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)

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. 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. 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. ISRCTN14296278 (18 Sep 2024), ISRCTN63914711 (8 Oct 2024), ISRCTN10064801 (20 Sep 2024), ISRCTN14990924 (8 Oct 2024).