Eirini Karyotaki

Objective: Single-session interventions (SSIs) have been proposed as a scalable approach to reduce anxiety and depressive symptoms; however, evidence for adults remains limited. This systematic review and meta-analysis synthesized randomized controlled trials (RCTs) evaluating SSIs relative to inactive or minimal-control conditions.Method: A systematic search identified adult RCTs. Outcomes were analyzed separately for anxiety and depression using three-level random-effects meta-analytic models. Effects were pooled across 1–13 weeks and within short-term (1–3 weeks) and medium-term (4–13 weeks) follow-up windows.Results: Twenty-one RCTs (N = 7,035) contributed 53 outcome-level effect sizes. Across 1–13 weeks, SSIs were associated with significant reductions in anxiety symptoms (g = −0.66, 95% CI [−0.98, −0.34]) and depressive symptoms (g = −0.49, 95% CI [−0.84, −0.13]). At 1–3 weeks, effects were significant for anxiety symptoms (g = −0.80, 95% CI [−1.24, −0.36]), but not depressive symptoms (g = −0.78, 95% CI [−1.78, 0.22]). At 4–13 weeks, effects were significant for both depressive symptoms (g = −0.29, 95% CI [−0.55, −0.02]) and anxiety symptoms (g = −0.48, 95% CI [−0.93, −0.02]). Heterogeneity was high, prediction intervals were wide, publication bias was detected for anxiety outcomes at 1–13 and 1–3 weeks and for depression at 1–13 weeks, and most studies had some concerns or high risk of bias.Conclusions: SSIs may reduce anxiety and depressive symptoms over the short-to-medium term in adults. Substantial heterogeneity, limited trial availability, publication bias, and risk of bias constrain confidence in the magnitude and generalizability of these effects. Rigorous trials with extended follow-up are needed to clarify effect durability and further inform the role within routine care.Keywords: anxiety, depression, meta-analysis, single-session interventions, systematic review

We have learned several lessons from our meta-analytic work in the past decades, and we discuss a few important ones. (a) Publication bias is still a major issue, seriously affecting outcomes of meta-analyses. (b) Preregistration of trials can still be improved because only 50% of trials comparing psychotherapy for depression with control conditions was prospective registered since 2021. (c) A considerable number of trials (at least 28% in published “individual participant data” meta-analyses of psychological interventions for mental-health problems) do not provide their primary data for such meta-analyses. (d) Manuals of treatments are often not open at all. (e) Open access of meta-analytic data sets will considerably increase efficiency, reduce waste of resources, and speed up clinical research.

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: Internet-based interventions vary with respect to the level of support provided, and the impact of support levels on outcomes has been unclear. Aims: To evaluate the relative effectiveness and acceptability of support levels in internet-based cognitive–behavioural therapy (iCBT) for depression. Method: This network meta-analysis included randomised controlled trials of stand-alone iCBT for adults with elevated levels of depressive symptoms, identified via systematic searches of PubMed, EMBASE, PsycINFO and the Cochrane Library (1 January 2025). The primary outcome was post-intervention effectiveness. The secondary outcome was study drop-out risk. Risk of bias was assessed with Cochrane RoB-2. A frequentist random-effects model was conducted (preregistered at https://osf.io/amw4r ). Results: We included 141 trials with 169 comparisons ( n = 32 197). iCBT with therapeutic support had the greatest effect in terms of reducing depressive symptoms compared with care-as-usual ( g = 0.42; 95% CI: 0.30 to 0.55). Such interventions outperformed offers with minimal coaching (encouragement only; g = 0.19, 95% CI: 0.03–0.35) and technical support ( g = 0.27, 95% CI: 0.08–0.45) but had similar effects to those with full coaching (i.e. standardised feedback), automated support, on-demand support or no support. Interventions providing technical support represented the least effective iCBT format and were not statistically superior to care as usual ( g = 0.15, 95% CI: −0.02 to 0.33). For acceptability, iCBT with minimal coaching showed the lowest drop-out rate (risk ratio = 1.13, (95% CI: 0.88–1.46), whereas technical support showed the highest (risk ratio = 1.6, 95% CI: 1.21–2.15). With pre-intervention human contact, all support levels were similarly effective; without it, therapeutic support outperformed other types of support ( g = 0.32–0.68) and drop-out risks increased. Conclusions: Low-intensity supported iCBT can be as effective as therapist-guided iCBT when initial human contact is present. Evidence regarding the potential harms of no-human support is needed before implementation.

Introduction: Despite evidence supporting child and adolescent cognitive behavioural therapy (CBT) globally, interventions remain largely unavailable within public systems. This gap requires implementation models integrating development, training, and scalability research within real-world settings and changes in management structures. Here we developed and implemented manualised psychotherapeutic protocols through a national capacity-building initiative in Greece. Methods: We designed a structured implementation pathway conducted through the Child and Adolescent Mental Health Initiative (CAMHI), a public–private partnership involving clinical and academic institutions across Greece: (1) pre-implementation research through national reviews and national surveys of health professionals; (2) co-development and iterative pilot implementation of evidence-based interventions through supervised practice within the National Health System; and (3) dissemination research supporting scalability and institutionalisation within public structures. Results: Pre-implementation research identified gaps in the availability of clinical protocols in Greek services; a survey of 120 psychologists and psychiatrists indicated the need for psychotherapeutic training. Three evidence-based protocols were co-developed: CBT for anxiety (6–12 years), CBT for depression (12–17 years), and behavioural parent training (BPT) for disruptive behaviour (4–14 years). During a three-stage pilot, 45 clinicians delivered interventions to 140 cases (anxiety n=52; depression n=25; BPT n=63); 117 (83·5%) completed treatment. Significant symptom reductions were observed for anxiety (d=−2·92; RCADS-25), depression (d=−1·79, RCADS-25), and disruptive behaviour (d=−2·3, SNAP-IV), with 63%, 38% and 44% showing reliable improvement at the treatment endpoint. A train-the-trainer model is under implementation for national scale-up. Institutionalisation includes integration into child and adolescent psychiatry curricula. Sustainability safeguards were established through Law 5015/2023, with the Ministry of Health assuming operations by 2027. Discussion: Pilot results demonstrate the feasibility of evidence-based psychotherapeutic interventions embedded within real-world child and adolescent services in Greece. Integrated implementation approaches provide a viable pathway for developing, refining, and scaling clinical manuals within public health provision.

Introduction: It is not clear which individual-patient- and study-level variables modify the effects in the comparison of combined treatment versus pharmacotherapy alone for adult depression. Methods: Randomized trials comparing combined treatment with pharmacotherapy alone were identified on September 1, 2024, and individual participant data (IPD) requested from the authors. One-stage IPD meta-analyses were conducted to estimate effects on depressive symptoms at posttreatment and follow-up, response, remission, and reliable improvement and to assess effect modifiers. Results: Of 75 eligible studies, 31 (41.33%) provided their IPD (3,703 participants). Combined treatment was more effective in reducing depressive symptoms at posttreatment (SMD = 0.45, 95% confidence interval [95% CI]: 0.27–0.64), 6- (SMD = 0.55, 95% CI: 0.25–0.85) and 12-month follow-up (SMD = 0.22, 95% CI: 0.02–0.43). The effect size was smaller in studies that provided IPD than in those that did not. No patient-level effect modifiers were identified. No difference between the two arms was found in studies using SSRIs (as opposed to other antidepressants) and recruiting specific target groups (versus unselected adult populations), and the difference between combined treatment and pharmacotherapy alone was larger if pharmacotherapy was not administered adequately, but these findings were not confirmed in sensitivity analyses. Several patient-level characteristics predicted higher depressive symptoms at posttreatment, regardless of treatment condition. Conclusion: Combined treatment outperforms pharmacotherapy alone regardless of individual characteristics. Thus, its delivery does not have to be limited to specific patient subgroups. However, IPD were available for only 41% of eligible studies, thus limiting this sample’s representativeness.

[This corrects the article DOI: 10.2196/18100.].

Introduction: Cognitive behavioural therapy (CBT) and interpersonal psychotherapy (IPT) are both efficacious treatments for depression, but it is less clear how both compare on outcome domains other than depression and in the longer term. Moreover, it is unclear which of these two psychotherapies works better for whom. This article describes the protocol for a systematic review and individual participant data (IPD) meta-analysis that aims to compare the efficacy of CBT and IPT for adults with depression on a range of outcomes in both the short and long term, and to explore moderators of the treatment effect. This study can enhance our understanding of treatments for depression and inform treatment personalisation. Methods and analysis: Systematic literature searches will be conducted in PubMed, PsycINFO, EMBASE and the Cochrane Library from inception to 1 January 2026, to identify randomised clinical trials (RCTs) comparing CBT and IPT for adult depression. Researchers of eligible studies will be invited to contribute their participant-level data. One-stage IPD meta-analyses will be conducted with mixed-effects models to examine (a) treatment efficacy on all outcome measures that are assessed at post-treatment or follow-up in at least two studies, and (b) various baseline participant characteristics as potential moderators of depressive symptom level at treatment completion. Ethics and dissemination: Ethical approval is not required for this study since it will be based on anonymised data from RCTs that have already been completed. The findings of the present study will be disseminated through a peer-reviewed journal or conference presentation.