Annet Kleiboer

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.

Background: Depressive symptoms are common among older adults and can significantly impact their quality of life. However, many older adults face barriers to accessing psychological treatment. Internet-based cognitive behavioral therapy (iCBT) is a promising alternative to face-to-face treatments, but its feasibility among older adults has been less extensively studied than in adult populations. Objective: This study evaluated the feasibility of guided iCBT for adults aged 55 years and older with mild to moderate depressive symptoms recruited from the general population. Methods: This study is a feasibility study with a single-group, pretest-posttest design (n=21), in which all participants received guided iCBT for 8 weeks. Assessments were conducted at baseline (T0) and after the intervention (T1). The primary outcome was feasibility, conceptualized as satisfaction, usability, engagement, and uptake of iCBT. Secondary outcome measures included depression severity, working alliance, and technical alliance. Results: Participants were mostly highly educated (13/21, 61.9%), female (18/21, 85.7%), had an average age of 59.85 (SD 4.19; range 55-68) years, and reported moderate digital literacy. Feasibility outcomes indicated high satisfaction and engagement and moderate usability. Working alliance was rated as good by both participants and coaches, and technical alliance was rated as moderate by the participants. There was a nonsignificant modest decrease in depressive symptoms (Cohen d=0.47). Of the 20 participants who started the intervention, all completed the first 2 modules, but completion declined across the remaining 6 modules, with only 1 (5%) participant completing all modules. Conclusions: This study found that guided iCBT has the potential to be a feasible option for older adults experiencing depressive symptoms, with participants reporting generally positive satisfaction, moderate engagement, and a moderate therapeutic bond with their coaches. However, below-average usability ratings and a moderate technical alliance suggest that some aspects of the platform require improvement. Future research should focus on improving usability and adherence, as well as testing the intervention in a larger and more diverse population.

BACKGROUND Improving the cost-effectiveness and scalability of mental health interventions remains challenging. The Multiphase Optimization Strategy (MOST) framework provides a structured aproach for developing, optimizing, and evaluating behavioral interventions by balancing effectiveness with efficiency, economy, and scalability. It does so across three phases: Preparation (theoretical grounding and component selection), Optimization (experimental testing), and Evaluation (confirmatory trial). Digital mental health interventions are especially suited to this modular approach, as they enable researchers to easily manipulate components and personalize delivery. OBJECTIVE To examine how the MOST framework has been applied in the digital mental health field and to provide recommendations for future application. METHODS Systematic searches were conducted in Embase, CINAHL, Web of Science, PsycInfo, and PubMed. Papers were included if they used MOST to develop or optimize a digitally delivered mental health intervention. Studies targeting children under 12, reviews, and theoretical or simulated applications were excluded. RESULTS Twenty-nine papers representing 17 research projects met the inclusion criteria. The preparation phase was often incomplete - fewer than half of the studies reported a conceptual model, and optimization criteria and pilot testing were inconsistently reported. Seven projects completed at least one optimization trial, typically employing factorial designs, but progression to intervention refinement or evaluation was limited. Projects conducting multiple optimization rounds were more likely to achieve an optimized intervention. CONCLUSIONS MOST is increasingly applied in digital mental health research but often only partially implemented. While factorial designs are widely adopted, critical preparatory elements are frequently missing. To fully realize MOST’s potential, future research should emphasize comprehensive application across all phases, iterative refinement and transparent reporting. CLINICALTRIAL -

BACKGROUND Depressive symptoms are common among older adults and can significantly impact their quality of life. However, many older adults face barriers to accessing psychological treatment. Internet-based cognitive behavioral therapy (iCBT) is a promising alternative to face-to-face treatments, but its feasibility among older adults has been less extensively studied than in adult populations. OBJECTIVE This study evaluated the feasibility of guided iCBT for adults aged 55 years and older with mild to moderate depressive symptoms recruited from the general population. METHODS This study is a feasibility study with a single-group, pretest-posttest design (n=21), in which all participants received guided iCBT for 8 weeks. Assessments were conducted at baseline (T0) and after the intervention (T1). The primary outcome was feasibility, conceptualized as satisfaction, usability, engagement, and uptake of iCBT. Secondary outcome measures included depression severity, working alliance, and technical alliance. RESULTS Participants were mostly highly educated (13/21, 61.9%), female (18/21, 85.7%), had an average age of 59.85 (SD 4.19; range 55-68) years, and reported moderate digital literacy. Feasibility outcomes indicated high satisfaction and engagement and moderate usability. Working alliance was rated as good by both participants and coaches, and technical alliance was rated as moderate by the participants. There was a nonsignificant modest decrease in depressive symptoms (Cohen d=0.47). Of the 20 participants who started the intervention, all completed the first 2 modules, but completion declined across the remaining 6 modules, with only 1 (5%) participant completing all modules. CONCLUSIONS This study found that guided iCBT has the potential to be a feasible option for older adults experiencing depressive symptoms, with participants reporting generally positive satisfaction, moderate engagement, and a moderate therapeutic bond with their coaches. However, below-average usability ratings and a moderate technical alliance suggest that some aspects of the platform require improvement. Future research should focus on improving usability and adherence, as well as testing the intervention in a larger and more diverse population.

Background: Increasing interest has centered on the psychotherapeutic working alliance as a means of understanding clinical change in digital mental health interventions in recent years. However, little is understood about how and to what extent a digital mental health program can have an impact on the working alliance and clinical outcomes in a blended (therapist plus digital program) cognitive behavioral therapy (bCBT) intervention for depression. Objective: This study aimed to test the difference in working alliance scores between bCBT and treatment as usual (TAU), examine the association between working alliance and depression severity scores in both arms, and test for an interaction between system usability and working alliance with regard to the association between working alliance and depression scores in bCBT at 3-month assessments. Methods: We conducted a secondary data analysis of the E-COMPARED (European Comparative Effectiveness Research on Blended Depression Treatment versus Treatment-as-usual) trial, which compared bCBT with TAU across 9 European countries. Data were collected in primary care and specialized services between April 2015 and December 2017. Eligible participants aged 18 years or older and diagnosed with major depressive disorder were randomized to either bCBT (n=476) or TAU (n=467). bCBT consisted of 6-20 sessions of bCBT (involving face-to-face sessions with a therapist and an internet-based program). TAU consisted of usual care for depression. The main outcomes were scores of the working alliance (Working Alliance Inventory-Short Revised–Client [WAI-SR-C]) and depressive symptoms (Patient Health Questionnaire-9 [PHQ-9]) at 3 months after randomization. Other variables included system usability scores (System Usability Scale-Client [SUS-C]) at 3 months and baseline demographic information. Data from baseline and 3-month assessments were analyzed using linear regression models that adjusted for a set of baseline variables. Results: Of the 945 included participants, 644 (68.2%) were female, and the mean age was 38.96 years (IQR 38). bCBT was associated with higher composite WAI-SR-C scores compared to TAU (B=5.67, 95% CI 4.48-6.86). There was an inverse association between WAI-SR-C and PHQ-9 in bCBT (B=−0.12, 95% CI −0.17 to −0.06) and TAU (B=−0.06, 95% CI −0.11 to −0.02), in which as WAI-SR-C scores increased, PHQ-9 scores decreased. Finally, there was a significant interaction between SUS-C and WAI-SR-C with regard to an inverse association between higher WAI-SR-C scores and lower PHQ-9 scores in bCBT (b=−0.030, 95% CI −0.05 to −0.01; P=.005). Conclusions: To our knowledge, this is the first study to show that bCBT may enhance the client working alliance when compared to evidence-based routine care for depression that services reported offering. The working alliance in bCBT was also associated with clinical improvements that appear to be enhanced by good program usability. Our findings add further weight to the view that the addition of internet-delivered CBT to face-to-face CBT may positively augment experiences of the working alliance. Trial Registration: ClinicalTrials.gov NCT02542891, https://clinicaltrials.gov/study/NCT02542891; German Clinical Trials Register DRKS00006866, https://drks.de/search/en/trial/DRKS00006866; Netherlands Trials Register NTR4962, https://www.onderzoekmetmensen.nl/en/trial/25452; ClinicalTrials.Gov NCT02389660, https://clinicaltrials.gov/study/NCT02389660; ClinicalTrials.gov NCT02361684, https://clinicaltrials.gov/study/NCT02361684; ClinicalTrials.gov NCT02449447, https://clinicaltrials.gov/study/NCT02449447; ClinicalTrials.gov NCT02410616, https://clinicaltrials.gov/study/NCT02410616; ISRCTN Registry ISRCTN12388725, https://www.isrctn.com/ISRCTN12388725?q=ISRCTN12388725&filters=&sort=&offset=1&totalResults=1&page=1&pageSize=10; ClinicalTrials.gov NCT02796573, https://classic.clinicaltrials.gov/ct2/show/NCT02796573 International Registered Report Identifier (IRRID): RR2-10.1186/s13063-016-1511-1