Steven D. Hollon

Purpose: Depression is highly prevalent in middle-aged women (MAW), but head-to-head comparisons of first-line interventions in this population are scarce. This systematic review and individual participant data (IPD) meta-analysis examined the comparative efficacy of antidepressant medication (ADM) and interpersonal psychotherapy (IPT) for MAW (aged 40–64) versus other adults (men and non-MAW) on depression, quality of life, and interpersonal problem measures. Methods: PubMed, PsycINFO, Embase, and the Cochrane Library were searched January 1, 2025 to identify randomized trials comparing ADM and IPT for adults with depression. IPD were requested and analyzed using mixed-effects models. Results: IPD were obtained from 9 of the 15 (60%) identified studies, comprising 1,490 participants (527 MAW, 963 other adults). MAW status did not significantly moderate ADM versus IPT comparative efficacy on depression ( p = .10) and interpersonal problems ( p = .29) outcomes. The two treatments did not significantly differ in treatment effect in the MAW group (depression: b = -0.03, p = .76; interpersonal problems: b = -0.20, p = .31). MAW status significantly moderated comparative efficacy on quality of life measures ( b  = 0.37, p = .02). Whereas IPT was non-significantly more efficacious than ADM for MAW ( b = -0.18, p = .15), ADM were non-significantly more efficacious than IPT for other adults ( b = 0.19, p = .051). Conclusion: This is the first IPD meta-analysis directly comparing depression treatments in MAW. The absence of treatment effect differences indicates that other factors (e.g., patient preference) may guide choice between IPT and ADM in this population.

Background: Depression is prevalent and debilitating. Although interventions exist, they are rarely delivered in accessible, scalable ways that retain their effectiveness. Cognitive behavioral immersion (CBI) is a coach-led cognitive behavioral skills program delivered in social virtual worlds that offers a potential solution. Objective: This parallel-group, web-based randomized controlled superiority trial compared CBI accessed via virtual reality headsets (CBI-VR) or flat-screen devices (CBI-FS) to a delayed access control. Methods: Inclusion criteria included a clinical level of depression symptoms, age ≥18 years, able and willing to give informed consent, access to a computer with an internet connection, and ability to speak and read English. Eligible participants were randomized using a random number generation script in a 1:1:1 ratio to conditions. CBI consisted of 8 weekly 1-hour groups led by coaches who taught cognitive behavioral skills. The intervention lasted 8 weeks; follow-up lasted 6 months. The primary outcome was depression symptoms; secondary outcomes were anxiety symptoms and quality of life. Recruitment and study procedures were conducted online. Outcomes were assessed through electronic self-report questionnaires. The study was unblinded. Hierarchical linear modeling was used to examine differences in rates of change among conditions. We explored the sense of presence as a potential mediator of intervention response. Results: Participants were recruited from February 2024 to January 2025; n=102 were randomized to each condition. Participants randomized to CBI-VR and CBI-FS attended an average of 5 intervention sessions. Primary analyses included all participants in the intent-to-treat sample that completed ≥2 outcome surveys to estimate within-person change (CBI-VR: n=98; CBI-FS: n=86; control: n=102). CBI-VR showed faster reductions in depressive and anxiety symptoms than either CBI-FS (depression: β =.21; 95% CI 0.02-0.40; P =.03 and anxiety: β =.20, 95% CI 0.03-0.38; P =.02) or the control (depression: β =.31, 95% CI 0.13-0.48; P <.001 and anxiety: β =.18, 95% CI 0.01-0.34; P =.03) across the 8-week intervention, with improvements largely maintained over the 6-month follow-up. CBI-VR also showed greater improvements in general quality of life ( β =−1.02; 95% CI −1.63 to −0.40; P =.001) and psychological well-being ( β =−1.01, 95% CI −1.44 to −0.59; P <.001) than the control from pre- to postintervention. The sense of physical presence in the environment was associated with CBI-VR’s effects on depression symptoms ( ab =−0.85, 95% CI −1.71 to −0.15). No adverse effects occurred in any group. Conclusions: This study evaluated the efficacy of an innovative coach-led cognitive behavioral skills group delivered via VR. To our knowledge, our trial is the first to demonstrate that CBI delivered via VR is effective. These findings extend prior work on digital cognitive behavioral therapy by supporting CBI-VR as an effective and viable intervention package for depression and anxiety symptoms. These findings may help inform future research on suitable technology that can help bridge mental health care gaps.

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.

Background: Depression and anxiety are among the most common mental health concerns globally. Efficacious treatments such as cognitive behavioral therapy exist but remain difficult to access and scale. Cognitive behavioral immersion (CBI)—a cognitive behavioral skills training intervention delivered by peer coaches in the metaverse—has been developed to address these barriers. CBI can be used through a virtual reality headset or via flat-screen devices such as phones, tablets, or computers. Pilot data have established its usability among participants with clinical levels of depression and anxiety. However, more research is needed to determine whether CBI causes decreases in these symptoms and how delivery via virtual reality compares to flat-screen devices. Objective: This protocol aims to conduct a randomized controlled trial evaluating the efficacy of immersive CBI accessed via a virtual reality headset (CBI-VR) as compared to a less immersive (but more accessible) CBI condition accessed via a flat-screen device (CBI-FS) and each to a delayed access control (DAC). Methods: A total of 306 adults experiencing clinical levels of depressive symptoms are being recruited nationally to participate in this web-based trial. Participants will be randomized according to a 1:1:1 ratio to one of three conditions: (1) CBI-VR, (2) CBI-FS, and (3) DAC. The CBI program consists of eight weekly 60-minute group sessions led by trained peer coaches who teach cognitive behavioral skills. The acute period of each condition will last 8 weeks with a follow-up period of 6 months. The primary outcome is depressive symptoms; secondary outcomes are anxiety symptoms and quality of life. Outcomes will be assessed once at baseline, weekly during the course of the intervention, and monthly during follow-ups. We will use hierarchical linear models to assess differences in the rate of symptom change among conditions. We will also explore potential prognostic (demographics and immersion) and prescriptive (cognitive behavioral skills, group alliance, and program engagement) predictors, as well as potential mechanisms (cognitive change and social support) of response. Results: We hypothesize that participants randomized to either CBI group will experience greater symptom improvement than those in DAC and that CBI-VR participants will improve more than CBI-FS participants. This study was funded in September 2023. Data collection began in February 2024. As of January 2025, all 306 participants have been enrolled. Data collection should conclude by September 2025. Data have not yet been analyzed. Expected results to be submitted for publication in the winter of 2025. Conclusions: This trial will determine if CBI via either device is efficacious as compared to DAC and whether virtual reality enhances outcomes. Findings will contribute to the literature on using the metaverse and virtual reality to facilitate effective accessible mental health interventions, particularly for depression. Trial Registration: ClinicalTrials.gov NCT06418997; https://clinicaltrials.gov/study/NCT06418997 International Registered Report Identifier (IRRID): DERR1-10.2196/65970

Purpose: The use of memory support strategies could help patients with major depressive disorder (MDD) to improve their memory for the content of therapy, leading to better treatment outcomes. Constructive memory support strategies prompt patients to construct new ideas. Non-constructive memory support strategies encourage the passive processing of therapy content. Building on previous work in a university setting, our goal was to investigate the effects of therapists’ natural use of memory support strategies in cognitive behavioral therapy (CBT) and interpersonal psychotherapy (IPT) for MDD in routine clinical practice. Methods: In the context of a multicenter randomized trial, comparing once- versus twice weekly sessions of CBT and IPT for MDD in routine clinical practice, videos of therapy sessions from 75 patients during different phases of treatment (n = 67 between session 1–4, n = 59 between session 5–8, n = 56 between session 9–12) were rated on therapist use of memory support strategies and how the patient responded to the information given by the therapist (patient learning behavior). Hypotheses were investigated with mixed models. Results: Memory support strategies were related to more patient learning behavior. Constructive memory support strategies were related to reduced depression in the next session, but not to recall or change in therapy skills or depression at the end of treatment. Conclusions: Memory support strategies might be beneficial in routine clinical practice in increasing patient learning behavior and reducing next session depression. Future studies should find out which strategy works for whom and whether a higher dose leads to change in depression over treatment.

BACKGROUND Depression and anxiety are among the most common mental health concerns globally. Efficacious treatments such as cognitive behavioral therapy exist but remain difficult to access and scale. Cognitive behavioral immersion (CBI)—a cognitive behavioral skills training intervention delivered by peer coaches in the metaverse—has been developed to address these barriers. CBI can be used through a virtual reality headset or via flat-screen devices such as phones, tablets, or computers. Pilot data have established its usability among participants with clinical levels of depression and anxiety. However, more research is needed to determine whether CBI causes decreases in these symptoms and how delivery via virtual reality compares to flat-screen devices. OBJECTIVE This protocol aims to conduct a randomized controlled trial evaluating the efficacy of immersive CBI accessed via a virtual reality headset (CBI-VR) as compared to a less immersive (but more accessible) CBI condition accessed via a flat-screen device (CBI-FS) and each to a delayed access control (DAC). METHODS A total of 306 adults experiencing clinical levels of depressive symptoms are being recruited nationally to participate in this web-based trial. Participants will be randomized according to a 1:1:1 ratio to one of three conditions: (1) CBI-VR, (2) CBI-FS, and (3) DAC. The CBI program consists of eight weekly 60-minute group sessions led by trained peer coaches who teach cognitive behavioral skills. The acute period of each condition will last 8 weeks with a follow-up period of 6 months. The primary outcome is depressive symptoms; secondary outcomes are anxiety symptoms and quality of life. Outcomes will be assessed once at baseline, weekly during the course of the intervention, and monthly during follow-ups. We will use hierarchical linear models to assess differences in the rate of symptom change among conditions. We will also explore potential prognostic (demographics and immersion) and prescriptive (cognitive behavioral skills, group alliance, and program engagement) predictors, as well as potential mechanisms (cognitive change and social support) of response. RESULTS We hypothesize that participants randomized to either CBI group will experience greater symptom improvement than those in DAC and that CBI-VR participants will improve more than CBI-FS participants. This study was funded in September 2023. Data collection began in February 2024. As of January 2025, all 306 participants have been enrolled. Data collection should conclude by September 2025. Data have not yet been analyzed. Expected results to be submitted for publication in the winter of 2025. CONCLUSIONS This trial will determine if CBI via either device is efficacious as compared to DAC and whether virtual reality enhances outcomes. Findings will contribute to the literature on using the metaverse and virtual reality to facilitate effective accessible mental health interventions, particularly for depression. CLINICALTRIAL ClinicalTrials.gov NCT06418997; https://clinicaltrials.gov/study/NCT06418997 INTERNATIONAL REGISTERED REPORT DERR1-10.2196/65970