Clinical and Cost-Effectiveness of Blended Cognitive Behavioral Therapy or Psychodynamic Therapy Versus Face-to-Face Psychotherapy for Depression (BLENDED Study): Protocol for a Pragmatic, Multicenter, Assessor-Blinded Randomized Controlled Noninferiority Trial.

Background: Depression is a highly prevalent disorder. Yet, there is still a considerable treatment gap because of capacity issues across clinical services, which create barriers to access to effective psychological therapies. In addition, many individuals with depression do not seek treatment, and waiting lists for psychotherapy are typically very long. Blended psychotherapy, which combines online components and in-person sessions, may help bridge the treatment gap as a cost-effective intervention that complements other types of treatment for depression, as it may reduce therapist time and potentially lower the threshold for people to seek treatment for their depression. Objective: This study aims to investigate the clinical effectiveness and cost-effectiveness of blended psychodynamic therapy (PDT) and cognitive behavioral therapy (CBT) for depression compared with face-to-face (FTF) PDT and CBT. Methods: A pragmatic, single-blind, multisite, noninferiority trial will randomize adult patients referred to mental health care centers in Flanders, Belgium, and diagnosed with major depressive disorder (MDD; n=504), to FTF or blended PDT and CBT. The primary outcome is to investigate whether blended therapy for depression (ie, blended PDT and CBT) is noninferior from baseline to 6-month follow-up after treatment termination compared with FTF PDT and CBT in terms of severity of depression assessed with the Beck Depression Inventory-II (BDI-II) based on intention-to-treat analyses. Secondary outcomes include severity of depression as measured with the BDI-II at 1 and 2 years after treatment termination; recovery from depression as assessed with the Structured Clinical Interview for DSM-5 disorders - Clinical Trials Version (SCID-5-CT) and the Patient Health Questionnaire-9 (PHQ-9) at treatment termination and at 6-month, 1-year, and 2-year follow-up; and quality of life as measured with the EuroQoL 5-Dimension 5-Level (EQ-5D-5L) at treatment termination and at 6-month, 1-year, and 2-year follow-up. The feasibility of implementing blended care will be investigated, and health economic analyses will address the cost-effectiveness of blended care versus FTF psychotherapy. Exploratory analyses will focus on possible predictors of treatment outcome and mechanisms of change. Sensitivity analyses will address the potential impact of the COVID-19 pandemic on therapeutic outcomes. Finally, a qualitative substudy aims to address patients' and therapists' subjective experience of blended psychotherapy. Results: The study was funded in July 2018, and the first patient was included in April 2019. As of September 2025, we have enrolled 463 patients. The first data lock (primary outcome) will take place in October 2025, and the results of the primary outcome are expected in February 2026. The second data lock is expected in March 2027, and the results of the 2-year follow-up are expected in September 2027. Conclusions: This trial promises to inform decisions concerning the implementation of blended versus FTF therapy for individuals with depression in routine clinical care.