Internet-Based Cognitive Behavioral Therapy for Depression
Authors: Karyotaki Eirini , Efthimiou Orestis , Miguel Clara , Maas genannt Bermpohl Frederic , Furukawa Toshi A. , Cuijpers Pim ,   Individual Patient Data Meta-Analyses for Depression (IPDMA-DE) Collaboration, Riper Heleen , Patel Vikram , Mira Adriana , Gemmil Alan W. , Yeung Albert S. , Lange Alfred , Williams Alishia D. , Mackinnon Andrew , Geraedts Anna , van Straten Annemieke , Meyer Björn , Björkelund Cecilia , Knaevelsrud Christine , Beevers Christopher G. , Botella Cristina , Strunk Daniel R. , Mohr David C. , Ebert David D. , Kessler David , Richards Derek , Littlewood Elizabeth , Forsell Erik , Feng Fan , Wang Fang , Andersson Gerhard , Hadjistavropoulos Heather , Christensen Heleen , Ezawa Iony D. , Choi Isabella , Rosso Isabelle M. , Klein Jan Philipp , Shumake Jason , Garcia-Campayo Javier , Milgrom Jeannette , Smith Jessica , Montero-Marin Jesus , Newby Jill M. , Bretón-López Juana , Schneider Justine , Vernmark Kristofer , Bücker Lara , Sheeber Lisa B. , Warmerdam Lisanne , Farrer Louise , Heinrich Manuel , Huibers Marcus J. H. , Kivi Marie , Kraepelien Martin , Forand Nicholas R. , Pugh Nicky , Lindefors Nils , Lintvedt Ove , Zagorscak Pavle , Carlbring Per , Phillips Rachel , Johansson Robert , Kessler Ronald C. , Brabyn Sally , Perini Sarah , Rauch Scott L. , Gilbody Simon , Moritz Steffen , Berger Thomas , Pop Victor , Kaldo Viktor , Spek Viola , Forsell Yvonne 
Published: January 2021

ImportancePersonalized 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.ObjectiveTo provide personalized estimates of short-term and long-term relative efficacy of guided and unguided iCBT for depression using patient-level information.Data SourcesWe searched PubMed, Embase, PsycInfo, and Cochrane Library to identify randomized clinical trials (RCTs) published up to January 1, 2019.Study SelectionEligible 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 SynthesisWe 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 MeasuresPatient Health Questionnaire–9 (PHQ-9) scores.ResultsOf 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 RelevanceIn 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.