Depression trajectories amongst individuals with opioid use disorder treated with extended-release naltrexone during 52-weeks, followed by a 52-week post-treatment period

ABSTRACT Background Research on depression and persistent mental distress in individuals with opioid use disorder (OUD) during and post-treatment with extended-release naltrexone (XR-NTX) is limited. Methods The NaltRec study, a naturalistic, multicenter, open-label clinical trial, were conducted in Norwegian hospitals from September 2018 to October 2022. Participants received XR-NTX injections for up to 52 weeks, followed by a 52-week post-treatment period. Outcome measures were assessed using Mini International Neuropsychiatric Interview, Montgomery-Åsberg Depression Rating Scale-Self rating, and items from the European version of the Addiction Severity Index. A growth mixture model (GMM) was employed to identify distinct subgroups of depressive symptoms, while between-subgroup differences in mental distress were evaluated using a generalized linear mixed model (GLMM). Results The population had a mean age of 37.8 years (SD 9.7), 24.1% were female, mean (SD, min-max) MADRS-S score were 15.0 (8.9, 0-41) at baseline. Subgroups were identified by the GMM: Group 1 (G1) with no to very mild depressive symptoms (69.5%) and Group 2 (G2) with moderate depressive symptoms (30.5%). G2 reported more frequent mental health conditions compared to G1 at baseline. Both subgroups presented decreasing depressive symptoms through the study period. Secondary outcome analysis showed G1 maintained low and stable mental distress levels, while G2 exhibited higher levels and increased odds of mental distress. Conclusion This study emphasizes the importance of comprehensive mental health assessments and continuous distress monitoring in individuals undergoing XR-NTX treatment. Although distress decreased, ongoing support seems essential to sustain improvements post-treatment, informing more effective protocols for those with OUD.