Opioid use disorder (OUD) is a chronic and severe psychiatric condition defined by a level of opioid use which significantly impairs interpersonal and social functioning. In the biopsychosocial model of addiction, research has shown that psychiatric, sociological and neurobiological factors individually affect OUD severity. However, how these factors interact in the determination of OUD severity remains poorly understood.

The Epigenetic Bonds of Opioid Use Profiles are a multidisciplinary project whose primary objective is to characterise psychiatric and social factors of OUD in a large cohort of patients. The secondary objectives are, first, to correlate psychosocial severity with blood-derived epigenetic biomarkers to provide a deeper understanding of determinants of OUD and, second, to examine over a 2 year follow-up the correlation between the evolution of OUD and psychosocial severity with epigenetic biomarkers at inclusion. An additional objective is to analyse the impact of drug consumption rooms on access to care for most severely affected patients with OUD. In total, 300 opioid users will be recruited at supervised injection sites in Strasbourg and Paris and at addiction care centres in Strasbourg and Lyon to explore four psychiatric (substance use disorders beyond opioids, depression, anxiety, post-traumatic stress disorder) and five social (social support and status, traumatic experiences, housing, imprisonment, access to care) factors. Opioid users will be followed for 24 months and reassessed for psychosocial factors at 3, 6, 12, 18 and 24 months. Opioid consumption will be measured in all subjects using questionnaires, complemented by toxicological screenings (mass spectrometry). Finally, DNA methylation and gene expression will be characterised in capillary blood using next-generation sequencing. Mixed models will be used to model the primary and secondary outcomes.

This ongoing study was approved by the French Ethics Committee ‘Sud Méditerranée III’ of University Hospital of Nîmes (approval 2023–2024, protocol IDRCB number 2022-A02477-36) and authorised by the French Data Protection Authority (authorisation decision DR-2023–277 in December 2023). Results will be presented in international and national conferences and published in peer-reviewed international journals.

NCT06021548.

Alliance ruptures constitute a high risk of premature treatment termination and poor psychotherapy outcome. The Alliance-Focused Training (AFT) is a promising transtheoretical approach to enhance therapists’ skills in dealing with alliance ruptures.

To evaluate the effectiveness of Modified AFT with doubling (MAFT-D), a randomised, patient and evaluator-blinded, multicentre trial was designed comparing MAFT-D (delivered to trainee therapists and supervisors) and psychotherapy training/treatment as usual (TAU) for therapists (n=120) and their patients with depressive disorders (n=240). A total of 17 cooperating centres, each offering either cognitive-behavioural or psychodynamic psychotherapy training, will contribute to recruitment. Stratification by centre (both for therapists and patients) and hence therapeutic approach (cognitive-behavioural vs psychodynamic psychotherapies), and by comorbid personality disorder (yes vs no, for patients) will be carried out. The two hierarchically ordered primary hypotheses are: In MAFT-D compared with TAU, a stronger reduction of depressive symptoms and a lower rate of patient dropout is expected from baseline to 20 weeks after baseline. Follow-up assessments are planned at 35 weeks, 20 months and 36 months postbaseline to evaluate the persistence of effects. Secondary patient-related and therapist-related outcomes as well as predictors, moderators and mediators of change will be investigated. Mixed models with repeated measures will be used for the primary analyses.

Ethical approvals were obtained by the institutional ethics review board of the main study centre as well as by review boards in each federal state where one or more cooperating centres are located (secondary votes). Following the Consolidated Standards of Reporting Trials statement for non-pharmacological trials, results will be reported in peer-reviewed scientific journals and disseminated to patient organisations and media.

DRKS00014842; https://drks.de/search/de/trial/DRKS00014842.