Effectiveness of Guided Self-Help Versus Internet-Delivered or Face-to-Face Cognitive Behavioral Therapy for Depression and Anxiety: Four Parallel Randomized Controlled Non-Inferiority Trials of the Finnish First-Line Therapies – Initiative (FLT-Step)

Background Low-intensity cognitive behavioral therapy (CBT) based guided self-help (GSH) and therapist-guided internet-delivered CBT (iCBT) have demonstrated equivalent effectiveness and superior cost-efficiency compared to traditional face-to-face CBT (fCBT) for treating depression and anxiety. This study aims to address critical gaps in the current understanding of the effectiveness and cost-effectiveness of various CBT interventions for depression and anxiety within a stepped care model. Methods This paper outlines FLT-step, a multi-center randomized controlled trial (RCT) study with four parallel study protocols for examining widely used CBT interventions in public healthcare using a stepped care approach. The objective is to compare the effectiveness and cost-effectiveness of three treatment approaches for depression (protocol 1) and anxiety (protocol 2) in a non-inferiority setting within the Finnish public healthcare: A) a stepped care model (GSH followed by fCBT for non-responders), B) fCBT, and C) therapist-guided iCBT. The non-inferiority margin was based on patient-detectable improvement and is set at 1.7 points on the Patient Health Questionnaire (PHQ-9, protocol 1) and 1.5 points on the Generalized Anxiety Disorder 7-item scale (GAD-7, protocol 2). We plan to recruit 948 adults (≥ 16 years old) with depression (PHQ-9 ≥ 10 p) and 948 adults with anxiety (GAD-7 ≥ 10 p). A randomized sub study will examine the effect of waiting time (≤4 or ≥ 5 weeks) for the treatment outcomes of depression (n = 115, protocol 3) or anxiety (n = 115, protocol 4), comparing the stepped care model (A) and fCBT (B). In all four RCTs, the primary outcome measures are the within-individual change in depression (PHQ-9) or anxiety (GAD-7) symptoms at six months. Secondary outcomes include wellbeing, work and social ability, costs associated with illness, and quality of life. The follow-up is planned to span up to 20 years. Finnish national registry data will be used to supplement participant data and create population-matched controls to evaluate whether the interventions can prevent clinical episodes, reduce long-term societal costs, and decrease somatic morbidity. Discussion This extensive RCT aims to deliver new insights into comparative effectiveness and cost-effectiveness of widely utilized low-intensity CBT treatments for depression and anxiety, and the impact of waiting times on outcomes. Trial Registrations (Registration date): ISRCTN14296278 (18 Sep 2024), ISRCTN63914711 (8 Oct 2024), ISRCTN10064801 (20 Sep 2024), ISRCTN14990924 (8 Oct 2024) Issue date: 3 Jul 2025 Eeva-Eerika Helminen and Suoma E. Saarni are equal first author contributions