Up to 30% of individuals with depression develop persistent depressive disorder (PDD), an often disabling and difficult to treat condition. The Cognitive Behavioural Analysis System of Psychotherapy (CBASP) is the only psychotherapy developed specifically for treating individuals with PDD. While several randomised controlled trials (RCTs) have demonstrated its efficacy in outpatient settings, evidence for its use in inpatient settings remains limited. Pilot studies of CBASP inpatient programmes in Germany have shown promising feasibility and effectiveness; however, no RCTs to date have systematically evaluated their outcomes. This study represents the first RCT to compare the short- and long-term efficacy and safety of CBASP with Behavioural Activation (BA), a first-line psychotherapy for depression, within an intensive multimodal inpatient setting.

In this prospective, multicentre, rater-blinded RCT with an active control group, we aim to recruit 396 adults (aged 18–70 years) with treatment-resistant PDD at eight German university hospitals. Participants will be randomly assigned to receive either (1) CBASP or (2) BA within an intensive treatment programme consisting of 10 weeks acute treatment in an inpatient and/or day clinic setting, followed by 6 weeks of outpatient continuation treatment. Primary and secondary outcome assessments will be conducted at multiple time points: baseline (T0), treatment onset (T1), after 5 and 10 weeks of acute treatment (T2, T3), at the end of continuation treatment (T4, week 16) and every 2 months up to week 64 (T5, naturalistic follow-up).

The primary outcome measure will be the change in depression severity, as assessed by the Hamilton Depression Rating Scale (24-item version), after 16 weeks of treatment (from T0 to T4). Secondary outcomes will include response, remission, deterioration and relapse rates, self-reported depression and anxiety symptoms and additional psychological variables. A cost-benefit analysis will evaluate the health-economic benefits of both interventions. Additionally, this RCT will explore personalised treatment selection and mechanisms of change, including potential moderators and mediators of treatment effects. The findings from this trial are expected to provide clinicians with evidence-based guidance on choosing CBASP versus BA for inpatients with treatment-resistant PDD.

This study has received ethical approval from the ethics committees of all participating university hospitals. All participants will provide written informed consent before enrolment. Study findings will be published in peer-reviewed journals and presented at national and international conferences. We have involved people with lived experience from the earliest pilots onward, using their feedback to refine our study design. Ongoing consultation at conferences and public events has further ensured that our research remains grounded in patient perspectives.

NCT04996433.

Alcohol use disorder (AUD) is a prevalent, chronic condition generating considerable global morbidity, mortality and socioeconomic burden. Despite the availability of established pharmacotherapies, overall treatment uptake remains low and effect sizes are moderate at best. Emerging evidence highlights substantial differences in treatment response between sexes and genders, yet these factors are rarely systematically considered in clinical trials or routine care. Existing reviews have limited scope and often exclude gender-diverse populations. This project aims to (1) Synthesise evidence on gender- and sex-specific efficacy, safety and adherence in AUD pharmacotherapies, (2) Evaluate the consideration of sex and gender beyond binary classifications in existing research and (3) Develop recommendations for gender- and sex-sensitive treatment strategies.

A systematic review and meta-analysis will be conducted using (PubMed, Web of Science, Scopus, Google Scholar, German Clinical Trials Register and ClinicalTrials.gov). We will include randomised controlled trials of pharmacotherapies for AUD with a minimum treatment duration of 4 weeks, reporting gender-specific and/or sex-specific results. The literature search will cover studies published up to October 2025, with inclusion restricted to articles published in English or German, regardless of setting. Two reviewers will independently screen records and assess risk of bias (Cochrane RoB), with evidence certainty evaluated using Grading of Recommendations Assessment, Development and Evaluation and aligned to Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 and Sex and Gender Equity in Research guidelines.

Ethics approval is not required as only data from already completed studies and supplementary information directly provided by study authors are used. Findings and recommendations will be disseminated in peer-reviewed journals and presented at conferences and workshops.

CRD420251079160.

Loneliness and adverse childhood experiences (ACEs) constitute significant risk factors for mental disorders, with loneliness emerging as a serious global public health concern. Recent research highlights the role of loneliness as a potential link between early life adversities and current psychopathology. However, most studies have been conducted in high-income, highly individualistic countries. This cross-sectional study explores the interplay between loneliness, social network size, recalled ACEs and depressive symptoms in Ethiopia—a low-income and collectivistic cultural context.

The study included 125 psychiatric outpatients at Jimma University Medical Center in Southwest Ethiopia diagnosed with major depressive disorder, bipolar disorder or psychotic disorders, as well as 131 non-clinical participants. Trained interviewers administered the University of California, Los Angeles (UCLA) Loneliness Scale, the Childhood Trauma Questionnaire, the Social Network Index and the WHO-5 Well-Being Index. We used Mann-Whitney U tests, partial correlation and mediation analysis for data analysis.

We found mild-to-moderate correlations between loneliness and ACEs (clinical group: rho=0.29, p1b₁=0.07, 95% CI (0.02 to 0.13); non-clinical group: indirect effect a₁b₁=0.03, 95% CI (0.01 to 0.07)). In contrast, social network size was neither correlated with ACEs nor did it mediate the association between ACEs and depressive symptoms in either group.

This study replicates previous findings that loneliness—rather than social network size—is associated with ACEs and mediates their impact on depressive symptoms. These results support the transcultural and transdiagnostic relevance of loneliness as a universal psychological mechanism, independent of societal structure.