-page":"S688","DOI":"10.1016\/j.jval.2019.09.1518","article-title":"PMH44 Increased use of augmentation therapies illustrates complex management of treatment resistant depression. Preliminary results from a real-word evidence registry in Europe, the 54135419dep4001 study","volume":"22","author":"J Morrens","year":"2019","journal-title":"Value in Health"},{"key":"pone.0245510.ref041","doi-asserted-by":"crossref","first-page":"250","DOI":"10.1016\/j.jad.2019.06.005","article-title":"Relationships between recurrence and polarity in major depressive disorders: Pooled analysis of the BRIDGE and BRIDGE-II-MIX cohorts","volume":"256","author":"M Barbuti","year":"2019","journal-title":"J Affect Disord"},{"issue":"1","key":"pone.0245510.ref042","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1192\/bjp.bp.110.086983","article-title":"Association between antidepressant resistance in unipolar depression and subsequent bipolar disorder: cohort study","volume":"200","author":"C Li","year":"2012","journal-title":"Br J Psychiatry"},{"issue":"2","key":"pone.0245510.ref043","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1080\/13651500701749867","article-title":"The bipolar diathesis of treatment-resistant major depressive disorder","volume":"12","author":"S Woo","year":"2008","journal-title":"Int J Psychiatry Clin Pract"},{"issue":"1\u20132","key":"pone.0245510.ref044","doi-asserted-by":"crossref","first-page":"268","DOI":"10.1016\/j.jad.2010.03.001","article-title":"Risk factors of treatment resistance in major depression: association with bipolarity","volume":"126","author":"D Dudek","year":"2010","journal-title":"J Affect Disord"},{"key":"pone.0245510.ref045","doi-asserted-by":"crossref","first-page":"362","DOI":"10.1016\/j.jad.2018.04.016","article-title":"Treatment-resistant Depression and Suicidality","volume":"235","author":"I Bergfeld","year":"2018","journal-title":"Review J Affect Disord"},{"key":"pone.0245510.ref046","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1016\/j.jad.2015.09.033","article-title":"Socio-demographic and clinical predictors of treatment resistant depression: a prospective European multicenter study","volume":"189","author":"M Balestri","year":"2016","journal-title":"Clinical Trial J Affect Disord"},{"issue":"4","key":"pone.0245510.ref047","doi-asserted-by":"crossref","first-page":"356","DOI":"10.1111\/sltb.12022","article-title":"Treatment-resistant depression and risk of suicide","volume":"43","author":"P Pfeiffer","year":"2013","journal-title":"Suicide Life Threat Behav"},{"issue":"11","key":"pone.0245510.ref048","doi-asserted-by":"crossref","first-page":"1905","DOI":"10.1176\/ajp.2006.163.11.1905","article-title":"Acute and longer-term outcomes in depressed outpatients requiring one or several treatment steps: a STAR*D report","volume":"163","author":"AJ Rush","year":"2006","journal-title":"Am J Psychiatry"},{"issue":"10","key":"pone.0245510.ref049","doi-asserted-by":"crossref","first-page":"e76882","DOI":"10.1371\/journal.pone.0076882","article-title":"Characterization of treatment resistant depression episodes in a cohort of patients from a US commercial claims database","volume":"8","author":"N Kubitz","year":"2013","journal-title":"PLoS One"},{"issue":"8","key":"pone.0245510.ref050","doi-asserted-by":"crossref","first-page":"e0221552","DOI":"10.1371\/journal.pone.0221552","article-title":"Epidemiology of pharmaceutically treated depression and treatment resistant depression in South Korea","volume":"14","author":"N Kim","year":"2019","journal-title":"PLoS One"},{"key":"pone.0245510.ref051","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1016\/j.psychres.2017.03.006","article-title":"Epidemiology of pharmaceutically treated depression and treatment resistant depression in Taiwan","volume":"252","author":"D Fife","year":"2017","journal-title":"Psychiatry Res"},{"issue":"1","key":"pone.0245510.ref052","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1007\/s40801-017-0126-5","article-title":"Estimating Prevalence and Healthcare Utilization for Treatment-Resistant Depression in Japan: A Retrospective Claims Database Study","volume":"5","author":"J Mahlich","year":"2018","journal-title":"Drugs Real World Outcomes"},{"issue":"7","key":"pone.0245510.ref053","doi-asserted-by":"crossref","first-page":"e00707","DOI":"10.1016\/j.heliyon.2018.e00707","article-title":"Treatment resistant depression incidence estimates from studies of health insurance databases depend strongly on the details of the operating definition","volume":"4","author":"D Fife","year":"2018","journal-title":"Heliyon"},{"issue":"4","key":"pone.0245510.ref054","doi-asserted-by":"crossref","DOI":"10.4088\/JCP.17m11845","article-title":"Incidence of, Risk Factors for, and Changes Over Time in Treatment-Resistant Depression in Denmark: A Register-Based Cohort Study","volume":"79","author":"FH Gronemann","year":"2018","journal-title":"J Clin Psychiatry"},{"key":"pone.0245510.ref055","doi-asserted-by":"crossref","DOI":"10.1176\/appi.books.9780890425596","volume-title":"Diagnostic and Statistical Manual of Mental Disorders","author":"American Psychiatric Association","year":"2013","edition":"5"},{"key":"pone.0245510.ref056","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1186\/s12911-015-0140-z","article-title":"From prescription drug purchases to drug use periods\u2013a second generation method (PRE2DUP)","volume":"15","author":"A Tanskanen","year":"2015","journal-title":"BMC Medical Informatics and Decision Making"},{"key":"pone.0245510.ref057","unstructured":"Hungarian Central Statistical Office. Population, vital statistics (1900-). 2020 [updated May 2020; cited 2020]. https:\/\/www.ksh.hu\/docs\/eng\/xstadat\/xstadat_long\/h_wdsd001a.html."},{"key":"pone.0245510.ref058","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1016\/j.jad.2019.10.005","article-title":"Socio-demographic and clinical risk factors of treatment-resistant depression: A Danish population-based cohort study","volume":"361","author":"F Gronemann","year":"2020","journal-title":"J Affect Disord"},{"key":"pone.0245510.ref059","doi-asserted-by":"crossref","first-page":"1221","DOI":"10.2147\/NDT.S104188","article-title":"Treatment response in relation to subthreshold bipolarity in patients with major depressive disorder receiving antidepressant monotherapy: a post hoc data analysis (KOMDD study)","volume":"12","author":"Y Park","year":"2016","journal-title":"Neuropsychiatr Dis Treat"},{"issue":"2","key":"pone.0245510.ref060","first-page":"157","article-title":"Antidepressant-resistant depression and the bipolar spectrum\u2014diagnostic and therapeutic considerations","volume":"31","author":"Z Rihmer","year":"2016","journal-title":"Psychiatr Hung"},{"key":"pone.0245510.ref061","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1016\/j.jad.2014.11.034","article-title":"A diagnosis of bipolar spectrum disorder predicts diagnostic conversion from unipolar depression to bipolar disorder: a 5-year retrospective study","volume":"174","author":"Y Woo","year":"2015","journal-title":"J Affect Disord"},{"issue":"8","key":"pone.0245510.ref062","doi-asserted-by":"crossref","first-page":"895","DOI":"10.1016\/j.euroneuro.2012.09.002","article-title":"Physical co-morbidity among treatment resistant vs. treatment responsive patients with major depressive disorder","volume":"23","author":"D Amital","year":"2013","journal-title":"Eur Neuropsychopharmacol"},{"key":"pone.0245510.ref063","doi-asserted-by":"crossref","first-page":"806","DOI":"10.1016\/j.jad.2020.05.150","article-title":"Treatment-Resistant depression enhances risks of dementia and alzheimer\u2019s disease: A nationwide longitudinal study","volume":"274","author":"YE Chan","year":"2020","journal-title":"J Affect Disord"},{"issue":"6","key":"pone.0245510.ref064","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1093\/ijnp\/pyy009","article-title":"Major depression and the degree of suicidality: results of the European Group for the Study of Resistant Depression (GSRD)","volume":"21","author":"M Dold","year":"2018","journal-title":"Int J Neuropsychopharmacol"},{"key":"pone.0245510.ref065","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1016\/j.jad.2020.02.023","article-title":"The identification, assessment and management of difficult-to-treat depression: an international consensus statement","volume":"267","author":"R McAllister-Williams","year":"2020","journal-title":"J Affect Disord"},{"issue":"3","key":"pone.0245510.ref066","doi-asserted-by":"crossref","first-page":"350","DOI":"10.1016\/j.jagp.2019.10.012","article-title":"An evaluation of the clinical and economic burden among older adult medicare-covered beneficiaries with treatment-resistant depression","volume":"28","author":"C Benson","year":"2020","journal-title":"Am J Geriatr Psychiatry"},{"issue":"5","key":"pone.0245510.ref067","doi-asserted-by":"crossref","first-page":"906","DOI":"10.1111\/j.1360-0443.2010.03351.x","article-title":"Alcohol and depression","volume":"106","author":"J Boden","year":"2011","journal-title":"Addiction"},{"issue":"3","key":"pone.0245510.ref068","doi-asserted-by":"crossref","first-page":"725","DOI":"10.3233\/JAD-161247","article-title":"Efficacy of Antidepressants for Depression in Alzheimer\u2019s Disease: Systematic Review and Meta-Analysis","volume":"58","author":"V Orgeta","year":"2017","journal-title":"J Alzheimers Dis"},{"issue":"4","key":"pone.0245510.ref069","article-title":"Antidepressants for the treatment of depression in people with cancer","volume":"4","author":"G Ostuzzi","year":"2018","journal-title":"Cochrane Database Syst Rev"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0245510","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,1,20]],"date-time":"2021-01-20T19:36:34Z","timestamp":1611171394000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0245510"}},"subtitle":[],"editor":[{"given":"Kenji","family":"Hashimoto","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2021,1,20]]},"references-count":69,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2021,1,20]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0245510","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,1,20]]}}}