Amy Gibson

Exposure to opioid maintenance treatment reduces long-term mortality

AIMS To (i) examine the predictors of mortality in a randomized study of methadone versus buprenorphine maintenance treatment; (ii) compare the survival experience of the randomized subject groups; and (iii) describe the causes of death. DESIGN Ten-year longitudinal follow-up of mortality among participants in a randomized trial of methadone versus buprenorphine maintenance treatment. SETTING Recruitment through three clinics for a randomized trial of buprenorphine versus methadone maintenance. PARTICIPANTS A total of 405 heroin-dependent (DSM-IV) participants aged 18 years and above who consented to participate in original study. MEASUREMENTS Baseline data from original randomized study; dates and causes of death through data linkage with Births, Deaths and Marriages registries; and longitudinal treatment exposure via State health departments. Predictors of mortality examined through survival analysis. FINDINGS There was an overall mortality rate of 8.84 deaths per 1000 person-years of follow-up and causes of death were comparable with the literature. Increased exposure to episodes of opioid treatment longer than 7 days reduced the risk of mortality; there was no differential mortality among methadone versus buprenorphine participants. More dependent, heavier users of heroin at baseline had a lower risk of death, and also higher exposure to opioid treatment. Older participants randomized to buprenorphine treatment had significantly improved survival. Aboriginal or Torres Strait Islander participants had a higher risk of death. CONCLUSIONS Increased exposure to opioid maintenance treatment reduces the risk of death in opioid-dependent people. There was no differential reduction between buprenorphine and methadone. Previous studies suggesting differential effects may have been affected by biases in patient selection.

The impact of opioid substitution therapy on mortality post-release from prison: retrospective data linkage study

AIMS Release from prison is a high-risk period for mortality. We examined the impact of opioid substitution therapy (OST), for opioid dependence during and after incarceration, upon mortality post-release. DESIGN A cohort was formed of all opioid-dependent people who entered OST between 1985 and 2010 and who, following first OST entry, were released from prison at least once between 2000 and 2012. We linked data on OST history, court and prison records and deaths. SETTING New South Wales (NSW), Australia. PARTICIPANTS A total of 16,453 people released from prison 60,161 times. MEASUREMENTS Crude mortality rates (CMRs) were calculated according to OST retention; multivariable Cox regressions for post-release periods were undertaken to examine the association between OST exposure (a time-dependent variable) and mortality post-release, for which covariates were updated per-release. FINDINGS There were 100,978 person-years (PY) post-release; 1050 deaths occurred. Most received OST while incarcerated (76.5%); individuals were receiving OST in 51% of releases. Lowest post-release mortality was among those continuously retained in OST post-release CMR 4 weeks post-release = 6.4 per 1000 PY; 95% confidence interval (CI) = 5.2, 7.8, highest among those with no OST (CMR = 36.7 per 1000 PY; 95% CI = 28.8, 45.9). Multi-factorial models showed OST exposure in the 4 weeks post-release reduced hazard of death by 75% (adjusted hazard ratio 0.25; 95% CI = 0.12, 0.53); OST receipt in prison had a short-term protective effect that decayed quickly across time. CONCLUSION In New South Wales, Australia, opioid substitution therapy in prison and post-release appears to reduce mortality risk in the immediate post-release period.

Mortality related to pharmacotherapies for opioid dependence: a comparative analysis of coronial records

INTRODUCTION AND AIMS The aim of this study was to compare the mortality associated with oral naltrexone, methadone and buprenorphine in opioid dependence treatment, employing a retrospective data analysis using coronial and prescription data. DESIGN AND METHODS The number of deaths were identified through national coronial data and number of treatment recipients were estimated from 2000 to 2003 prescriptions and restricted medications data. Mortality rates were expressed as deaths per number of treatment episodes and per person-years at high and low risk of fatal opioid overdose. RESULTS Thirty-two oral naltrexone, one buprenorphine and 282 methadone-related deaths were identified. Mortality rates in the highest risk period in deaths per 100 person-years were 22.1 (14.6 - 32.2) for oral naltrexone following treatment cessation and 3.0 (2.3 - 3.9) for methadone during treatment induction. Rates in the lowest risk period in deaths per 100 person-years were 1.0 (0.3 - 2.2) during oral naltrexone treatment and 0.34 (0.3 - 0.4) during post-induction methadone treatment. The relative risk of death for oral naltrexone subjects was 7.4 times (high-risk period, p < 0.0001) or 2.8 times (low-risk period, p = 0.055) that of methadone subjects. DISCUSSION AND CONCLUSIONS This is the first comparison of mortality associated with these three pharmacotherapies for opioid dependence. The risk of death related to oral naltrexone appears higher than that related to methadone treatment.

The increasing mortality burden of liver disease among opioid‐dependent people: cohort study

AIMS Hepatitis C (HCV) infection is highly prevalent among injection drug users (IDUs) and likely to cause significant mortality over time, but little research attention has focused upon the magnitude of this risk, particularly among ageing users. This study examined trends over time in mortality attributed to liver disease, and in particular contrasting this with other more commonly studied causes of death [acquired immune deficiency syndrome (AIDS), suicide and overdose] among an ageing cohort of heroin-dependent people in Australia. DESIGN Data linkage study of methadone treatment entrants with the National Deaths Index. SETTING  A cohort entering methadone treatment for heroin dependence in New South Wales, Australia, 1980-85. PARTICIPANTS   A total of 2489 people entering methadone treatment for heroin dependence and 54,847 person-years (PY) of follow-up. MEASUREMENTS   Linkage of data on all methadone entrants between 1980 and 1985 with data from the Australian National Deaths Index, linked using probabilistic record linkage software. FINDINGS There were 8.2 deaths per 1000 PY [95% confidence interval (CI) 7.5-9.0], with standardized mortality ratios (SMRs) of 4.6 (95% CI 4.2-5.0). Almost one in five (17%) of deaths were from underlying liver-related causes, most commonly viral hepatitis. The overall mortality rate for any liver cause was 1.4 deaths per 1000 PY (95% CI 1.1-1.7), 17 times higher than to the general population (95% CI 13.4-21.3), with relative elevations more marked for females (SMR 27.9; 95% CI 17.7-41.9) than males (SMR 14.5; 95% CI 10.8-19.0). Liver mortality increased over time, becoming the most common cause of death by the end of follow-up. CONCLUSIONS   Liver disease has become the most common cause of mortality among ageing opioid-dependent people in an ageing Australian cohort. There is an imperative to reduce the long-term risks of HCV and other risks to the liver, including alcohol consumption, which are typically not the major clinical focus for this group.

A pilot study of buprenorphine – naloxone combination tablet (Suboxone®) in treatment of opioid dependence

In Australia, maintenance treatment for opioid dependence involves supervised daily administration of a dose of methadone or buprenorphine. A sublingual tablet combining buprenorphine and naloxone in a 4:1 ratio (Suboxone) has been developed, designed to deter diversion and intravenous misuse, and may be suitable for unsupervised administration. The aim of this study was to investigate the tolerability of Suboxone, and investigate whether unsupervised administration can be effective in stabilized patients. Employed patients on buprenorphine maintenance, who had ceased heroin use, were switched to Suboxone and provided with weekly supplies of medication to take without supervised administration. Subjects were monitored closely with weekly clinical reviews, and research interviews at baseline, 3 and 6 months. Only 11% of people receiving buprenorphine met eligibility criteria. Seventeen subjects were recruited. Fifteen were retained for the full 6 months. No subject appeared destabilized by unsupervised dosing. Suboxone was well tolerated. The current trial demonstrated that unsupervised administration with regular clinical monitoring can be effective in selected patients. However, using access to unsupervised dosing to promote abstinence from heroin probably limits the potential benefits of unsupervised administration to a very small proportion of patients.

Opioid substitution therapy as a strategy to reduce deaths in prison: retrospective cohort study

Objectives To describe deaths in prison among opioid-dependent people, and examine associations between receipt of opioid substitution therapy (OST) and risk of death in prison. Design Retrospective cohort study. Setting Adult prisons in New South Wales (NSW), Australia. Participants 16 715 opioid-dependent people who were received to prison between 2000 and 2012. Interventions Opioid substitution therapy. Primary outcome measures Natural and unnatural (suicide, drug-induced, violent and other injury) deaths in prison. Results Cohort members were in prison for 30 998 person-years (PY), during which time there were 51 deaths. The all-cause crude mortality rate (CMR) in prison was 1.6/1000 PY (95% CI 1.2 to 2.2/1000 PY), and the unnatural death CMR was 1.1/1000 PY (95% CI 0.8 to 1.6/1000 PY). Compared to time out of OST, the hazard of all-cause death was 74% lower while in OST (adjusted HR (AHR): 0.26; 95% CI 0.13 to 0.50), and the hazard of unnatural death was 87% lower while in OST (AHR: 0.13; 95% CI 0.05 to 0.35). The all-cause and unnatural death CMRs during the first 4 weeks of incarceration were 6.6/1000 PY (95% CI 3.8 to 10.6/1000 PY) and 5.5/1000 PY (95% CI 2.9 to 9.4/1000 PY), respectively. Compared to periods not in OST, the hazard of all-cause death during the first 4 weeks of incarceration was 94% lower while in OST (AHR: 0.06; 95% CI 0.01 to 0.48), and the hazard of unnatural death was 93% lower while in OST (AHR: 0.07; 95% CI 0.01 to 0.53). Conclusions Mortality of opioid-dependent prisoners was significantly lower while in receipt of OST.

A longitudinal comparison of retention in buprenorphine and methadone treatment for opioid dependence in New South Wales, Australia

BACKGROUND AND AIMS To examine characteristics of first-time methadone and buprenorphine clients and factors associated with risk of leaving first treatment in New South Wales (NSW), Australia. DESIGN Retrospective linkage study of opioid substitution therapy (OST) treatment, court, custody and mortality data. SETTING NSW, Australia. PARTICIPANTS First-time OST entrants (August 2001-December 2010). MEASUREMENTS Characteristics of clients were examined. Time-dependent Cox models examined factors associated with the risk of leaving first treatment, with demographic, criminographic and treatment variables jointly considered. Interactions between medication and other variables upon risk of leaving treatment were examined. FINDINGS There were 15 600 treatment entrants: 7183 (46%) commenced buprenorphine, 8417 (54%) commenced methadone; the proportion entering buprenorphine increased over time. Those starting buprenorphine switched medications more frequently and had more subsequent treatment episodes. Buprenorphine retention was also poorer. On average, 44% spent 3+ months in treatment compared with 70% of those commencing methadone; however, buprenorphine retention for first-time entrants improved over time, whereas methadone retention did not. Multivariable Cox models indicated that in addition to sex, age, treatment setting and criminographic variables, the risk of leaving a first treatment episode was greater on any given day for those receiving buprenorphine, and was dependent on the year treatment was initiated. There was no interaction between any demographic variables and medication received, suggesting no clear evidence of any particular groups for whom each medication might be better suited in terms of improving retention. CONCLUSIONS Although retention rates for buprenorphine treatment have improved in New South Wales, Australia, individuals starting methadone treatment still show higher retention rates.

The contributions of viral hepatitis and alcohol to liver-related deaths in opioid-dependent people

BACKGROUND Mortality rates are elevated among heroin-dependent populations compared to the general population. Liver disease is emerging as an important contributor to mortality as the heroin-dependent population ages. Two major risk factors for liver disease are hepatitis C virus infection and chronic heavy alcohol use. Both of these are highly prevalent among heroin dependent people, but their relative contribution to liver-related mortality is poorly understood. METHODS Data recording all prescriptions of opioid substitution treatment in New South Wales, Australia, 1997-2005, were linked to the National Death Index. Crude and standardised mortality rates and standardised mortality ratios were calculated for liver-related and other major causes of death. Frequency counts were obtained for viral hepatitis and alcohol mentions in underlying liver deaths. RESULTS There were 208 underlying liver deaths for a CMR of 72.4 per 100,000 py (95% CI 62.9, 82.9), and liver deaths occurred at 9.8 times the general population rate (95% CI 8.5, 11.2). There were increases in liver-related mortality over time. Viral hepatitis was mentioned in three-quarters (n=156, 76%), and alcohol in 43% (n=90) of underlying liver deaths. CONCLUSIONS Liver-related deaths were shown to be increasing in this heroin-dependent population, and the majority of these deaths involved chronic viral hepatitis infection. Increased uptake of treatment for hepatitis C virus infection is crucial to reducing the burden of liver-related mortality in this population. Hepatitis B vaccination, and screening of OST patients for alcohol use disorders and delivery of brief interventions as clinically indicated may also be of benefit.

A cost - effectiveness analysis of buprenorphine-assisted heroin withdrawal

The purpose of this study was to conduct a cost-effectiveness analysis of detoxification from heroin using buprenorphine in a specialist clinic versus a shared care setting. A randomized controlled trial was conducted with a total of 115 heroin-dependent patients receiving a 5-day treatment regime of buprenorphine. The specialist clinic was a community-based treatment agency in inner-city Sydney. Shared care involved treatment by a general practitioner supplemented by weekend dispensing and some concurrent counselling at the specialist clinic. Quantification of resource use was limited to inputs for treatment provision. The primary outcome measure used in the economic analysis was the proportion of each group that completed detoxification and achieved an initial 7-day period of abstinence. Buprenorphine detoxification in the shared care setting was estimated to be 24 dollars more expensive per patient than treatment at the clinic, which had an average treatment cost of 332 dollars per patient. Twenty-three per cent of the shared care patients and 22% of the clinic patients reported no opiate use during the withdrawal period. These results suggest that the provision of buprenorphine treatment for heroin dependence in shared care and clinic appear to be equally cost-effective.

Costs and outcomes of treatments for excessive alcohol consumption: Making policy decisions with the available data

Aim: To determine which treatments for risky or dependent alcohol consumption provide the best health outcomes for a given expenditure. Methods: Economic evaluation expressing results in cost per unit outcome, from the perspective of the Australian healthcare system. Interventions considered include brief interventions; psychosocial interventions (motivational approaches, cognitive-behavioural approaches and self-guided materials); and pharmacotherapies (acamprosate and naltrexone). Treatment outcomes and standard treatment costs were measured for selected studies, and costs per unit outcome were calculated. Findings: Twenty-nine studies were selected for the analysis. As treatment outcomes were not consistently expressed in a single unit across interventions, two outcomes were used in the analysis: percentage change in alcohol consumption and percentage change in the proportion of abstinent days. Brief interventions provided the best cost per unit outcome, followed by psychosocial interventions, then pharmacotherapies. Conclusions: By using two treatment outcomes instead of one we demonstrated that some treatments for alcohol dependence provide better value for money, but as a result we were unable to complete a formal health economic evaluation. Consistent measurement of alcohol consumption outcomes in research studies would facilitate similar economic evaluations in the future. This work illustrates the difficulties of using research studies with non-comparable outcomes to inform policy on the cost-effectiveness of different treatments.