Background <p>Depression is a major public health problem with a rising prevalence and a negative impact on quality of life, mortality, and morbidity. While effective treatments, such as behavioral activation, are available, they are only effective for approximately half of the patients. Adherence to activities between therapy sessions is associated with better outcomes in behavioral activation, yet adherence rates could be improved. Just-in-time adaptive interventions (JITAIs) offer the potential to improve adherence to activities and thus improve outcomes in behavioral activation for depression; however, to date, they have not yet been studied.</p> Methods <p>This mixed-methods study uses a participatory design phase with 12 participants with depression and 4 therapists to develop JITAIs for behavioral activation in depression, through focus groups and thematic analyses to answer the specific design question. A subsequent evaluation phase consists of a micro-randomized trial to assess the proximal effects of JITAIs and a nonrandomized quasi-experimental design to evaluate the feasibility and changes in distal outcomes compared with treatment as usual (TAU). Participants diagnosed with depression will be recruited from a mental health institution: 52 receiving TAU plus JITAIs and 52 receiving TAU only. The primary outcome is feasibility, and JITAIs are considered feasible when the dose-received adherence rate is greater than 60%. The secondary outcomes are acceptance as measured via the System Usability Scale, the Client Satisfaction Questionnaire and the Twente Engagement with E-health Technologies Scale. Ecological momentary assessments of depression and well-being are used as proximal outcomes, and the Patient Health Questionnaire-9, the Mental Health Continuum–Short Form, the Questionnaire about the Process of Recovery, and the EuroQol-5 Dimension are used as distal outcomes at the end of treatment.</p> Discussion <p>This study aims to develop and evaluate JITAIs to support behavioral activation in the treatment of depression. If feasible, JITAIs have the potential to be further examined in randomized controlled trials and benefit people with depression by providing a scalable way to improve adherence and outcomes in behavioral activation.</p> Trial registration <p>The Netherlands Clinical Trial Register (NL-OMON57144), prospectively registered on October 22, 2024.</p>