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Objective: There is a significant interindividual variability in treatment outcomes in methadone maintenance treatment (MMT) for opioid use disorder (OUD). This prospective cohort study examines the impact of comorbid psychiatric disorders on continued illicit opioid use in patients receiving MMT for OUD. Methods: Data were collected from 935 patients receiving MMT in outpatient clinics between June 2011 and June 2015. Using linear regression analysis, we evaluated the impact of having a comorbid psychiatric disorder on continued illicit opioid use during MMT, adjusting for important confounders. The main outcome measure was percentage of opioid-positive urine screens for 6 months. We conducted a subgroup analysis to determine the influence of specific comorbid psychiatric disorders, including substance use disorders, on continued illicit opioid use. Results: Approximately 80% of participants had at least one comorbid psychiatric disorder in addition to OUD, and 42% of participants had a comorbid substance use disorder. There was no significant association between having a psychiatric comorbidity and continuing opioid use (P=0.248). Results from subgroup analysis, however, suggest that comorbid tranquilizer (ß=20.781, P,0.001) and cocaine (ß=6.344, P=0.031) use disorders are associated with increased rates of continuing opioid use. Conclusion: Results from our study may serve to guide future MMT guidelines. Specifically, we find that cocaine or tranquilizer use disorder, comorbid with OUD, places patients at high risk for poor MMT outcomes. Treatment centers may choose to gear more intensive therapy toward such populations. [ABSTRACT FROM AUTHOR]

INTRODUCTION: Concomitant opioid abuse is a serious problem among patients receiving methadone maintenance treatment (MMT) for opioid use disorder. This is an exploratory study that aims to identify predictors of the length of time a patient receiving MMT for opioid use disorder remains abstinent (relapse-free). METHODS: Data were collected from 250 MMT patients enrolled in addiction treatment clinics across Southern Ontario. The impact of certain clinical and socio-demographic factors on the outcome (time until opioid relapse) was determined using a Cox proportional hazard model. RESULTS: History of injecting drug use behavior (hazard ratio (HR): 2.26, P = 0.042), illicit benzodiazepine consumption (HR: 1.07, P = 0.002), and the age of onset of opioid abuse (HR: 1.10, P < 0.0001) are important indicators of accelerated relapse among MMT patients. Conversely, current age is positively associated with duration of abstinence from illicit opioid use, serving as a protective factor against relapse (HR: 0.93, P = 0.003). CONCLUSION: This study helps to identify patients at increased risk of relapse during MMT, allowing health care providers to target more aggressive adjunct therapies toward high-risk patients. [ABSTRACT FROM AUTHOR]

Background: Eligibility criteria that result in the exclusion of a substantial number of patients from randomized trials jeopardize the generalizability of treatment effect to much of the clinical population. This is important when evaluating opioid substitution and antagonist therapies (OSATs), especially given the challenges associated with treating the opioid-dependent population. We aimed to identify OSAT trials' eligibility criteria, quantify the percentage of the clinical population excluded by these criteria, and determine how OSAT guidelines incorporate evidence from these trials.Methods: We performed a systematic review to identify the eligibility criteria used across trials. We searched Medline, EMBASE, PsycINFO, Web of Science, Cochrane Library, Cochrane Clinical Trials Registry (CTR), World Health Organization International CTR Platform Search Portal, and the National Institutes of Health CTR databases from inception to January 1, 2014. To quantify the effect of trials' eligibility criteria on generalizability, we applied these criteria to data from an observational study of opioid-dependent patients (n = 394). We then accessed the Canadian, American, British, and World Health Organization (WHO) OSAT guidelines to evaluate how evidence is used in the recommendations.Results: Among the 60 trials identified the majority (≥50 % of trials) exclude patients with psychiatric (60 %) and physical comorbidity (51.7 %). Additionally, we found 19 trials exclude patients with current alcohol/substance-use problems (31.7 %), and 29 (48.3 %) exclude patients taking psychotropic medications. These criteria were restrictive and in some cases rendered 70 % of the observational sample ineligible. North American OSAT guidelines made strong recommendations supported by evidence with poor generalizability. National Institute of Health and Care Excellence (NICE) and WHO guidelines for opioid misuse provide a critical assessment of the literature used to inform their recommendations.Conclusions: Trials assessing OSATs often exclude patients with concurrent disorders. If the excluded patients respond differently to treatment, results from these trials are likely to overestimate the true effectiveness of OSATs. North American guidelines should consider these limitations when drafting clinical recommendations. [ABSTRACT FROM AUTHOR]

Background: Genetic variability may influence methadone metabolism, dose requirements, and risk of relapse. Objectives: To determine whether the CYP2B6*6 or ABCB1 (rs1045642) polymorphisms are associated with variation in methadone response (plasma concentration, dose, or response to treatment). Methods: Two independent reviewers searched Medline, EMBASE, CINAHL, PsycINFO, and Web of Science databases. We included studies that reported methadone plasma concentration, methadone response, or methadone dose in relation to the CYP2B6*6 or ABCB1 polymorphisms. Results: We screened 182 articles and extracted 7 articles for inclusion in the meta-analysis. Considerable agreement was observed between the two independent raters on the title (kappa, 0.82), abstract (kappa, 0.43), and full text screening (kappa, 0.43). Trough (R) methadone plasma concentration was significantly higher in CYP2B6*6 homozygous carriers when compared to non-carriers (standardized mean difference [SMD] = 0.53, 95% confidence interval [CI], 0.05–1.00, p = 0.03) with minimal heterogeneity (I2 = 0%). Similarly, trough (S) methadone plasma concentration was higher in homozygous carriers of the *6 haplotype when compared to non-carriers, (SMD = 1.44, 95% CI 0.27–2.61, p = 0.02) however significant heterogeneity was observed (I2 = 69%). Carriers of the CYP2B6*6 haplotype were not found to be significantly different from non-carriers with respect to dose or response to treatment. We found no significant association between the ABCB1 polymorphism and the trough (R), (S) plasma concentrations, methadone dose, or methadone response. Conclusion: Although the number of studies included and sample size were modest, this is the first meta analysis to show participants homozygous for the CYP2B6*6 genotype have higher trough (R) and (S) methadone plasma concentrations, suggesting that methadone metabolism is significantly slower in *6 homozygous carriers. [ABSTRACT FROM AUTHOR]

Introduction: Despite the demonstrated benefit of methadone, the incidence opioid-related overdose, and its associated mortality continues to rise at an alarming rate. The impact of high prevalence comorbid features such as chronic liver disease (CLD) on methadone treatment response remain unclear.Aim: To determine whether CLD is associated with poor response to methadone treatment.Methods: Using a well-established multi-center cohort from the Genetics of Opioid Addiction Study (GENOA), we evaluated if presence of CLD among 1234 eligible patients with opioid use disorder receiving methadone treatment impacted health and behavioural responses to treatment. CLD was classified as any liver disorder/dysfunction present for a minimum period of six months. Serial urine toxicology assessments were used to determine treatment response. The effect of CLD was determined using a multi-variable logistic regression model.Results: CLD was present in 25 % (n = 314) of the population. On average, patients with CLD were found to be older (mean age 44 vs 36 years, p < 0.0001), unemployed (81.8 % vs 61 %, p < 0.0001), and receiving government disability benefits at significantly higher rates (21.9 % vs 11 %, p < 0.0001). Increased levels of physical craving, emotional stress, as well as health risk behaviors were noted in CLD patients. Findings from the multi-variable model demonstrate a 68 % increased risk for dangerous opioid consumption behaviors (Odds Ration [OR]: 1.68, 95 % Confidence Interval [CI] 1.22, 2.31, p = 0.001) among patients with CLD. Methadone dose (OR: 0.76, 95 % CI 0.70, 0.81, p < 0.0001) was shown to be protective with a significant risk reduction of 24 % per 20 mg increase in methadone. Duration in treatment was also found to be protective (OR: 0.99, 95 % CI 0.97, 0.99, p < 0.0001).Conclusion: CLD poses a distinct risk for patients with opioid addiction. Closer drug monitoring, and substance use contingency management should be considered to reduce mortality risk in these patients. [ABSTRACT FROM AUTHOR]

Inpatient addiction medicine services (AMS) were developed in response to the growing needs of hospitalized individuals with substance use disorders (SUDs). AMS aim to enable timely initiation of pharmacologic treatment, build hospital capacity to support patients who use substances, and facilitate transition to community services. As an emerging service being adopted in hospitals across North America, the model of care, populations served, substance use trends, and clinical trajectory has not been widely described. This work aims to characterize patients accessing care through the AMS, establishing predictors for clinical trajectories in hospital including patient-initiated discharge (PID) and hospital re-admission. Using a retrospective cohort design, we describe all patients seen by the AMS between 2018 and 2022 across four hospitals in Hamilton, Ontario. Patients seen by AMS were hospitalized and qualified for a SUD based on DSM-V criteria. The study used descriptive statistics to describe the cohort, where appropriate adjusted time-to-event survival models were constructed to identify predictors for hospital re-admission. Patients seen by the AMS (n = 695) frequently lacked access to primary care (47.0 %) and less than half (44.3 %) were receiving community addiction services on admission. The majority met criteria for opioid use disorder (OUD), with injecting being the primary consumption route (54.8 %). Patients exhibited high acuity, with 34.2 % requiring critical care measures. Provision of OAT substantially increased to 77.9 % of patients (29 % on admission). PID occurred in 17.8 % of patients and was significantly associated with an admitting diagnosis of suicidal ideation, infection, heart failure, and distinct substance use profiles including methamphetamine, fentanyl, and heroin use (p < 0.05). PID conferred a 66 % increased risk for re-admission (Hazard-Ratio: 1.66; 95 % CI: 1.08, 2.54; p = 0.02). Patients served by AMS primarily include individuals with OUD presenting with the associated medical complications and substantial deficits in the social determinants of health (e.g., high housing insecurity, poverty, and disability). PID occurs among 1 in 5 people and is associated with higher rates of re-admission. By identifying individuals at higher risk of adverse outcomes, these results provide an opportunity to improve outcomes in this high-risk, high-vulnerability population. • Patients served by hospital-based addiction medicine services primarily include individuals with opioid use disorders presenting with the associated medical complications and substantial deficits in the social determinants of health including high housing insecurity, poverty, and disability. • Hospitalization is an important opportunity to engage people who use substances, where the majority of patients seen by addiction medicine consultation services are unconnected to medical care upon admission, and even fewer are receiving community addiction services. Increased uptake of life-saving treatments such as opioid agonist treatments can be facilitated by this service. • Patient-initiated departure occurs frequently in patients with substance use disorders and is significantly associated with (1) readmission to hospital, (2) substance use profiles including methamphetamine and fentanyl use, as well (3) distinct admission diagnoses such as suicidal ideation, infection, and congestive heart failure. [ABSTRACT FROM AUTHOR]