Mortality risk and causes of death among people who use opioids in a take-home naloxone cohort.

BACKGROUND: People who use opioids (PWUO) have an excess mortality from a range of causes. The cumulative effect of behavioral, social, and health risk factors complicates the interpretation of the effects of suitable interventions. This study explores mortality causes among a cohort of PWUO in the take-home naloxone (THN) program. METHODS: This was a prospective cohort study of PWUO who received THN between 2015 and 2023. Participant data was linked with death registry data. Crude mortality rates and standardized mortality ratios (SMRs) were calculated for all causes, internal causes, and accidental opioid overdoses (AOOs). In addition to age and gender, risk factors like main route of administration, polydrug use, self-experienced overdoses, and using while alone were fitted in a Cox Regression model to explore factors associated with mortality. RESULTS: The 2194 participants had a considerably higher mortality ratio for all causes investigated when compared to the general population (SMR=10.9, 95 % CI = 9.3,12.6). AOOs were the most prevalent cause of death (49 %). Those who reported frequent opioid use while alone had an elevated risk of dying of 2.6 (95 % CI = 1.1,6.4) compared to those who never used while alone. CONCLUSIONS: Frequent opioid use while alone was associated with elevated mortality risk, supporting the importance of overdose prevention education with naloxone distribution, and additional efforts to improve environmental and social areas for safer drug-use practices among PWUO. The variety of mortality causes found in this study illustrates the need for multifaceted and targeted interventions for people at risk of overdosing.

Leaving Their Drugs at the Gate? Exploring Changes in Drug Use From Before to During Incarceration in Norway.

As the number of incarcerated persons who use drugs increases in many countries, it is important to understand the nature of drug use in prison by exploring how substance use patterns change from before to during incarceration. In this study, we rely on cross-sectional, self-report data from The Norwegian Offender Mental Health and Addiction (NorMA) study to identify the nature of changes in drug use among incarcerated respondents who reported having used either narcotics, non-prescribed medications, or both, during the 6 months before their incarceration (n = 824). Results show that about 60% (n = 490) stop using drugs. Of the remaining 40% (n = 324), about 86% changed their use patterns. Most commonly, incarcerated people stopped using stimulants and started using opioids; switching from cannabis to stimulants was the least common change. Overall, the study illustrates that the prison context leads most individuals to change their use patterns, some in unanticipated ways.

Risks and overdose responses: Participant characteristics from the first seven years of a national take-home naloxone program.

BACKGROUND: In 2014, the Norwegian government funded a large-scale take-home naloxone (THN) program to address high overdose mortality rates. The aims of this study are to describe characteristics among persons trained to receive THN, describe actions taken following THN use at an overdose event and to explore factors associated with naloxone use. METHODS: This was a prospective cohort study of individuals who received THN from 2014 to 2021. Descriptive characteristics were collected at initial training. When returning for refill, participants reported on their previous naloxone use. In a multivariable logistic regression model exploring associations with naloxone use: gender, age, opioid use history, concomitant drug use, injecting, history of experienced or witnessed overdose were included. RESULTS: In total, 3527 individuals were included in this study. There were 958 individuals who returned for refills 2303 times. Most participants were male (63.6%), with a history of opioid use (77.5%). Those who reported naloxone use were more likely to have a history of opioid use (aOR= 4.1; 95% CI=2.77,6.1), were younger (aOR=0.98; 95% CI=0.97,0.99) and had witnessed overdoses (aOR=3.3; 95% CI=1.98,5.34). Among current opioid users, the odds were higher for injectors (aOR=1.57; 95% CI=1.18,2.1). Naloxone use was reported 1282 times. Additional actions such as waking the person and calling the ambulance were frequently reported. Survival was reported in almost all cases (94%). CONCLUSION: People who use drugs are a suitable target group for THN-programs, as they seem to be willing and capable to reverse overdoses effectively. Given their personal risk factors for overdosing, recipients will likely also benefit from overdose prevention education.

Who is using take-home naloxone? An examination of supersavers.

BACKGROUND: As the opioid overdose crisis persists and take-home naloxone (THN) programmes expand, it is important that the intervention is targeted towards those most likely to use it. We examined THN program participants to 1) describe those that return for refills, specifically those that reported multiple use (supersavers), and 2) to examine what rescuer characteristics were associated with higher rates of THN use. METHODS: This study included a cohort of consenting THN recipients from June 2014-June 2021 who completed initial and refill questionnaires from a widespread program in Norway. Age, gender, number of witnessed and experienced overdoses were assessed for associations with higher reported rates of THN use. 'Supersavers' reported 3 or more THN uses. RESULTS: A total of 1054 participants returned for a THN refill during the study period. Of these, 558 reported their last THN to have been used on an overdose. Supersavers (those that reported 3 or more THN uses) were younger, primarily reported current opioid use, and had witnessed higher rates of overdoses at the time of initial training when compared to non-supersavers (those that reported 0-2 THN uses). CONCLUSIONS: THN programs should continue to emphasize and prioritize THN for people actively using drugs, particularly those who have witnessed overdoses previously.

Staff preferences towards electronic data collection from a national take-home naloxone program: a cross-sectional study.

BACKGROUND: During the scaling-up of a national Norwegian take-home naloxone (THN) program, data collection methods shifted from paper-based to electronic. The aim of this study was to explore staff preferences towards the shift in data collection. METHODS: In January-February 2020, a survey was sent out via email to personnel involved with the THN program (n = 200). The survey included 17 questions, and covered staff demographics, experiences distributing THN, preferences towards data collection (both paper and electronically), and an open response section. Descriptive statistics were performed for the survey results. The open response section was recorded from each questionnaire and was coded into major themes by the authors. RESULTS: In total, 122 staff completed the survey. Of these, 62% had experience with both electronic and paper-based forms, and there was a near unanimous preference towards electronic data collection over paper-based forms. From the free-text responses, staff found the electronic form to be a useful tool for conversation and overdose prevention education, and that the electronic form was easier to manage than the paper forms. CONCLUSION: The shift towards electronic data collection was necessary for the feasibility of the Norwegian national THN program. This study found that staff not only tolerated the shift, but in most cases preferred this organizational change.

An evaluation of eight short versions of the Drug Use Disorder Identification Test (DUDIT). A prison population study.

Background: The eleven-item Drug Use Disorder Identification Test (DUDIT) is a recommended screening tool, but its length may impede its use in prison intake assessments. Hence, we examined the performance of eight brief DUDIT screeners against the full DUDIT, employing a sample of male inmates. Methods: Our study included male participants in the Norwegian Offender Mental Health and Addiction (NorMA) study who reported pre-prison drug use and who had been incarcerated three months or less (n = 251). We performed receiver operating characteristic curve (ROC) analyses and estimated the area under the curve (AUROC) to assess the performance of DUDIT-C (four drug consumption items) and five-item versions that consisted of DUDIT-C and one additional item. Results: Almost all (95%) screened positive on the full DUDIT (scores ≥6) and 35% had scores that were indicative of drug dependence (scores ≥25). The DUDIT-C performed very well in detecting likely dependence (AUROC=0.950), but some of the five-item versions performed significantly better. Of these, the DUDIT-C + item 5 (craving) had the highest AUROC (0.097). A cut-point of ≥9 on the DUDIT-C and ≥11 on the DUDIT-C + item 5 identified virtually all (98% and 97%, respectively) cases of likely dependence, with a specificity of 73% and 83%, respectively. At these cut-points, the occurrence of false positives was modest (15% and 10%, respectively) and only 4-5% were false negatives. Conclusions: The DUDIT-C was highly effective in detecting likely drug dependence (according to the full DUDIT), but some combinations of DUDIT-C and one additional item performed better.

Medication assisted treatment (MAT) in criminal justice settings as a double-edged sword: balancing novel addiction treatments and voluntary participation.

Medication-Assisted Treatment (MAT) provides an opportunity to address opioid addiction among justice-involved individuals, an often difficult to reach population. This potential has been increasingly recognized by agencies, policymakers and pharmaceutical companies. The result has been a marked increase in the number of drug courts, prisons and agencies in which MAT, notably with long-acting injectable medications, is offered. While this is a positive development, ensuring that vulnerable individuals are in a position voluntarily participation within the complex criminal justice environment is necessary. The unequal authority and agency inherent in the nature of these environments should be recognized. Therefore, rigorous protections, mirroring the goals of the consent processes required for medical or sociobehavorial research, should be employed when MAT is offered to protect individual autonomy.

Intact responses to non-drug rewards in long-term opioid maintenance treatment.

Disruption of non-drug reward processing in addiction could stem from long-term drug use, addiction-related psychosocial stress, or a combination of these. It remains unclear whether long-term opioid maintenance treatment (OMT) disrupts reward processing. Here, we measured subjective and objective reward responsiveness in 26 previously heroin-addicted mothers in >7 years stable OMT with minimal psychosocial stress and illicit drug use. The comparison group was 30 healthy age-matched mothers (COMP). Objective reward responsiveness was assessed in a two-alternative forced-choice task with skewed rewards. Results were also compared to performance from an additional 968 healthy volunteers (meta-analytic approach). We further compared subprocesses of reward-based decisions across groups using computational modelling with a Bayesian drift diffusion model of decision making. Self-reported responsiveness to non-drug rewards was high for both groups (means: OMT = 6.59, COMP = 6.67, p = 0.84, BF10 = 0.29), yielding moderate evidence against subjective anhedonia in this OMT group. Importantly, the mothers in OMT also displayed robust reward responsiveness in the behavioral task (t19 = 2.72, p = 0.013, BF10 = 3.98; d = 0.61). Monetary reward changed their task behavior to the same extent as the local comparison group (reward bias OMT = 0.12, COMP = 0.12, p = 0.96, BF10 = 0.18) and in line with data from 968 healthy controls previously tested. Computational modelling revealed that long-term OMT did not even change decision subprocesses underpinning reward behavior. We conclude that reduced sensitivity to rewards and anhedonia are not necessary consequences of prolonged opioid use.

Ambulance-attended opioid overdoses: An examination into overdose locations and the role of a safe injection facility.

Background: Although the United States and numerous other countries are amidst an opioid overdose crisis, access to safe injection facilities remains limited. Methods: We used prospective data from ambulance journals in Oslo, Norway, to describe the patterns, severity, and outcomes of opioid overdoses and compared these characteristics among various overdose locations. We also examined what role a safe injection facility may have had on these overdoses. Results: Based on 48,825 ambulance calls, 1054 were for opioid overdoses from 465 individuals during 2014 and 2015. The rate of calls for overdoses was 1 out of 48 of the total ambulance calls. Males made up the majority of the sample (n = 368, 79%), and the median age was 35 (range: 18-96). Overdoses occurred in public locations (n = 530, 50.3%), the safe injection facility (n = 353, 33.5%), in private homes (n = 83, 7.9%), and other locations (n = 88, 8.3%). Patients from the safe injection facility and private homes had similarly severe initial clinical symptoms (Glasgow Coma Scale median =3 and respiratory frequency median =4 breaths per minute) when compared with other locations, yet the majority from the safe injection facility did not require further ambulance transport to the hospital (n = 302, 85.6%). Those overdosed in public locations (odds ratio [OR] = 1.66, 95% confidence interval [CI] = 1.17-2.35), and when the safe injection facility was closed (OR =1.4, 95% CI =1.04-1.89), were more likely to receive transport for further treatment. Conclusions: Our findings suggest that the opening hours at the safe injection facility and the overdose location may impact the likelihood of ambulance transport for further treatment.

Use of drugs for alcohol use disorder in Norway 2004­16. / Bruk av medikamenter for alkoholbrukslidelser i Norge 2004­16.

BACKGROUND: Alcohol use disorder can lead to serious illness and early death. The lifetime prevalence rate among the Norwegian population is estimated at 7-10 %. Many patients are never admitted to any kind of treatment programme, and it is assumed that few of those who are treated receive medicinal treatment. There are a variety of drugs on the market that can help reduce alcohol consumption and maintain abstinence. We wanted to gain an insight into the prescription prevalence rate and practice for these drugs. MATERIAL AND METHOD: We obtained encrypted data from the Norwegian Prescription Database of everyone who received drugs for alcohol use disorder in the period 2004-2016. The drugs included were disulfiram, acamprosate, naltrexone 50 mg and nalmefene. RESULTS: The annual prescription prevalence rate increased from 0.85 to 1.13 per 1000 during the observation period. Half of all patients only received prescribed drugs once, and Disulfiram was the most commonly prescribed drug. There was a slight increase in the prevalence rate in age groups up to and including 55 years, and a significant increase for the over-55s. CONCLUSION: There was a slight increase in the prescription prevalence rate during the observation period. Disulfiram was the most commonly prescribed drug. The prescription increase was greatest among women and in the group of over-55s.

Rapid widespread distribution of intranasal naloxone for overdose prevention.

BACKGROUND: Take home naloxone programs have been successful internationally in training bystanders to reverse an opioid overdose with naloxone, an opioid antagonist. A multi-site naloxone distribution program began in Norway in 2014 as part of a national overdose prevention strategy. The aim of this study was to a) describe the program, and b) present findings from the government-supported intervention. METHODS: From July 2014 to December 2015, staff from multiple low-threshold facilities trained clients on how to use intranasal naloxone. Distribution occurred without an individual prescription or physician present. Questionnaires from initial and refill trainings were obtained, and distribution rates were monitored. RESULTS: There were 2056 naloxone sprays distributed from one of the 20 participating facilities, with 277 reports of successful reversals. Participants exhibited known risks for overdosing, with injecting (p=0.02, OR=2.4, 95% CI=1.14, 5.00) and concomitant benzodiazepine use (p=0.01, OR=2.6, 95% CI=1.31, 5.23) being significant predictors for having had high rates of previous overdoses. Suggested target coverage for large-scale programs was met, with an annual naloxone distribution rate of 144 per 100,000 population, as well as 12 times the cities mean annual number of opioid-related deaths. CONCLUSION: A government-supported multisite naloxone initiative appears to achieve rapid, high volume distribution of naloxone to an at-risk population.

Circumstances surrounding non-fatal opioid overdoses attended by ambulance services.

INTRODUCTION AND AIMS: Opioid overdose fatalities are a significant concern globally. Non-fatal overdoses have been described as a strong predictor for future overdoses, and are often attended by the ambulance services. This paper explores characteristics associated with non-fatal overdoses and aims to identify possible trends among these events in an urban area in Norway. DESIGN AND METHODS: This is a retrospective analysis of non-fatal overdoses from Bergen ambulance services from 2012 to 2013. Demographic, temporal and geographic data were explored. RESULTS: During the two years, 463 non-fatal opioid overdoses were attended by ambulance services. Ambulance call-outs occurred primarily during the late afternoon and evening hours of weekdays. Summer months had more overdoses than other seasons, with a peak in August. Overdoses were nearly twice as likely to occur in a public location in August (risk ratio 1.92, P = 0.042). Ambulance response times were more likely to be longer to private locations, and these victims were more likely to be treated and left at the scene. There was no difference in arrival time for drug-related and non-drug related dispatch. DISCUSSION AND CONCLUSIONS: The temporal patterns suggest that non-fatal overdoses occur during non-recreational time periods. The longer ambulance response time and disposition for private addresses indicate potential opportunities for peer interventions. Our analysis describes circumstances surrounding non-fatal overdoses and can be useful in guiding relevant, targeted prevention interventions. [Madah-Amiri D, Clausen T, Myrmel L, Brattebø G, Lobmaier P. Circumstances surrounding non-fatal opioid overdoses attended by ambulance services. Drug Alcohol Rev 2017;36:288-294].

Utilizing a train-the-trainer model for multi-site naloxone distribution programs.

BACKGROUND: In order to have a substantial impact on overdose prevention, the expansion and scaling-up of overdose prevention with naloxone distribution (OPEND) programs are needed. However, limited literature exists on the best method to train the large number of trainers needed to implement such initiatives. METHODS: As part of a national overdose prevention strategy, widespread OPEND was implemented throughout multiple low-threshold facilities in Norway. Following a two-hour 'train-the trainer course' staff were able to distribute naloxone in their facility. The course was open to all staff, regardless of educational background. To measure the effectiveness of the course, a questionnaire was given to participants immediately before and after the session, assessing knowledge on overdoses and naloxone, as well as attitudes towards the training session and distributing naloxone. RESULTS: In total, 511 staff were trained during 41 trainer sessions. During a two-month survey period, 54 staff participated in a questionnaire study. Knowledge scores significantly improved in all areas following the training (p<0.001). Attitude scores improved, and the majority of staff found the training useful and intended to distribute naloxone to their clients. CONCLUSION: Large-scale naloxone distribution programs are likely to continue growing, and will require competent trainers to carry out training sessions. The train-the-trainer model appears to be effective in efficiently training a high volume of trainers, improving trainers' knowledge and intentions to distribute naloxone. Further research is needed to assess the long term effects of the training session, staffs' subsequent involvement following the trainer session, and knowledge transferred to the clients.

The Norwegian Offender Mental Health and Addiction Study - Design and Implementation of a National Survey and Prospective Cohort Study.

The Norwegian prison inmates are burdened by problems before they enter prison. Few studies have managed to assess this burden and relate it to what occurs for the inmates once they leave the prison. The Norwegian Offender Mental Health and Addiction (NorMA) study is a large-scale longitudinal cohort study that combines national survey and registry data in order to understand mental health, substance use, and criminal activity before, during, and after custody among prisoners in Norway. The main goal of the study is to describe the criminal and health-related trajectories based on both survey and registry linkage information. Data were collected from 1,499 inmates in Norwegian prison facilities during 2013-2014. Of these, 741 inmates provided a valid personal identification number and constitute a cohort that will be examined retrospectively and prospectively, along with data from nationwide Norwegian registries. This study describes the design, procedures, and implementation of the ongoing NorMA study and provides an outline of the initial data.

Injectable and implantable sustained release naltrexone in the treatment of opioid addiction.

Sustained release technologies for administering the opioid antagonist naltrexone (SRX) have the potential to assist opioid-addicted patients in their efforts to maintain abstinence from heroin and other opioid agonists. Recently, reliable SRX formulations in intramuscular or implantable polymers that release naltrexone for 1-7 months have become available for clinical use and research. This qualitative review of the literature provides an overview of the technologies currently available for SRX and their effectiveness in reducing opioid use and other relevant outcomes. The majority of studies indicate that SRX is effective in reducing heroin use, and the most frequently studied SRX formulations have acceptable adverse events profiles. Registry data indicate a protective effect of SRX on mortality and morbidity. In some studies, SRX also seems to affect other outcomes, such as concomitant substance use, vocational training attendance, needle use, and risk behaviour for blood-borne diseases such as hepatitis or human immunodeficiency virus. There is a general need for more controlled studies, in particular to compare SRX with agonist maintenance treatment, to study combinations of SRX with behavioural interventions, and to study at-risk groups such as prison inmates or opioid-addicted pregnant patients. The literature suggests that sustained release naltrexone is a feasible, safe and effective option for assisting abstinence efforts in opioid addiction.

Naltrexone depot formulations for opioid and alcohol dependence: a systematic review.

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.

Challenges to antagonist blockade during sustained-release naltrexone treatment.

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.