Effectiveness of Treatment Modalities for Those With Diagnosed Opioid Use Disorder and Co-occurring Disorders

Substance abuse has always been an issue in society. As time has passed, the adverse consequences of substance abuse have become more evident. These consequences include physical and mental addiction, disruption of purposeful and productive everyday life, disruption of the family unit, spread of diseases, and death. Recently, the rate of overdose has rapidly increased due to the potency and accessibility of illicit opiates. Fentanyl and carfentanyl have been added to many opioid and non-opioid substances to provide a more euphoric experience, to intensify the addiction of the client, and for economic reasons because they are much more potent than heroin. Unfortunately, these products are often deadly, and the number of overdoses has increased 500 percent over the past ten years in the United States. Individuals with substance addiction are very likely to have a co-occurring mental illness. In 2017, 7.9 million patients had diagnosed with co-occurring disorders. Treatments for those with substance use disorders and co-occurring disorders are under constant scrutiny for their effectiveness. This study investigates the effectiveness of methadone maintenance treatment comparatively with non-methadone treatments for those with opioid use disorder and co-occurring disorders. The data was gathered from an anonymous behavioral health treatment facility that specialized in substance use disorders in southern Massachusetts. The study analyzed archival data from 1,000 clients’ treatment episodes over 1 year. The clients were randomly chosen, and treatment choices were identified. The length of time in treatment help to determine whether the treatment is successful or unsuccessful

Investigating cognition in chronic opioid use: Potential role for the gut microbiota

Impairment in cognitive functioning is a core component of opioid dependence due to its importance in the course of addiction and its role in treatment, but the effect of opioid use on cognition in individuals undergoing early stages of treatment is under examined, particularly in the Australian population. Although existing pharmacological options have demonstrated some efficacy in treating opioid dependence, they are limited in their ability to treat the cognitive dysfunction present in opioid dependent individuals. Hence, there is a need for novel treatment options that address these limitations. The commensal gut microbiota can engage in bidirectional communication with the brain and thus influence brain function, including cognition. Dysbiosis of the microbiota has been reported in several areas of addiction and concomitant cognitive impairment, and may serve as a target for potential future novel treatments. The effect of opioid use on the gut microbiota is inconclusive, however. The present thesis aimed to: a) investigate cognition in individuals with a history of chronic opioid use during the early stages of rehabilitation treatment in an Australian setting; b) examine the effect of opioid use on the gut microbiota, and; c) outline the functional potential of the gut microbiota in opioid use and how it may relate to key signalling pathways of the microbiota-gut-brain axis. In Chapter 2, Australian participants at early stages of community-based rehabilitative treatment (including treatment with methadone or buprenorphinenaloxone, BNX) underwent neurocognitive testing. Results demonstrated impaired cognitive functioning compared to the general population, but no significant differences between performance in BNX compared to methadone-treated participants. BNX treatment was associated with a longer length of stay, which could indicate greater treatment adherence. The potential influence of treatment and non-treatment related parameters were also examined. Treatment related factors (e.g., time since last dose, life-time length of treatment) had a significant relationship with cognitive performance in BNX-treated participants, but not methadone treated participants. Neurocognitive performance was also significantly influenced by non-treatment related demographics factors, such as age and BMI. Together, these findings demonstrate cognitive impairment in people undergoing residential rehabilitation for opioid addiction and highlight treatment and demographics parameters that could potentially influence cognitive outcomes and should be considered in future studies. In Chapter 3, a systematic literature review was conducted to investigate the effect of opioids on the gut microbiota. Results demonstrated that opioid use resulted in dysbiosis of the gut microbiota, and identified specific microbes that were repeatedly dysbiotic across clinical and preclinical studies for the first time. Opioid use also resulted in alterations to key signalling pathways of the microbiota-gut-brain axis, suggesting the potential for opioid induced dysbiosis of the gut microbiota to influence cognition. These results may have significant implications for future research aiming to better understand the pathology of opioid dependence, and may inform the development of future novel treatments that improve the lives of people with opioid dependence

The Experiences of Women Entering Methadone Treatment for Opioid Use: an Interpretive Phenomenological Inquiry

The United States is facing a momentous public health problem of prescription and illicit opioid use among women. Traditionally in health literature women have received less attention than men and this is especially true with regard to drug use. In terms of recovery from opioid use, treatment centers that use methadone as a pharmaceutical replacement for illicit opioids have been present in the US for decades, and women have been enrolling in treatment since its inception. However, there is little in the literature about the characteristics of these women, why they choose methadone treatment, and what their experiences are while in treatment. The study explores the experiences of thirteen women entering methadone treatment at a clinic in urban Fort Worth, Texas. Through the narrative descriptions of their history of drug use, reasons for deciding to get help, accounts of why they chose methadone and their experiences during their time in treatment are answered. An Interpretive Phenomenological qualitative research method was employed throughout to gather and understand the stories of women drug users searching for help. This method explores their beliefs about challenges, pitfalls and triumphs of recovery. Results from this study will add to the knowledge base about women and substance use disorders as well as women and change. Findings will help nurses and those in other disciplines to better understand the problem of opioid use among US women and assist women in traversing through the addiction journey

Prenatal methadone exposure and the developing brain

Opioid use globally is increasing resulting in rising numbers of pregnant women exposing their unborn babies to opioid drugs, with an estimated 30,000 children each year in Europe born to mothers who have used opioids during pregnancy. Methadone is the recommended opioid substitute during pregnancy. Although maternal and perinatal outcomes for pregnant opioid users can be improved by maintenance methadone, there are increasing uncertainties about the safety of methadone on the developing brain and subsequent neurodevelopmental outcomes of children who are exposed prenatally to methadone. Advanced MRI techniques, such as diffusion MRI (dMRI), allow detailed non-invasive investigation of brain microstructure. Imaging biomarkers such as fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD) and radial diffusivity (RD) derived from dMRI, are robust markers of white matter development, with FA associated with later neurodevelopmental outcome. Tract-based spatial statistics (TBSS) enables group-wise comparison of dMRI data and has been optimised for the neonatal brain. The aim of this thesis was to test the hypotheses that: (i) systematic review of existing published literature shows that prenatal methadone exposure is associated with altered neurodevelopment, visual development and / or brain tissue injury apparent on imaging; (ii) infants with prenatal methadone exposure have altered brain white matter microstructure when compared with term born unexposed control infants, which is manifest by a reduced FA and increased MD and increased RD; (iii) infants with prenatal methadone exposure have reduced total brain volumes and regional brain volumes when compared with term born unexposed infants. A systematic review of the literature was performed and where amenable data were pooled in random effects meta-analysis. 43 studies were included, 29 reported neurodevelopmental outcomes, 12 reported visual, and 2 reported neuroimaging data. 8 studies were meta-analysed and effect size was expressed as weighted mean difference (WMD) in developmental quotient scores. Childhood neurodevelopment, visual development and behaviour were altered in association with prenatal methadone exposure. Meta-analysis point estimates of cognitive indices (WMD of -4.43, 95% CI -7.24 to -1.63) and motor indices (PDI scores: WMD of -5.42, 95% CI -10.55 to -0.28) in 2 year old children exposed to prenatal methadone were lower than in age matched children with no prenatal drug exposure. Term born methadone-exposed infants were recruited and underwent an MRI scan shortly after birth. These were compared with 20 non-exposed term controls. An optimised Tract-based Spatial Statistics (TBSS) pipeline was used to perform voxel-wise statistical comparison of FA data. Prenatal methadone exposure was associated with microstructural alteration in major white matter tracts which were present at birth and when head circumference was adjusted for; these changes persisted in the anterior and posterior limbs of the internal capsule and the inferior longitudinal fasciculus (p<0.05). In a subgroup of prenatal methadone exposed infants, lower white matter volumes (p = 0.049) and higher cerebrospinal fluid volumes (p = 0.001) were demonstrated when compared to healthy term control infants. This thesis has shown that through systematic review of the literature, there is an association between prenatal methadone exposure and both lower neurodevelopmental scores and visual dysfunction. TBSS showed that prenatal methadone exposure is associated with atypical white matter development compared with unexposed controls. Reduced FA in the white matter skeleton is apparent soon after birth, indicating an association between methadone exposure and brain development in utero; polydrug use among maternal cases limits causal inference. The data do not confirm the safety of methadone for medically assisted treatment of heroin addiction in pregnancy

Neuropsychological function as a result of chronic exposure to methadone and other opioids

It is increasingly recognised that chronic exposure to opioids has been associated with neuropsychological impairment during both active use and following a period of abstinence. The overall objective of this thesis was to review the relevant prior literature in a systematic manner and subsequently to describe the effects of chronic exposure to prescribed and illicit opioids using an ambispective cohort study design. A systematic literature review was conducted to identify if chronic (defined as a period for more than 3 months) exposure to opioids (prescribed and/or illicit) was associated with measurable neuropsychological deficits. This review was conducted accordingly to the Meta-analysis of Observational Studies in Epidemiology (MOOSE) and the Preferred Reporting Items for Systematic reviews and Meta-Analysis (PRISMA) guidelines. The results were subsequently described within three cognitive domains of intelligence, executive function and memory and learning. Out of a total of 905 articles extracted between 1964 and 2009, 49 articles were considered appropriate for selection and review. Studies of current and abstinent chronic opioid users (illicit heroin users, patients prescribed methadone for illicit opioid dependence and patients taking opioids as part of the management of chronic pain) have identified performance deficits in measures of executive functioning and memory. These have included impairments within the domains of cognitive and motor impulsivity, strategic planning, cognitive flexibility, attention and memory. However other studies found no clear deficits when comparing the performance of healthy controls. The literature suggested that these neuropsychological deficits may be subject to at least partial recovery following initiation of methadone or total withdrawal from any opioids.This review also highlighted several methodological issues that affect the reliability, validity and clinical relevance of the results obtained. Subsequently a two year ambispective cohort design study was conducted which tested representative opioid exposed participants and healthy controls. Cohorts of participants with validated histories of illicit heroin use (HEROIN, n=24), stabilised methadone maintenance (METHADONE, n=29), chronic opioid prescriptions for pain (CHRONIC PAIN, n=28) and controls (HEALTHY CONTROL, n=28) were recruited. The study was designed to test neuropsychological performance in the HEALTHY CONTROL and CHRONIC PAIN groups on one occasion; and for the HEROIN and METHADONE groups on three and two occasions respectively. The intention was to describe neuropsychological performance in the HEROIN group under conditions of stable illicit heroin use, in controlled opioid withdrawal and when subsequently stabilised on methadone. For the METHADONE group, participants were tested twice, six months apart, to test for changes induced by chronic exposure to methadone. Eligible, screened and consented individuals were tested on nine tests from the CANTAB test battery. Data were analysed using univariate or repeated measures ANCOVA with a between subjects factor of GROUP. Further a priori subgroup analyses were conducted using (1) a two-group factor reflecting DEPENDENCE status and (2) a two-group factor reflecting INJECTING status separately as between subject factors. The homogeneity of variance across groups in repeated-measures design ANCOVAs was assessed by the Mauchly Sphericity Test. NART, age in years, SIMD, total Fagerström score, years in education and past alcohol use in years were used as covariates. A significance level of p<0.01 was applied due to multiple testing, in addition to the post-hoc Bonferroni correction procedure. On the Cambridge Gambling Task (CGT), HEROIN users placed higher bets earlier and risked more. They also showed increased motor impulsivity, impaired strategic planning and visuospatial memory on the Affective Go-NoGo (AGN), Stockings of Cambridge (SOC), and Delayed Matching to Sample(DMS) respectively. METHADONE users deliberated longer and placed higher bets earlier on the CGT, but did not show a tendency to risk more. METHADONE users were also more inattentive and demonstrated poor strategic planning and visuospatial memory on the Spatial Span (SSP) task. The CHRONIC PAIN participants did not exhibit significant impairment in neuropsychological performance on all the CANTAB tasks. Participants from the HEROIN, METHADONE and CHRONIC PAIN groups did not present with impaired cognitive flexibility. Chronic opioid dependence is associated with neuropsychological impairment reflected in altered performance on measures of risk taking and strategic planning. These data support the hypothesis that these neuropsychological impairments reflect an underlying trait vulnerability to drug taking and/or dependence rather than an effect of chronic exposure to opioids. Notably, motor impulsivity and visuo-spatial memory in HEROIN users improved after three weeks stability with methadone. Methadone use seems to confer improvement in some aspects of neuropsychological performance following cessation of heroin and sustains other deficits during long term stable methadone treatment. Dependence and injecting status do not contribute to the causation or deterioration of the identified neuropsychological impairments. Further long term longitudinal studies to help elucidate cognitive endophenotypes responsible for the components in the initiation, continuation and deterioration of neuropsychological deficits present in an opioid dependent population is necessary.EThOS - Electronic Theses Online ServiceGBUnited Kingdo