BACKGROUND:Opioid dependence is associated with substantial health and social burdens, and opioid agonist treatment (OAT) is highly effective in improving multiple outcomes for people who receive this treatment. Methadone and buprenorphine are common medications provided as OAT. We aimed to examine buprenorphine compared with methadone in the treatment of opioid dependence across a wide range of primary and secondary outcomes. METHODS:We did a systematic review and meta-analysis in accordance with GATHER and PRISMA guidelines. We searched Embase, MEDLINE, CENTRAL, and PsycINFO from database inception to Aug 1, 2022; clinical trial registries and previous relevant Cochrane reviews were also reviewed. We included all RCTs and observational studies of adults (aged ≥18 years) with opioid dependence comparing treatment with buprenorphine or methadone. Primary outcomes were retention in treatment at 1, 3, 6, 12, and 24 months, treatment adherence (measured through doses taken as prescribed, dosing visits attended, and biological measures), or extra-medical opioid use (measured by urinalysis and self-report). Secondary outcomes were use of benzodiazepines, cannabis, cocaine, amphetamines, and alcohol; withdrawal; craving; criminal activity and engagement with the criminal justice system; overdose; mental and physical health; sleep; pain; global functioning; suicidality and self-harm; and adverse events. Single-arm cohort studies and RCTs that collected data on buprenorphine retention alone were also reviewed. Data on study, participant, and treatment characteristics were extracted. Study authors were contacted to obtain additional data when required. Comparative estimates were pooled with use of random-effects meta-analyses. The proportion of individuals retained in treatment across multiple timepoints was pooled for each drug. This study is registered with PROSPERO (CRD42020205109). FINDINGS:We identified 32 eligible RCTs (N=5808 participants) and 69 observational studies (N=323 340) comparing buprenorphine and methadone, in addition to 51 RCTs (N=11 644) and 124 observational studies (N=700 035) that reported on treatment retention with buprenorphine. Overall, 61 studies were done in western Europe, 162 in North America, 14 in north Africa and the Middle East, 20 in Australasia, five in southeast Asia, seven in south Asia, two in eastern Europe, three in central Europe, one in east Asia, and one in central Asia. 1 040 827 participants were included in these primary studies; however, gender was only reported for 572 111 participants, of whom 377 991 (66·1%) were male and 194 120 (33·9%) were female. Mean age was 37·1 years (SD 6·0). At timepoints beyond 1 month, retention was better for methadone than for buprenorphine: for example, at 6 months, the pooled effect favoured methadone in RCTs (risk ratio 0·76 [95% CI 0·67-0·85]; I·=74·2%; 16 studies, N=3151) and in observational studies (0·77 [0·68-0·86]; I·=98·5%; 21 studies, N=155 111). Retention was generally higher in RCTs than observational studies. There was no evidence suggesting that adherence to treatment differed with buprenorphine compared with methadone. There was some evidence that extra-medical opioid use was lower in those receiving buprenorphine in RCTs that measured this outcome by urinalysis and reported proportion of positive urine samples (over various time frames; standardised mean difference -0·20 [-0·29 to -0·11]; I·=0·0%; three studies, N=841), but no differences were found when using other measures. Some statistically significant differences were found between buprenorphine and methadone among secondary outcomes. There was evidence of reduced cocaine use, cravings, anxiety, and cardiac dysfunction, as well as increased treatment satisfaction among people receiving buprenorphine compared with methadone; and evidence of reduced hospitalisation and alcohol use in people receiving methadone. These differences in secondary outcomes were based on small numbers of studies (maximum five), and were often not consistent across study types or different measures of the same constructs (eg, cocaine use). INTERPRETATION:Evidence from trials and observational studies suggest that treatment retention is better for methadone than for sublingual buprenorphine. Comparative evidence on other outcomes examined showed few statistically significant differences and was generally based on small numbers of studies. These findings highlight the imperative for interventions to improve retention, consideration of client-centred factors (such as client preference) when selecting between methadone and buprenorphine, and harmonisation of data collection and reporting to strengthen future syntheses. FUNDING:Australian National Health and Medical Research Council.

In England and Scotland, the number of drug-related poisonings in 2017 was the highest ever recorded. 1 National Records of ScotlandDrug-related deaths in Scotland in 2017. https://www.nrscotland.gov.uk/statistics-and-data/statistics/statistics-by-theme/vital-events/deaths/drug-related-deaths-in-scotland/2017Date: July 3, 2018 Date accessed: May 13, 2019 Google Scholar , 2 Office for National StatisticsDeaths related to drug poisoning in England and Wales: 2017 registrations. https://www.ons.gov.uk/peoplepopulationandcommunity/birthsdeathsandmarriages/deaths/bulletins/deathsrelatedtodrugpoisoninginenglandandwales/2017registrations#main-pointsDate: Aug 6, 2018 Date accessed: May 13, 2019 Google Scholar Opioid-related deaths are the biggest contributor to drug-related deaths, and have driven the recent increase in such deaths. In 2017, 815 opioid-related deaths were recorded in Scotland (double the number recorded in 2007) 1 National Records of ScotlandDrug-related deaths in Scotland in 2017. https://www.nrscotland.gov.uk/statistics-and-data/statistics/statistics-by-theme/vital-events/deaths/drug-related-deaths-in-scotland/2017Date: July 3, 2018 Date accessed: May 13, 2019 Google Scholar and 1829 were recorded in England (a 40% increase since 2007; figure). 2 Office for National StatisticsDeaths related to drug poisoning in England and Wales: 2017 registrations. https://www.ons.gov.uk/peoplepopulationandcommunity/birthsdeathsandmarriages/deaths/bulletins/deathsrelatedtodrugpoisoninginenglandandwales/2017registrations#main-pointsDate: Aug 6, 2018 Date accessed: May 13, 2019 Google Scholar This marked increase in avoidable mortality must be recognised as a public health crisis. The UK Government must help end Scotland's drug-related death crisisJo Kimber and colleagues1 are right to call for the government to announce a public health crisis in response to a record number of drug-related poisonings in the UK. Recognising and responding to public health emergencies is a core responsibility of government. Full-Text PDF The fentanyl epidemic in Estonia: opportunities for a comprehensive public health responseJo Kimber and colleagues have announced a public health crisis in response to the record number of drug-related overdoses in Scotland, England, and Wales.1 Illicitly manufactured fentanyl emerged in Estonia in 2003, and, within a year, replaced heroin as the most common drug in the illicit drug market.2,3 Because of fentanyl use, Estonia had the highest mortality due to drug overdoses in Europe for 2007–17.2 Full-Text PDF

Introduction and Aims Mortality studies of people who inject drugs (PWID) are mostly of older people and drug treatment cohorts. We estimate mortality rates, describe causes of death, and years of potential life lost in a community-recruited cohort of young PWID characterised by high incidence of hepatitis C virus (HCV) infection. Design and Methods Participant identifiers of 215 PWID from the south-western Sydney sub-cohort of the HCV Cohort were linked to National Death Index records from 1999 to 2010 and crude mortality rates and standardised mortality ratios estimated. Australian life tables were used to calculate years of potential of life lost. Results Fifteen participants died (7.0%) in 2095 person years (PY) of follow-up. Median age at death was 30.6 years (interquartile range 24.9-32.2). The crude mortality rate was 0.72 per 100PY (95% confidence interval 0.29-0.79) with a standardised mortality ratio of 11.09 (95% confidence interval 6.68-18.39). One-third of deaths were due to accidental drug overdose (5/15) and one-fifth were suicides (3/15). All deaths from defined causes (13/15) were potentially avoidable. Decedents lost on average 49.8 years of potential life. Discussion and Conclusions Mortality and potential life lost further highlight the impact of accidental overdose deaths and suicide among young PWID. Integration of overdose and suicide prevention into youth-orientated outreach, including innovation in online and mobile technology should be evaluated.

Injecting drug use is associated with considerable morbidity and mortality. Estimates of the size of the population of people who inject drugs are critical to inform service planning and estimate disease burden due to injecting drug use. We aimed to estimate the size of the population of people who inject drugs in Australia.

RR 1.74; 95% CI 1.06 to 2.87; and at high doses (≥ 16 mg), 5 studies, 1001 participants, RR 1.82; 95% CI 1.15 to 2.90. However, there is moderate quality of evidence that only high-dose buprenorphine (≥ 16 mg) was more effective than placebo in suppressing illicit opioid use measured by urinanalysis in the trials, 3 studies, 729 participants, standardised mean difference (SMD) -1.17; 95% CI -1.85 to -0.49, Notably, low-dose, (2 studies, 487 participants, SMD 0.10; 95% CI -0.80 to 1.01), and medium-dose, (2 studies, 463 participants, SMD -0.08; 95% CI -0.78 to 0.62) buprenorphine did not suppress illicit opioid use measured by urinanalysis better than placebo. There is high quality of evidence that buprenorphine in flexible doses adjusted to participant need,was less effective than methadone in retaining participants, 5 studies, 788 participants, RR 0.83; 95% CI 0.72 to 0.95. For those retained in treatment, no difference was observed in suppression of opioid use as measured by urinalysis, 8 studies, 1027 participants, SMD -0.11; 95% CI -0.23 to 0.02 or self report, 4 studies, 501 participants, SMD -0.11; 95% CI -0.28 to 0.07, with moderate quality of evidence. Consistent with the results in the flexible-dose studies, in low fixed-dose studies, methadone (≤ 40 mg) was more likely to retain participants than low-dose buprenorphine (2 6 mg), (3 studies, 253 participants, RR 0.67; 95% CI: 0.52 to 0.87). However, we found contrary results at medium dose and high dose: there was no difference between medium-dose buprenorphine (7 15 mg) and medium-dose methadone (40 85 mg) in retention, (7 studies, 780 participants, RR 0.87; 95% CI 0.69 to 1.10) or in suppression of illicit opioid use as measured by urines, (4 studies, 476 participants, SMD 0.25; 95% CI -0.08 to 0.58) or self report of illicit opioid use, (2 studies, 174 participants, SMD -0.82; 95% CI -1.83 to 0.19). Similarly, there was no difference between high-dose buprenorphine (≥ 16 mg) and high-dose methadone (≥ 85 mg) in retention (RR 0.79; 95% CI 0.20 to 3.16) or suppression of self-reported heroin use (SMD -0.73; 95% CI -1.08 to -0.37) (1 study, 134 participants). Few studies reported adverse events ; two studies compared adverse events statistically, finding no difference between methadone and buprenorphine, except for a single result indicating more sedation among those using methadone. Authors’ conclusions Buprenorphine is an effective medication in the maintenance treatment of heroin dependence, retaining people in treatment at any dose above 2 mg, and suppressing illicit opioid use (at doses 16 mg or greater) based on placebo-controlled trials. However, compared to methadone, buprenorphine retains fewer people when doses are flexibly delivered and at low fixed doses. If fixed medium or high doses are used, buprenorphine and methadone appear no different in effectiveness (retention in treatment and suppression of illicit opioid use); however, fixed doses are rarely used in clinical practice so the flexible dose results are more relevant to patient care. Methadone is superior to buprenorphine in retaining people in treatment, and methadone equally suppresses illicit opioid use. P L A I N L A N G U A G E S U M M A R Y Buprenorphine maintenance versus placebo or methadone maintenance for opioid dependence Background Methadone is widely used as a replacement for illicit opioid use such as heroin in medically-supported opioid substitution maintenance programmes. Two other drugs have been used to help reduce illicit opioid use, specifically buprenorphine and LAAM (levo-alphaacetylmethadol). LAAM is not used in current clinical practice. Buprenorphine is currently used and can reduce illicit opioid use compared with placebo, although it is less effective than methadone. Buprenorphine is an opioid drug that is not as potent as heroin and methadone, although the effects of buprenorphine may last longer. Buprenorphine can be taken once every two days. The trials include different formulations of buprenorphine: sublingual solution, sublingual tablets, combined buprenorphine/naloxone sublingual tablet and an implant. Key results The review of trials found that buprenorphine at high doses (16 mg) can reduce illicit opioid use effectively compared with placebo, and buprenorphine at any dose studied retains people in treatment better than placebo. Buprenorphine appears to be less effective than methadone in retaining people in treatment, if prescribed in a flexible dose regimen or at a fixed and low dose (2 6 mg per day). Buprenorphine prescribed at fixed doses (above 7 mg per day) was not different from methadone prescribed at fixed doses (40 mg or more per day) in retaining people in treatment or in suppression of illicit opioid use. 2 Buprenorphine maintenance versus placebo or methadone maintenance for opioid dependence (Review) Copyright © 2014 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. S U M M A R Y O F F I N D I N G S F O R T H E M A I N C O M P A R I S O N [Explanation] Buprenorphine maintenance compared with methadone maintenance for opioid dependence Patient or population: People with opioid dependence. Settings: Inpatient and outpatient Intervention: Buprenorphine maintenance at flexible doses Comparison: Methadone maintenance at flexible doses Outcomes Relative effect (95% CI) No of Participants (studies) Quality of the evidence (GRADE) Comments Retention in treatment RR 0.83 (0.73 to 0.95)* 11 (1391); 5 double-blind (788) 6 open-label (603) ⊕⊕⊕⊕ high Greater retention in the methadone group. * the heterogeneity is significant. When the double-blind studies are analysed separately the heterogeneity is not significant and the RR is 0.83 (0.72 to 0.95) Morphine-positive urines SMD -0.11 (-0.23 to 0.02) 8 (1027) ⊕⊕⊕© moderate No difference. Self-reported heroin use SMD -0.11 (-0.28 to 0.07) 4 (501) ⊕⊕⊕© moderate No difference. Cocaine-positive urines SMD 0.10 (-0.05 to 0.25) 6 (919) ⊕⊕⊕© moderate No difference. Benzodiazepine-positive urines SMD 0.05 (-0.09 to 0.18] 6 (859) ⊕⊕⊕© moderate No difference. *The basis for the assumed risk (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: Confidence interval; RR: Risk Ratio; SMD: standardised mean difference GRADE Working Group grades of evidence High quality: Further research is very unlikely to change our confidence in the estimate of effect. Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate. Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate. Very low quality: We are very uncertain about the estimate. 3 Buprenorphine maintenance versus placebo or methadone maintenance for opioid dependence (Review) Copyright © 2014 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

Psychiatric disorders are frequently comorbid with substance use disorders, with this comorbidity being particularly pronounced in those individuals seeking treatment for either addiction or psychiatric disorders. 1 Kessler RC The epidemiology of dual diagnosis. Biol Psychiatry. 2004; 56: 730-737 Summary Full Text Full Text PDF PubMed Scopus (458) Google Scholar Confirming this, results of the Danish register-based study reported in The Lancet Psychiatry by Carsten Hjorthøj and colleagues 2 Hjorthøj C Østergaard MLD Benros ME et al. Association between alcohol and substance use disorders and all-cause and cause-specific mortality in schizophrenia, bipolar disorder, and unipolar depression: a nationwide, prospective, register-based study. Lancet Psychiatry. 2015; (published online Aug 13.)http://dx.doi.org/10.1016/S2215-0366(15)00207-2 Google Scholar showed high rates of substance use disorders (cannabis, alcohol, or so-called hard drugs) in people diagnosed with schizophrenia, bipolar disorder, or major depression. 2 Hjorthøj C Østergaard MLD Benros ME et al. Association between alcohol and substance use disorders and all-cause and cause-specific mortality in schizophrenia, bipolar disorder, and unipolar depression: a nationwide, prospective, register-based study. Lancet Psychiatry. 2015; (published online Aug 13.)http://dx.doi.org/10.1016/S2215-0366(15)00207-2 Google Scholar Of particular note, 22% of the 41 470 people in the study population diagnosed with schizophrenia were classified as having a hard-drug use disorder. Results of previous research have suggested that prognosis might be poor for psychiatric patients with comorbid substance use disorders. 3 Najt P Fusar-Poli P Brambilla P Co-occurring mental and substance abuse disorders: a review on the potential predictors and clinical outcomes. Psychiatry Res. 2011; 186: 159-164 Summary Full Text Full Text PDF PubMed Scopus (158) Google Scholar Importantly, as shown by the findings of Hjorthøj and colleagues, alcohol, cannabis, and hard-drug use disorders are also associated with substantially raised mortality relative both to the general population and to people with a severe mental disorder in the absence of a substance use disorder. Several specific findings are worthy of further comment. Association between alcohol and substance use disorders and all-cause and cause-specific mortality in schizophrenia, bipolar disorder, and unipolar depression: a nationwide, prospective, register-based studyMortality in people with mental illness is far higher in individuals with substance use disorders than in those without, particularly in people who misuse alcohol and hard drugs. Mortality-reducing interventions should focus on patients with a dual diagnosis and seek to prevent or treat substance use disorders. Full-Text PDF

Prisoners experience high rates of drug dependence, health problems and premature mortality. Without intervention, they often come into further contact with the criminal justice system, creating further health risk. Opioid dependence is common among prisoners, yet treatment with opioid substitution therapy (OST) may reduce or prevent morbidity, mortality and offending. Using retrospective data linkage, this study evaluated engagement with treatment, patterns of offending, incarceration and mortality among opioid-dependent people who received OST in New South Wales, Australia between 1985 and 2010. The results highlight that the prison setting provides an important opportunity to engage people in OST. Notably, OST treatment in prison and immediately post-release was found to be highly protective against mortality both while incarcerated and after release. Considering some of the known benefits of OST, this study provides strong evidence to support the value of OST programs within the criminal justice system.

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.

BACKGROUND:Opioid dependence increases risk of premature mortality. Opioid substitution therapy with methadone or buprenorphine reduces mortality risk, especially for drug-related overdose. Clinical guidelines recommend methadone as the first line of opioid substitution therapy. We aimed to test whether buprenorphine treatment has a lower mortality risk than does methadone treatment by comparing all-cause mortality and drug-related overdose mortality at treatment induction, after in-treatment medication switches, and following treatment cessation. METHODS:We did a retrospective cohort study of all patients with opioid dependency (n=32,033) in New South Wales, Australia, who started a methadone or buprenorphine treatment episode from Aug 1, 2001, to Dec 31, 2010, including 190,232·6 person-years of follow-up. We compared crude mortality rates (CMRs) for all-cause and drug-related overdose mortality, and mortality rate ratios (MRRs) according to age, sex, period in or out of treatment, medication type, and in-treatment switching. FINDINGS:Patients who initiated with buprenorphine had reduced all-cause and drug-related mortality during the first 4 weeks of treatment compared with those who initiated with methadone (adjusted all-cause MRR 2·17, 95% CI 1·29-3·67; adjusted drug-related MRR 4·88, 1·73-13·69). For the remaining time on treatment, drug-related mortality risk did not differ (adjusted MRR 1·18, 95% CI 0·89-1·56), but weak evidence suggested that all-cause mortality was lower for buprenorphine than methadone (1·66, 1·40-1·96). In the 4 weeks after treatment cessation, all-cause mortality did not differ, but drug-related mortality was lower for methadone (adjusted all-cause MRR 1·12, 0·79-1·59; adjusted drug-related MRR 0·50, 0·29-0·86). Patients who switched from buprenorphine to methadone during treatment had lower mortality in the first 4 weeks of methadone treatment than matched controls who received methadone only (CMR difference 7·1 per 1000 person-years, 95% CI 0·1-14·0); no mortality difference was noted for switches from buprenorphine to methadone or for switches to either medication beyond the first 4 weeks of treatment. INTERPRETATION:In a setting with high risk of death in the first 4 weeks of opioid substitution therapy, buprenorphine seemed to reduce mortality in this period, but little difference between buprenorphine and methadone was noted thereafter or for in-treatment switching of medications. Cross-cohort corroboration of our findings and further assessment of the stepped treatment model is warranted. FUNDING:Australian National Health & Medical Research Council.

Background: Injecting drug use is a major risk factor for the acquisition and transmission of HIV and Hepatitis C virus (HCV). Prevention of these infections among people who inject drugs (PWID) is critical to reduce ongoing transmission, morbidity and mortality.Methods: A review of reviews was undertaken involving systematic literature searches of Medline, Embase, CINAHL, PsychINFO, IBSS and the Cochrane Library (2000-2011) to identify English language reviews regarding the effectiveness of harm reduction interventions in relation to HIV transmission, HCV transmission and injecting risk behaviour (IRB). Interventions included needle and syringe programmes (NSP); the provision of injection paraphernalia; opiate substitution treatment (OST); information, education and counselling (IEC); and supervised injecting facilities (SIFs). Reviews were classified into 'core' or 'supplementary' using critical appraisal criteria, and the strength of review-level evidence was assessed.Results: Twelve core and thirteen supplementary reviews were included. From these reviews we identified: (i) for NSP: tentative review-level evidence to support effectiveness in reducing HIV transmission, insufficient review-level evidence relating to HCV transmission, but sufficient review-level evidence in relation to-TR-B; (ii) for OST: sufficient review-level evidence of effectiveness in relation to HIV transmission and IRB, but tentative review-level evidence in relation to HCV transmission; (iii) for IEC, the provision of injection paraphernalia and SIFs: tentative review-level evidence of effectiveness in reducing IRB; and either insufficient or no review-level evidence for these interventions in relation to HIV or HCV transmission.Conclusion: Review-level evidence indicates that harm reduction interventions can reduce IRB, with evidence strongest for OST and NSP. However, there is comparatively little review-level evidence regarding the effectiveness of these interventions in preventing HCV transmission among PWID. Further studies are needed to assess the effectiveness and impact of scaling up comprehensive packages of harm reduction interventions to minimise HIV and HCV transmission among PWID. (C) 2013 Elsevier B.V. All rights reserved.

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.

BACKGROUND:Although Indigenous Australians are over-represented among heroin users, there has been no study examining offending, time in custody, and opioid substitution therapy (OST) treatment utilisation among Indigenous opioid-dependent (including heroin) people at the population level, nor comparing these to non-Indigenous opioid-dependent people. The aims of this study were to compare the nature and types of charges, time in custody and OST treatment utilisation between opioid-dependent Indigenous and non-Indigenous Australians in contact with the criminal justice system.METHODS:This was a population-based, retrospective data linkage study using records of OST entrants in New South Wales, Australia (1985-2010), court appearances (1993-2011) and custody episodes (2000-2012). Charge rates per 100 person-years were compared between Indigenous and non-Indigenous Australians by sex, age and calendar year. Statistical comparisons were made for variables describing the cumulative time and percentage of follow-up time spent in custody, as well as characteristics of OST initiation and overall OST treatment utilisation.RESULTS:Of the 34,962 people in the cohort, 6,830 (19.5%) were Indigenous and 28,132 (80.5%) non-Indigenous. Among the 6,830 Indigenous people, 4,615 (67.6%) were male and 2,215 (32.4%) female. The median number of charges per person against Indigenous people (25, IQR 31) was significantly greater than non-Indigenous people (9, IQR 16) (p < 0.001). Overall, Indigenous people were charged with 33.2% of the total number of charges against the cohort and 44.0% of all violent offences. The median percentage of follow-up time that Indigenous males and females spent in custody was twice that of non-Indigenous males (21.7% vs. 10.1%, p < 0.001) and females (6.0% vs. 2.9%, p < 0.001). The percentage of Indigenous people who first commenced OST in prison (30.2%) was three times that of non-Indigenous people (11.2%) (p < 0.001). Indigenous males spent less time in OST compared to non-Indigenous males (median percentage of follow-up time in treatment: 40.5% vs. 43.1%, p < 0.001).CONCLUSIONS:Compared to non-Indigenous opioid-dependent people, Indigenous opioid-dependent people in contact with the criminal justice system are charged with a greater number of offences, spend longer in custody and commonly initiate OST in prison. Hence, contact with the criminal justice system provides an important opportunity to engage Indigenous people in OST.

INTRODUCTION AND AIMS To estimate the number of deaths that would have occurred among patients receiving oral naltrexone for opioid use under the Special Access Scheme if these patients had received methadone. DESIGN AND METHODS We analysed mortality in cohorts treated with oral naltrexone and methadone. Data were from 1097 patients of in WA providing oral naltrexone for opioid use under the SAS,1998-2000, and all participants in WA (n = 2520) and New South Wales (NSW) (n = 11,174) methadone programs over the same period. We calculated mortality rates among patients receiving naltrexone and methadone, and excess mortality among patients receiving naltrexone. RESULTS Oral naltrexone patients had higher mortality than those treated with methadone, even when favourable assumptions were made about the effects of naltrexone on mortality. Total oral naltrexone mortality was significantly greater than for methadone in WA (rate ratio 3.5; 95% confidence interval 2.2-5.8) and NSW (rate ratio 3.5; 95% confidence interval 2.4-5.0). Among 1097 oral naltrexone patients we estimate that there were 25-29 deaths over two years that would probably not have occurred if these patients had received methadone. The major reason was higher mortality rate post-treatment cessation. DISCUSSION AND CONCLUSIONS Large-scale use of oral naltrexone to treat opioid users may not have, as intended, saved lives. Implant naltrexone continues to be prescribed under the SAS in the absence of reliable efficacy and safety data. There is a need to review widespread use of unregistered medications under the SAS, particularly with vulnerable patient groups.

There are few data about the incarceration of opioid-dependent people involving large representative cohorts. We aimed to determine the prevalence and duration of incarceration in a large cohort of opioid-dependent people in Australia using data linkage methods, and estimate the costs associated with their incarceration.Method: Retrospective linkage study of all entrants to opioid substitution therapy (OST) for the treatment of opioid dependence in NSW, 1985–2010, with data on incarceration, 2000-2012. The number and duration of incarcerations were calculated. The average daily cost of incarceration was applied to days of incarceration in the cohort.Results: Among 47,196 opioid-dependent people, 37% (43% of men and 24% of women) had at least one episode of incarceration lasting one or more days. Men had a median of three(ranging between 1-47) incarcerations, and women, two (1-35). Indigenous men spent 23% of follow-up time incarcerated, compared with 8% for non-Indigenous men; similarly, Indigenous women spent a substantially greater proportion of time incarcerated than non-Indigenous women (8% vs. 2%). Costs of incarceration of this cohort between 2000 and 2012 totalled nearly AUD $3 billion.Conclusions: This is the first study to examine incarceration of opioid-dependent people across an entire population of such users. Our findings suggest that a substantial minority of opioid-dependent people experience incarceration, usually on multiple occasions and at significant cost. Treatment for opioid dependence, inside and outside prisons, may help reduce incarceration of this cohort.

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.

INTRODUCTION AND AIMS:Few population-based studies have examined differences in opioid substitution therapy (OST) treatment utilisation between men and women. Using a population of opioid-dependent people in New South Wales, Australia, first-episode and long-term OST treatment utilisation profiles were compared between men and women, differentiating between treatment initiation in the community and in custody.DESIGN AND METHODS:Retrospective data linkage study using records of new OST entrants (2001-2010) and custody episodes (2000-2012). First OST treatment episode and overall treatment utilisation characteristics were compared between men and women initiating treatment in the community or in custody. Treatment retention was evaluated at 3, 6, 9 and 12 months after first commencing OST and overall, as the median proportion of follow-up time spent in treatment.RESULTS:There were 15,600 new OST entrants in the cohort--10,930 were men (70.1%) and 4670 women (29.9%); 12,584 (80.7%) initiated treatment in the community and 3016 (19.3%) in custody. More men initiated OST in custody (24.0% vs. 8.3%, P < 0.001) and only received OST in custody (57.5% vs. 41.8%, P < 0.001). Women were retained longer in their first OST treatment episode at all four time points in both treatment settings and in treatment overall (community: 46.6% vs. 39.1%, P < 0.001; custody: 41.3% vs. 30.8%, P < 0.001).DISCUSSION AND CONCLUSIONS:There are a number of key differences in OST treatment utilisation profiles between men and women. Whereas men commonly initiate and only receive OST in custody, treatment retention is higher among women, independent of the setting treatment is initiated.

AIMS:Studies of offending among people who use drugs typically focus upon small and potentially unrepresentative samples. We examined an entire population of opioid-dependent clients' contact with the criminal justice system to develop more accurate population-wide measures of offending among opioid-dependent people in Australia.DESIGN:Retrospective data linkage study.SETTING:All entrants to opioid substitution therapy (OST) for opioid dependence in New South Wales, Australia, between 1985 and 2010, with data on court appearances from 1 December 1993 to 31 March 2011.PARTICIPANTS:All 48 069 valid cohort members who received OST between 1985 and 2010.MEASUREMENTS:Person-years (PY) of observation and charge rates for major crime categories estimated by sex, age and time.FINDINGS:A total of 638 545 charges were laid against cohort members between 1993 and 2011. Eight in 10 males (79.7%) and 67.9% of females had at least one charge; rates were 94.15 per 100 PY [95% confidence interval (CI) = 93.89-94.41] among males, and 53.19 per 100 PY (95% CI = 52.91-53.46) among females, and highest at 15-19 years [175.74/100 PY males (95% CI = 174.45-177.03), 75.60/100 PY females (95% CI = 74.46-76.76)] and 20-24 years [144.61/100 PY males (95% CI = 143.70-145.53), 84.50/100 PY females (95% CI = 83.53-85.48)]. The most frequent charges were theft (24.5% of charges), traffic/vehicle (16.3%), offences against justice (10.5%), illicit drug (10.0%), intentional injury (9.9%) and public order offences (8.9%). Overall, 20.8% of the cohort accounted for 67.4% of charges. The most frequently appearing 5.6% of the cohort accounted for 24.3% of costs ($75.5 million).CONCLUSIONS:Among opioid-dependent people in Australia, a minority account for the majority of the criminal justice contact and levels of offending are not consistent over time, sex or age.