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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]

Background: Despite the growing numbers of men and women with opioid use disorder in Canada, sex-specific issues in treatment have not been re-examined in the current population of patients with opioid addiction. We aimed to evaluate sex differences in substance use, health, and social functioning among men and women currently receiving methadone treatment for opioid use disorder in Ontario, Canada. Methods: We recruited 503 participants with opioid dependence disorder receiving methadone maintenance treatment. We collected data on demographics, treatment characteristics, psychiatric history, addiction severity, and drug use patterns through urinalysis. We performed adjusted univariate analyses and logistic regression to identify distinct factors affecting men and women. Results: Among our sample of 54 % (n = 266) men and 46 % women (n = 226) with mean age 38.3 years, less than half of participants were employed (35.6 %) and married (31.8 %) and had completed a high school education (27.9 %). Compared to men, women had frequent physical and psychological health problems, family history of psychiatric illness, and childcare responsibilities and began using opioids through a physician prescription. Men had higher rates of employment, cigarette smoking, and cannabis use compared to women. Conclusions: Our results have revealed different patterns of substance use, health, and social functioning among men and women currently receiving methadone treatment for opioid addiction in Ontario, Canada. This information can be used to develop an integrative treatment regimen that caters to the individual needs of men and women, as well as to inform methadone treatment protocols to include specialized services (including vocational counseling, childcare and parenting assistance, medical assistance, relationship or domestic violence counseling, etc.) and increase their availability and accessibility on a larger scale. [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: The heritability of opioid use disorder has been widely investigated; however, the influence of specific genes on methadone treatment outcomes is not well understood. The association between response to methadone treatment and genes that are involved in substance use behaviors and reward mechanisms is poorly understood, despite evidence suggesting their contribution to opioid use disorder. The aim of this study was to investigate the effect of brain-derived neurotrophic factor (BDNF) and dopamine receptor D2 (DRD2) polymorphisms on continued opioid use among patients on methadone treatment for opioid use disorder. Methods: BDNF 196G>A (rs6265) and DRD2-241A>G (rs1799978) genetic variants were examined in patients with opioid use disorder who were recruited from methadone treatment clinics across Southern Ontario, Canada. We collected demographic information, substance use history, blood for genetic analysis, and urine to measure opioid use. We used regression analysis to examine the association between continued opioid use and genetic variants, adjusting for age, sex, ethnicity, methadone dose, duration in treatment, and number of urine screens. Results: Among 240 patients treated with methadone for opioid use disorder, 36.3 percent (n = 87) and 11.3 percent (n = 27) had at least one risk allele for rs6265 and rs1799978, respectively. These genetic variants were not significantly associated with continued opioid use while on methadone maintenance treatment [rs6265: odds ratio (OR) = 1.37, 95 % confidence interval (CI) = 0.792, 2.371, p = 0.264; rs1799978: OR 1.27, 95 % CI 0.511, 3.182, p = 0.603]. Conclusions: Despite an association of BDNF rs6265 and DRD2 rs1799978 with addictive behaviors, these variants were not associated with continued illicit opioid use in patients treated with methadone. Problematic use of opioids throughout treatment with methadone may be attributed to nongenetic factors or a polygenic effect requiring further exploration. Additional research should focus on investigating these findings in larger samples and different populations. [ABSTRACT FROM AUTHOR]

Background: Opioid use disorder is a serious international concern with limited treatment success. Men and women differ in their susceptibility to opioid use disorder and response to methadone treatment and can therefore benefit from sex-specific treatment. We performed a systematic review of the literature on outcomes of methadone maintenance treatment for opioid use disorder in men and women related to drug use, health status and social functioning. Methods: We searched PubMed, Embase, PsycINFO and CINAHL for observational or randomized controlled studies involving adults 18 years of age or older undergoing methadone treatment for opioid use disorder. Studies were included if they investigated sex differences in methadone treatment outcomes. Two authors independently reviewed and extracted data. Meta-analyses were performed when possible; risk of bias and quality of evidence were also assessed. Results: Twenty studies with 9732 participants were included, of which 18 were observational and 2 were randomized controlled trials. Men and women differed significantly in alcohol use (odds ratio [OR] 0.52, 95% confidence interval [CI] 0.31 to 0.86), amphetamine use (OR 1.47, 95% CI 1.12 to 1.94), legal involvement (OR 0.63, 95% CI 0.47 to 0.84) and employment during treatment (OR 0.39, 95% CI 0.21 to 0.73). Opioid use patterns were similar among men and women. Risk of bias was moderate, and quality of evidence was generally low. Interpretation: Sex differences were evident in polysubstance use, legal involvement and employment status among men and women receiving methadone treatment for opioid use disorders. Although the quality of evidence was low, our review highlights the need for improved implementation of sex-specific treatment strategies. [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]