Benzodiazepine agonist treatment for patients with benzodiazepine dependence undergoing opioid agonist treatment: a study protocol for the randomized controlled trial BMX-BAR.

Background: There is a lack of knowledge on effective treatment methods for comorbid benzodiazepine dependence in populations undergoing opioid agonist treatment (OAT). Tapering and discontinuation of benzodiazepines has long been considered the standard treatment, even though there is limited evidence for this practice. There is also limited research on benzodiazepine agonist treatment; however, peer and clinical experiences indicate that such approaches may be beneficial for a subgroup of the patients with long-lasting benzodiazepine dependence not responding to other treatment approaches.

Methadone metabolism and cytochrome P450 polymorphisms: a systematic review and meta-analysis.

Introduction: Confusion regarding methadone metabolism exists, hampering optimal clinical use. A systematic review was conducted to assess the impacts of cytochrome P450 (CYP) genetic polymorphisms on methadone outcomes.

Methods: MEDLINE, EMBASE, Web of Science, PsycINFO, and CENTRAL were searched to identify studies reporting methadone dose-adjusted plasma concentrations, clearance, maintenance dose, or treatment response in relation to polymorphisms in humans.

Universal Health Coverage of Opioid Agonist Treatment in Norway: An Equity-Adjusted Economic Evaluation.

Background: Detailed information on the efficiency of health services targeting opioid use disorder (OUD) and treatment with opioid agonist treatment (OAT) is sparse. Many countries, including Norway, are still falling short of universal health coverage (UHC) of OAT. This study aims to evaluate the incremental lifetime costs and effects of treating OUD with OAT as compared to no OAT in Norway and scaling up the treatment to a universal coverage level using equity-adjusted health economic evaluations.

Effect of integrated hepatitis C virus treatment on psychological distress in people with substance use disorders.

People with substance use disorders (SUD) have a high prevalence of chronic hepatitis C virus (HCV) infection and mental health disorders. We aimed to assess the impact of integrated HCV treatment on psychological distress measured by Hopkins-symptom-checklist-10 (SCL-10). This multi-center randomized controlled trial evaluated psychological distress as a secondary outcome of integrated HCV treatment (INTRO-HCV trial).

Methadone pharmacokinetics in opioid agonist treatment: Influencing factors and clinical implications.

Background: A considerable inter-individual variability has been reported in the relationship between methadone doses applied and serum concentrations achieved in methadone maintenance treatment. However, the underlying causes for this variability are not fully understood.

Objectives: We investigated the influence of genetic, pathophysiological and pharmacological factors on serum methadone concentration-to-dose ratio (CDR) and discussed the clinical implications of the findings.

Attention-deficit/hyperactivity disorder (ADHD) symptoms and their relation to diagnosed ADHD, sociodemographic characteristics, and substance use among patients receiving opioid agonist therapy: a Norwegian cohort study.

Background: Attention-deficit/hyperactivity disorder (ADHD) symptoms may challenge sufficient treatment of substance use and mental disorders. The literature on the extent of such symptoms among patients receiving opioid agonist therapy (OAT) is scarce. This study examined ADHD symptoms using the ADHD self-report scale (ASRS) and the association between the 'ASRS-memory' and 'ASRS-attention' scores and substance use and sociodemographic characteristics among patients receiving OAT.

The efficacy of integrated hepatitis C virus treatment in relieving fatigue in people who inject drugs: a randomized controlled trial.

Background: Most people who inject drugs (PWIDs) suffer from severe fatigue, and chronic hepatitis C virus (HCV) infection may play a role in this. However, there is scarce evidence about interventions that alleviate fatigue among PWIDs. The present study investigated the effect of integrated HCV treatment on fatigue in this population compared to the effect of standard HCV treatment, adjusted for sustained virological response of the HCV treatment.

Harm reduction and abstinence-based models for treatment of substance use disorders during the COVID-19 pandemic: a global perspective.

The COVID-19 pandemic has significantly affected treatment services for people with substance use disorders (SUDs). Based on the perspectives of service providers from eight countries, we discuss the impact of the pandemic on SUD treatment services. Although many countries quickly adapted in provision of harm reduction services by changes in policy and service delivery, some went into a forced abstinence-based strategy.

Impact of liver fibrosis and clinical characteristics on dose-adjusted serum methadone concentrations.

Background: There is limited knowledge on the causes of large variations in serum methadone concentrations and dose requirements.

Objectives: We investigated the impact of the degree of liver fibrosis on dose-adjusted steady-state serum methadone concentrations.

Methods: We assessed the clinical and laboratory data of 155 Norwegian patients with opioid use disorder undergoing methadone maintenance treatment in outpatient clinics in the period 2016-2020.

Effectiveness and Safety of Low-Threshold Opioid-Agonist Treatment in Hard-To-Reach Populations with Opioid Dependence.

Objectives: Opioid-use disorder is related to premature death worldwide. Opioid-agonist treatment (OAT) is an effective treatment for opioid dependence. OAT delivery platforms may influence treatment access and outcomes, especially for the most vulnerable groups.

Changes in substance use during outpatient treatment for substance use disorders: a prospective Norwegian cohort study from 2016 to 2020.

Background: Continuous use of amphetamines, alcohol, benzodiazepines, cannabis, cocaine, or opioids contributes to health impairments, increased morbidity, and overdose deaths among patients with substance use disorders (SUDs). This study evaluates the impact of inpatient detoxification, injecting substance use, age, and gender on substance use over time among patients undergoing outpatient SUD treatment.

Methods: We used data from a cohort of SUD patients in Norway obtained from health assessments of self-reported substance use and sociodemographic and clinical factors.

Integrated treatment of hepatitis C virus infection among people who inject drugs: A multicenter randomized controlled trial (INTRO-HCV).

Background: The standard pathways of testing and treatment for hepatitis C virus (HCV) infection in tertiary healthcare are not easily accessed by people who inject drugs (PWID). The aim of this study was to evaluate the efficacy of integrated treatment of chronic HCV infection among PWID.

Methods And Findings: INTRO-HCV is a multicenter, randomized controlled clinical trial.

Subjective symptoms and serum methadone concentrations: what should guide dose adjustments in methadone maintenance treatment? A naturalistic cohort study from Norway.

Background: There is little evidence-based guidance on how to optimize methadone dosages among patients with opioid addiction undergoing methadone maintenance treatment (MMT). This study aims to investigate whether self-perceived opioid withdrawal symptoms, adverse effects, and self-reported substance use in patients on MMT are related to serum methadone concentrations and the role that these variables could play in clinical decisions on dose adjustments.

Methods: This naturalistic prospective cohort study included clinical and laboratory measurements from 83 patients undergoing MMT in outpatient clinics in Bergen, Norway, from May 2017 to January 2020.

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.

On the path towards universal coverage of hepatitis C treatment among people receiving opioid agonist therapy (OAT) in Norway: a prospective cohort study from 2013 to 2017.

Objectives: We aimed to calculate cumulative hepatitis C virus (HCV) treatment coverage among individuals enrolled in opioid agonist therapy (OAT) in Norway between 2013 and 2017 and to document the treatment transition to direct-acting antiviral (DAA) agents. Moreover, we aimed to describe adherence to DAAs in the same cohort.

Design: Prospective cohort, registry data.

Potentially addictive drugs dispensing to patients receiving opioid agonist therapy: a register-based prospective cohort study in Norway and Sweden from 2015 to 2017.

Objectives: To compare the use of benzodiazepines, z-hypnotics, gabapentinoids, opioids and centrally acting stimulants (CAS) among patients who had received opioid agonist therapy (OAT) in Norway and Sweden during the period 2015 - 2017.

Design: A register-based prospective cohort study using information about dispensed drugs from the Norwegian Prescription Database and Swedish Prescribed Drug Register.

Setting: Patients who were dispensed OAT opioids from pharmacies.

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.

Living a normal life? Follow-up study of women who had been in opioid maintenance treatment during pregnancy.

Background: There are few longitudinal follow-up studies of patients in opioid maintenance treatment (OMT). For this reason we performed a follow-up study of a cohort of 67 women who had used OMT-medications during pregnancy an average of ten years earlier. The aim of our study was to explore how the women were doing over time regarding OMT medication adherence and use of other legal and illegal substances, as well as to evaluate the mortality for the women and custody situation for the children in the cohort.

Dispensations of benzodiazepines, z-hypnotics, and gabapentinoids to patients receiving opioid agonist therapy; a prospective cohort study in Norway from 2013 to 2017.

Background: Dispensations of benzodiazepines, z-hypnotics, and gabapentinoids to patients on opioid agonist therapy (OAT) are common and have pros and cons. The objectives of the current study are to define the dispensation rates of these potentially addictive drugs, and whether the number and the mean daily doses of dispensed OAT opioids and discontinuing OAT, are associated with being dispensed benzodiazepines, z-hypnotics and gabapentinoids among patients on OAT in Norway in the period 2013 to 2017.

Methods: Information about all dispensed opioids, benzodiazepines, z-hypnotics and gabapentinoids were recorded from the Norwegian Prescription Database (NorPD).

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.

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.

Methadone serum concentrations and influencing factors: A naturalistic observational study.

Rationale: Although methadone maintenance treatment (MMT) has long been used for opioid addiction, our knowledge on its pharmacokinetics is still limited.

Objectives: We aimed to investigate effects of age, gender, and various co-medications on methadone serum concentration-to-dose ratio (CDR) in a naturalistic setting.

Methods: In total, 4425 routine serum methadone concentrations obtained from 1691 MMT patients in the period October 1999 to July 2017 were included.

Integrated care of severe infectious diseases to people with substance use disorders; a systematic review.

Background: Various integrated care models have been used to improve treatment completion of medications for chronic hepatitis B virus (HBV), chronic hepatitis C virus (HCV), Mycobacterium tuberculosis (TB), and Human immunodeficiency virus (HIV) among people with substance use disorders (SUD). We have conducted a systematic review to evaluate whether integrated models have impacts of the treatment of infectious diseases among marginalized people with SUD.

Methods: We searched MEDLINE/PubMed (1946 to 2018, on July 26, 2018) and Embase (from 1974 to 2018, on July 26, 2018) for randomized controlled trials (RCTs) and cohort studies evaluating diverse integrated models' effects on sustained virological response (SVR), HIV suppression, HBV curation or suppression, completion of TB treatment regimen among people with SUD.

Combined Effect of CYP2B6 Genotype and Other Candidate Genes on a Steady-State Serum Concentration of Methadone in Opioid Maintenance Treatment.

Background: A considerable interindividual variability in methadone pharmacokinetics is seen in patients on methadone maintenance treatment. The aim of this study was to clarify the impact of the reduced function CYP2B6*6 variant allele together with variants in other candidate genes on a steady-state methadone concentration in a naturalistic setting.

Methods: Information of methadone serum concentration, dose, age, sex, and CYP2C9, CYP2C19, and CYP2D6 genotypes were collected from a routine therapeutic drug monitoring database, whereas variant alleles in CYP2B6 and CYP3A5 were retrospectively genotyped.