{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T21:18:17Z","timestamp":1782940697738,"version":"3.54.5"},"reference-count":71,"publisher":"BMJ","issue":"5","content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["BMJ Open"],"accepted":{"date-parts":[[2016,5,4]]},"published-print":{"date-parts":[[2016,5]]},"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>In the general population, alcohol use disorder and depression more often occur together than any other combination of a mental illness with a substance use disorder. It is important to have a cost-effective intervention that is able to reach at-risk individuals in the early stages of developing alcohol use disorders and depression disorders.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and analysis<\/jats:title>\n                    <jats:p>This paper presents the protocol for a 3-arm multicentre randomised controlled trial (RCT) to test the efficacy and cost-effectiveness of the combined internet-based self-help intervention Take Care of You (TCOY) to reduce alcohol misuse and depression symptoms in comparison with a waiting list control group and a comparable intervention focusing on problematic alcohol use only. The active interventions consist of modules designed to reduce alcohol use, based on the principles of motivational interviewing and methods of cognitive behavioural therapy, together with additional modules in the combined study arm to reduce symptoms of depression. Data will be collected at baseline, as well as at 3 and 6\u2005months postrandomisation. The primary outcome is the quantity of alcohol used in the past 7\u2005days. A number of secondary outcome measures will be studied. These include the Centre of Epidemiologic Studies of Depression Scale (CES-D) and a combined measure with the criteria of values below the cut-off for severe alcohol use disorder and for CES-D. Data analysis will follow the intention-to-treat principle using (generalised) linear mixed models. In order to investigate the interventions\u2019 cost-utility and cost-effectiveness, a full economic evaluation will be performed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Ethics and dissemination<\/jats:title>\n                    <jats:p>This RCT will be executed in compliance with the Helsinki Declaration and has been approved by 2 local Ethics Committees. Results will be reported at conferences and in peer-reviewed publications. Participant-friendly summaries of trial findings will be published on the TCOY websites.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial registration number<\/jats:title>\n                    <jats:p>ISRCTN10323951.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/bmjopen-2016-011457","type":"journal-article","created":{"date-parts":[[2016,5,25]],"date-time":"2016-05-25T23:35:30Z","timestamp":1464219330000},"page":"e011457","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":34,"title":["Efficacy of an internet-based self-help intervention to reduce co-occurring alcohol misuse and depression symptoms in adults: study protocol of a three-arm randomised controlled trial"],"prefix":"10.1136","volume":"6","clinical-trial-number":[{"clinical-trial-number":"isrctn10323951","registry":"10.18810\/isrctn"},{"clinical-trial-number":"isrctn10323951","registry":"10.18810\/isrctn"}],"author":[{"given":"Michael P","family":"Schaub","sequence":"first","affiliation":[{"name":"Swiss Research Institute for Public Health and Addiction, University of Zurich, Zurich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthijs","family":"Blankers","sequence":"additional","affiliation":[{"name":"Department of Research, Arkin Mental Health Care, Amsterdam, The Netherlands"},{"name":"Department of Psychiatry, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dirk","family":"Lehr","sequence":"additional","affiliation":[{"name":"Department of Health Psychology and Applied Biological Psychology, Leuphana University Lueneburg, Lueneburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leif","family":"Boss","sequence":"additional","affiliation":[{"name":"Division of Health Training Online, Innovation Incubator, Leuphana University Lueneburg, Lueneburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heleen","family":"Riper","sequence":"additional","affiliation":[{"name":"Division of Health Training Online, Innovation Incubator, Leuphana University Lueneburg, Lueneburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jack","family":"Dekker","sequence":"additional","affiliation":[{"name":"Department of Research, Arkin Mental Health Care, Amsterdam, The Netherlands"},{"name":"Department of Clinical Psychology, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna E","family":"Goudriaan","sequence":"additional","affiliation":[{"name":"Department of Research, Arkin Mental Health Care, Amsterdam, The Netherlands"},{"name":"Department of Psychiatry, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Larissa J","family":"Maier","sequence":"additional","affiliation":[{"name":"Swiss Research Institute for Public Health and Addiction, University of Zurich, Zurich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Severin","family":"Haug","sequence":"additional","affiliation":[{"name":"Swiss Research Institute for Public Health and Addiction, University of Zurich, Zurich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manuel","family":"Amann","sequence":"additional","affiliation":[{"name":"Swiss Research Institute for Public Health and Addiction, University of Zurich, Zurich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michelle","family":"Dey","sequence":"additional","affiliation":[{"name":"Swiss Research Institute for Public Health and Addiction, University of Zurich, Zurich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"Wenger","sequence":"additional","affiliation":[{"name":"Swiss Research Institute for Public Health and Addiction, University of Zurich, Zurich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David D","family":"Ebert","sequence":"additional","affiliation":[{"name":"Clinical Psychology and Psychotherapy, Friedrich-Alexander University Erlangen Nuremberg, Erlangen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2016,5,25]]},"reference":[{"key":"2025120520120068000_6.5.e011457.1","unstructured":"WHO (2013). Draft comprehensive mental health action plan 2013\u20132020. http:\/\/bit.ly\/Vhhh8s"},{"key":"2025120520120068000_6.5.e011457.2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(13)61611-6"},{"key":"2025120520120068000_6.5.e011457.3","unstructured":"WHO (2014). Global status report on alcohol and health 2014. http:\/\/apps.who.int\/iris\/bitstream\/10665\/112736\/1\/9789240692763_eng.pdf"},{"key":"2025120520120068000_6.5.e011457.4","doi-asserted-by":"publisher","DOI":"10.1111\/j.1360-0443.1993.tb02093.x"},{"key":"2025120520120068000_6.5.e011457.5","doi-asserted-by":"publisher","DOI":"10.4088\/JCP.v67n0211"},{"key":"2025120520120068000_6.5.e011457.6","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1016\/j.drugalcdep.2011.01.011","article-title":"Alcohol involvement as a function of co-occurring alcohol use disorders and major depressive episode: Evidence from The National Epidemiologic Survey on Alcohol and Related Conditions","volume":"117","author":"Cranford","year":"2011","journal-title":"Drug Alcohol Depend"},{"key":"2025120520120068000_6.5.e011457.7","doi-asserted-by":"publisher","DOI":"10.1016\/j.drugalcdep.2005.03.009"},{"key":"2025120520120068000_6.5.e011457.8","doi-asserted-by":"publisher","DOI":"10.1016\/S0010-440X(98)90058-X"},{"key":"2025120520120068000_6.5.e011457.9","doi-asserted-by":"crossref","first-page":"246","DOI":"10.15288\/jsa.2005.66.246","article-title":"Psychiatric disorders among at-risk consumers of alcohol in the general population","volume":"66","author":"Bott","year":"2005","journal-title":"J Stud Alcohol"},{"key":"2025120520120068000_6.5.e011457.10","doi-asserted-by":"publisher","DOI":"10.1093\/ije\/dyt175"},{"key":"2025120520120068000_6.5.e011457.11","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1186\/s12888-015-0518-6","article-title":"Evaluating the efficacy of a web-based self-help intervention with and without chat counseling in reducing the cocaine use of problematic cocaine users: the study protocol of a pragmatic three-arm randomized controlled trial","volume":"15","author":"Schaub","year":"2015","journal-title":"BMC Psychiatry"},{"key":"2025120520120068000_6.5.e011457.12","doi-asserted-by":"crossref","first-page":"e166","DOI":"10.2196\/jmir.2244","article-title":"Web-based cognitive behavioral self-help intervention to reduce cocaine consumption in problematic cocaine users: randomized controlled trial","volume":"14","author":"Schaub","year":"2012","journal-title":"J Med Internet Res"},{"key":"2025120520120068000_6.5.e011457.13","doi-asserted-by":"crossref","first-page":"e232","DOI":"10.2196\/jmir.4860","article-title":"A web-based self-help intervention with and without chat counseling to reduce cannabis use in problematic cannabis users: three-arm randomized controlled trial","volume":"17","author":"Schaub","year":"2015","journal-title":"J Med Internet Res"},{"key":"2025120520120068000_6.5.e011457.14","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1186\/1471-244X-13-305","article-title":"Can reduce\u2014the effects of chat-counseling and web-based self-help, web-based self-help alone and a waiting list control program on cannabis use in problematic cannabis users: a randomized controlled trial","volume":"13","author":"Schaub","year":"2013","journal-title":"BMC Psychiatry"},{"key":"2025120520120068000_6.5.e011457.15","doi-asserted-by":"publisher","DOI":"10.1016\/j.drugalcdep.2013.05.012"},{"key":"2025120520120068000_6.5.e011457.16","doi-asserted-by":"crossref","first-page":"e1","DOI":"10.2196\/mental.3278","article-title":"A web-based intervention for users of amphetamine-type stimulants: 3-month outcomes of a randomized controlled trial","volume":"1","author":"Tait","year":"2014","journal-title":"JMIR Ment Health"},{"key":"2025120520120068000_6.5.e011457.17","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0099912"},{"key":"2025120520120068000_6.5.e011457.18","doi-asserted-by":"publisher","DOI":"10.2196\/jmir.1691"},{"key":"2025120520120068000_6.5.e011457.19","doi-asserted-by":"crossref","first-page":"348","DOI":"10.1159\/000438673","article-title":"Effectiveness of a web-based cognitive behavioural intervention for subthreshold depression: pragmatic randomised controlled trial","volume":"84","author":"Buntrock","year":"2015","journal-title":"Psychother Psychosom"},{"key":"2025120520120068000_6.5.e011457.20","doi-asserted-by":"crossref","first-page":"226","DOI":"10.4103\/0253-7176.135367","article-title":"A review of web based interventions for managing tobacco use","volume":"36","author":"Balhara","year":"2014","journal-title":"Indian J Psychol Med"},{"key":"2025120520120068000_6.5.e011457.21","doi-asserted-by":"publisher","DOI":"10.1586\/erp.12.67"},{"key":"2025120520120068000_6.5.e011457.22","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0119895"},{"key":"2025120520120068000_6.5.e011457.23","doi-asserted-by":"publisher","DOI":"10.1016\/j.cpr.2012.02.004"},{"key":"2025120520120068000_6.5.e011457.24","doi-asserted-by":"publisher","DOI":"10.1176\/appi.ajp.2012.12010112"},{"key":"2025120520120068000_6.5.e011457.25","doi-asserted-by":"publisher","DOI":"10.1111\/add.12441"},{"key":"2025120520120068000_6.5.e011457.26","doi-asserted-by":"publisher","DOI":"10.1186\/1471-244X-11-64"},{"key":"2025120520120068000_6.5.e011457.27","doi-asserted-by":"crossref","first-page":"e71","DOI":"10.2196\/jmir.5178","article-title":"An online intervention for co-occurring depression and problematic alcohol use in young people: primary outcomes from a randomized controlled trial","volume":"18","author":"Deady","year":"2016","journal-title":"J Med Internet Res"},{"key":"2025120520120068000_6.5.e011457.28","unstructured":"Marlatt GA . Relapse prevention: maintenance strategies in treatment of addictive behaviors. New York: Guildford, 1985."},{"key":"2025120520120068000_6.5.e011457.29","unstructured":"Miller WR , Rollnick S . Motivational interviewing: helping people change. 3rd edn. New York: Guilford Press, 2012."},{"key":"2025120520120068000_6.5.e011457.30","doi-asserted-by":"publisher","DOI":"10.2196\/jmir.1602"},{"key":"2025120520120068000_6.5.e011457.31","doi-asserted-by":"crossref","first-page":"2224","DOI":"10.1186\/s12889-015-2375-0","article-title":"Evaluating the (cost-)effectiveness of guided and unguided internet-based self-help for problematic alcohol use in employees\u2014a three arm randomized controlled trial","volume":"15","author":"Boss","year":"2015","journal-title":"BMC Public Health"},{"key":"2025120520120068000_6.5.e011457.32","doi-asserted-by":"crossref","first-page":"807","DOI":"10.1186\/1471-2458-14-807","article-title":"Efficacy and cost-effectiveness of minimal guided and unguided internet-based mobile supported stress-management in employees with occupational stress: a three-armed randomised controlled trial","volume":"14","author":"Ebert","year":"2014","journal-title":"BMC Public Health"},{"key":"2025120520120068000_6.5.e011457.33","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-12-535601-5.50009-3"},{"key":"2025120520120068000_6.5.e011457.34","doi-asserted-by":"crossref","unstructured":"D\u2019Zurilla TJ , Nezu AM . Social problem solving in adults. In: Kendall PC, ed. Advances in cognitive\u2013behavioral research and therapy. Elsevier, 1982:201\u201374.","DOI":"10.1016\/B978-0-12-010601-1.50010-3"},{"key":"2025120520120068000_6.5.e011457.35","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1186\/1471-244X-14-25","article-title":"Evaluating the efficacy and cost-effectiveness of web-based indicated prevention of major depression: design of a randomised controlled trial","volume":"14","author":"Buntrock","year":"2014","journal-title":"BMC Psychiatry"},{"key":"2025120520120068000_6.5.e011457.36","doi-asserted-by":"publisher","DOI":"10.5271\/sjweh.3449"},{"key":"2025120520120068000_6.5.e011457.37","doi-asserted-by":"publisher","DOI":"10.1186\/1471-244X-13-306"},{"key":"2025120520120068000_6.5.e011457.38","doi-asserted-by":"crossref","first-page":"776","DOI":"10.2337\/dc14-1728","article-title":"Efficacy of a web-based intervention with mobile phone support in treating depressive symptoms in adults with type 1 and type 2 diabetes: a randomized controlled trial","volume":"38","author":"Nobis","year":"2015","journal-title":"Dia Care"},{"key":"2025120520120068000_6.5.e011457.39","doi-asserted-by":"publisher","DOI":"10.2196\/jmir.1138"},{"key":"2025120520120068000_6.5.e011457.40","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0062873"},{"key":"2025120520120068000_6.5.e011457.41","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.psych.57.102904.190038"},{"key":"2025120520120068000_6.5.e011457.42","unstructured":"Sobell MB , Sobell LC . Problem drinkers: guided self-change treatment. New York: Guilford Press, 1993."},{"key":"2025120520120068000_6.5.e011457.43","doi-asserted-by":"publisher","DOI":"10.1111\/j.1530-0277.2007.00403.x"},{"key":"2025120520120068000_6.5.e011457.44","doi-asserted-by":"publisher","DOI":"10.1177\/014662167700100306"},{"key":"2025120520120068000_6.5.e011457.45","first-page":"344","article-title":"Die deutsche Version der CES-D als Instrument der gerontologischen Forschung","volume":"46","author":"Riediger","year":"1998","journal-title":"Z Klin Psychol Psychiatr Psychother"},{"key":"2025120520120068000_6.5.e011457.46","doi-asserted-by":"publisher","DOI":"10.1016\/j.drugalcdep.2012.05.029"},{"key":"2025120520120068000_6.5.e011457.47","doi-asserted-by":"publisher","DOI":"10.1159\/000259089"},{"key":"2025120520120068000_6.5.e011457.48","doi-asserted-by":"publisher","DOI":"10.1016\/S0165-1781(01)00329-8"},{"key":"2025120520120068000_6.5.e011457.49","doi-asserted-by":"publisher","DOI":"10.1016\/j.drugalcdep.2012.05.029"},{"key":"2025120520120068000_6.5.e011457.50","doi-asserted-by":"publisher","DOI":"10.1192\/bjp.188.4.323"},{"key":"2025120520120068000_6.5.e011457.51","doi-asserted-by":"publisher","DOI":"10.5271\/sjweh.2917"},{"key":"2025120520120068000_6.5.e011457.52","doi-asserted-by":"publisher","DOI":"10.1016\/0149-7189(79)90094-6"},{"key":"2025120520120068000_6.5.e011457.53","unstructured":"Schmidt J , N\u00fcbling R . ZUF-8. Fragebogen zur messung der patientenzufriedenheit. In: Br\u00e4hler E , Schumacher J , Strau\u00df B . Hrsg. Diagnostische verfahren in der psychotherapie. G\u00f6ttingen: Hogrefe, 2002:392\u20136."},{"key":"2025120520120068000_6.5.e011457.54","doi-asserted-by":"publisher","DOI":"10.1080\/16506073.2015.1008033"},{"key":"2025120520120068000_6.5.e011457.55","doi-asserted-by":"crossref","first-page":"489","DOI":"10.3109\/00952990.2015.1056447","article-title":"The importance of distribution-choice in modeling substance use data: a comparison of negative binomial, beta binomial, and zero-inflated distributions","volume":"41","author":"Wagner","year":"2015","journal-title":"Am J Drug Alcohol Abuse"},{"key":"2025120520120068000_6.5.e011457.56","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2012.87802"},{"key":"2025120520120068000_6.5.e011457.57","doi-asserted-by":"publisher","DOI":"10.1016\/S0197-2456(01)00196-9"},{"key":"2025120520120068000_6.5.e011457.58","doi-asserted-by":"publisher","DOI":"10.1055\/s-2005-858698"},{"key":"2025120520120068000_6.5.e011457.59","first-page":"53","article-title":"Calculation of standardised unit costs from a societal perspective for health economic evaluation","volume":"77","author":"Bock","year":"2015","journal-title":"Gesundheitswesen"},{"key":"2025120520120068000_6.5.e011457.60","doi-asserted-by":"publisher","DOI":"10.1186\/1472-6963-13-217"},{"key":"2025120520120068000_6.5.e011457.61","doi-asserted-by":"publisher","DOI":"10.1007\/s11136-011-9903-x"},{"key":"2025120520120068000_6.5.e011457.62","doi-asserted-by":"publisher","DOI":"10.1002\/hec.1124"},{"key":"2025120520120068000_6.5.e011457.63","doi-asserted-by":"publisher","DOI":"10.1007\/s10198-004-0264-z"},{"key":"2025120520120068000_6.5.e011457.64","doi-asserted-by":"crossref","first-page":"708","DOI":"10.1016\/j.jval.2012.02.008","article-title":"Interim scoring for the EQ-5D-5L: Mapping the EQ-5D-5L to EQ-5D-3L value sets","volume":"15","author":"van Hout","year":"2012","journal-title":"Value in Health"},{"key":"2025120520120068000_6.5.e011457.65","doi-asserted-by":"publisher","DOI":"10.1016\/j.jval.2012.02.008"},{"key":"2025120520120068000_6.5.e011457.66","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.f1049"},{"key":"2025120520120068000_6.5.e011457.67","doi-asserted-by":"publisher","DOI":"10.1016\/j.jval.2015.02.001"},{"key":"2025120520120068000_6.5.e011457.68","doi-asserted-by":"crossref","unstructured":"Drummond M , Sculpher M , Torrance G , et al . Methods for the economic evaluation of health care programmes. Oxford: Oxford University Press, 2005.","DOI":"10.1093\/oso\/9780198529446.001.0001"},{"key":"2025120520120068000_6.5.e011457.69","doi-asserted-by":"publisher","DOI":"10.1186\/1472-6963-6-68"},{"key":"2025120520120068000_6.5.e011457.70","doi-asserted-by":"crossref","first-page":"1083","DOI":"10.1007\/s40273-015-0287-6","article-title":"Adjusting for baseline covariates in net benefit regression: how you adjust matters","volume":"33","author":"Isaranuwatchai","year":"2015","journal-title":"Pharmacoeconomics"},{"key":"2025120520120068000_6.5.e011457.71","doi-asserted-by":"publisher","DOI":"10.1016\/j.jad.2011.08.004"}],"container-title":["BMJ Open"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/bmjopen-2016-011457","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,6]],"date-time":"2025-12-06T04:12:17Z","timestamp":1764994337000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmjopen.bmj.com\/lookup\/doi\/10.1136\/bmjopen-2016-011457"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,5]]},"references-count":71,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2016,5,25]]},"published-print":{"date-parts":[[2016,5]]}},"alternative-id":["10.1136\/bmjopen-2016-011457"],"URL":"https:\/\/doi.org\/10.1136\/bmjopen-2016-011457","relation":{},"ISSN":["2044-6055","2044-6055"],"issn-type":[{"value":"2044-6055","type":"print"},{"value":"2044-6055","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,5]]}}}