Clinical and Cost-Effectiveness of PSYCHOnlineTHERAPY: Study Protocol of a Multicenter Blended Outpatient Psychotherapy Cluster Randomized Controlled Trial for Patients With Depressive and Anxiety Disorders

Introduction: Internet- and mobile-based interventions (IMIs) and their integration into routine psychotherapy (i.e., blended therapy) can offer a means of complementing psychotherapy in a flexible and resource optimized way. Objective: The present study will evaluate the non-inferiority, cost-effectiveness, and safety of two versions of integrated blended psychotherapy for depression and anxiety compared to standard cognitive behavioral therapy (CBT). Methods: A three-armed multicenter cluster-randomized controlled non-inferiority trial will be conducted comparing two implementations of blended psychotherapy (PSYCHOnlineTHERAPY(fix/flex)) compared to CBT. Seventy-five outpatient psychotherapists with a CBT-license will be randomized in a 1:1:1 ratio. Each of them is asked to include 12 patients on average with depressive or anxiety disorders resulting in a total sample size of N = 900. All patients receive up to a maximum of 16 psychotherapy sessions, either as routine CBT or alternating with Online self-help sessions (fix: 8/8; flex: 0–16). Assessments will be conducted at patient study inclusion (pre-treatment) and 6, 12, 18, and 24 weeks and 12 months post-inclusion. The primary outcome is depression and anxiety severity at 18 weeks post-inclusion (post-treatment) using the Patient Health Questionnaire Anxiety and Depression Scale. Secondary outcomes are depression and anxiety remission, treatment response, health-related quality of life, patient satisfaction, working alliance, psychotherapy adherence, and patient safety. Additionally, several potential moderators and mediators including patient characteristics and attitudes toward the interventions will be examined, complemented by ecological day-to-day digital behavior variables via passive smartphone sensing as part of an integrated smart-sensing sub-study. Data-analysis will be performed on an intention-to-treat basis with additional per-protocol analyses. In addition, cost-effectiveness and cost-utility analyses will be conducted from a societal and a public health care perspective. Additionally, qualitative interviews on acceptance, feasibility, and optimization potential will be conducted and analyzed. Discussion: PSYCHOnlineTHERAPY will provide evidence on blended psychotherapy in one of the largest ever conducted psychotherapy trials. If shown to be non-inferior and cost-effective, PSYCHOnlineTHERAPY has the potential to innovate psychotherapy in the near future by extending the ways of conducting psychotherapy. The rigorous health care services approach will facilitate a timely implementation of blended psychotherapy into standard care. Trial Registration: The trial is registered in the German Clinical Trials Register (DRKS00023973; date of registration: December 28th 2020).