A critical finding in this study was the longer retention observed in AYAs with co-occurring mental health disorders, particularly depression and PTSD. Our findings were consistent with prior literature among adults with OUD. Previous reports demonstrated that co-occurring PTSD was associated with higher adherence to MOUD among African American adults enrolled in substance use treatment programs [18]. Managing PTSD and OUD simultaneously may enhance patient outcomes significantly [19]. Similarly, adults with depression had longer retention in the clinic compared to those without depression [20]. This positive influence of depression on patient engagement in treatment for OUD might have occurred due to buprenorphine’s potential antidepressant properties, which could help alleviate depression and support in overcoming opioid dependence [21].

We observed that most of the participants in our clinic were females. While epidemiologic data generally showed higher rates of substance use disorders among males, treatment-seeking behaviors were more likely to occur among females [22]. This may reflect a higher likelihood among young females to seek treatment compared to males, as the previous literature suggests females are more likely to access healthcare services for substance use disorders [23]. Males with OUD are often more likely to use multiple substances [24]. In contrast, females are more likely to experience co-occurring mental health disorders [25]. Therefore, treatment programs should consider incorporating tailored behavioral interventions, integrating gender-specific motivational interviewing techniques and counseling to address underlying factors that contribute to continued substance use. Understanding how males and females respond differently to psychiatric interventions and MOUD is important to develop personalized treatment strategies for AYAs with OUD.

We did not find an association between anxiety and retention time; however, taking medication for anxiety was associated with increased retention time, suggesting that treatment of anxiety is beneficial. Our findings are consistent with a previous study, which found no association between anxiety and treatment retention [26]. Anxiety often exacerbates opioid misuse by heightening distress responses, and sensitivity to anxiety can predict treatment dropout [27,28]. Evidence indicated that addressing anxiety-specific symptoms could reduce dropout rates and improve treatment outcomes [29]. This suggests that appropriate pharmacologic management of anxiety may mitigate some challenges associated with anxiety in OUD treatment.

This study revealed that co-occurring alcohol use disorder was associated with higher retention time. However, previous research found co-occurring alcohol dependence was associated with a lower six-month treatment retention rate compared to patients aged 12–64 years without alcohol use disorder [30]. This discrepancy may be attributed to variations in age and the severity of these disorders among patients. Conversely, we found that cannabis use disorder was linked to lower retention time. Other studies also observed that baseline cannabis use was significantly linked to increased dropout rates in treatment programs for adults, particularly in heavy users [31]. Cannabis use can impair cognition and alter judgment [32], which can subsequently lead to worse treatment outcomes.

This study also found consistently positive UDTs for MOUD across most groups, with no significant differences between those with or without comorbidities. This indicated that patients were adherent to MOUD regimens, regardless of existing comorbidities. Our findings showed that older age was associated with improved adherence to MOUD. Older adolescents and young adults may possess more developed self-management skills, contributing to better treatment adherence [33]. This aligned with previous research demonstrating a positive association between age and retention in medication-assisted treatment for OUD [34,35]. Additionally, we observed that taking medications for depression and anxiety can improve medication adherence. Antidepressant use has improved treatment adherence and outcomes for adults with co-occurring depression and substance use disorders [36]. A meta-analysis concluded that antidepressants were beneficial for adults with both depression and SUDs [37]. Furthermore, nonadherence to psychiatric medications was associated with shorter treatment stays and poorer outcomes in adults with OUD [38].

The overall low median proportion of positive UDTs for illicit substances suggests that 90% of patients were abstaining from illicit substances during treatment. However, we found that male sex and cannabis use disorder were associated with higher odds of testing positive for THC. Males have had higher rates and frequency of cannabis use [39]. More importantly, AYAs receiving buprenorphine-naloxone or its combination with naltrexone had lower odds of testing positive for THC, which aligned with previous studies showing a decline in cannabis use during opioid maintenance therapy in adults [40,41,42]. This suggests that MOUD may provide ancillary benefits in reducing cannabis use among AYAs with OUD.

This study has several important clinical implications for managing AYAs with OUD and co-occurring mental health and/or SUDs. The positive association between depression, PTSD, anxiety medication use, and longer retention highlights the importance of integrated care models that simultaneously address both mental health and opioid use disorders. Incorporating mental health care into OUD treatment settings may improve engagement, adherence, and overall treatment outcomes, particularly for those with comorbidities [43]. Medication-assisted treatment remains a cornerstone of OUD care. Integrating MOUD with evidence-based psychotherapies, such as cognitive behavioral therapy and motivational interviewing, can address the psychological aspects of substance use and foster behavioral change [44,45]. This requires building multidisciplinary teams that include medical, behavioral, and social service providers. These teams work together to address the medical, psychological, and social needs of patients. One key strategy could be the co-location of mental health and substance use treatment services within the same facility [46]. This physical proximity reduces logistical barriers, allowing patients to access comprehensive care without navigating separate systems. Data integration and sharing among healthcare providers also could contribute to coordinated care by minimizing duplication of services and improving communication [47]. Additionally, building community-based partnerships with social support organizations can extend care beyond the clinical setting [48]. The association between older age and improved medication adherence for OUD suggests that targeted interventions should focus on younger AYAs who may face more challenges with MOUD adherence. Tailored strategies, such as increased support from healthcare providers, peer groups, or digital health interventions, may help address adherence barriers. Moreover, taking MOUD significantly lowered the odds of positive UDT for THC, indicating the broader benefits of MOUD use beyond that for opioid dependence. Clinicians should consider the potential for MOUD to provide ancillary benefits when designing care plans for AYAs with OUD, especially those with polysubstance use.

This study is the first to comprehensively assess the association of mental health and substance use disorders, MOUD, and retention and UDT results among AYAs with OUD. By examining retention time and UDT results for MOUD as primary outcomes, we provided a holistic view of treatment engagement and adherence in this population. However, several limitations must be acknowledged. First, the retrospective design of this study cannot establish causal relationships between psychiatric comorbidities and patient outcomes. While we identified associations between mental health disorders and retention time, it remains unclear whether longer retention time was due to the presence of mental health comorbidities or the availability and quality of mental health services at the clinic. Unmeasured confounders, such as family support and socioeconomic status may have impacted retention time and treatment adherence as well. Future research should address these potential confounders. Another limitation of this study is the difficulty in interpreting the relationship between PTSD, alcohol use disorder, and longer retention. While our findings suggest an association between these disorders and increased retention time, it is plausible that this may indicate a greater need for mental health support rather than a direct reflection of treatment effectiveness. Additionally, the observed reduction in THC positivity associated with buprenorphine-naloxone use may serve as a proxy for overall treatment adherence rather than a direct pharmacological effect. Furthermore, we were unable to assess whether individuals with longer retention time received more intensive mental health care or had higher mental health service utilization, as these points of data were not documented in the electronic medical records used in this study. Consequently, it was not feasible to conduct additional analyses, such as stratifying retention by the intensity of mental health care or exploring dose–response relationships between medication adherence and retention outcomes. Future prospective studies are needed to investigate the potential mediating role of mental health care intensity and treatment adherence in the relationship between psychiatric comorbidities and treatment retention. Such studies should systematically capture data on mental health service utilization, medication adherence, and treatment intensity to better understand causal pathways. Additionally, the study was conducted at the SUD clinic within a single healthcare system, which may limit the generalizability of the findings to other settings. The sample may not fully represent the broader population of adolescents and young adults with OUD, particularly as the study population was predominantly White (94.9%), limiting applicability to more diverse racial and ethnic groups. Future studies should prioritize including diverse groups of AYAs to understand the varying factors influencing treatment engagement and adherence across different demographic groups or utilize comprehensive national datasets to improve generalizability. Future studies should also explore practical strategies for integrating mental health care and substance use treatment into OUD management for AYAs to improve treatment engagement and adherence.