Risk of death during and after opiate substitution treatment in primary care: prospective observational study in UK General Practice Research Database (original) (raw)
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BMJ (Clinical research ed.), 2017
Objective To compare the risk for all cause and overdose mortality in people with opioid dependence during and after substitution treatment with methadone or buprenorphine and to characterise trends in risk of mortality after initiation and cessation of treatment.Design Systematic review and meta-analysis.Data sources Medline, Embase, PsycINFO, and LILACS to September 2016.Study selection Prospective or retrospective cohort studies in people with opioid dependence that reported deaths from all causes or overdose during follow-up periods in and out of opioid substitution treatment with methadone or buprenorphine.Data extraction and synthesis Two independent reviewers performed data extraction and assessed study quality. Mortality rates in and out of treatment were jointly combined across methadone or buprenorphine cohorts by using multivariate random effects meta-analysis.Results There were 19 eligible cohorts, following 122 885 people treated with methadone over 1.3-13.9 years and 1...
Causes of death in a cohort treated for opioid dependence between 1985 and 2005
Addiction, 2014
Aims To examine changes in causes of death in a cohort treated for opioid dependence, across time and age; quantify years of potential life lost (YPLL); and identify avoidable causes of death. Design People in New South Wales (NSW) who registered for opioid substitution therapy (OST), 1985-2005, were linked to a register of all deaths in Australia. Setting NSW, Australia. Measurements Crude mortality rates (CMRs), age-sex-standardized mortality rates (ASSRs) and standardized mortality ratios (SMRs) across time, sex and age. Years of potential life lost (YPLL) were calculated with reference to Australian life tables and by calculating years lost before the age of 65 years. Findings There were 43 789 people in the cohort, with 412 216 person-years of follow-up. The proportion of the cohort aged 40+ years increased from 1% in 1985 to 39% in 2005. Accidental opioid overdoses, suicides, transport accidents and violent deaths declined with age; deaths from cardiovascular disease, liver disease and cancer increased. Among men, 89% of deaths were potentially avoidable; among women, 86% of deaths were avoidable. There were an estimated 160 555 YPLL in the cohort, an average of 44 YPLL per decedent and an average of 29 YPLL before age 65 years. Conclusions Among a cohort of opioid-dependent people in New South Wales, 1985Wales, -2005, almost nine in 10 deaths in the cohort were avoidable. There is huge scope to improve mortality among opioid-dependent people.
European Addiction Research, 2004
Opiate users (n = 135) from southern England, Glasgow and Edinburgh were interviewed about opiate overdose (lifetime). Fifty-six percent had overdosed. The majority (66%) reported mixing opiates with at least one other drug (mainly alcohol and/or benzodiazepines) at their last overdose. Patients identified misjudgements of purity, mixing drugs and misjudgements of tolerance as causes of overdose. The sample was divided into groups: (1) 'no prescription', (2) prescribed 'diazepam only', (3) prescribed 'methadone only' and (4) prescribed 'methadone + diazepam'. The 'methadone + diazepam' group reported more lifetime and deliberate overdoses, the 'methadone only' group were more likely to have used several drugs at the time of their last overdose and the 'no prescription' group to have used only heroin. Drug users' overdose risk may vary as a result of their prescribed and non-prescribed drug use. Interventions should be developed and tailored according to clients' needs and current use patterns.
Addiction, 2007
Background Specialist drug treatment is critical to overdose prevention; methadone maintenance is effective, but we lack evidence for other modalities. We evaluate the impact of a range of treatments for opiate dependence on overdose mortality. Methods Prospective cohort study of 10 454 heroin users entering treatment 1998-2001 in Italy followed-up for 10 208 person-years in treatment and 2914 person-years out of treatment. Standardized overall mortality ratios (SMR) estimate excess mortality risk for heroin users in and out of treatment compared to the general population. Cox models compare the hazard ratio (HR) of overdose between heroin users in treatment and out of treatment. Results There were 41 overdose deaths, 10 during treatment and 31 out of treatment, generating annual mortality rates of 0.1% and 1.1% and SMRs of 3.9 [95% confidence interval (CI) 2.8-5.4] and 21.4 (16.7-27.4), respectively. Retention in any treatment was protective against overdose mortality (HR 0.09 95% CI 0.04-0.19) compared to the risk of mortality out of treatment, independent of treatment type and potential confounders. The risk of a fatal overdose was 2.3% in the month immediately after treatment and 0.77% in the subsequent period; compared to the risk of overdose during treatment the HR was 26.6 (95% CI 11.6-61.1) in the month immediately following treatment and 7.3 (3.3-16.2) in the subsequent period. Conclusions We demonstrate that a range of treatments for heroin dependence reduces overdose mortality risk. However, the considerable excess mortality risk in the month following treatment indicates the need for greater health education of drug users and implementation of relapse and overdose death prevention programmes. Further investigation is needed to measure and weigh the potential benefits and harms of short-term therapies for opiate use.
Addiction, 2011
Aims To review the literature on mortality among dependent or regular users of opioids across regions, according to specific causes, and related to a number of demographic and clinical variables. Methods Multiple search strategies included searches of Medline, EMBASE and PsycINFO, consistent with the methodology recommended by the Metaanalysis of Observational Studies in Epidemiology (MOOSE) group; grey literature searches; and contact of experts for any additional unpublished data from studies meeting inclusion criteria. Random-effects meta-analyses were conducted for crude mortality rates (CMRs) and standardized mortality ratios (SMRs), with stratified analyses where possible. Meta-regressions examined potentially important sources of heterogeneity across studies. Results Fiftyeight prospective studies reported mortality rates from opioid-dependent samples. Very high heterogeneity across studies was observed; pooled all-cause CMR was 2.09 per 100 person-years (PY; 95% CI; 1.93, 2.26), and the pooled SMR was 14.66 (95% CI: 12.82, 16.50). Males had higher CMRs and lower SMRs than females. Out-of-treatment periods had higher mortality risk than in-treatment periods (pooled RR 2.38 (CI: 1.79, 3.17)). Causes of death varied across studies, but overdose was the most common cause. Multivariable regressions found the following predictors of mortality rates: country of origin; the proportion of sample injecting; the extent to which populations were recruited from an entire country (versus subnational); and year of publication. Conclusions Mortality among opioiddependent users varies across countries and populations. Treatment is clearly protective against mortality even in non-randomized observational studies. Study characteristics predict mortality levels; these should be taken into account in future studies.
Addiction (Abingdon, England), 2017
To investigate clustering of all-cause and overdose deaths after a transfer of patients and their care to alternative treatment provider and after the end of opioid substitution therapy (OST) in opioid-dependent individuals in specialist addiction treatment. Mortality data were identified within a sample of 5,445 patients with opioid use disorder who had received OST treatment between 1st April 2008 and 31st December 2013 from a large mental healthcare provider in United Kingdom. We investigated the circumstances and distribution of the 332 deaths identified within the observation window with a specific focus on overdose deaths (n=103) after a planned discharge, drop-out and transfer between services. Crude mortality rates for overdose mortality 7/14/28/180 days after the end of treatment/transfer for overdose mortality. Of 47 individuals who died from overdose after having been transferred between services, 9 died in the first 2 weeks (crude mortality rate [CMR] 136.4, 64.3 - 243.1...
Addiction (Abingdon, England), 2018
To estimate whether opioid substitution treatment (OST) with buprenorphine or methadone is associated with a greater reduction in the risk of all-cause mortality (ACM) and opioid drug-related poisoning (DRP) mortality. Cohort study with linkage between clinical records from Clinical Practice Research Datalink and mortality register. UK primary care. A total of 11 033 opioid-dependent patients who received OST from 1998 to 2014, followed-up for 30 410 person-years. Exposure to methadone (17 373, 61%) OST episodes or buprenorphine (9173, 39%) OST episodes. ACM was available for all patients; information on cause of death and DRP was available for 5935 patients (54%) followed-up for 16 363 person-years. Poisson regression modelled mortality by treatment period with an interaction between OST type and treatment period (first 4 weeks on OST, rest of time off OST, first 4 weeks off OST, rest of time out of OST censored at 12 months) to test whether ACM or DRP differed between methadone an...
BMC Psychiatry, 2008
Background: To study mortality rate and causes of death among all hospitalized opioid addicts treated for self-poisoning or admitted for voluntary detoxification in Oslo between 1980 and 1981, and to compare their mortality to that of the general population. Methods: A prospective cohort study was conducted on 185 opioid addicts from all medical departments in Oslo who were treated for either self-poisoning (n = 93, 1980), voluntary detoxification (n = 75, 1980/1981) or both (n = 17). Their median age was 24 years; with a range from 16 to 41, and 53% were males. All deaths that had occurred by the end of 2000 were identified from the Central Population Register. Causes of death were obtained from Statistics Norway. Standardized mortality ratios (SMRs) were computed for mortality, in general, and in particular, for different causes of death. Results: During a period of 20 years, 70 opioid addicts died (37.8%), with a standardized mortality ratio (SMR) equal to 23.6 (95% CI, 18.7-29.9). The SMR remained high during the whole period, ranging from 32.4 in the first five-year period, to 13.4 in the last five-year period. There were no significant differences in SMR between self-poisonings and those admitted for voluntarily detoxification. The registered causes of death were accidents (11.4%), suicide (7.1%), cancer (4.3%), cardiovascular disease (2.9%), other violent deaths (2.9%), other diseases (71.4%). Among the 50 deaths classified as other diseases, the category "drug dependence" was listed in the vast majority of cases (37 deaths, 52.9% of the total). SMRs increased significantly for all causes of death, with the other diseases group having the highest SMR; 65.8 (95% CI, 49.9-86.9). The SMR was 5.4 (95% CI, 1.3-21.5) for cardiovascular diseases, and 4.3 (95% CI, 1.4-13.5) for cancer. The SMR was 13.2 (95% CI, 6.6-26.4) for accidents, 10.7 (95% CI, 4.5-25.8) for suicides, and 28.6 (95% CI, 7.1-114.4) for other violent deaths. Conclusion: The risk of death among opioid addicts was significantly higher for all causes of death compared with the general population, implying a poor prognosis over a 20-year period for this young patient group.
Drug and Alcohol Dependence, 2009
Background: The small size of previous studies of mortality in opioid dependent people has prevented an assessment of the extent to which elevated mortality risks are consistent across time, clinical and/or patient groups. The current study examines reductions in mortality related to treatment in an entire treatment population. Methods: Data from the New South Wales (NSW) Pharmaceutical Drugs of Addiction System, recording every "authority to dispense" methadone or buprenorphine as opioid replacement therapy, 1985-2006, was linked with data from the National Deaths Index, a record of all deaths in Australia. Crude mortality rates and standardized mortality ratios were calculated according to age, sex, calendar year, period in-or out-of-treatment, medication type, previous treatment exposure and cause of death. Results: Mortality among 42,676 people entering opioid pharmacotherapy was elevated compared to age and sex peers. Drug overdose and trauma were the major contributors. Mortality was higher out of treatment, particularly during the first weeks, and it was elevated during induction onto methadone but not buprenorphine. Mortality during these risky periods changed across time and treatment episodes. Overall, mortality was similarly reduced (compared to out-of-treatment) whether patients were receiving methadone or buprenorphine. It was estimated that the program produced a 29% reduction in mortality across the entire cohort. Conclusions: Mortality among treatment-seeking opioid-dependent persons is dynamic across time, patient and treatment variables. The comparative reduction in mortality during buprenorphine induction may be offset by the increased risk of longer out-of-treatment time periods. Despite periods of elevated risk, this large-scale provision of pharmacotherapy is estimated to have resulted in significant reductions in mortality.