Clinical Effectiveness and Cost-Effectiveness of Blended Treatment for Major Depression Compared With Treatment as Usual Within Routine Care in Europe: A Noninferiority Randomized Controlled Trial.

Background: Cognitive behavioral therapy (CBT) is an effective and widely used treatment for major depressive disorder (MDD). However, access is limited by long waiting lists and a shortage of trained therapists. Evidence-based guided and self-guided digital interventions can address these challenges, but their large-scale adoption in routine primary and specialized mental health care has been slow. Blended CBT (bCBT), combining face-to-face therapy with structured, guided digital treatment modules, may increase treatment capacity while maintaining the benefits of therapist support.

Objective: The European Comparative Effectiveness Research on Internet-based Depression Treatment study, conducted across 9 European countries, is the first large-scale comparative bCBT study for MDD. The hypothesis was that bCBT is clinically noninferior and cost-effective when compared with treatment as usual (TAU), which mainly consisted of face-to-face CBT.

Methods: A multisite randomized controlled trial was conducted with a noninferiority margin of d=0.20. Main inclusion criteria were age ≥18 years, a diagnosis of MDD based on the Mini International Neuropsychiatric Interview, and a baseline Patient Health Questionnaire-9 (PHQ-9) score of ≥5. The primary outcome was the PHQ-9, with secondary outcomes including MDD remission at 12 months, therapeutic alliance, and costs. Intention-to-treat analyses were performed, and linear mixed modeling was used to assess intervention effects. Cost-effectiveness analyses were conducted from a health care perspective.

Results: A total of 835 patients were included in the study. bCBT was shown to be noninferior to TAU on the primary PHQ-9 outcome during treatment (3 months after the baseline assessment, d=-0.26, 95% CI -0.43 to -0.09), at 6 months (posttreatment, d=-0.21, 95% CI -0.39 to-0.04), and at 12-month follow-up (d=-0.01, 95% CI -0.19 to 0.17). Furthermore, the bCBT group had a significantly lower likelihood of experiencing an MDD episode at 12 months (odds ratio 0.67, 95% CI 0.45-0.99). Subgroup analyses indicated that participants with and with no antidepressant use at baseline in both groups benefited equally from their treatment. Deterioration rates (Reliable Change Index) were below 5% in both groups. bCBT appeared acceptable for patients and therapists, with a strong working alliance in both groups. From a health care perspective, bCBT was not cost-effective at 12 months' assessment, as its total costs were not significantly lower than TAU. However, the probability that bCBT is cost-effective is high (0.95) at a willingness to pay (WTP) of €3800 per improvement in the PHQ-9 score, and 0.76 at a WTP of €10,000 per MDD case prevented (average 2017 exchange rate was €1=US $1.13).

Conclusions: bCBT offers an effective and safe digitally supported alternative to face-to-face TAU for patients with MDD and their therapists in routine clinical care. From a health care perspective, its cost-effectiveness depends on policymakers' WTP for the additional clinical benefits achieved.