Methadone hydrochloride is an old drug that has been in vogue off and on. It has complex pharmacodynamics and can be potentially fatal in inexperienced settings. Drug switching from an opioid to methadone or vice versa requires knowledge of equianalgesic dosing. It is critical when using the drug to monitor for signs and symptoms of toxicity so that overdosing or toxicity can be identified in a timely manner. This review discusses these important topics so that methadone can be used safely and effectively.

This study examined the state of the literature on the effectiveness of medication assisted treatment (MAT; methadone, buprenorphine, naltrexone) delivered in prisons and jails on community substance use treatment engagement, opioid use, recidivism, and health risk behaviors following release from incarceration. Randomized controlled trials (RCTs) and quasi-experimental studies published through December 2017 that examined induction to or maintenance on methadone (n = 18 studies), buprenorphine (n = 3 studies), or naltrexone (n = 3 studies) in correctional settings were identified from PsycINFO and PubMed databases. There were a sufficient number of methadone RCTs to meta-analyze; there were too few buprenorphine or naltrexone studies. All quasi-experimental studies were systematically reviewed. Data from RCTs involving 807 inmates (treatment n = 407, control n = 400) showed that methadone provided during incarceration increased community treatment engagement (n = 3 studies; OR = 8.69, 95% CI = 2.46; 30.75), reduced illicit opioid use (n = 4 studies; OR = 0.22, 95% CI = 0.15; 0.32) and injection drug use (n = 3 studies; OR = 0.26, 95% CI = 0.12; 0.56), but did not reduce recidivism (n = 4 studies; OR = 0.93, 95% CI = 0.51; 1.68). Data from observational studies of methadone showed consistent findings. Individual review of buprenorphine and naltrexone studies showed these medications were either superior to methadone or to placebo, or were as effective as methadone in reducing illicit opioid use post-release. Results provide the first meta-analytic summary of MATs delivered in correctional settings and support the use of MATs, especially with regard to community substance use treatment engagement and opioid use; additional work is needed to understand the reduction of recidivism and other health risk behaviors.

Background: Opioid use disorder (OUD) has been an increasing concern in Canada as mortality rates continue to rise. Though OUD treatments, such as methadone maintenance treatment (MMT), reduce its burden, they could potentially cause harm due to OUD’s variance in severity and presentation across individuals. It is hypothesized that genetic variants such as single nucleotide polymorphisms (SNPs) could predispose patients to respond differently to MMT. In addition, sex differences have been observed in opioid use patterns, treatment outcomes, and genetic make-up. As such, this thesis aims to identify significant SNPs associated with treatment outcomes in genome-wide association studies, and test biologically relevant SNPs with MMT outcomes of interest, while highlighting sex differences. This is achieved through a systematic review protocol, a systematic review, and a candidate gene study. Methods: A protocol was prepared for the planning of the first ever systematic review of genome-wide significant findings of medication-assisted treatment outcomes for OUD patients. The systematic review assessed the literature findings and study qualities, narratively summarizing significant associations. Next, a candidate gene study analyzed the association between SNPs in OPRM1 and CYP2B6 genes, and continued opioid use, relapse, and methadone dose within an ancestrally European sample (n=1226). Sex-stratified and sex-interaction analyses were also conducted. Results: The systematic review included 5 studies and qualitatively assessed 43 unique genetic variants. The candidate gene study showed no significant associations between the selected OPRM1 and CYP2B6 SNPs and outcomes of interest. While no significant differences between the sexes were observed, rs73568641 and rs3745274 showed near significance associations in only one sex, females, and males, respectively. Discussion: Through the study of genetic variants associated with treatment outcomes in the literature and our sample of ancestrally European individuals on MMT, we were able to highlight gaps in pharmacogenetics research and identify areas of focus for future studies. / Thesis / Master of Science (MSc) / Recently, opioid use disorder (OUD) has been declared a national crisis in Canada. OUD treatments are helpful in reducing opioid use and adverse events. However, their dosing and metabolism in patients can impact continued opioid use, relapse, or treatment dose changes. Due to the variability in response between individuals, there might be a genetic basis to treatment outcomes. This thesis explores which genetic variants reported in previous studies are involved in OUD treatment outcomes. Then, it tests select genetic variants in OPRM1 and CYP2B6 genes to see if they are linked to specific outcomes in an Ontario population and tries to identify if these associations differ by sex. No significant associations were found, though associations in males and females had near-significant results in one sex but not the other. Despite suggesting sex’s possible involvement in treatment outcomes, more research is necessary to confirm these findings.

Wong, Ngai Sze. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2008. / Includes bibliographical references (leaves 177-190). / Abstracts in English and Chinese. / ABSTRACT --- p.I / 論文摘要 --- p.II / ACKNOWLEDGEMENT --- p.III / TABLES OF CONTENTS --- p.V / LIST OF ACRONYMS --- p.IX / LIST OF TABLES --- p.X / LIST OF FIGURES --- p.XI / LIST OF APPENDICES --- p.XIII / Chapter CHPATER 1 --- INTRODUCTION --- p.1 / Chapter 1.1. --- BACKGROUND & CONTEXT --- p.2 / Chapter 1.1.1. --- Methadone Maintenance Treatment --- p.2 / Chapter 1.1.1.1. --- Definition of Methadone Maintenance Treatment --- p.2 / Chapter 1.1.1.2. --- The Role of Methadone Maintenance Treatment --- p.3 / Chapter 1.1.1.3. --- Methadone Maintenance Treatment in Hong Kong --- p.4 / Chapter 1.1.2. --- Utilization of Methadone Treatment --- p.6 / Chapter 1.1.2.1. --- Definition of Utilization --- p.6 / Chapter 1.1.2.2. --- Utilization Study in Methadone Treatment --- p.8 / Chapter 1.1.3. --- Geographic Information System Application --- p.10 / Chapter 1.2. --- STUDY AREA --- p.12 / Chapter 1.3. --- RATIONALE & SIGNIFICANCE OF STUDY --- p.15 / Chapter 1.4. --- RESEARCH QUESTIONS --- p.17 / Chapter 1.5. --- RESEARCH OBJECTIVES --- p.18 / Chapter 1.6. --- STUDY PROCEDURES --- p.21 / Chapter 1.7. --- STRUCTURE OF THE STUDY --- p.23 / Chapter CHAPTER 2 --- LITERATURE REVIEW OF METHADONE TREATMENT UTILIZATION STUDY --- p.25 / Chapter 2.1 --- METHADONE TREATMENT UTILIZATION STUDIES --- p.26 / Chapter 2.1.1 --- Individual Determinants --- p.27 / Chapter 2.1.1.1 --- Predisposing Factors --- p.27 / Chapter 2.1.1.1 --- Enabling Factors --- p.29 / Chapter 2.1.1.2 --- Illness Level --- p.31 / Chapter 2.1.2 --- Health Service System --- p.35 / Chapter 2.1.2.1 --- Resource --- p.35 / Chapter 2.1.1.1 --- Organization --- p.36 / Chapter 2.2 --- ANALYSIS METHODS IN METHADONE TREATMENT UTILIZATION STUDIES --- p.40 / Chapter 2.2.1 --- Common Measures --- p.40 / Chapter 2.2.2 --- Study Approach --- p.41 / Chapter 2.2.3 --- Analysis Methods --- p.42 / Chapter 2.2.4 --- Geographic Information System --- p.43 / Chapter 2.3 --- METHADONE TREATMENT UTILIZATION STUDY IN HONG KONG --- p.44 / Chapter 2.4 --- SUMMARY OF LITERATURE REVIEW --- p.45 / Chapter CHAPTER 3 --- METHODOLOGY --- p.46 / Chapter 3.1. --- DEFINITION OF UTILIZATION AND LOCAL UTILIZATION --- p.47 / Chapter 3.2. --- CONCEPTUAL FRAMEWORK FOR MMT UTILIZATION --- p.50 / Chapter 3.2.1. --- Framework Selection --- p.50 / Chapter 3.2.2. --- Components of Andersen & Newman，s Framework for Health Service Utilization --- p.52 / Chapter 3.3. --- DATA SOURCE --- p.54 / Chapter 3.3.1. --- Official Data --- p.55 / Chapter 3.3.2. --- Survey --- p.56 / Chapter 3.3.3. --- Interviews --- p.57 / Chapter 3.3.4. --- Case Study-Survey in a Methadone Clinic in Tai Po --- p.57 / Chapter 3.3.4.1. --- Survey Subject --- p.57 / Chapter 3.3.4.2. --- Rationale for the Survey --- p.58 / Chapter 3.3.4.3. --- Sampling Methods --- p.59 / Chapter 3.3.4.4. --- Questionnaire Design --- p.61 / Chapter 3.3.5. --- Digitized Maps --- p.62 / Chapter 3.4. --- DATA PROCESSING AND MANAGEMENT --- p.63 / Chapter 3.4.1. --- District Utilization and Local Utilization Calculation --- p.63 / Chapter 3.4.2. --- Questionnaire Data Processing --- p.63 / Chapter 3.4.2.1. --- Data Entry & Coding --- p.63 / Chapter 3.4.2.2. --- Digitizing a GIS Layer --- p.64 / Chapter 3.4.2.3. --- Estimated Location of User Home --- p.64 / Chapter 3.4.2.4. --- Sufficiency Level --- p.67 / Chapter 3.4.3. --- Database Management --- p.68 / Chapter 3.5. --- TECHNIQUES TO ANALYZE DATA --- p.70 / Chapter 3.5.1. --- Descriptive Analysis for Spatiotemporal Utilization Pattern --- p.70 / Chapter 3.5.2. --- Quantitative Analysis for Factor Exploration --- p.70 / Chapter 3.5.2.1. --- Assumptions for Correlation and Regression Analysis --- p.70 / General Assumptions --- p.70 / Data Assumptions --- p.72 / Factor Assumptions --- p.73 / Chapter 3.5.2.2. --- Factors Included in the Study Framework --- p.74 / Societal Determinants --- p.75 / Health Services System --- p.76 / Individual Determinants --- p.78 / Chapter 3.5.2.3. --- Pearson´ةs Correlation --- p.80 / Chapter 3.5.2.4. --- Multiple Stepwise Linear Regression --- p.81 / Chapter 3.5.3. --- Quantitative Analysis for Spatial Factor Study --- p.84 / Chapter 3.5.3.1. --- Catchments --- p.84 / Chapter 3.5.3.2. --- Spatial Autocorrelation --- p.89 / Chapter 3.5.4. --- Curve Estimation --- p.90 / Chapter 3.6. --- GIS Customized Tools --- p.90 / Chapter 3.6.1. --- GIS System Literature Review --- p.90 / Chapter 3.6.2. --- Customized Tools Design --- p.92 / Chapter CHAPTER 4 --- ANALYSIS OF MMT UTILIZATION: A CASE STUDY IN HONG KONG … --- p.95 / Chapter 4.1. --- GENERAL DESCRIPTION --- p.96 / Chapter 4.2. --- HEROIN ADDICTION IN HONG KONG --- p.98 / Chapter 4.2.1. --- Spatiotemporal Pattern of Heroin Addiction --- p.98 / Chapter 4.2.2. --- Characteristics of Heroin Users in Hong Kong --- p.103 / Chapter 4.3. --- MMT USERS IN HONG KONG --- p.107 / Chapter 4.3.1. --- Characteristics of Methadone Clinics --- p.107 / Chapter 4.3.2. --- Characteristics of MMT Users --- p.108 / Chapter 4.3.2.1. --- Predisposing Factors of MMT Users --- p.108 / Chapter 4.3.2.2. --- Spatial movement of MMT user --- p.108 / Chapter 4.3.2.3. --- Clinic Environment-Gathering Place --- p.108 / Chapter 4.3.2.4. --- Unique Clinics --- p.109 / Chapter 4.3.3. --- Spatiotemporal Patterns of MMT Users --- p.110 / Chapter 4.4. --- INDIVIDUAL UTILIZATION STUDY - SURVEY IN A METHADONE CLINIC IN TAIPO --- p.114 / Chapter 4.4.1. --- Methadone Clinic Users in Tai Po --- p.114 / Chapter 4.4.2. --- Characteristics of Respondents --- p.114 / Chapter 4.4.2.1. --- Demographic Characteristics --- p.114 / Chapter 4.4.2.2. --- Utilization Level --- p.115 / Chapter 4.4.2.3. --- Spatial Factors and Distribution --- p.116 / Chapter 4.4.3. --- Factors Affecting the Utilization of Tai Po Methadone Clinic --- p.120 / Chapter 4.5. --- CATCHMENTS OF METHADONE CLINICS IN HONG KONG --- p.122 / Chapter 4.5.1. --- Voronoi polygons --- p.123 / Chapter 4.5.2. --- Network Analysis based on travel time --- p.124 / Chapter 4.5.2.1. --- Catchments of Methadone Clinic in Tai Po --- p.125 / Chapter 4.5.2.2. --- Projected Catchments for All Clinics in Hong Kong --- p.126 / Chapter 4.6. --- SPATIOTEMPORAL PATTERN AND SPATIAL RELATIONS OF MMT UTILIZATION --- p.128 / Chapter 4.6.1. --- MMT Utilization --- p.128 / Chapter 4.6.2. --- MMT Local Utilization --- p.131 / Chapter 4.6.3. --- Spatial Relations of MMT Utilization --- p.133 / Chapter 4.7. --- PREDICTORS OF MMT UTILIZATION AND LOCAL UTILIZATION --- p.134 / Chapter 4.7.1. --- Health Care Systems --- p.135 / Chapter 4.7.1.1. --- Resource --- p.135 / Operating Hours --- p.135 / Nearest clinic distance --- p.137 / Distance between a clinic and its nearest clinic in other districts --- p.138 / Chapter 4.7.1.2. --- Accessibility --- p.138 / Chapter 4.7.2. --- Individual Determinants --- p.139 / Chapter 4.7.2.1. --- Predisposing Determinants --- p.140 / Age --- p.140 / Gender --- p.140 / Education --- p.141 / Chapter 4.7.2.2. --- Behavioral Determinant´ؤInjection --- p.141 / Chapter 4.8. --- FUTURE MMT UTILIZATION IN HONG KONG --- p.143 / Chapter 4.9. --- SERVICE GAPS --- p.144 / Chapter 4.10. --- SUMMARY OF STUDY RESULTS --- p.152 / Chapter CHAPTER 5 --- DISCUSSION --- p.153 / Chapter 5.1. --- DISCUSSIONS ON THE RELEVANCE OF UTILIZATION PREDICTORS --- p.154 / Chapter 5.2. --- DISCUSSIONS ON METHADONE CLINIC CLOSURE --- p.159 / Chapter 5.3. --- RESEARCH LIMITATION --- p.164 / Chapter 5.3.1. --- Data Limitation --- p.164 / Chapter 5.3.2. --- Time & Resource Limitation --- p.165 / Chapter 5.3.3. --- Technical Limitation --- p.165 / Chapter 5.4. --- RECOMMENDATIONS --- p.167 / Chapter 5.4.1. --- Recommendations for Methadone Treatment System --- p.167 / Chapter 5.4.2. --- For the Society --- p.169 / Chapter 5.4.3. --- For Further Study --- p.172 / Chapter CHAPTER 6 --- CONCLUSION --- p.174 / BIBLIOGRAPHY --- p.177 / APPENDICES --- p.191

published_or_final_version / Public Administration / Master / Master of Social Sciences

Opioid drug related death is the topic of this thesis. Each of the published works submitted in this volume has investigated an aspect of opioid drug related death. The publications have been grouped into three sub-themes: i. Characteristics of opioid drug related deaths ii. Methadone-related deaths in and out of treatment iii. Improving the quality of treatment for opioid drug dependence: a focus on injectable opioid treatment The introduction and background (Chapter1) will briefly review-the-relevant literature on opioid drug death predating my own contribution to the field. The next chapter of the thesis, 'Publications' (Chapter 2), will comprise the body of published work being submitted for the degree of Doctor of Medicine. Each article is accompanied by text on the preceding page outlining my individual contribution to that research study. The thesis will conclude with a discussion of the published works (Discussion, Chapter 3) which summarises the chief findings and reflects on the international significance and impact of the work. Finally, the Conclusion (Chapter 4) will submit suggestions for areas of future research into opioid drug related death.

Thesis (Ph.D.)--University of Melbourne, Dept. of Medicine, Western Hospital, 2007. / Typescript. Includes bibliographical references (leaves 145-181).

Thesis (Ph. D.)--University of Wisconsin--Madison, 1974. / Typescript. Vita. eContent provider-neutral record in process. Description based on print version record. Includes bibliography.

Methadone treatment continues to be the most widely used treatment modality for heroin addiction despite continued controversy. The efficacy of methadone treatment has been determined primarily by statistical research of program outcomes. This study explored heroin addicts' perceptions of methadone treatment.

Tho present thesis represents a summary or research done by the author (and others) that was conducted with heroin addicts and drug abusers undergoing behavioral and pharmacological therapy at Stockton State Hospital, Stockton, California. From June 1970 to December 1970 the Research Department of Stockton State Hospital, in conjunction with the Drug Abuse Program at Stockton State Hospital, conducted research investigating a number of difference facets relating to inpatient programs for heroin addicts undergoing methadone maintenance and drug abusers. These facets included the investigation and evaluation of (a) motivational factors; affecting the voluntary participation of inpatient heroin addicts and drug abusers in behavioral and pharmacological therapy, (b) the effectiveness of the synthetic narcotic methadone hydrocloride as a primary reinforcing technique for appropriate behavior, (c) the effectiveness of various therapeutic approaches used in conjunction with behavioral modification techniques, and (d) the effect of methadone on perceptual and motor functioning in the heroin addict under-going methadone maintenance. The present thesis is a compilation cf these research projects.