Large variations in all-cause and overdose mortality among >13,000 patients in and out of opioid maintenance treatment in different settings: a comparative registry linkage study

BackgroundOpioid maintenance treatment (OMT) has the potential to reduce mortality rates substantially. We aimed to compare all-cause and overdose mortality among OMT patients while in or out of OMT in two different countries with different approaches to OMT.MethodsTwo nation-wide, registry-based cohorts were linked by using similar analytical strategies. These included 3,637 male and 1,580 female patients enrolled in OMT in Czechia (years 2000–2019), and 6,387 male and 2,078 female patients enrolled in OMT in Denmark (years 2007–2018). The direct standardization method using the European (EU-27 plus EFTA 2011–2030) Standard was employed to calculate age-standardized rate to weight for age. All-cause and overdose crude mortality rates (CMR) as number of deaths per 1,000 person years (PY) in and out of OMT were calculated for all patients. CMRs were stratified by sex and OMT medication modality (methadone, buprenorphine, and buprenorphine with naloxone).ResultsAge-standardized rate for OMT patients in Czechia and Denmark was 9.7/1,000 PY and 29.8/1,000 PY, respectively. In Czechia, the all-cause CMR was 4.3/1,000 PY in treatment and 10.8/1,000 PY out of treatment. The overdose CMR was 0.5/1,000 PY in treatment and 1.2/1,000 PY out of treatment. In Denmark, the all-cause CMR was 26.6/1,000 PY in treatment and 28.2/1,000 PY out of treatment and the overdose CMR was 7.3/1,000 PY in treatment and 7.0/1,000 PY out of treatment.ConclusionCountry-specific differences in mortality while in and out of OMT in Czechia and Denmark may be partly explained by different patient characteristics and treatment systems in the two countries. The findings contribute to the public health debate about OMT management and may be of interest to practitioners, policy and decision makers when balancing the safety and accessibility of OMT

Addictive medication in relation to drug treatment and overdose death

Background The involvement of the addictive medications, benzodiazepines (BZDs) and prescription opioids, including opioid maintenance treatment (OMT) medications, have increasingly contributed to the high overdose death rates in Denmark and Norway during the past decades. Investigating prescription patterns and patient behavior in relation to drug treatment and overdose deaths is important to increase our knowledge on how these addictive medications are used, misused, and how they may contribute to overdose deaths. Study aims The overall aim of the thesis was to acquire new knowledge of the involvement of addictive medications in the treatment of populations with drug use disorders (DUDs) and also in overdose deaths to improve treatment approaches and reduce detrimental outcomes in a vulnerable group of individuals. More specifically the aim was to investigate prescription patterns and use of addictive medication in relation to drug treatment and overdose deaths among populations in Denmark and Norway. Furthermore, to compare overdose cases with and without detection of legally prescribed addictive medications and investigate factors associated with having detection of non-prescribed addictive medication. Materials and methods This thesis was based on three different cohorts/samples from two countries: A Danish nationwide cohort including individuals admitted for treatment for DUDs in 2000-2010 (n=33,203); a Norwegian sample including overdose deaths in the capital city, Oslo, in 2006-2008 (n=167), and; a Danish sample including overdose deaths in Copenhagen, Aarhus, and Odense Municipality in 2008-2011 (n=130). The cohorts/samples were linked with data from population registries, local based registries, and journal reviews by using a unique identification number assigned to all Danish and Norwegian citizens. Results Overall, in the period after entering treatment and in the period prior to overdose death, addictive medication was often prescribed to individuals with DUD. In both periods, inappropriate prescription patterns were identified. During the first year after admission to DUD treatment, about one-quarter of the individuals (26.2%) were prescribed BZDs. Of these, about one-third (35.5%) were prescribed BZDs at dose levels that might indicate inappropriate use, and about one-third (34.6%) were prescribed more than one type of BZDs. Particularly individuals with opioid use (43.2%) were commonly prescribed BZDs. Admitting to treatment for a DUD did not increase the specialized psychiatric treatment coverage of this patient group, disregarding use of prescribed BZDs. Among overdose deaths in Denmark and Norway, the prescribed doses of the addictive medications among the deceased were in general higher than recommended. Further, the control/monitoring measures were insufficient and allowing use of multiple prescribing physicians (Norway), low levels of supervised intake of OMT medication (Denmark), and use of multiple prescribed addictive medications (Denmark). We investigated the deceased with detection of prescribed vs. non-prescribed addictive medication. In the Norwegian sample, we found that a lower proportion of the deceased (with detection of the target medications) had been prescribed BZDs (28.1%), strong analgesics (33.3%), or BZDs plus strong analgesics (50.0%) four weeks prior to death. However, in Denmark the majority of deceased with methadone-related overdose deaths (63.1%) were prescribed methadone as part of OMT at the time of death. In the Norwegian sample, detection of non-prescribed BZDs and/or strong analgesics was associated with younger age (a-OR=4.9; 95% CI, 1.4-18.0) and to have a permanent place of residence outside Oslo (a- OR=2.9; 1.1-8.1). In the Danish sample, detection of non-prescribed methadone was associated with younger age of 30 years or below (a-OR=9.5; 1.8-50.5), concomitant detection of 6-MAM/heroin (a-OR=3.1; 1.2-7.8), and non-prescrib

Benzodiazepine prescription for patients in treatment for drug use disorders: a nationwide cohort study in Denmark, 2000–2010

Background Benzodiazepines are frequently prescribed to patients with drug use disorders. However, it has previously been difficult to distinguish whether this frequent prescribing was due to underlying psychiatric disorders or inappropriate prescribing. In a nationwide cohort study, we investigated the prescribing of benzodiazepines to patients with drug use disorders in connection with treatment admission. Methods Benzodiazepine prescriptions to patients (N = 33203) aged 18 to 67 years admitting for outpatient treatment for drug use disorders in Denmark, 2000 to 2010, were studied by using linked data from nationwide health registries. Factors associated with increasing amounts of benzodiazepine use within the first year after admission were assessed by multinomial logistic regression. Proportions of very long-term benzodiazepine prescription were calculated. Results During the first year after admission to treatment, 26.2 % of patients were prescribed benzodiazepines. Of these, 35.5 % were prescribed benzodiazepines at dose levels that might indicate inappropriate use (>365 Defined Daily Dose per year), and 34.6 % were prescribed more than one type of benzodiazepines. Diazepam was the most commonly prescribed type. Among patients with opioid use, 43.2 % were prescribed benzodiazepines which were three times higher than for patients with cannabis (12.2 %) or central stimulating drugs (13.8 %) as their primary drug use. Admitting to treatment for a drug use disorder did not increase the specialized psychiatric treatment coverage of this patient group, disregarding use of prescribed benzodiazepines. 29.5 % were new users of prescribed benzodiazepines, and of these, 27.5 % continued into very long-term use (≥4 years after admission) during the study period. Conclusions Benzodiazepines were commonly prescribed to patients admitting to treatment for drug use disorders, and included prescription of multiple and non-optimal types, high doses, and very long-term prescriptions. These findings point towards inappropriate prescribing of benzodiazepines in many cases more than treatment for psychiatric disorders

Psychiatric disorders in a population of deceased drug users

Purpose To estimate the prevalence of psychiatric morbidity and dual diagnosis in a population of decedents with positive drug toxicology and evaluate changes over time between 2001–2002 and 2011–2012. Materials and methods A total of 520 autopsied drug users with positive toxicology were included in the study from 2001 to 2002 and from 2011 to 2012. Materials included autopsy reports, toxicological screening during autopsy and data from the Danish national health registers, including psychiatric diagnoses from psychiatric hospitals and ambulatory functions, dispensed prescription use from pharmacies and registered treatment for drug use disorders. Results In 2001–2002, 63.3% of the decedents had only positive toxicology, 22.5% also had psychiatric morbidity, and 14.2% had a dual diagnosis. In 2011–2012, 56.4% had only positive toxicology, 26.1% also had psychiatric morbidity, and 17.5% had a dual diagnosis. None of the changes were significant. Decedents with only positive toxicology became older at time of death over time; decedents with psychiatric morbidity and a dual diagnosis did not. The prevalence of nonprescribed psychotropic medication, methadone and benzodiazepines increased. Conclusion Decedents with psychiatric morbidity and dual diagnosis did not increase their lifespan over a 10-year period. Decedents with only positive toxicology increasingly consumed nonprescribed psychotropic medication and may have suffered from undiagnosed psychiatric disorders. The prevalence of prescribed and nonprescribed benzodiazepines and methadone increased and may have contributed to premature mortality

Treatment Status and Use of Psychoactive Substances in Deceased Drug Users

Background: Studies on drug use are limited by the study populations available, which usually only include drug users in treatment settings. Therefore, the knowledge base is limited on drug users not entering treatment for drug use disorder (DUD). Using registers from departments of forensic medicine enables research on decedents with DUD, irrespective of treatment status. Objectives: The aim of this study is to characterize and compare drug users not receiving treatment and drug users receiving treatment, in relation to cause of death, toxicological findings, and use of nonprescribed medication. Methods: Retrospective register-based study on deceased drug users with supplemental data from the Registry of Drug Abusers Undergoing Treatment and the Register of Medicinal Product Statistics in 2 observation periods: 2001–2002 and 2011–2012. Results: Two-thirds of the population were not receiving treatment at the time of death in both observation periods. Drug users receiving treatment were more likely to die from accidental poisonings than drug users not receiving treatment. There was no difference in mean age at the time of death between the 2 groups, and both groups were older in the second observation period. There was no difference in toxicological findings according to treatment status and the 2 groups did not differ in the presence of nonprescribed medication found in the blood at the time of death. Discussion/Conclusions: The proportion of drug users that received treatment prior to death has not increased, and deceased drug users are mostly not in treatment for their drug use at the time of death

Opioid maintenance treatment of pregnant women in the Scandinavian countries

Background: WHO guidelines emphasise the need for descriptions of clinical practice and observational studies on risk and benefits of pharmacotherapies in pregnancy. The aims of the present study were to: (1) Describe opioid maintenance treatment (OMT) in the Scandinavian countries in general, and specifically for pregnant women, (2) Describe a project which utilises a new approach using registry-linkage data to examine associations between prenatal exposure to OMT and child outcomes: a Scandinavian cohort study of pregnant women in OMT during pregnancy (ScopeOMT). Data: Guidelines describing the treatment of persons with opioid use disorders in general, and specifically for pregnant women. Scandinavian registry-linkage data from ScopeOMT. Results: Registry data show that approximately 800 pregnant women received OMT during pregnancy in the period of the ScopeOMT study. Similarities across the Scandinavian countries include access to free healthcare and treatment; multidisciplinary teams trained to support pregnant women in OMT; buprenorphine as the recommended drug when initiating therapy; and a holistic focus on the patients' lives. An important difference is that Norwegian women who use illegal substances that may harm the foetus may be admitted - voluntarily, or against their will - for parts of, or the remainder of the pregnancy to inpatient treatment at specialised clinics. Conclusion: Many similarities in the treatment provided to opioid-dependent persons in the Scandinavian countries place this area in an excellent position to combine the efforts and carry out observational studies concerning the safety of OMT during pregnancy.Peer reviewe