The impact of opiate substitution treatment on mortality risk in drug addicts: a natural experiment study

Background Opiate substitution treatment (OST) is the main treatment for people addicted to heroin and other opioid drugs. However, there is limited information on how the delivery of this treatment affects mortality risk. Objectives To investigate the associations of mortality risk with periods during treatment and following cessation of treatment, medication type, co-prescription of other medication and dosing regimens during titration and detoxification. The trends with time of prescribed medication, dose and treatment duration were also explored. Design Prospective longitudinal observational study. Setting UK primary care between 1998 and 2014. Participants A total of 12,780 patients receiving methadone, buprenorphine or dihydrocodeine. Main outcome measures All-cause mortality relating to 657 deaths and drug-related poisoning relating to 113 deaths. Data sources Clinical Practice Research Datalink with linked information on cause of death from the Office for National Statistics. Results For both outcomes, the lowest mortality risk was observed after 4 weeks of treatment and the highest risk was observed in the first 4 weeks following cessation of treatment [e.g. for drug-related poisoning, incidence rate ratio (IRR) 8.15, 95% confidence interval (CI) 5.45 to 12.19]. There was evidence that the treatment period risks varied with OST medication. The largest difference in risk was for the first 4 weeks of treatment for both outcomes, with patients on buprenorphine being at lower risk than those on methadone (e.g. for drug-related poisoning, IRR 0.08, 95% CI 0.01 to 0.48). The co-prescription of benzodiazepines was associated with linearly increasing the risk of drug-related deaths by dose (IRR 2.02, 95% CI 1.66 to 2.47), whereas z-drugs (zolpidem, zopiclone and zaleplon) were associated with increased risk of both all-cause (IRR 1.83, 95% CI 1.59 to 2.12) and drug-related (IRR 3.31, 95% CI 2.45 to 4.47) mortality. There was weak evidence that higher initial and final doses were associated with increased all-cause mortality risk. In the first 4 weeks of treatment, the risk increased by 4% for each 5-mg increment in methadone dose (1-mg increase in buprenorphine) (hazard ratio 1.04, 95% CI 1.00 to 1.09). In the first 4 weeks after treatment ceased, a similar increment in final dose increased the risk by 3% (hazard ratio 1.03, 95% CI 0.99 to 1.07). There were too few deaths to evaluate the effects on drug-related poisoning. The proportion of OST patients receiving buprenorphine increased between 1998 and 2006. Median treatment duration was consistently shorter for buprenorphine than for methadone for each year studied (overall median duration of 48 and 106 days, respectively). Limitations As this was an observational study, the possibility remains of bias from unmeasured factors, which covariate adjustment and inverse probability weighting can eliminate only partially. Conclusions Using buprenorphine as an alternative to methadone may not reduce mortality overall despite resulting in lower IRRs from shorter treatment duration. Clinical guidance needs to consider strengthening warnings about the co-prescription of a range of drugs for OST patients. Future work Our analyses need to be replicated using other clinical data sets in the UK and in other countries. New interventions and trials are required to investigate improving the retention of OST patients in primary care. Funding The National Institute for Health Research Health Services and Delivery Research programme.

Benzodiazepine maintenance in opiate substitution treatment: Good or bad? A retrospective primary care case-note review

Background: Co-prescribing benzodiazepines to patients in opiate substitution treatment is controversial and often alleged to increase mortality. In an inner-London general practice, patients with problematic benzodiazepine co-dependence were allowed benzodiazepine maintenance treatment (BMT) since 1994, providing an opportunity for analysis. Method: 1) Case-note review of all 278 opiate substitution treatment patients, accruing 1289 patient treatment years; 46% had concurrent BMT. 2) National Health Service database search for patients who died after leaving accrued a further 883 years of information; only patients who left the UK were unaccounted for (4%). Three groups were studied: 1) never obtained benzodiazepine prescription (NOB): n=80); 2) briefly/occasionally prescribed benzodiazepines (BOP): n=71; 3) BMT: n=127. Outcomes measured: Treatment retention (months); deaths/100 patient treatment years; deaths after leaving the service/100 years of information. Results: Treatment retention: NOB: 34 months; BOP: 51 months; BMT: 72 months. In-treatment mortality: NOB: 1.79/100 patient treatment years; BOP: 0.33/100 patient treatment years; BMT: 1.31/100 patient treatment years. Deaths after leaving service: NOB: 2.24/100 years of information, BOP: 0.63/100 years of information. However, mortality for previously BMT-patients increased by 450% to 5.90/100 years of information. Discussion: BMT patients had longer treatment retention than NOB or BOP and lower mortality than NOB patients. It is unlikely that patients had access to prescribed benzodiazepines on leaving the service because of restrictions in the national guidelines but co-dependent patients are a high-risk group who may stand to gain most benefit from opiate substitution treatment if combined with benzodiazepine-maintenance.

HBV and HCV serological monitoring among injection drugs users in opiate substitution treatment in Bosnia and Herzegovina

Introduction: Use of intravenous heroin carries a risk of serious medical conditions, including acquiring blood-borne infections. Therefore, hepatitis B virus (HBV) and hepatitis C virus (HCV) infection represent a threat for people who inject drugs (PWID). The objectives of this study were to determine the extent and characteristics of risk factors for acquiring HBV and HCV infection in PWID included in opiate substitution treatment in the southern part of Bosnia and Herzegovina (B&H). Methodology: The study included 120 adult PWID of both sexes who participated in opiate substitution treatment. All participants were interviewed, and their blood samples were tested for the presence of the surface hepatitis B virus antigen (HBsAg) and hepatitis C virus antibodies (anti-HCV). Prevalence data were obtained and compared to the serological status. Results: HBsAg prevalence among PWID was 0.8% (1/120), whereas seroprevalence of anti-HCV was 52.5% (63/120). PWID exposed to risk-behavior factors (such as unsafe sexual activity, serving prison sentence, and tattooing) were more frequently anti-HCV positive. Sharing drug paraphernalia was found to be the most significant risk factor. The highest predictive values for acquiring HCV-infection were attributed to PWID who used heroin for more than three years and who were unmarried. Conclusions: HBsAg prevalence among PWID is rare (0.8%), while HCV-infection (52.5%) presents an important health and social issue among PWID in B&H. Sharing drug paraphernalia and intravenous heroin use longer than three years were the most prominent risk-behavior factors among the patients we investigated.