The methadone maintenance treatment population suffers from high rates of comorbid psychiatric and substance use disorders. Despite a more than 40-year treatment history, not all patients are satisfied with methadone treatment and more than half of the patients complain of significant inter-dose withdrawal at least some of the time. The objectives of this research were to investigate the pharmacological response to methadone under the influence of comorbid major depressive disorder and smoking; and to identify factors other than physical withdrawal symptoms that can differentiate patients based on their complaints of dissatisfaction with treatment. In Study 1, seven depressed methadone maintenance patients experienced more opioid withdrawal symptomatology over a 24-hour methadone-dosing interval than 10 nondepressed methadone patients. Depression severity was significantly correlated with trough opioid withdrawal severity. This suggests that depression or depressive symptoms are related to reported opioid withdrawal. In Study 2, many factors other than physical opioid withdrawal symptoms were able to differentiate patients who were satisfied with treatment (holders, n=25), partially satisfied with treatment (partial holders, n=35), and not satisfied with treatment(nonholders, n=30). Results suggested that these patient satisfaction groups cluster differently depending on physical opioid withdrawal, mood, psychological distress, and personality. Nonholders experienced more physical withdrawal symptoms, craving for opioids, and negative drug effects. Holders had less psychological distress and experienced less negative mood states than the other groups. Partial holders had less agreeable personalities compared to patients in the other groups. In Study 3, opioid and nicotine withdrawal symptoms and effects were measured in 40 methadone-maintained patients who were current smokers during trough and peak methadone effects, both pre and post-nicotine administration. Cigarette smoking enhanced opioid withdrawal suppression during the peak methadone condition, methadone attenuated nicotine withdrawal, and methadone and nicotine shared many of the same main effects, suggesting that smoking and methadone effects may be inseparable dimensions. In summary, the results of these studies suggest that in addition to physical symptoms, mood related factors are important to opioid withdrawal perception and that the mood factors and drug interactions can impact on a patient’s perception of satisfaction with methadone treatment.

Thesis (Ph.D.) in Nursing--University of Maine, 2009. / Includes vita. Includes bibliographical references (leaves 134-152).

Hepatitis C (HCV) is an infectious disease of the liver which affects more than 250,000 Canadians; the majority of those living with the disease have experience with injection drug use. Treatment for HCV involves a strict protocol, has only a 50% success rate and has harsh side effects. Interest in HCV treatment among people who use drugs is high, but actual uptake of treatment remains low. The objective of this research was to explore the barriers to accessing HCV treatment for individuals who were accessing methadone. A mixed methods approach was used; a cross sectional survey and an in-depth interview were administered to clients of a methadone maintenance program. The two sets of data identified three main barriers to HCV treatment; stigma, the toxicity of treatment, and day-to-day struggles. Future research should be conducted to further explore how stigma guides decisions around HCV treatment, particularly in a methadone treatment setting.

Children born to methadone maintained mothers are at high risk of adverse socio-emotional and behavioural outcomes. However, existing studies inadequately report the extent of maternal methadone and other drug use, focus on a narrow range of outcomes, and have given little consideration to the possible impact of child protection and placement experiences. As part of a prospective longitudinal study, mothers of 53 methadone-exposed (ME) children and 54 non-exposed comparison children were interviewed at four time-points from term to the child turning 4.5-years. Detailed information about infant clinical, maternal and family background characteristics was recorded. The nature of all child out-of-home placements was reported at regular intervals using life history calendar methods. At 4.5 years, all caregivers completed the Strengths and Difficulties Questionnaire (SDQ) and were interviewed using the Developmental and Well-Being Assessment (DAWBA) to examine the extent of child socio-emotional and behavioural adjustment problems as well as risk for a range of clinical disorders. By age 4.5 years, ME children were rated by their caregivers as having higher levels of emotional (p = .01), peer-relationship (p = .01), hyperactivity/inattention (p = .01), conduct (p = .01) and total problems (p = .01) than comparison children on the SDQ. Between-groups differences persisted for conduct problems (p = .003) and total difficulties (p = .006) even after controlling for a range of covariates associated with maternal methadone maintenance therapy, including single motherhood, maternal educational achievement, family socioeconomic status (SES), and other drug use in pregnancy. On the DAWBA, children in the ME group were also significantly more at risk than comparison children for externalising disorders spanning ADHD (p = .02), hyperkinesis (p =.01), oppositional defiant disorder (p < .001), and conduct disorder (p = .007). Examination of all study children‟s family situation at 3-monthly intervals over the first 4.5-years revealed that 43% of children in the ME group had experienced at least one foster care placement (range: 1 – 7). In contrast, no comparison children had any placement experience (p < .01). Within the methadone group, maternal risk factors that predicted the likelihood of child placement included maternal methadone dose in pregnancy (p <.01), SES (p = .03), maternal depression (p <.01) and the extent of tobacco (p = .01) and illicit substance use while pregnant (p = .05). ME children exposed to placement showed some increased risk for internalising disorders such as separation anxiety disorder (p = .35) and specific phobia disorder (p = .35), whereas ME children remaining in their biological mothers‟ care tended to have an increased risk for externalising disorders such as ADHD, hyperkinesis and oppositional defiant disorder, although these differences did not reach statistical significance (ps < .05). Child placement did not appear to be independently contributing to the later mental health risks for ME children, at least to age 4.5-years. Rather, a very similar set of maternal psychosocial risk factors were associated with both out-of-home placement and child adjustment problems, thus highlighting the importance of socio-environmental adversity leading to both child removal from parental care and externalising behaviour problems. Further longer-term follow-up of ME children will be important to fully understand the emerging relationships between out-of-home care and the mental health outcomes of ME children. These study findings have important clinical and public health implications. First, the increased risk for socio-emotional and behavioural adjustment problems and disorder as observed among the ME group suggests that appropriate clinical support is needed to address the problems experienced by these children, with the preschool years being a timely opportunity for early targeted interventions. Second, given that high risk ME children are also a population likely to encounter considerable early environmental instability, public healthcare protocols should be introduced to meet the specific developmental needs of young ME children as they transition through and adjust to the placement process.

Over the past ten years, there has been a consistent increase in opioid use, which has resulted in an increase in enrolment in methadone maintenance therapy [MMT]. With retention in MMT being a key factor, in order to understand the process of retention, it is important to gain an understanding of individual perceptions and experiences. No research in Ottawa, Ontario has addressed the perspective of MMT from people enrolled in MMT; therefore, nursing based research was undertaken. The objective was to understand the process and experiences associated with MMT from the perspective of persons who are enrolled in treatment. Twelve participants were engaged in semi-structured interviews. These participants described that, although MMT can positively affect the people who use such a treatment option, it continues to have a negative impact that repeatedly affects MMT initiation and delivery. The theoretical framework of Hardt and Negri’s “Triple Imperative of Empire” was used to analyze the research participants’ interviews within the current MMT program, to help develop a more inclusive healthcare service that addressed the current barriers hindering access and retention in treatment. The integration of this framework can help engage persons in treatment, tailor treatment to patient specific needs, and as a result increase access and retention in MMT programs.

We examined internal consistency and test-retest reliability of a measure of dispositional optimism, the Life Orientation Test-Revised, in 121 opiate-dependent patients seeking methadone treatment. Internal consistency was adequate at baseline (α=.69) and follow-up (α=.72). Low socioeconomic status and being on disability were significantly associated with reduced internal consistency; ethnic and educational differences approached significance. Test-retest reliability was good (ICC=.72), varying across gender, race, ethnicity, education, employment and income (ICC Range=.24-.85). Criterion validity was strong; the LOT-R was significantly negatively correlated with hopelessness (r=-.65, p<.001) and depression (r=-.60, p<.001). Findings support the use of this measure of optimism and pessimism to assess positive cognitive and emotional attributes and improve treatment strategies for opiate-dependent individuals. Future research should address the measurement and significance of optimism in minority, low socioeconomic status and poorly-educated individuals.

Background: The consequences of continued opioid abuse among patients treated with opioid substitution therapy (OST) are serious and can result in abnormal cardiovascular function, overdose, and mortality. Conflicting evidence exists that both implicates and refutes the role of chronic non-cancer pain (CNCP) as a major risk factor for continued opioid abuse within the addiction treatment setting. This thesis aims to 1) evaluate the impact of chronic pain on the treatment outcomes of patients with opioid addiction receiving OST, 2) determine whether a clinical or inflammatory profile exists to distinguish pain in this population, 3) explore the sources of heterogeneity in previous studies examining this question, 4) determine the best therapy for patients with chronic pain, and 5) evaluate the most effective treatment for opioid addiction. We anticipate chronic pain to be an important predictor of continued opioid abuse such that patients with comorbid pain will require careful consideration when managed on OST. Methods: We systematically reviewed the literature to determine the impact of pain in opioid addiction patients receiving methadone maintenance treatment (MMT). We determined the clinical and inflammatory profile of MMT patients using data from the Genetics of Opioid Addiction (GENOA) research collaborative between the Canadian Addiction Treatment Centres (CATC) and the Population Genomic Program. GENOA is a prospective cohort study aimed to determine the genetic, biological, and psychosocial determinants of treatment prognosis for opioid addiction patients receiving MMT. GENOA recruits patients ≥ 18 years of age meeting the DSM-IV criteria for opioid dependence. All GENOA participants are receiving MMT for the management of opioid addiction. Baseline data from the GENOA pilot study (n=235) were used to evaluate the impact of pain on illict opioid use behaviour and determine the clinical and inflammatory profile of patients with comorbid pain. We explored sources of heterogeneity in previous studies using data from the full-phase GENOA study (n=444), examining the prognostic value of different pain measures for predicting illicit opioid use. We then performed a multiple treatment comparison of all opioid substitution and antagonist therapies in efforts to determine the best intervention for improving treatment outcomes for patients with comorbid pain. We lastly determined the most effective treatment for opioid addiction by performing a network meta-analysis using data from a systematic review of opioid maintenance therapy trials. Results: Our initial systematic review confirmed a lack of consensus in the literature, whereby some studies suggest pain increases risk for illicit opioid use and other studies suggest pain has no effect on substance use behaviour. Findings from the analysis of GENOA pilot data confirmed chronic pain to be an important predictor of sustained opioid abuse and also showed patients with pain to have elevated Interferon-Gamma. Using data from the GENOA prospective cohort study we determined the Brief Pain Inventory (a commonly used pain measurement in pervious studies) to be highly sensitive with poor prognostic value. Our final reviews propose 1) there is limited evidence to suggest any OST is superior for managing patients with comorbid pain, and 2) heroin and high-dose methadone are the most effective treatments for improving treatment retention. The final systematic review and network meta-analysis in this thesis also highlights a major problem in the treatment of opioid use disorders, primarily the lack of consensus as to what outcomes matter for determining success in patients with addiction. Conclusion: Patients with comorbid pain and addiction are at high-risk for continued opioid abuse and should be managed closely by clinicians administering OST. Contention in the previous literature likely resulted from the use of pain measurements with poor prognostic value. No OST demonstrated superiority for managing patients with chronic pain. While our findings indicate heroin is the most effective treatment across multiple endpoints, we use this thesis to provide readers with 1) a sense of the feasibility issues associated with heroin administration, 2) a summary of the limitations of this evidence base, and 3) recommendations for how to improve the addiction trials’ design for future research. / Thesis / Doctor of Philosophy (PhD)

Background: Social adversities are prevalent among those with psychiatric disorders and may be involved in poor outcomes among patients receiving treatment. Identification of social risk factors influencing outcomes will help provide targeted interventions for at-risk patients. This thesis explored the role of social and behavioural factors in relation to adverse psychiatric outcomes, specifically relapse to substance use and attempted suicide. Methods: We used scoping study methodology to perform a comprehensive review to identify the gaps in the literature examining social functioning and MMT outcomes. This review informed our primary cohort study examining the association between social factors and continued opioid use in MMT. Lastly, we conducted a case-control study to identify risk factors for suicide attempts by comparing psychiatric patients with and without suicide attempt history (cases and controls, respectively). Multivariable logistic regression analyses were conducted in both primary studies to examine the association between predictors and outcomes. Results: The review included 101 observational studies and determined the need for further research on social factors and MMT outcomes among a current sample of Canadian patients. Our cohort study included 1043 participants (mean age=38.4 years, standard deviation [SD]=11.06); 45.8% women) to investigate this and found that unemployment, criminal activity and interpersonal conflict with friends significantly increased odds of illicit opioid use. In examining risk factors for suicide attempts, we recruited 146 cases (mean age=45.18 years, SD=14.70 years; 55% female) and 104 control participants (mean age=45.01 years, SD=14.23 years; 50% female). No sociodemographic differences existed between groups, however higher impulsivity and borderline personality symptoms significantly increased odds of attempted suicide. Conclusions: Findings from these studies may indicate the need for structured monitoring of at-risk psychiatric patients. It may be important to develop tools to measure social and behavioural factors in clinical settings and promote further integration of social services in treatment settings. / Thesis / Master of Science (MSc)

Background Heroin dependence is associated with increased risk of the transmission of blood-borne viral (BBV) infections such as HIV, as a result of unsafe injecting practices. Opioid Substitution Treatment (OST) Programmes including Methadone Maintenance Treatment (MMT) programmes are a recommended way of addressing heroin dependence with the dual aims of reducing both heroin use and associated harms. However, OST programmes, particularly in prison settings, are often unavailable, in spite of large numbers of prisoners with heroin dependence and the high risk of HIV transmission in the prison setting. Little is currently known about the delivery of OST programmes within prison settings. A systematic literature review conducted within this study revealed that there are only a small number of studies from middle and lower-income countries and the perspectives of the range of stakeholders are often underrepresented. Aim and setting of this study This aim of this study was to understand the role of Methadone Maintenance Treatment (MMT) programmes within the context of HIV prevention programmes and to identify barriers and facilitators that influence the implementation, routine delivery and sustainability of methadone programmes in Indonesian prisons. Study design Three prison settings were selected as part of a qualitative case study. These comprised: a narcotics prison that provided methadone, a general prison that provided methadone, and a general prison, where there was no methadone programme. This allowed the exploration of multiple perspectives of prisoners and the diverse range of staff involved in the implementation of programmes. Interview and observational data were supplemented by data from medical case notes. Qualitative data underwent thematic analysis, with the help of framework analysis for data management. Principal findings This study found that there were many misconceptions about methadone programmes. HIV infection was not recognised as a problem and prison staff, healthcare staff and prisoners alike lacked understanding of the roles of methadone programmes. Prisoners participating in programmes were often stigmatised, while many prisoners believed methadone withdrawal was dangerous and could lead to death. These factors all contributed to low level participation, observed in both prisons with methadone programmes. Lack of confidentiality and associated stigmatisation as well as inappropriate assessment criteria also contributed to this, as did a lack of support systems. A reduction in international funding and a shift in national drug policy priorities away from the provision of methadone to drug-free Therapeutic Community (TC) programmes, together with a failure to embed methadone programmes within the daily prison routine currently pose challenges to effective implementation, delivery and programme sustainability. Conclusion Educating policy makers and practitioners could improve understanding of the roles of methadone programmes and increase support for programme delivery within prisons. It is therefore recommended that Indonesian government and prison policy focuses on ensuring effective delivery and sustainability of methadone programmes for people with heroin dependence in the prison setting.

Through changes in the code of statutes, SOSFS 2009:27 (M), opioid addicts are excluded since March 1 2010 from possibilities to be accepted for substitution treatment. Opiate addicts are solitary admitted for substitution treatment from that date. Opioid addicts are excluded admission for treatment regardless of the fact that they fulfil the ICD-10 diagnosis F.11.2, i.e. opioid/opiate addictive criteria. The alteration in the statutes was carried out in reference to the fact that evidence for this kind of treatment intended for opioid addicts was missing. Both groups i.e. opiate – and opioid addicts, are nevertheless experienced in clinical work , to have extensive problems with addiction, health, social situation along with the risk of premature death.     The purpose with this study is to identify what differences and/or similarities there are in background varieties and the severity of the problems  between the groups. This is conducted with the use of a population (n=127) with comparable background material, e.g. collected Addictions Severe Index- interviews, scientifically survey and compare background factors and the severity of the problems.      The main discovery in this study is that one can demonstrate great similarities between the groups regarding background as well as the severity of the problems. It is therefore of great interest, on a individual as well as a social oriented level, that pursued studies regarding diagnostic safety and on processes in substitution program are needed to generate further knowledge as a foundation for development of future care and changes in the code of statutes.