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Aims: To document organ pathologies detected post‐mortem in patients receiving opioid agonist treatment for opioid use disorder and estimate the extent to which individual characteristics are associated with pulmonary, cardiovascular, hepatic or renal pathologies. Design Two‐year cross‐sectional nation‐wide study. Setting: Norway. Participants: Among all 200 patients who died during opioid agonist treatment between 1 January 2014 and 31 December 2015, 125 patients (63%) were autopsied. Among these, 122 patients (75% men) had available autopsy reports and were included. The mean age at the time of death was 48 years. Measurements Information on pulmonary, cardiovascular, hepatic and renal pathologies were retrieved from forensic or medical autopsy reports, with no (0) and yes (1) as outcome variables and age, sex and body mass index as covariates in logistic regression analyses. Findings Pathologies in several organs were common. Two‐thirds (65%) of the decedents had more than two organ system diseases. The most common organ pathologies were chronic liver disease (84%), cardiovascular disease (68%) and pulmonary emphysema (41%). In bivariate analyses, only older age was associated with any pulmonary pathology [odds ratio (OR) = 1.06; 95% confidence interval (CI) = 1.01–1.10], cardiovascular pathology (OR = 1.11; 95% CI = 1.05–1.17) and renal pathology (OR = 1.05; 95% CI = 1.00–1.11). Older age remained independently associated with cardiovascular pathology (OR = 1.10; 95% CI = 1.04–1.16) and renal pathology (OR = 1.06; 95% CI = 1.01–1.12) adjusted for body mass index and sex. Conclusions: Among autopsied Norwegians who died during opioid agonist treatment in 2014 and 2015, two‐thirds had more than two organ system diseases, despite their mean age of 48 years at the time of death. Older age was independently associated with at least one cardiovascular or renal pathology after adjusting for sex and body mass index. [ABSTRACT FROM AUTHOR]

ABSTRACT Aims This study investigates changes in criminal involvement among patients in opioid maintenance treatment (OMT) over a 7-year period prior to, during and after treatment, particularly in relation to differences in treatment engagement. Design, setting and participants Treatment data on all patients who started OMT in Norway between 1997 and 2003 ( n = 3221) were cross-linked with national criminal records. The period of observation was divided into four phases; pre-treatment, in-treatment, between treatments and post-treatment. Findings During OMT, rates of criminal convictions for the cohort were reduced to fewer than half of waiting-list levels [incidence rate (IR) 0.63 versus 1.57]. Patients in continuous treatment had the fewest convictions (IR 0.47) during treatment. The highest rates were found among patients out of treatment after several treatment episodes (IR 1.52). All groups had significantly fewer criminal convictions during treatment compared to before treatment. Staying in OMT for 2 years or more was associated with significantly reduced rates of convictions during treatment. Younger age and pre-treatment criminal convictions were associated with significantly ( P < 0.001) more convictions during treatment. Those who left treatment, permanently or temporarily, relapsed into high levels of convictions outside treatment. Conclusions Criminal activity appears to be reduced in Norway during opiate maintenance treatment. Younger age and prior history of criminal activity are important risk factors for continued criminal activity during treatment. [ABSTRACT FROM AUTHOR]

SUMMARY Naltrexone is an opioid receptor antagonist that blocks the reinforcing effects of opioids and reduces alcohol consumption and craving. It has no abuse potential, mild and transient side effects, and thus appears an ideal pharmacotherapy for opioid dependence. Its effectiveness in alcohol dependence is less evident, but compliance with naltrexone combined with psychosocial support has been repeatedly shown to improve drinking outcomes. Limited compliance with oral naltrexone treatment is a known drawback. Several naltrexone implant and injectable depot formulations are being investigated and provide naltrexone release for at least 1 month. Studies among opioid-dependent patients indicate significant reductions in heroin use, but sample sizes are usually small. In alcohol dependence, two large multicenter trials report alcohol and craving reductions for naltrexone and placebo groups, indicating a significant but moderate effect. The pharmacokinetic profile of the injectable formulation indicates reliable naltrexone release over 1 month at therapeutic levels. Implant formulations releasing naltrexone up to 7 months are reported. Findings on safety and tolerability confirm the generally mild adverse effects described for naltrexone tablets. However, further research on therapeutic levels (i.e., opioid blocking) is warranted. The majority of naltrexone implants lacks approval for regular clinical use and larger longitudinal studies are needed. The available naltrexone depot formulations have the potential to significantly improve medication compliance in opioid and alcohol dependence. In certain circumstances, they may constitute a promising new treatment option. [ABSTRACT FROM AUTHOR]

BSTRACT [ABSTRACT FROM AUTHOR]

Aims Naltrexone is a competitive opioid antagonist that effectively blocks the action of heroin and other opioid agonists. Sustained-release naltrexone formulations are now available that provide long-acting opioid blockade. This study investigates the use of heroin and other opioids among opioid-dependent patients receiving treatment with long-acting naltrexone implants, their subjective experience of drug ‘high’ after opioid use, and factors associated with opioid use. Methods Participants ( n = 60) were opioid-dependent patients receiving treatment with naltrexone implants. Outcome data on substance use, drug ‘high’, depression and criminal activity were collected over a 6-month period. Blood samples were taken to monitor naltrexone plasma levels, and hair samples to verify self-reported opioid use. Findings More than half [ n = 34 or 56%; 95% confidence interval (CI) 44–68%)] the patients challenged the blockade with illicit opioids during the 6-month treatment period; 44% ( n = 26; 95% CI 32–56%) were abstinent from opioids. Mean opioid use was reduced from 18 [standard deviation (SD)13] days during the month preceding treatment to 6 days (SD 11) after 6 months. Of the respondents questioned on opioid ‘high’ ( n = 31), nine patients (30%; 95% CI 16–47%) reported partial drug ‘high’ following illicit opioid use, and three (12%; 95% CI 3–26%) reported full ‘high’. Opioid use was associated with use of non-opioid drugs and criminal behaviour. Conclusions Challenging naltrexone blockade with heroin on at least one occasion is common among sustained-release naltrexone patients, but only a minority of patients use opioids regularly. Challenges represent a warning sign for poor outcomes and often occur in the context of polydrug use and social adjustment problems. [ABSTRACT FROM AUTHOR]

Aims This study investigates how age of opioid users is related to causes of death prior to, during and after opioid maintenance treatment (OMT), and estimates risks of death from various causes in relation to age. Design, setting and participants Data on all opiate dependents in Norway (1997–2003) who applied for and were accepted for OMT ( n = 3789) were cross-linked with the Norwegian death register. The total observation time was 10 934 person-years. Findings A total of 213 deaths was recorded. Of these, 73% were subject to autopsy, and causes of death were known for 208 cases: the overall death rate was 1.9%. Deaths were due to drug overdose (54%), somatic (32%) and traumatic causes (14%). Overdose deaths among all age groups were reduced during OMT but age had a differential effect upon risk when out of treatment. Younger opioid users were at greater risk of overdose before entering treatment; older users were at greater risk after leaving treatment. Older OMT patients were at higher risk of both somatic and traumatic deaths, and deaths during OMT were most likely to be due to somatic causes. Conclusions The high rates of overdose prior to and after treatment emphasize the need to provide rapid access to OMT, to retain patients in treatment and to re-enrol patients. The high prevalence among older patients of deaths due to somatic causes has implications for screening, treatment and referral, and may also lead to increased treatment costs. [ABSTRACT FROM AUTHOR]

Aims To determine the prevalence of corrected QT interval (QTc) prolongation among patients in opioid maintenance treatment (OMT) and to investigate mortality potentially attributable to QTc prolongation in the Norwegian OMT programme. Participants and setting Two hundred OMT patients in Oslo were recruited to the QTc assessment study between October 2006 and August 2007. The Norwegian register of all patients receiving OMT in Norway (January 1997–December 2003) and the national death certificate register were used to assess mortality. Mortality records were examined for the 90 deaths that had occurred among 2382 patients with 6450 total years in OMT. Design and measures The QTc interval was assessed by electrocardiography (ECG). All ECGs were examined by the same cardiologist, who was blind to patient history and medication. Mortality was calculated by cross-matching the OMT register and the national death certificate register: deaths that were possibly attributable to QTc prolongation were divided by the number of patient-years in OMT. Findings In the QTc assessment sample ( n = 200), 173 patients (86.5%) received methadone and 27 (13.5%) received buprenorphine. In the methadone group, 4.6% ( n = 8) had a QTc above 500 milliseconds; 15% ( n = 26) had a QTc interval above 470 milliseconds; and 28.9% ( n = 50) had a QTc above 450 milliseconds. All patients receiving buprenorphine ( n = 27) had QTc results <450 milliseconds. A positive dose-dependent association was identified between QTc length and dose of methadone, and all patients with a QTc above 500 milliseconds were taking methadone doses of 120 mg or more. OMT patient mortality, where QTc prolongation could not be excluded as the cause of death, was 0.06/100 patient-years. Only one death among 3850 OMT initiations occurred within the first month of treatment. Conclusion Of the methadone patients, 4.6% had QTc intervals above 500 milliseconds. The maximum mortality attributable to QTc prolongation was low: 0.06 per 100 patient-years. [ABSTRACT FROM AUTHOR]

Programme completion is predictive of post-treatment abstinence and other improvements in persons with opioid dependence, while continued agonist treatment is associated with better outcomes than no agonist treatment. This study aimed to assess relationships between follow-up outcomes of a 9-month buprenorphine programme, completion and current agonist therapy status. Sixty-eight of 75 opioid-dependent former participants were assessed at study entry and 24 months thereafter. Outcome measures were opioid abstinence, substance use and psychosocial performance. Group comparisons were made between buprenorphine programme completers (n = 38) and non-completers (n = 30), and between participants who were currently in agonist therapy (n = 37) and those who were not. Performance at follow-up was compared to that at study entry. Nine people were abstinent from all opioids at follow-up. Completers and non-completers were similar in follow-up performance and patterns of change, while participants' current agonist therapy status was related to both substance use and psychosocial outcomes. Reductions in street opioid use and injecting were seen regardless of completion and agonist therapy status. Retaining patients in agonist replacement therapy over time is more likely than completion of a time-limited programme to influence long-term outcomes. Time-limited buprenorphine replacement therapy appears to be inappropriate for persons with opioid dependence. [Kornør H, Waal H, Sandvik L. Time-limited buprenorphine replacement therapy for opioid dependence: 2-year follow-up outcomes in relation to programme completion and current agonist therapy status. Drug Alcohol Rev 2007;26:135 – 141] [ABSTRACT FROM AUTHOR]

This study assessed treatment retention, compliance and completion of a 9-month buprenorphine replacement programme. In addition, changes in drug use and other relevant variables, as well as predictors of completion, were examined. Seventy-five opioid-dependent out-patients (mean age 26 years; 33% females) who aimed for opioid abstinence were enrolled into the study. Assessments were undertaken prior to buprenorphine induction and again at 3, 6 and 9 months. Forty patients (53%) completed the buprenorphine programme. At 9 months, 67 patients (87%) were still in counselling. Mean attendance rates for buprenorphine dosing and counselling sessions were 0.91 and 0.74, respectively. There were significant and persistent reductions in drug use during treatment with, however, a reversed tendency in the 9th month. Psychiatric problems escalated at 9 months, and three patients died during the detoxification phase. Completion was predicted by fewer previous treatment episodes. Detoxification from buprenorphine is associated with substantial psychological distress and an increased death risk. Buprenorphine replacement therapy should be continued until the patient chooses to leave, and close monitoring during the detoxification phase is essential. [Kornør H, Waal H, Ali RL. Abstinence-orientated buprenorphine replacement therapy for young adults in out-patient counselling . Drug Alcohol Rev 2006;25:123 – 130] [ABSTRACT FROM AUTHOR]

It appears that the literature on agonist maintenance therapies for opioid dependence pays more attention to outcomes during, rather than after, treatment. This review aims to (a) estimate to what extent opioid abstinence can be expected from former maintenance patients, (b) examine possible relationships between patient and treatment characteristics and abstinence rates and (c) assess the need for research in the field of abstinence-orientated maintenance treatment in general, and time-limited buprenorphine maintenance treatment in particular. Database searches supplemented by cross-references resulted in 12 studies included in the review. The studies were mostly naturalistic follow-up studies of former methadone maintenance patients, authored by US researchers in the 1970s. Buprenorphine was used in only one of the studies, and then as a transition between methadone and abstinence. There were considerable variations in definition and assessment of abstinence. Pooled abstinence rates ranged from 22% to 86%. The single factor associated most frequently with abstinence was voluntary participation in detoxification programmes with eligibility criteria (‘therapeutic detoxification’). When ‘therapeutic detoxification’ was compared to ‘non-therapeutic detoxification’ the pooled abstinence rates were 48% and 22%, respectively. Abstinence-orientated maintenance therapy may be suitable for a subgroup of patients, but there is a substantial need for research updates. [Kornør H, Waal H. From opioid maintenance to abstinence: a literature review. Drug Alcohol Rev 2005;24:267 – 274] [ABSTRACT FROM AUTHOR]

To evaluate individual variations in plasma concentrations over time in patients with naltrexone implants. Ten opioid-dependent patients received up to four implants. Plasma samples were collected regularly for the analyses of naltrexone and the metabolite β-naltrexol. The median naltrexone Cmax was 12.3 (range 5.8–22.1) ng ml−1, the median Tmax was 1 day (range 3 h to 35 days), and the median length of time that plasma concentrations were above 1 ng ml−1 was 55 (range 30–80) days. Two patients reported heroin use without experiencing any effect. Tissue reactions were recorded in two patients after repeated implantation. Marked individual and intraindividual variations in naltrexone concentrations were observed. Further studies should be performed to evaluate the need for therapeutic drug monitoring during naltrexone implant treatment. [ABSTRACT FROM AUTHOR]

The author discusses the article "Naltrexone in the treatment of opioid-dependent pregnant women: the case for a considered and measured approach to research" by H. E. Jones and colleagues in the April 2012 issue. The author hopes that the paper will initiate an international project enabling a gradual increase of knowledge on naltrexone treatment efficiency with the possibility of detecting early signs of long-term developmental problems.

In this article, the author comments on J. Grabowski's paper which argues that the organization of U.S. drug and alcohol research in separate National Institutes of Health (NIH) institutes is outdated. He says that considerations of cost-benefit and cost-effectiveness would benefit joint organization. He agrees that the barriers between drug and alcohol research belong to the past; however, he says that it would likely be wise to prioritize agreements of predominant goals.

Aims: To present the substances and their concentrations detected post-mortem in patients receiving opioid agonist treatment (OAT) stratified by cause of death, estimate the pooled opioid and benzodiazepine concentrations using established conversion factors for blood concentrations from the Norwegian Road Traffic Act, and explore the association between drug-induced cause of death and the pooled opioid and benzodiazepine concentrations., Design: Cross-sectional nationwide study., Setting: Norway., Participants: One hundred and seven patients who died during OAT (i.e. within 5 days after the last intake of OAT medication) between 1 January 2014 and 31 December 2015, with post-mortem femoral blood available for toxicology. Data were collected from hospital records, the Norwegian Cause of Death Registry and autopsy reports., Measurements: Presence of alcohol and non-alcohol substances in the bloodstream at time of death, determined through records of toxicology of post-mortem femoral blood., Findings: A median of four substances was detected across the causes of death. At least one benzodiazepine was detected in 81 (76%) patients. The median pooled opioid concentration was significantly higher in drug-induced deaths compared with other causes of death (362 ng/mL versus 182 ng/mL, P < 0.001), in contrast to the pooled benzodiazepine concentration (5466 versus 5701 ng/mL, P = 0.353). The multivariate regression analysis showed that only increasing pooled opioid concentration (ng/ML) was associated with increased odds of a drug-induced cause of death (odds ratio, 1.003; 95% confidence interval: 1.001-1.006)., Conclusions: In Norway, overall opioid concentration seems to play an important role in drug-induced deaths during opioid agonist treatment in patients prescribed methadone or buprenorphine. Patients prescribed buprenorphine tend to replace their agonist with full agonists, while patients prescribed methadone tend to have high opioid concentrations from methadone as the only opioid., (This article is protected by copyright. All rights reserved.)