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Original Investigation
January 20, 2021

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

Author Affiliations
  • 1Institute of Social and Preventive Medicine, University of Bern, Bern, Switzerland
  • 2Department of Clinical Neuro- and Developmental Psychology, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands
  • 3Department of Global Health and Social Medicine, Harvard Medical School, Boston, Massachusetts
  • 4Department of Psychiatry, University of Oxford, Oxford, England
  • 5Amsterdam Public Health Research Institute, Amsterdam, the Netherlands
  • 6Department of Clinical Psychology and Psychotherapy, University of Wuppertal, Wuppertal, Germany
  • 7Department of Health Promotion and Human Behavior, Department of Clinical Epidemiology, Kyoto University Graduate School of Medicine/School of Public Health, Kyoto, Japan
JAMA Psychiatry. Published online January 20, 2021. doi:10.1001/jamapsychiatry.2020.4364
Key Points

Question  What are the patient-specific relative outcomes of guided vs unguided internet-based cognitive behavioral therapy (iCBT) for depression over the short and the long term?

Findings  In this systematic review and meta-analysis of 39 studies comprising 9751 participants, individuals with mild/subthreshold depression was associated with little or no benefit from therapeutic guidance, while guided iCBT was associated with more effectiveness in individuals with moderate and severe depression. Both iCBT modalities outperformed the TAU regardless of depression severity.

Meaning  Although guided iCBT was associated with greater improvement compared with unguided iCBT on average, many people with depression may still benefit from the iCBT without therapeutic guidance, and optimizing treatment assignment would considerably expand treatment coverage worldwide.


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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