Internet-Based Cognitive Behavioral Therapy for Depression: A Systematic Review and Individual Patient Data Network Meta-analysis

doi:10.1001/jamapsychiatry.2020.4364

. 2021 Apr 1;78(4):361-371.

doi: 10.1001/jamapsychiatry.2020.4364.

Internet-Based Cognitive Behavioral Therapy for Depression: A Systematic Review and Individual Patient Data Network Meta-analysis

Eirini Karyotaki^{1

2

3}, Orestis Efthimiou^{1

4}, Clara Miguel^{2

5}, Frederic Maas Genannt Bermpohl⁶, Toshi A Furukawa^{6

7}, Pim Cuijpers^{2

5}; Individual Patient Data Meta-Analyses for Depression (IPDMA-DE) Collaboration; Heleen Riper^{2

5

8}, Vikram Patel³, Adriana Mira^{9

10}, Alan W Gemmil¹¹, Albert S Yeung¹², Alfred Lange¹³, Alishia D Williams¹⁴, Andrew Mackinnon^{15

16}, Anna Geraedts¹⁷, Annemieke van Straten^{2

5}, Björn Meyer^{18

19}, Cecilia Björkelund²⁰, Christine Knaevelsrud²¹, Christopher G Beevers²², Cristina Botella^{23

24}, Daniel R Strunk²⁵, David C Mohr²⁶, David D Ebert²⁷, David Kessler^{28

29}, Derek Richards^{30

31}, Elizabeth Littlewood³², Erik Forsell³³, Fan Feng³⁴, Fang Wang³⁵, Gerhard Andersson^{33

36}, Heather Hadjistavropoulos³⁷, Heleen Christensen¹⁵, Iony D Ezawa²⁵, Isabella Choi³⁸, Isabelle M Rosso^{39

40}, Jan Philipp Klein⁴¹, Jason Shumake²², Javier Garcia-Campayo^{42

43}, Jeannette Milgrom¹¹, Jessica Smith⁴⁴, Jesus Montero-Marin⁴⁵, Jill M Newby^{14

15}, Juana Bretón-López^{23

24}, Justine Schneider⁴⁶, Kristofer Vernmark^{36

47}, Lara Bücker⁴⁸, Lisa B Sheeber⁴⁹, Lisanne Warmerdam⁵⁰, Louise Farrer⁵¹, Manuel Heinrich²¹, Marcus J H Huibers^{2

5}, Marie Kivi⁵², Martin Kraepelien³³, Nicholas R Forand^{53

54}, Nicky Pugh³⁷, Nils Lindefors³³, Ove Lintvedt⁵⁵, Pavle Zagorscak²¹, Per Carlbring⁵⁶, Rachel Phillips⁵⁷, Robert Johansson⁵⁶, Ronald C Kessler⁵⁸, Sally Brabyn³¹, Sarah Perini⁵⁹, Scott L Rauch³⁹, Simon Gilbody^{32

60}, Steffen Moritz⁴⁸, Thomas Berger⁶¹, Victor Pop⁶², Viktor Kaldo^{33

63}, Viola Spek⁶², Yvonne Forsell⁶⁴

Affiliations

¹ Institute of Social and Preventive Medicine, University of Bern, Bern, Switzerland.
² Department of Clinical Neuro- and Developmental Psychology, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands.
³ Department of Global Health and Social Medicine, Harvard Medical School, Boston, Massachusetts.
⁴ Department of Psychiatry, University of Oxford, Oxford, England.
⁵ Amsterdam Public Health Research Institute, Amsterdam, the Netherlands.
⁶ Department of Clinical Psychology and Psychotherapy, University of Wuppertal, Wuppertal, Germany.
⁷ Department of Health Promotion and Human Behavior, Department of Clinical Epidemiology, Kyoto University Graduate School of Medicine/School of Public Health, Kyoto, Japan.
⁸ Department of Research and Innovation, GGZ inGeest, Specialized Mental Health Care, Amsterdam, the Netherlands.
⁹ PROMOSAM Excellence in Research Program, MINECO, Valencia, Spain.
¹⁰ Department of Personality, Evaluation and Psychological Treatment, Valencia University, Valencia, Spain.
¹¹ Parent-Infant Research Institute, Department of Clinical and Health Psychology, Heidelberg Repatriation Hospital, Austin Health, Ivanhoe, Victoria, Australia.
¹² Depression Clinical and Research Program, Massachusetts General Hospital, Harvard University, Boston, Massachusetts.
¹³ Department of Clinical Psychology, University of Amsterdam, Amsterdam, the Netherlands.
¹⁴ Department of Psychology, University of New South Wales, Sydney, New South Wales, Australia.
¹⁵ Prince of Wales Hospital, Black Dog Institute, University of New South Wales, Sydney, New South Wales, Australia.
¹⁶ Center for Mental Health, University of Melbourne, Melbourne, Victoria, Australia.
¹⁷ HumanTotalCare, Utrecht, the Netherlands.
¹⁸ Research Department, Gaia AG, Hamburg, Germany.
¹⁹ Department of Psychology, City, University of London, London, England.
²⁰ Primary Health Care, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg School of Public Health and Community Medicine, Gothenburg, Sweden.
²¹ Department for Clinical Psychological Intervention, Freie Universität Berlin, Berlin, Germany.
²² Department of Psychology and Institute for Mental Health Research, The University of Texas at Austin.
²³ Department of Basic Psychology, Clinic and Psychobiology, Jaume I University, Castellon, Spain.
²⁴ CIBER Fisiopatología Obesidad y Nutrición (CIBERObn), Instituto Salud Carlos III, Madrid, Spain.
²⁵ Department of Psychology, The Ohio State University, Columbus, Ohio.
²⁶ Center for Behavioral Intervention Technologies, Department of Preventive Medicine, Northwestern University, Chicago, Illinois.
²⁷ Department of Clinical Psychology and Psychotherapy, Friedrich-Alexander-University Erlangen-Nürnberg, Erlangen, Germany.
²⁸ Centre for Academic Primary Care, Bristol Medical School (Population Health Sciences), University of Bristol, Bristol, England.
²⁹ National Institute for Health Research Bristol Biomedical Research Centre, University Hospitals Bristol NHS Foundation Trust and University of Bristol, Bristol, England.
³⁰ E-mental Health Research Group, Trinity College Dublin School of Psychology, Dublin, Ireland.
³¹ Clinical Research & Innovation, SilverCloud Health, Dublin, Ireland.
³² Department of Health Sciences, University of York, York, England.
³³ Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet & Stockholm Health Care Services, Region Stockholm, Stockholm, Sweden.
³⁴ Benson Henry Institute for Mind Body Medicine, Massachusetts General Hospital, Harvard University, Boston, Massachusetts.
³⁵ Department of Psychology and Sleep Medicine, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China.
³⁶ Department of Behavioral Sciences and Learning, Linköping University, Linköping, Sweden.
³⁷ Department of Psychology, University of Regina, Regina, Saskatchewan, Canada.
³⁸ Central Clinical School, Brain and Mind Centre, Faculty of Medicine and Health, University of Sydney, Sydney, New South Wales, Australia.
³⁹ McLean Hospital, Belmont, Massachusetts.
⁴⁰ Harvard Medical School, Boston, Massachusetts.
⁴¹ Department of Psychiatry and Psychotherapy, Luebeck University, Luebeck, Germany.
⁴² Aragon Institute for Health Research (IIS Aragón), Miguel Servet University Hospital, Zaragoza, Spain.
⁴³ Primary Care Prevention and Health Promotion Research Network, RedIAPP, Madrid, Spain.
⁴⁴ Imperial Clinical Trials Unit, Imperial College London, London, England.
⁴⁵ Warneford Hospital, Department of Psychiatry, University of Oxford, Oxford, England.
⁴⁶ Institute of Mental Health, University of Nottingham, Nottingham, England.
⁴⁷ Psykologpartners, Linkoping, Sweden.
⁴⁸ Department of Psychiatry and Psychotherapy, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
⁴⁹ Oregon Research Institute, Eugene, Oregon.
⁵⁰ National Health Care Institute, Diemen, the Netherlands.
⁵¹ Centre for Mental Health Research, The Australian National University, Canberra, Australia.
⁵² Department of Psychology and AgeCap, University of Gothenburg, Gothenburg, Sweden.
⁵³ Department of Psychiatry and Behavioral Health, The Ohio State University Wexner Medical Center, Columbus, Ohio.
⁵⁴ Department of Psychiatry, The Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead, New York.
⁵⁵ Norwegian Center for E-health research, Tromsø, Norway.
⁵⁶ Department of Psychology, Stockholm University, Stockholm, Sweden.
⁵⁷ Faculty of Medicine, Imperial College London School of Public Health, London, England.
⁵⁸ Department of Health Care Policy, Harvard Medical School, Boston, Massachusetts.
⁵⁹ The Clinical Psychology Centre, Sydney, New South Wales, Australia.
⁶⁰ Hull York Medical School, University of York, York, England.
⁶¹ Department of Clinical Psychology and Psychotherapy, University of Bern, Bern, Switzerland.
⁶² Department of Clinical and Medical Health Psychology, Tilburg University, Tilburg, the Netherlands.
⁶³ Department of Psychology, Faculty of Health and Life Sciences, Linnaeus University, Växjö, Sweden.
⁶⁴ Section of Epidemiology and Public Health Intervention Research, Department of Global Public Health, Karolinska Institutet, Stockholm Health Care Services, Region Stockholm, Sweden.

PMID: 33471111
PMCID: PMC8027916
DOI: 10.1001/jamapsychiatry.2020.4364

Internet-Based Cognitive Behavioral Therapy for Depression: A Systematic Review and Individual Patient Data Network Meta-analysis

Eirini Karyotaki et al. JAMA Psychiatry. 2021.

. 2021 Apr 1;78(4):361-371.

doi: 10.1001/jamapsychiatry.2020.4364.

Authors

Affiliations

¹ Institute of Social and Preventive Medicine, University of Bern, Bern, Switzerland.
² Department of Clinical Neuro- and Developmental Psychology, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands.
³ Department of Global Health and Social Medicine, Harvard Medical School, Boston, Massachusetts.
⁴ Department of Psychiatry, University of Oxford, Oxford, England.
⁵ Amsterdam Public Health Research Institute, Amsterdam, the Netherlands.
⁶ Department of Clinical Psychology and Psychotherapy, University of Wuppertal, Wuppertal, Germany.
⁷ Department of Health Promotion and Human Behavior, Department of Clinical Epidemiology, Kyoto University Graduate School of Medicine/School of Public Health, Kyoto, Japan.
⁸ Department of Research and Innovation, GGZ inGeest, Specialized Mental Health Care, Amsterdam, the Netherlands.
⁹ PROMOSAM Excellence in Research Program, MINECO, Valencia, Spain.
¹⁰ Department of Personality, Evaluation and Psychological Treatment, Valencia University, Valencia, Spain.
¹¹ Parent-Infant Research Institute, Department of Clinical and Health Psychology, Heidelberg Repatriation Hospital, Austin Health, Ivanhoe, Victoria, Australia.
¹² Depression Clinical and Research Program, Massachusetts General Hospital, Harvard University, Boston, Massachusetts.
¹³ Department of Clinical Psychology, University of Amsterdam, Amsterdam, the Netherlands.
¹⁴ Department of Psychology, University of New South Wales, Sydney, New South Wales, Australia.
¹⁵ Prince of Wales Hospital, Black Dog Institute, University of New South Wales, Sydney, New South Wales, Australia.
¹⁶ Center for Mental Health, University of Melbourne, Melbourne, Victoria, Australia.
¹⁷ HumanTotalCare, Utrecht, the Netherlands.
¹⁸ Research Department, Gaia AG, Hamburg, Germany.
¹⁹ Department of Psychology, City, University of London, London, England.
²⁰ Primary Health Care, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg School of Public Health and Community Medicine, Gothenburg, Sweden.
²¹ Department for Clinical Psychological Intervention, Freie Universität Berlin, Berlin, Germany.
²² Department of Psychology and Institute for Mental Health Research, The University of Texas at Austin.
²³ Department of Basic Psychology, Clinic and Psychobiology, Jaume I University, Castellon, Spain.
²⁴ CIBER Fisiopatología Obesidad y Nutrición (CIBERObn), Instituto Salud Carlos III, Madrid, Spain.
²⁵ Department of Psychology, The Ohio State University, Columbus, Ohio.
²⁶ Center for Behavioral Intervention Technologies, Department of Preventive Medicine, Northwestern University, Chicago, Illinois.
²⁷ Department of Clinical Psychology and Psychotherapy, Friedrich-Alexander-University Erlangen-Nürnberg, Erlangen, Germany.
²⁸ Centre for Academic Primary Care, Bristol Medical School (Population Health Sciences), University of Bristol, Bristol, England.
²⁹ National Institute for Health Research Bristol Biomedical Research Centre, University Hospitals Bristol NHS Foundation Trust and University of Bristol, Bristol, England.
³⁰ E-mental Health Research Group, Trinity College Dublin School of Psychology, Dublin, Ireland.
³¹ Clinical Research & Innovation, SilverCloud Health, Dublin, Ireland.
³² Department of Health Sciences, University of York, York, England.
³³ Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet & Stockholm Health Care Services, Region Stockholm, Stockholm, Sweden.
³⁴ Benson Henry Institute for Mind Body Medicine, Massachusetts General Hospital, Harvard University, Boston, Massachusetts.
³⁵ Department of Psychology and Sleep Medicine, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China.
³⁶ Department of Behavioral Sciences and Learning, Linköping University, Linköping, Sweden.
³⁷ Department of Psychology, University of Regina, Regina, Saskatchewan, Canada.
³⁸ Central Clinical School, Brain and Mind Centre, Faculty of Medicine and Health, University of Sydney, Sydney, New South Wales, Australia.
³⁹ McLean Hospital, Belmont, Massachusetts.
⁴⁰ Harvard Medical School, Boston, Massachusetts.
⁴¹ Department of Psychiatry and Psychotherapy, Luebeck University, Luebeck, Germany.
⁴² Aragon Institute for Health Research (IIS Aragón), Miguel Servet University Hospital, Zaragoza, Spain.
⁴³ Primary Care Prevention and Health Promotion Research Network, RedIAPP, Madrid, Spain.
⁴⁴ Imperial Clinical Trials Unit, Imperial College London, London, England.
⁴⁵ Warneford Hospital, Department of Psychiatry, University of Oxford, Oxford, England.
⁴⁶ Institute of Mental Health, University of Nottingham, Nottingham, England.
⁴⁷ Psykologpartners, Linkoping, Sweden.
⁴⁸ Department of Psychiatry and Psychotherapy, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
⁴⁹ Oregon Research Institute, Eugene, Oregon.
⁵⁰ National Health Care Institute, Diemen, the Netherlands.
⁵¹ Centre for Mental Health Research, The Australian National University, Canberra, Australia.
⁵² Department of Psychology and AgeCap, University of Gothenburg, Gothenburg, Sweden.
⁵³ Department of Psychiatry and Behavioral Health, The Ohio State University Wexner Medical Center, Columbus, Ohio.
⁵⁴ Department of Psychiatry, The Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead, New York.
⁵⁵ Norwegian Center for E-health research, Tromsø, Norway.
⁵⁶ Department of Psychology, Stockholm University, Stockholm, Sweden.
⁵⁷ Faculty of Medicine, Imperial College London School of Public Health, London, England.
⁵⁸ Department of Health Care Policy, Harvard Medical School, Boston, Massachusetts.
⁵⁹ The Clinical Psychology Centre, Sydney, New South Wales, Australia.
⁶⁰ Hull York Medical School, University of York, York, England.
⁶¹ Department of Clinical Psychology and Psychotherapy, University of Bern, Bern, Switzerland.
⁶² Department of Clinical and Medical Health Psychology, Tilburg University, Tilburg, the Netherlands.
⁶³ Department of Psychology, Faculty of Health and Life Sciences, Linnaeus University, Växjö, Sweden.
⁶⁴ Section of Epidemiology and Public Health Intervention Research, Department of Global Public Health, Karolinska Institutet, Stockholm Health Care Services, Region Stockholm, Sweden.

PMID: 33471111
PMCID: PMC8027916
DOI: 10.1001/jamapsychiatry.2020.4364

Erratum in

Error in Display of Author Name.
[No authors listed] [No authors listed] JAMA Psychiatry. 2024 Mar 1;81(3):320. doi: 10.1001/jamapsychiatry.2023.5122. JAMA Psychiatry. 2024. PMID: 38150233 Free PMC article. No abstract available.

Abstract

Importance: Personalized treatment choices would increase the effectiveness of internet-based cognitive behavioral therapy (iCBT) for depression to the extent that patients differ in interventions that better suit them.

Objective: To provide personalized estimates of short-term and long-term relative efficacy of guided and unguided iCBT for depression using patient-level information.

Data sources: We searched PubMed, Embase, PsycInfo, and Cochrane Library to identify randomized clinical trials (RCTs) published up to January 1, 2019.

Study selection: Eligible RCTs were those comparing guided or unguided iCBT against each other or against any control intervention in individuals with depression. Available individual patient data (IPD) was collected from all eligible studies. Depression symptom severity was assessed after treatment, 6 months, and 12 months after randomization.

Data extraction and synthesis: We conducted a systematic review and IPD network meta-analysis and estimated relative treatment effect sizes across different patient characteristics through IPD network meta-regression.

Main outcomes and measures: Patient Health Questionnaire-9 (PHQ-9) scores.

Results: Of 42 eligible RCTs, 39 studies comprising 9751 participants with depression contributed IPD to the IPD network meta-analysis, of which 8107 IPD were synthesized. Overall, both guided and unguided iCBT were associated with more effectiveness as measured by PHQ-9 scores than control treatments over the short term and the long term. Guided iCBT was associated with more effectiveness than unguided iCBT (mean difference [MD] in posttreatment PHQ-9 scores, -0.8; 95% CI, -1.4 to -0.2), but we found no evidence of a difference at 6 or 12 months following randomization. Baseline depression was found to be the most important modifier of the relative association for efficacy of guided vs unguided iCBT. Differences between unguided and guided iCBT in people with baseline symptoms of subthreshold depression (PHQ-9 scores 5-9) were small, while guided iCBT was associated with overall better outcomes in patients with baseline PHQ-9 greater than 9.

Conclusions and relevance: In this network meta-analysis with IPD, guided iCBT was associated with more effectiveness than unguided iCBT for individuals with depression, benefits were more substantial in individuals with moderate to severe depression. Unguided iCBT was associated with similar effectiveness among individuals with symptoms of mild/subthreshold depression. Personalized treatment selection is entirely possible and necessary to ensure the best allocation of treatment resources for depression.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Björkelund reports grants from Swedish Social Insurance Agency Sweden during the conduct of the study. Dr Knaevelsrud reported grants from Techniker Krankenkasse (Public Health Care Company) during the conduct of the study and personal fees from Oberbergklinik and Servier outside the submitted work. Dr Beevers reported grants from the National Institutes of Health and personal fees from Association for Psychological Science outside the submitted work. Dr Mohr reported personal fees from Otsuka Pharmaceuticals, Apple Inc, Pear Therapeutics, One Mind Foundation, and other support from Adaptive Health Equity Interest outside the submitted work. Dr Ebert reported other support from GET.ON Insitute (HelloBetter Shareholder of digital therapeutic company); personal fees from Minddistrict Consultancy, Lantern Consultancy Fees, Sanofi Consultancy, and Novartis Consultancy Fees outside the submitted work; and holding IP rights to several digital therapeutics for the prevention and treatment of mental health disorders. Dr Richards reported other support from SilverCloud Health Salary outside the submitted work. Dr Hadjistavropoulos reported grants from Canadian Institutes of Health Research, Saskatchewan Health Research Foundation, and Rx&D Research Foundation during the conduct of the study. Dr Christensen reported potentially receiving royalties to MoodGYM if it is successful commercially and is Director of the Black Dog Institute, which creates e-health interventions. Dr Klein reported grants from German Ministry of Health II A 5-2512 FSB 052 during the conduct of the study; grants from Servier; personal fees from Springer, Beltz, Elsevier, and Hogrefe outside the submitted work; and payments for workshops on psychotherapy for chronic depression and on psychiatric emergencies. Dr Shumake reported grants from National Institute for Mental Health during the conduct of the study. Dr García-Campayo reports grants from Instituto de salud Carlos III during the conduct of the study. Dr Heinrich reported grants from Techniker Krankasse (Public Health Care Company) during the conduct of the study. Dr Zagorscak reported grants from Techniker Krankenkasse (Public Health Care Company) during the conduct of the study. Dr R. Kessler reported personal fees from Datastat Inc and personal fees from Sage Pharmaceuticals, and Takeda during the conduct of the study. Dr Rauch reported grants from USA MRAA during the conduct of the study. Dr Furukawa reported grants from Mitsubishi-Tanabe and personal fees from Mitsubishi-Tanabe, MSD, and Shionogi outside the submitted work; in addition, Dr Furukawa had a patent for 2018-177688 pending for smartphone CBT apps and a patent for copyrights licensed for Kokoro-app smartphone CBT app. No other disclosures were reported.

Figures

**Figure 2.. Aggregated Meta-analytic Effect Sizes for Efficacy at Posttreatment**
The number in each cell shows the relative treatment effect size between the column-defining treatment and the row-defining treatment. The outcome is depression symptom severity in Patient Health Questionnaire–9 (PHQ-9), and results are presented as mean difference (MD) (95% CIs). Estimates in light blue are derived from aggregated data network meta-analysis, where MD less than 0 favors the column-defining treatment of each cell. Estimates in light brown are derived from the pairwise meta-analyses, where MD less than 0 favors the row-defining treatment of each cell. iCBT indicates internet-based cognitive behavioral therapy; TAU, treatment as usual; WL, waiting list.

**Figure 3.. Aggregated Meta-analytic Effect Sizes for Efficacy Over the Long Term**
Interpretation of this Figure as per Figure 2. iCBT indicates internet-based cognitive behavioral therapy; TAU, treatment as usual; WL, waiting list.

See this image and copyright information in PMC

Comment in

Internet-Based Therapy for Depression Found Effective.
[No authors listed] [No authors listed] Am J Nurs. 2021 Jul 1;121(7):18. doi: 10.1097/01.NAJ.0000758456.97053.7c. Am J Nurs. 2021. PMID: 34156368

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References

1. McLaughlin KA. The public health impact of major depression: a call for interdisciplinary prevention efforts. Prev Sci. 2011;12(4):361-371. doi:10.1007/s11121-011-0231-8 - DOI - PMC - PubMed
1. Ustün TB, Ayuso-Mateos JL, Chatterji S, Mathers C, Murray CJL. Global burden of depressive disorders in the year 2000. Br J Psychiatry. 2004;184(5):386-392. doi:10.1192/bjp.184.5.386 - DOI - PubMed
1. Wittchen H-U, Jacobi F, Rehm J, et al. . The size and burden of mental disorders and other disorders of the brain in Europe 2010. Eur Neuropsychopharmacol. 2011;21(9):655-679. doi:10.1016/j.euroneuro.2011.07.018 - DOI - PubMed
1. Chisholm D, Sweeny K, Sheehan P, et al. . Scaling-up treatment of depression and anxiety: a global return on investment analysis. Lancet Psychiatry. 2016;3(5):415-424. doi:10.1016/S2215-0366(16)30024-4 - DOI - PubMed
1. Cuijpers P, Noma H, Karyotaki E, Vinkers CH, Cipriani A, Furukawa TA. A network meta-analysis of the effects of psychotherapies, pharmacotherapies and their combination in the treatment of adult depression. World Psychiatry. 2020;19(1):92-107. doi:10.1002/wps.20701 - DOI - PMC - PubMed

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[1] McLaughlin KA. The public health impact of major depression: a call for interdisciplinary prevention efforts. Prev Sci. 2011;12(4):361-371. doi:10.1007/s11121-011-0231-8 - DOI - PMC - PubMed

[2] McLaughlin KA. The public health impact of major depression: a call for interdisciplinary prevention efforts. Prev Sci. 2011;12(4):361-371. doi:10.1007/s11121-011-0231-8 - DOI - PMC - PubMed

[3] Ustün TB, Ayuso-Mateos JL, Chatterji S, Mathers C, Murray CJL. Global burden of depressive disorders in the year 2000. Br J Psychiatry. 2004;184(5):386-392. doi:10.1192/bjp.184.5.386 - DOI - PubMed

[4] Ustün TB, Ayuso-Mateos JL, Chatterji S, Mathers C, Murray CJL. Global burden of depressive disorders in the year 2000. Br J Psychiatry. 2004;184(5):386-392. doi:10.1192/bjp.184.5.386 - DOI - PubMed

[5] Wittchen H-U, Jacobi F, Rehm J, et al. . The size and burden of mental disorders and other disorders of the brain in Europe 2010. Eur Neuropsychopharmacol. 2011;21(9):655-679. doi:10.1016/j.euroneuro.2011.07.018 - DOI - PubMed

[6] Wittchen H-U, Jacobi F, Rehm J, et al. . The size and burden of mental disorders and other disorders of the brain in Europe 2010. Eur Neuropsychopharmacol. 2011;21(9):655-679. doi:10.1016/j.euroneuro.2011.07.018 - DOI - PubMed

[7] Chisholm D, Sweeny K, Sheehan P, et al. . Scaling-up treatment of depression and anxiety: a global return on investment analysis. Lancet Psychiatry. 2016;3(5):415-424. doi:10.1016/S2215-0366(16)30024-4 - DOI - PubMed

[8] Chisholm D, Sweeny K, Sheehan P, et al. . Scaling-up treatment of depression and anxiety: a global return on investment analysis. Lancet Psychiatry. 2016;3(5):415-424. doi:10.1016/S2215-0366(16)30024-4 - DOI - PubMed

[9] Cuijpers P, Noma H, Karyotaki E, Vinkers CH, Cipriani A, Furukawa TA. A network meta-analysis of the effects of psychotherapies, pharmacotherapies and their combination in the treatment of adult depression. World Psychiatry. 2020;19(1):92-107. doi:10.1002/wps.20701 - DOI - PMC - PubMed

[10] Cuijpers P, Noma H, Karyotaki E, Vinkers CH, Cipriani A, Furukawa TA. A network meta-analysis of the effects of psychotherapies, pharmacotherapies and their combination in the treatment of adult depression. World Psychiatry. 2020;19(1):92-107. doi:10.1002/wps.20701 - DOI - PMC - PubMed

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Internet-Based Cognitive Behavioral Therapy for Depression: A Systematic Review and Individual Patient Data Network Meta-analysis

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