Too much or too little opioids to patients receiving opioid agonist therapy in Norway (2013–2017): a prospective cohort study

Background Dispensations of opioid analgesics to patients on opioid agonist therapy (OAT) may increase the risk of overdoses. The current study’s objectives are to investigate the dispensation rates and mean daily doses of dispensed opioid analgesics among patients who received OAT opioids in Norway during 2013–2017 and evaluate whether discontinuing OAT opioids affects the dispensed dose of opioid analgesics. Methods Information on opioids was collected from the Norwegian Prescription Database. Dispensation rates were calculated by dividing the number of patients who were dispensed at least one opioid analgesic by the number of patients who were dispensed an OAT opioid. We calculated the mean daily dose of opioid analgesics in oral morphine equivalents. The OAT opioid dose was defined as a ratio between the dispensed doses divided by the mean recommended dose. We used logistic regression to estimate the association between the dispensation of an opioid analgesic, a dose of OAT opioids, having chronic pain, and being on palliative care. Results A total of 10,371 patients were dispensed at least one OAT opioid during the study period. In 2017, 18% were dispensed an opioid analgesic with a mean daily dose of 29 mg of oral morphine equivalents. Being dispensed an opioid analgesic was associated with having chronic pain (adjusted odds ratio (aOR): 3.6, 95% confidence interval: 3.2–4.2), being on palliative care (aOR: 6.1, 4.7–7.9), and receiving an OAT opioid dose below half of the recommended OAT dose (aOR: 1.7, 1.4–2.0). Similar results were seen in 2013–2016. The discontinuation of OAT opioids could increase the dose of dispensed opioid analgesics. Conclusion Reducing the dispensation of opioid analgesics can be achieved by increasing the OAT opioid dose for patients on a low OAT dose, and by extending the period needed to taper off the OAT opioid dose at discontinuation

Dispensation of attention deficit hyperactivity disorder (ADHD) medications in patients receiving opioid agonist therapy; a national prospective cohort study in Norway from 2015 to 2017

Background It is estimated that up to a third of patients on opioid agonist therapy (OAT) have attention deficit hyperactivity disorder (ADHD). Treatment by ADHD medication, including a centrally acting stimulant (CAS) or atomoxetine is one of the essential approaches. This study evaluates the use of dispensed ADHD medications in the Norwegian OAT population in the period from 2015 to 2017. Types and doses of ADHD medications, co-dispensations of other potentially addictive drugs like benzodiazepines, z-hypnotics, gabapentinoids, and non-OAT opioids, as well as direct-acting antivirals (DAA) against hepatitis C infection, are investigated. Methods Information about all dispensed ADHD medication, OAT opioids, and the defined potentially addictive drugs were recorded from the Norwegian Prescription Database. Dispensation rates, the types, and the doses of dispensed ADHD medications were estimated by summarizing the number of dispensations, and the dispensed doses. Logistic regression analyses were employed to assess the associations between ADHD medication, and OAT opioid use, and dispensations of other potentially addictive drugs and DAAs against hepatitis C infection. Results A total of 9235 OAT patients were included. The proportion of patients who were dispensed ADHD medication increased from 3.5 to 4.6% throughout the study period. The three most dispensed CAS were short- and intermediate-acting methylphenidate (55%), lisdexamphetamine (24%), and dexamphetamine (17%) in 2017. Buprenorphine, rather than methadone, as OAT opioid (adjusted odds ratio: 1.6, CI: 1.2–2.1) was associated with being dispensed ADHD medication. Among patients who received CAS and OAT opioids each calendar year, the dispensed doses of methylphenidate increased from 63 mg/day in 2015 to 76 mg/day in 2017 (p = 0.01). Sixty percent of patients receiving ADHD medications were also dispensed other addictive drugs concomitantly in 2017. Similar results were found in 2015 and 2016. Conclusion Co-prescription of ADHD medications was low among patients on OAT in Norway, considering a high prevalence of ADHD in this patient group. On the other hand, concurrent dispensations of multiple addictive drugs were common in this population. Understanding the underlying reasons for such prescribing is essential, and research on how to optimize ADHD medication of patients with ADHD receiving OAT is needed

Uptake and predictors of direct-acting antiviral treatment for hepatitis C among people receiving opioid agonist therapy in Sweden and Norway: a drug utilization study from 2014 to 2017

Background Treatment with direct-acting antiviral agents (DAAs) offers an opportunity to eliminate hepatitis C virus (HCV) endemic among people who inject drugs (PWID) and people enrolled in opioid agonist therapy (OAT) programs. The objective of this study was to estimate and to compare HCV treatment uptake after the introduction of DAAs among patients receiving OAT in Sweden and Norway. We also aimed to evaluate predictors of DAAs treatment among OAT patients in both countries. Methods This observational study was conducted with data from The Swedish Prescribed Drug Register and The Norwegian Prescription Database. We studied dispensed medications to calculate HCV treatment among OAT patients from 2014 to 2017 in Sweden and Norway. HCV prevalence was estimated from primary and secondary sources. Dispensations of medicines from different therapeutic areas, which served as proxy for co-morbidities in 2017, were conditionally adjusted for age, gender, and OAT medications. Logistic regression was used to evaluate these parameters. Results In total 3529 individuals were identified with dispensed OAT in the Swedish cohort and 7739 individuals in the Norwegian cohort. HCV treatment was utilized by 407 persons in Sweden and 920 in Norway during the study period. Annual HCV and DAA treatment uptake increased in both countries. The estimated cumulative HCV treatment uptake at the end of 2017 was 31% in Norway and 28% in Sweden. DAA treatment was associated with increased age (aOR 1.8; 95% CI 1.0–3.2) and the dispensation of drugs used for diabetes (aOR 3.2; 95% CI 1.8–5.7) in Sweden. In Norway, lipid modifying agents and antibacterials were associated with decreased odds (aOR 0.4; 95%CI 0.2–0.9, aOR 0.8; 95%CI 0.6–1.0). Conclusions An increase in DAA treatment and HCV treatment uptake was observed among Swedish and Norwegian OAT patients whilst introducing new direct-acting antiviral treatment regimens. However, more than two thirds of the OAT population in Norway and Sweden were untreated at the beginning of 2018. A further scale-up is crucial in order to control and eliminate the HCV endemic among OAT patients

Impact of clinical and sociodemographic factors on fatigue among patients with substance use disorder: a cohort study from Norway for the period 2016–2020

Background The impact of clinical and sociodemographic factors on fatigue remains unknown among patients with substance use disorders (SUD). This study aims to evaluate fatigue among patients with SUD using a nine-item fatigue severity scale (FSS-9) and identify the impact that clinical and sociodemographic factors – such as injecting substance use, chronic infectious diseases, liver fibrosis, opioid agonist therapy (OAT), debt difficulties, and housing situation – have on fatigue. Methods We used data from a cohort of patients with SUD in Norway with annual health assessments surveying FSS-9 and some clinical and sociodemographic factors. A total of 915 FSS-9 measurements were collected from 654 patients during the period 2016–2020. We defined baseline as the first annual health assessment when the health assessments were listed chronologically. Time was defined as years from baseline. We used a linear mixed model to analyse whether the clinical and sociodemographic factors affected the FSS-9 sum score, presented with beta coefficients (β) with 95% confidence intervals (CI). Results The mean sum score of the FSS-9 was 43 (standard deviation: 16) at baseline. Females compared with males (adjusted mean difference of FSS-9 sum score: 4.1, 95% CI: 1.3–7.0), having debt difficulties compared with having no debt difficulties (2.9;0.4–5.3), and frequent use of benzodiazepines (5.7;3.0–8.4) or amphetamines (-5.0;-8.0– -2.0) compared to less frequent or no use of these substances changed the FSS-9 baseline sum score. The other clinical and sociodemographic factors did not predict any clinically relevant change in the FSS-9 sum score from baseline to the following health assessments. Conclusion Patients with SUD suffer from high levels of fatigue. Female patients, patients with debt difficulties, and those with extensive use of benzodiazepines are at particular risk of being fatigued. This should be taken into consideration when planning health services

Integrated treatment of hepatitis C virus infection among people who inject drugs: study protocol for a randomised controlled trial (INTRO-HCV)

Background A large proportion of people who inject drugs (PWID) living with hepatitis C virus (HCV) infection have not been treated. It is unknown whether inclusion of HCV diagnostics and treatment into integrated substance use disorder treatment and care clinics will improve uptake and outcome of HCV treatment in PWID. The aim is to assess the efficacy of integrating HCV treatment to PWID and this paper will present the protocol for an ongoing trial. Methods INTRO-HCV is a multicentre, randomised controlled clinical trial that will compare the efficacy of integrated treatment of HCV in PWID with the current standard treatment. Integrated treatment includes testing for HCV, assessing liver fibrosis with transient elastography, counselling, treatment delivery, follow-up and evaluation provided by integrated substance use disorder treatment and care clinics. Most of these clinics for PWID provide opioid agonist therapy while some clinics provide low-threshold care without opioid agonist therapy. Standard care involves referral to further diagnostics, treatment and treatment follow-up given in a hospital outpatient clinic with equivalent medications. The differences between the delivery platforms in the two trial arms involve use of a drop-in approach rather than specific appointment times, no need for additional travelling, less blood samples taken during treatment, and treatment given from already known clinicians. The trial will recruit approximately 200 HCV infected individuals in Bergen and Stavanger, Norway. The primary outcomes are time to treatment initiation and sustained virologic response, defined as undetectable HCV RNA 12 weeks after end of treatment. Secondary outcomes are cost-effectiveness, treatment adherence, changes in quality of life, fatigue and psychological well-being, changes in drug use, infection related risk behaviour, and risk of reinfection. The target group is PWID with HCV diagnosed receiving treatment and care within clinics for PWID. Discussion This study will inform on the effects of an integrated treatment program for HCV in clinics for PWID compared to standard care aiming to increase access to treatment and improving treatment adherence. If the integrated treatment model is found to be safe and efficacious, it can be considered for further scale-up. Trial registration ClinicalTrials.gov.no. NCT03155906