Dismantling, optimising, and personalising internet cognitive behavioural therapy for depression: a systematic review and component network meta-analysis using individual participant data

Toshi A. Furukawa, Aya Suganuma, Edoardo G. Ostinelli, Gerhard Andersson, Christopher G. Beevers, Jason Shumake, Thomas Berger, Florien Willemijn Boele, Claudia Buntrock, Per Carlbring, Isabella Choi, Helen Christensen, Andrew Mackinnon, Jennifer Dahne, Marcus J. H. Huibers, David D. Ebert, Louise Farrer, Nicholas R. Forand, Daniel R. Strunk, Iony D. EzawaErik Forsell, Viktor Kaldo, Anna Geraedts, Simon Gilbody, Elizabeth Littlewood, Sally Brabyn, Heather D. Hadjistavropoulos, Luke H. Schneider, Robert Johansson, Robin Kenter, Marie Kivi, Cecilia Bjorkelund, Annet Kleiboer, Heleen Riper, Jan Philipp Klein, Johanna Schroder, Bjorn Meyer, Steffen Moritz, Lara Bucker, Ove Lintvedt, Peter Johansson, Johan Lundgren, Jeannette Milgrom, Alan W. Gemmill, David C. Mohr, Jesus Montero-Marin, Javier Garcia-Campayo, Stephanie Nobis, Anna-Carlotta Zarski, Kathleen O'Moore, Alishia D. Williams, Jill M. Newby, Sarah Perini, Rachel Phillips, Justine Schneider, Wendy Pots, Nicole E. Pugh, Derek Richards, Isabelle M. Rosso, Scott L. Rauch, Lisa B. Sheeber, Jessica Smith, Viola Spek, Victor J. Pop, Burcin Unlu, Kim M. P. van Bastelaar, Sanne van Luenen, Nadia Garnefski, Vivian Kraaij, Kristofer Vernmark, Lisanne Warmerdam, Annemieke van Straten, Pavle Zagorscak, Christine Knaevelsrud, Manuel Heinrich, Clara Miguel, Andrea Cipriani, Orestis Efthimiou, Eirini Karyotaki, Pim Cuijpers

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Internet cognitive behavioural therapy (iCBT) is a viable delivery format of CBT for depression. However, iCBT programmes include training in a wide array of cognitive and behavioural skills via different delivery methods, and it remains unclear which of these components are more efficacious and for whom.

We did a systematic review and individual participant data component network meta-analysis (cNMA) of iCBT trials for depression. We searched PubMed, PsycINFO, Embase, and the Cochrane Library for randomised controlled trials (RCTs) published from database inception to Jan 1, 2019, that compared any form of iCBT against another or a control condition in the acute treatment of adults (aged ≥18 years) with depression. Studies with inpatients or patients with bipolar depression were excluded. We sought individual participant data from the original authors. When these data were unavailable, we used aggregate data. Two independent researchers identified the included components. The primary outcome was depression severity, expressed as incremental mean difference (iMD) in the Patient Health Questionnaire-9 (PHQ-9) scores when a component is added to a treatment. We developed a web app that estimates relative efficacies between any two combinations of components, given baseline patient characteristics. This study is registered in PROSPERO, CRD42018104683.

We identified 76 RCTs, including 48 trials contributing individual participant data (11 704 participants) and 28 trials with aggregate data (6474 participants). The participants' weighted mean age was 42·0 years and 12 406 (71%) of 17 521 reported were women. There was suggestive evidence that behavioural activation might be beneficial (iMD −1·83 [95% credible interval (CrI) −2·90 to −0·80]) and that relaxation might be harmful (1·20 [95% CrI 0·17 to 2·27]). Baseline severity emerged as the strongest prognostic factor for endpoint depression. Combining human and automated encouragement reduced dropouts from treatment (incremental odds ratio, 0·32 [95% CrI 0·13 to 0·93]). The risk of bias was low for the randomisation process, missing outcome data, or selection of reported results in most of the included studies, uncertain for deviation from intended interventions, and high for measurement of outcomes. There was moderate to high heterogeneity among the studies and their components.

The individual patient data cNMA revealed potentially helpful, less helpful, or harmful components and delivery formats for iCBT packages. iCBT packages aiming to be effective and efficient might choose to include beneficial components and exclude ones that are potentially detrimental. Our web app can facilitate shared decision making by therapist and patient in choosing their preferred iCBT package.

Japan Society for the Promotion of Science.
Original languageEnglish
Pages (from-to)500-511
Number of pages12
JournalThe Lancet. Psychiatry
Issue number6
Early online date3 May 2021
Publication statusPublished - Jun 2021


FundersFunder number
NIHR Oxford and Thames Valley180083
Oxford Cognitive Health Clinical Research Facility
Techniker Krankenkasse
National Institute of Mental HealthP50MH119029, 006, RP-2017, RP-2017–08ST2–006, R01 MH111610
National Institute on Drug AbuseK23 DA045766
Wellcome Trust104908/Z/14/Z
Canadian Institutes of Health Research152917
National Institute for Health Research
Japan Society for the Promotion of Science17K19808
Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung
Fondazione Cariplo
NIHR Oxford Biomedical Research CentreBRC-1215–20005


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