Effectiveness of guided self-help, guided internet-delivered cognitive behavioral therapy, and face-to-face cognitive behavioral therapy for depression and anxiety: protocols of 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 guided internet-delivered CBT (GiCBT) have demonstrated equivalent effectiveness and superior cost-efficiency compared to traditional face-to-face CBT (fCBT) for treating depression and anxiety. This study addresses 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: We describe a pragmatic multi-center randomized controlled trial (RCT) study with four parallel study protocols (the Finnish First-Line Therapies –Initiative study, FLT-step) for examining three widely used CBT interventions in public healthcare using a stepped care approach according to the FLT-Initiative. The study was preregistered in spring 2024, and participant recruitment began in September 2024. We 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) stepped care (GSH followed by fCBT for non-responders), (B) fCBT, and (C) GiCBT. Non-inferiority margins reflect patient-detectable improvement: 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 substudy 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 will extend 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 will provide robust evidence on the comparative effectiveness and cost-effectiveness of low-intensity CBT treatments for depression and anxiety, and clarify 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).