Levomethadone Selectively Reduces Emotional Impulsivity in ASRS-Positive ADHD-OUD Patients, Independent of Dose...

Background: Emotional dysregulation and impulsivity represent key risk factors for adverse trajectories in adults with ADHD and are frequently observed among patients with opioid use disorder (OUD). Levomethadone, the R-enantiomer of methadone, provides more stable dopaminergic modulation than the racemic formulation and may improve emotional control. The primary objective was to examine emotional, clinical, and substance use changes after the switch to levomethadone and to determine whether these trajectories differed according to ADHD screening status. This study evaluated emotional, clinical, and behavioral outcomes-including substance use-after transitioning from racemic methadone to levomethadone maintenance therapy, focusing on the moderating role of ADHD symptoms and dose escalation. Methods: Eighty-three OUD patients in methadone maintenance were assessed at baseline, T1 (mean = 2.13 months, SD = 0.65), and T2 (mean = 6.20 months, SD = 0.91). Emotional dysregulation (RIPOST), clinical severity (Clinical Global Impression), and days of substance use were analyzed using Linear Mixed Models (participants with ≥1 valid follow-up). ADHD symptoms (Adult ADHD Self-Report Scale DSM-5) were evaluated with Wilcoxon signed-rank tests. Dose escalation (↑levomethadone) was defined as ≥1 increase during follow-up and was only included in the mixed models. Substance use analyses were restricted to baseline active users. Results: Emotional impulsivity significantly decreased over time only in participants screening positive for ADHD symptoms (ASRS ≥ 14), independent of dose escalation. Emotional instability also declined but across the full cohort. CGI scores improved in all participants. Substance use patterns showed a modest overall improvement, with reductions most evident for sedatives and alcohol. The findings indicate a specific effect of levomethadone on affective regulation and clinical stabilization, particularly in individuals with impulsivity traits. Conclusions: Levomethadone maintenance appears to improve emotional regulation and global functioning beyond dose-related effects, supporting its potential value in complex OUD patients with clinically relevant ADHD symptomatology. Combined treatment with levomethadone and methylphenidate may further enhance executive control and craving regulation in this population.