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BAKGRUNN Vedvarende bruk av opioider kan ha uheldige konsekvenser. Vi har undersøkt vedvarende opioidbruk i pasientgruppersom fikk forskrevet opioider på ulike indikasjoner(langvarig smerte, palliativ behandling, andre (hvitresept)),samt gruppenessamtidige bruk av enkelte andre vanedannende legemidler. MATERIALE OG METODE Personer med minst én utlevering av et opioid i Reseptregisteret i perioden 2011–19 ble inkludert. Vedvarende bruk i et kalenderår ble definertsom uthenting av > 180 definerte døgndoser eller > 4 500 mg orale morfinekvivalenterfordelt på minst tre kvartaler. RESULTATER Antall vedvarende opioidbrukere var 50 422 i 2011 og 59 996 i 2019 (10,1 % og 10,7 % av alle opioidbrukere). I perioden økte antalletsom fikk opioider på blå resept forlangvarige smerter, med 9 952 personer, men flertallet (n = 38 006, 63,3 %) fikk fortsa utlevert opioider utelukkende på hvitresept i 2019. Henholdsvis15 623 (41,1 %) og 14 881 (39,2 %) av de vedvarende opioidbrukerne som fikk utlevert opioider kun på hvitresept i 2019, fikk også utlevert benzodiazepiner og z-hypnotika samme år. Av de 23 967 vedvarende brukerne som også fikk utlevert benzodiazepiner, fikk 88 % utlevert opioider og benzodiazepiner på samme dag minst én gang i løpet av 2019. FORTOLKNING Vedvarende forskrivning av opioider på hvitresept og samtidig forskrivning av andre vanedannende legemidler kan tyde på uheldig bruk uten klarindikasjon.

INTRODUCTION: Opioid maintenance treatment (OMT) varies across settings and between countries. We plan to use data from several nationwide health and population registers to further improve the knowledge base established from earlier studies. Our aim is to study OMT adherence trajectories and to identify factors associated with improved outcomes for OMT patients across the Czech Republic, Norway and Denmark, in order to further improve OMT and our understanding of the key elements of treatment success.METHODS AND ANALYSIS: The registry-based cohort approach across the three countries allows us to link data from a range of registers on the individual level, by using personal identifiers in nationwide cohorts of OMT and non-OMT patients and the general non-using populations. A total of ~21 500 OMT patients over the last two decades in all three countries will be included in the study. The following outcome variables (based on the International Classification of Diseases, 10th Revision codes) will be obtained from relevant registers: treatment adherence to OMT, comorbidity (somatic and mental health), and all-cause and cause-specific mortality. Outcomes of the country-specific analyses will be pooled.ETHICS AND DISSEMINATION: The national OMT cohorts have been approved by the ethics committees in the respective countries. Data will be stored according to national and local guidelines and treated confidentially, and all data will be analysed separately for each country and compared across countries. Findings will be disseminated in peer-reviewed scientific journals, national and international conferences, and in briefings to inform clinical decision-making.

Additional file 2. Pen’s Parade: SCL-10 = Symptoms checklist 10; ten items scale for measuring mental health status/psychological distress. The figure shows distribution in SCL-10 mean values at baseline (n = 707) by fixed black line. The dotted lines represent the mean reported SCL-10 score of the Norwegian reference population (1.36) and standard reference of 1.85 indicating one or more mental disorders above this cut-off, respectively. Source: Strand BH, Dalgard OS, Tambs K, Rognerud M: Measuring the mental health status of the Norwegian population: a comparison of the instruments SCL-25, SCL-10, SCL-5 and MHI-5 (SF-36). Nordic journal of psychiatry 2003.

Additional File 1. Supplementary tables and figures

Additional file 3. STROBE Statement. Checklist of items that should be included in reports of cohort studies

Additional file 1. STROBE Statement. Checklist of items that should be included in reports of cohort studies.

Additional file 1. STROBE Statement. Checklist of items included in reports of cohort studies.

Additional file 5. Mean (SD) item scores for single items on the FSS-9 at baseline and follow-up. Legend: FSS-9: Nine-item Fatigue Severity Scale; I: Item; OAT: Opioid agonist therapy; SD: Standard Deviation. Follow-up: The FSS-9 score on the last health assessment during the study period among patients with two or more annual health assessments. Mean (SD) item scores for single items on the FSS-9 for patients using methadone or buprenorphine as OAT opioid.

Additional file 3. Aspartate aminotransferase to platelet ratio index (APRI). Description: APRI: Aspartate aminotransferase to platelet ratio index. The figure displays the APRI score equation. The AST upper limit of normal range was defined as 45 IU/L (male) and 35 IU/L (female).

Additional file 4. Potential correlations between sociodemographic and clinical factors and fatigue. The figure shows that potential sociodemographic and clinical comorbidities may affect fatigue among patients with substance use disorders.

Background Opioid dependence carries the highest disease burden of all illicit drugs. Opioid agonist therapy (OAT) is an evidence-based medical intervention that reduces morbidity and mortality. There is limited knowledge on the health-related quality of life (HRQoL) of long-term patients in OAT. This study measures HRQoL and self-perceived health of long-term patients on OAT, compares the scores to a Norwegian reference population, and assesses changes in these scores at 1-year follow up. Methods We conducted a nested prospective cohort study among nine OAT outpatient clinics in Norway. 609 OAT patients were included, 245 (40%) followed-up one year later. Data on patient characteristics, HRQoL, and self-perceived health was collected. HRQoL was assessed with the EQ-5D-5L, which measures five dimensions (mobility, self-care, usual activities, pain/discomfort and anxiety/depression) on a five-point Likert scale (from “no problems” to “extreme problems”). An UK value set was applied to calculate index values (from 0 to 1) for the EQ-5D-5L and compare them to a Norwegian reference population. Self-perceived health was measured with EQ-VAS (from 0 to 100). Results Mean (standard deviation (SD)) EQ-5D-5L index value at baseline was 0.699 (0.250) and EQ-VAS 57 (22) compared to 0.848 (0.200) and 80(19) for the Norwegian reference population. There were large variations in EQ-5D-5L index values, where 43% had > 0.8 and 5% had

Additional file 6. Linear mixed model of fatigue (FSS-9) adjusted for sociodemographic and clinical factors among patients receiving methadone as an OAT opioid at baseline (N = 209). Legends: APRI: Aspartate transaminase to platelet ratio index; CI: Confidence interval; CRP: C-reactive protein; FSS-9: Nine-item Fatigue Severity Scale; eGFR: estimated glomerular filtration rate; HIV: Human Immunodeficiency virus; kPa: Kilopascal; OAT: Opioid Agonist Therapy. 1) Age per 10 years was centred according to mean age (43 years) in the study sample at baseline. 2) Includes amphetamine or cocaine use. The OAT opioid ratio: a ratio between the received dose of OAT opioids per day divided by the expected mean dose of OAT opioids (buprenorphine 18 mg, buprenorphine-naloxone 18/4.5 mg or methadone 90 mg). The educational level: highest level of education was coded 0–4 with 4 as the highest educational level. Unstable housing situation: living on the street, homeless shelter, or with family and friends at any time in the past 30 days prior to the health assessment. Debt difficulties: struggling with repaying current illegal and legal debt. Injecting substance use: Having injected a substance in the past 12 months prior to the health assessment. Frequent use of substances: at least weekly during the past 12 months prior to the health assessment. Viral load of HCV: From − 0.5 to 0.5, where the range ≥ − 0.5 to 0 identifies the high viral load (HCV PCR ≥ 800,000 IE/ml). Zero (0) defined patients without HCV infection. When using the Bonferroni corrected p-values (αaltered = 0.05 / 43 = 0.0012), the predictors did not affect the FSS-9 sum score significantly. The table displays a linear mixed model analysis (Restricted Maximum Likelihood regression) evaluating sociodemographic and clinical factors’ (predictors) changes in the FSS-9 sum score at baseline and their influence on changes in the FSS-9 sum score (time trend) per year from baseline among patients receiving methadone as an OAT opioid. The predictors’ effect estimates and time trends estimate adjusted mean differences in the FSS-9 sum score.

Additional file 4. Equations to calculate diazepam equivalents. Legends: Equations used to calculate lowest, mean, and highest equipotency dose of included benzodiazepines and z-hypnotics.

Additional file 2. The US-English and the Norwegian versions of FSS-9. Description: Legends: FSS-9; Nine-item Fatigue Severity Scale. All items in the FSS-9 are ranged as a Likert scale from 1 to 7, where 1 indicates “strongly disagree” and 7 “strongly agree”.

Additional file 3. Opioid agonist therapy and hepatitis C treatment in Norway and Sweden

Purpose A pervasive problem in registry-based pharmacoepidemiological studies is what exposure duration to assign to individual prescriptions. The parametric waiting time distribution (WTD) has been proposed as a method to estimate such durations. However, when prescription durations vary due to seasonal stockpiling, WTD estimates will vary with choice of index date. To counter this, we propose using random index dates. Methods Within a calendar period of a given length, δ, we randomly sample individual index dates. We include the last prescription redemption prior to the index date in the analysis. Only redemptions within distance δ of the index date are included. In a simulation study with varying types and degrees of stockpiling at the end of the year, we investigated bias and precision of the reverse WTD with fixed and random index dates, respectively. In addition, we applied the new method to estimate durations of Norwegian warfarin prescriptions in 2014. Results In simulation settings with stockpiling, the reverse WTD with random index dates had low relative biases (−0.65% to 6.64%) and high coverage probabilities (92.0% to 95.3%), although when stockpiling was pronounced, coverage probabilities decreased (2.7% to 85.8%). Using a fixed index date was inferior. The estimated duration of warfarin prescriptions in Norway using random index dates was 131 (130; 132) days. Conclusions In the presence of seasonal stockpiling, the WTD with random index dates provides estimates of prescription durations, which are more stable, less biased and with better coverage when compared to using a fixed index date. Preprint

Additional file 1. The number of months from baseline to the second or third health assessment. No.: Number of patients; SD: Standard deviation; ref.: Reference. The table displays the number of patients with one, two, and three health assessments, including a nine-item Fatigue Severity Scale score. The table displays the time between baseline and the second and third health assessments.

Additional file 7. Linear mixed model of fatigue (FSS-9) adjusted for sociodemographic and clinical factors among patients receiving buprenorphine as an OAT opioid at baseline (N = 321). Legends: APRI: Aspartate transaminase to platelet ratio index; CI: Confidence interval; CRP: C-reactive protein; FSS-9: Nine-item Fatigue Severity Scale; eGFR: estimated glomerular filtration rate; HIV: Human Immunodeficiency virus; kPa: Kilopascal; OAT: Opioid Agonist Therapy. 1) Age per 10 years was centred according to mean age (43 years) in the study sample at baseline. 2) Includes amphetamine or cocaine use. The OAT opioid ratio: a ratio between the received dose of OAT opioids per day divided by the expected mean dose of OAT opioids (buprenorphine 18 mg, buprenorphine-naloxone 18/4.5 mg or methadone 90 mg). The educational level: highest level of education was coded 0–4 with 4 as the highest educational level. Unstable housing situation: living on the street, homeless shelter, or with family and friends at any time during the past 30 days prior to the health assessment. Debt difficulties: struggling with repaying current illegal and legal debt. Injecting substance use: Having injected a substance during the past 12 months prior to the health assessment. Frequent use of substances: at least weekly during the past 12 months prior to the health assessment. Viral load of HCV: From − 0.5 to 0.5, where the range ≥ − 0.5 to 0 identifies the high viral load (HCV PCR ≥ 800,000 IE/ml). Zero (0) defined patients without HCV infection. When using the Bonferroni corrected p-values (αaltered = 0.05 / 43 = 0.0012), the predictors did not affect the FSS-9 sum score significantly. The table displays a linear mixed model analysis (Restricted Maximum Likelihood regression) evaluating sociodemographic and clinical factors’ (predictors) changes in the FSS-9 sum score at baseline and their influence on changes in the FSS-9 sum score (time trend) per year from baseline among patients receiving buprenorphine as an OAT opioid. The predictors’ effect estimates and time trends estimate adjusted mean differences in the FSS-9 sum score.

Additional file 1. Methodology description: estimating chronic hepatitis C (HCV) prevalence among people on opioid agonist therapy (OAT) in Norway and Sweden

Background: The use of antiseizure medications (ASMs) in the pediatric population is poorly studied. The purpose of this study was to investigate changes in the use of ASMs in children and adolescents compared to adults, and to elucidate safety considerations of certain drugs. Method: In this population-based pharmacoepidemiological study we used the Norwegian Prescription Database (NorPD), 2009–2018. The use of ASMs is presented as 1-year prevalence per 1000: number of ASM users in a year * 1000 / number of inhabitants that year. Variables included predetermined 5-year age groups, gender, ASMs, diagnosis-specific reimbursement codes, user, and population numbers. Selected ASMs used for specific indications or subgroups included ethosuximide, sulthiame, rufinamide, stiripentol, and clobazam. Gender differences in the use of valproate was examined due to safety considerations in girls/women. Results: The total number of ASM users (all indications) for the age groups 0–19 and 20–59 years was 5807 and 47,481 respectively in 2009, and 5906 and 61,447 respectively in 2018. The 1-year prevalence for children/ adolescents (0–19 years) using ASMs in epilepsy remained stable from 2008 to 2018, 4.3–4.2/1000 inhabitants, as compared to 8.2–7.6/1000 in adults (20–59 years). Valproate, lamotrigine, and levetiracetam were the three most used ASMs in epilepsy in children/adolescents, similar to adults. The selected ASMs were mainly used in children/ adolescents, accounting for 0.74/1000 in 2018 versus 0.17/1000 in adults. A significant increase was seen for sulthiame (8-fold), ethosuximide (4-fold), clobazam (3-fold), and stiripentol (2-fold). The use of ASMs in non-epilepsy indications was limited and stable (17% in 2018); mainly lamotrigine in psychiatry in adolescents (15–19 years). This finding was in contrast to extensive non-epilepsy use in adults (71% in 2018). Conclusion: Changes in the use of ASMs in children/adolescents differ as compared to adults, most notably extensive and increasing use of selected ASMs and limited non-epilepsy. This is an important part of pharmacovigilance and patient safety evaluations.

Table S1 QOL10 item responses among 531 patients entering substance use disorder treatment, N(%) (DOCX 14 kb)

Table S2 QOL10 item-total correlations (DOCX 14 kb)

Background and Aims Our understanding of the long‐term safety of prenatal exposure to opioid maintenance treatment (OMT) is insufficient. We compared childhood morbidity (0–3 years) between OMT‐exposed and relevant comparison groups. Design Nation‐wide, registry‐based cohort study. Registries on reproductive health, addiction treatment, hospitalization and death were linked using identification numbers. Setting The Czech Republic (2000–14). Participants Children with different prenatal exposure: (i) mother in OMT during pregnancy (OMT; n = 218), (ii) mother discontinued OMT before pregnancy (OMT‐D; n = 55), (iii) mother with opioid use disorder, but not in OMT during pregnancy (OUD; n = 85) and (iv) mother in the general population (GP) (n = 1 238 452) Measurements Episodes of hospitalization were observed as outcomes. Information on in‐patient contacts, length of stay and diagnoses (International Classification of Diseases version 10) were assessed. Binary logistic regressions were conducted to estimate the associations between OMT exposure and the outcomes, crude and adjusted for the socio‐economic status and smoking. Findings No significant differences were found in the overall proportion of hospitalization among OMT‐exposed children, children of OMT‐D and children of women with OUD [54.1%, 95% confidence interval (CI) = 47.3–60.1%; 47.3%, 95% CI = 33.9–61.1%; 51.8%, 95% CI = 40.7%–62.6%], while the proportion was significantly lower (35.8%, 95% CI = 35.7–35.8%) in the GP. There were no significant differences in risk of specific diagnoses between OMT‐exposed children, children of OMT‐D and children of women with OUD. In the adjusted analyses, differences between OMT‐exposed and children in the GP were still present for infections and parasitic diseases (OR = 2.0, 95% CI = 1.4–2.7), diseases of the digestive system (OR = 1.7, 95% CI = 1.2–2.6) and diseases of the skin and subcutaneous tissue (OR = 1.9, 95% CI = 1.2–3.2). Conclusion This study did not find clear evidence for an increase in risk of morbidity during the first 3 years of life in children with prenatal opioid maintenance treatment exposure compared with children of women who discontinued such treatment before pregnancy or suffered from opioid use disorder without this treatment. Compared the general population, there appears to be an increased risk of hospitalizations for infectious, gastrointestinal and skin diseases.

Background and Aims Opioid maintenance treatment (OMT) is recommended to opioid‐dependent females during pregnancy. However, it is not clear which medication should be preferred. We aimed to compare neonatal outcomes after prenatal exposure to methadone (M) and buprenorphine (B) in two European countries. Design Nation‐wide register‐based cohort study using personalized IDs assigned to all citizens for data linkage. Setting The Czech Republic (2000–14) and Norway (2004–13). [Correction added after online publication on 26 April 2018: The Czech Republic (2000–04) corrected to (2000–14).] Participants Opioid‐dependent pregnant Czech (n = 333) and Norwegian (n = 235) women in OMT who received either B or M during pregnancy and their newborns. Measurements We linked data from health registries to identify the neonatal outcomes: gestational age, preterm birth, birth weight, length and head circumference, small for gestational age, miscarriages and stillbirth, neonatal abstinence syndrome (NAS) and Apgar score. We performed multivariate linear regression and binary logistic regression to explore the associations between M and B exposure and outcomes. Regression coefficient (β) and odds ratio (OR) were computed. Findings Most neonatal outcomes were more favourable after exposure to B compared with M, but none of the differences was statistically significant. For instance, in the multivariate analysis, birth weight was β = 111.6 g [95% confidence interval (CI) = −10.5 to 233.6 and β = 83.1 g, 95% CI = −100.8 to 267.0] higher after B exposure in the Czech Republic and Norway, respectively. Adjusted OR of NAS for B compared with M was 0.94 (95% CI = 0.46–1.92) in the Norwegian cohort. Conclusions Two national cohorts of women receiving opioid maintenance treatment during pregnancy showed small but not statistically significant differences in neonatal outcomes in favour of buprenorphine compared with methadone. publishedVersion

ORs and 95 % CIs for the association between nighttime road traffic noise (Lnight) and sleep medication use by 5 dB increase in noise level. (DOCX 24 kb)

Simplified directed acyclic graph for the association between road traffic noise and sleep medication use. Some variables have been grouped for legibility. a Includes the variables age, sex, and having children â ¤ 5 years b Includes the variables education and household income c Includes the variables smoking status, alcohol use, caffeine use, physical activity, and night shift work. (DOCX 64 kb)

Purpose An increasing consumption of opioids in the general population has been reported in several countries also among pregnant women. Limited information is available regarding the effect of prenatal exposure to analgesic opioids on long-term neurocognitive function in children. The primary aim of the study was to determine the association between prenatal exposure to analgesic opioids and language competence and communication skills at 3 years of age. Methods The Norwegian Mother and Child Cohort Study (MoBa) prospectively included pregnant women during the period from 1999 to 2008. Participants reported medication use at pregnancy weeks 17–18 and 30, and 6 months after birth. Children's language competence and communication skills were reported by mothers on validated scales. Results A total of 45 211 women with 51 679 singleton pregnancies were included. The use of analgesic opioids was reported in 892 pregnancies (1.7%). In adjusted analyses, no association between opioid use and reduced language competence or communication skills was found, OR = 1.04 (95%CI: 0.89–1.22) and OR = 1.10 (95%CI: 0.95–1.27), respectively. Both pain and use of paracetamol were associated with a small reduction in communication skills. No such association was found for language competence. Conclusion The use of analgesic opioids in pregnant women does not seem to affect language development or communication skills in children at 3 years of age. Copyright © 2017 John Wiley & Sons, Ltd. This is the peer reviewed version of the following article: Skovlund, E., Handal, M., Selmer, R., Brandlistuen, R. E., and Skurtveit, S. (2017) Language competence and communication skills in 3-year-old children after prenatal exposure to analgesic opioids. Pharmacoepidemiol Drug Saf, 26: 625–634., which has been published in final form at http://onlinelibrary.wiley.com/doi/10.1002/pds.4170/abstract . This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving. Locked until 07 february 2018 due to copyright restrictions

Introduction and Aims: Crime rates are high in substance‐using populations; therefore, investigation of factors associated with crime in these populations is highly relevant. We describe crime prevalence and associations between crime, pattern of substance use and psychosocial factors, such as self‐control and social network. Design and Methods: This is a cross‐sectional study including substance users (n = 549; mean age 34 years; 27% women) entering treatment at 21 treatment centres across Norway (December 2012 to April 2015). Data on demographics, substance use, psychosocial variables and crime in the 6 months prior to treatment were obtained through interviews. Adjusted odds ratios (aOR) with 95% confidence intervals (CI) were estimated through logistic regression. Results: Sixty‐four percent of participants had committed crime in the 6 months prior to treatment. Of these, 93% committed income‐generating crime. Several factors were associated with increased likelihood of having committed crime: use of stimulants (aOR = 1.82, 95% CI 1.04–3.17), use of a higher number of different substances (aOR = 1.16, 95% CI 1.04–1.31) and spending most of their time with family or friends using addictive substances (aOR = 2.38, 95% CI 1.10–5.16 and aOR = 2.22, 95% CI 1.32–3.73). Protective factors associated with decreased likelihood of committing crime were being older (aOR = 0.95, 95% CI 0.92–0.97) and having higher self‐control (aOR = 0.94, 95% CI 0.91–0.97). Discussion and Conclusions: Stimulant use, higher number of different substances used, lower self‐control, primarily a substance‐using social network and being younger were associated with crime in this substance‐using population. Treatment clinics should consider these risk factors for crime, and suitable interventions should be implemented and evaluated. This research has been published in Drug and Alcohol Review. © 2016 Wiley

Background: There are concerns about potential increasing use of over-the-counter (OTC) analgesics. The aims of this study were to examine 1) the prevalence of self-reported use of OTC analgesics; 2) the prevalence of combining prescription analgesics drugs with OTC analgesics and 3) whether lifestyle factors such as physical activity were associated with prevalence of daily OTC analgesic use. Methods: Questionnaire data from the Nord–Trøndelag health study (HUNT3, 2006–08), which includes data from 40,000 adult respondents. The questionnaire included questions on use of OTC analgesics, socioeconomic conditions, health related behaviour, symptoms and diseases. Data were linked to individual data from the Norwegian Prescription Database. A logistic regression was used to investigate the association between different factors and daily use of paracetamol and/or non-steroid anti-inflammatory drugs (NSAIDs) in patients with and without chronic pain. Results: The prevalence of using OTC analgesics at least once per week in the last month was 47%. Prevalence of paracetamol use was almost 40%, compared to 19% and 8% for NSAIDs and acetylsalicylic acid (ASA), respectively. While the use of NSAIDs decreased and the use of ASA increased with age, paracetamol consumption was unaffected by age. Overall more women used OTC analgesics. About 3-5% of subjects using OTC analgesics appeared to combine these with the same analgesic on prescription. Among subjects reporting chronic pain the prevalence of OTC analgesic use was almost twice as high as among subjects without chronic pain. Subjects with little physical activity had 1.5-4 times greater risk of daily use of OTC compared to physically active subjects. Conclusions: Use of OTC analgesics is prevalent, related to chronic pain, female gender and physical inactivity. © 2015 Dale et al.; licensee BioMed Central. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

Background: The tapering of methadone or buprenorphine during pregnancy is an understudied and controversial issue. The aim of this study was to determine to what extent women tapered their opioid medication dose during pregnancy and what the neonatal outcomes were for those who tapered compared to the women who did not. Methods: The study was a mixed prospective/retrospective national cohort study of 123 Norwegian women in opioid maintenance treatment (OMT) during pregnancy and their neonates. A standardized questionnaire was administered to the women and medical information that could be used for verification was collected from hospitals and municipalities. Results: Two of the women came off the OMT-medication during pregnancy and another 15% tapered their OMT-medication dose more than 50%. The birth weights of methadone-exposed neonates of the women who tapered more than 50% were significantly higher than for the methadone-exposed neonates of the women tapering between 11 and 50%. No other significant differences were found. Conclusion: Pregnant women in OMT who taper their OMT-medication dose should be monitored closely. We need studies that document the maternal well-being and fetal safety of maternal tapering of the OMT-medication during pregnancy. This is the peer-reviewed but unedited manuscript version of the following article: Tapering from Methadone or Buprenorphine during Pregnancy: Maternal and Neonatal Outcomes in Norway 1996-2009. Welle-Strand GK, Skurtveit S, Tanum L, Waal H, Bakstad B, Bjarkø L, Ravndal E. Eur Addict Res. 2015;21(5):253-61. The final, published version is available at http://www.karger.com/?doi=10.1159/000381670

Dette er forfatters versjon av artikkelen. Forlagets publiserte versjon finnes på http://link.springer.com Repeated use of prescribed opioids may lead to serious side effects, and it is important to examine risk factors for repeated use. The aim of this study was to investigate the association between maternal use of prescribed opioids and the use of prescribed opioids by their offspring. Data were drawn from two nationwide registers linked by the unique person identity numbers: the Norwegian Population and Housing Census in 2001 and the Norwegian Prescription Database (2004-2009). The study population consisted of 97,574 adolescents aged 15-16 years in 2001 and their mothers. Repeated use of opioids was defined as filling 4+ and 15+ prescriptions during 2004-2009 by the offspring and mothers, respectively. Non-steroidal anti-inflammatory drugs (NSAIDs) are not potentially addictive, and were used as a reference analgesic drug group. The proportion of repeated users were higher among individuals whose mothers were registered with repeated use of opioids (8.4 %) compared to those with mothers without repeated use (2.4 %). Odds ratio was 3.1 (95% CI 2.7-3.6) when adjusted for mothers socioeconomic characteristics and the gender of the offspring. Low maternal socio-economic status increased the risk of repeated opioid use among their offspring. Maternal repeated use of NSAIDs increased the likelihood of repeated use of NSAIDs among offspring OR 1.8 (95% CI 1.7 – 2.0).

This is the accepted manuscript version of the article. Published version is available at Pharmacoepidemiology & Drug Safety This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self Archiving. Purpose: To examine occurrence of chronic diseases and antimicrobial treatment in an asthma population 8-29 years old, compared to the general population. Methods: In this cross-sectional study, the asthma population was identified from the general population (retrieved from a census covering the entire Norwegian population) by using filled prescriptions on asthma drugs as a proxy measure of current asthma. The outcome was excess occurrence of specific diseases (comorbidity) among asthmatics, compared to the age-specific general population. Diseases were defined by filled prescriptions with specific diagnostic codes with asthma, compared with the age-specific general population. Diseases were defined by filled prescriptions with specific diagnostic codes (International Classification of Primary Care 2nd edition [ICPC-2] or International Classification of Diseases 10th revision [ICD-10]) during a 1-year period in the Norwegian Prescription Database. Nine chronic diseases were examined: ADHD, epilepsy, migraine, mental illness, cardiovascular disease, diabetes, autoimmune disorders, gastro-oesophageal reflux disease (GORD), allergy. Additionally, antibacterials recommended for respiratory tract infections and antivirals were examined (defined by ATC codes). Standardized Morbidity Ratios (SMR) for each disease was calculated. Results: 59% of the population had at least one of nine chronic diseases examined, compared to 18% in the general population. Few individuals had more than one additional chronic disease (6% of males, 8% of females). SMRs were increased for all diseases except diabetes, implying higher than expected occurrence of the specific diseases in asthmatics. This pattern was observed in both age groups (8-19 and 20-29 years) and genders. Allergy and GORD had highest SMR (range 3.2-4.8) while the other diseases were in the range 1.2-2.5. Conclusions: An excess occurrence of comorbidities was found in the population with asthma. A majority of asthmatics had one additional chronic disease, and few had more than one.

A large number of activities, such as conferences and seminars for doctors and midwives, and production of teaching material have been undertaken. Two questionnaire surveys ”Voices of Women in the Barents Region” were carried out in 2000 and 2002. The results showed an ongoing process of change in Russian maternity wards for the benefit of mothers and babies. Проект Y 9714 «Родители и роды в Баренц регионе» под рабочим названием “Родовспоможение доброжелательное к семье “(РДС) в рамках Программы Здравоохранения Баренц региона 1999–2003 гг. был первоначально инициирован как продолжение предыдущего проекта «Инициатива больницы доброжелательной к ребенку» (ИБДОР), который осуществлялся при финансовой поддержке Норвегии в период с 1994 по 1999 гг. Основной задачей инициативы являлась поддержка грудного вскармливания посредством усовершенствования практик грудного вскармливания в родильных домах Северо-запада России. Эта работа была продолжена и в рамках нового проекта, поскольку та же группа российских врачей-энтузиастов, которая работала над продвижением грудного вскармливания, согласилась продолжить свою деятельность на добровольной основе на благо российских женщин и детей. Новый проект РДС, главным образом, сфокусированный на антенатальном и акушерском уходе, начался в 1999 году с организации двух небольших Обучающих центров по поддержке грудного вскармливания. Один из них был открыт на базе роддома № 3 г. Мурманска, а второй — в городском роддоме № 7 г. Архангельска. Позднее оба этих центра были интегрированы в официальную структуру обоих учреждений. Переход к вопросам ухода при беременности и родах сопровождался проведением большого количества мероприятий. Около 600 медицинских работников, главным образом, докторов, акушерок и медицинских сестер приняли участие в международных и межобластных конференциях и семинарах в обоих регионах, а также в г. Нарьян-Мар. Обзор мероприятий проекта представлен в Приложении 1 настоящего отчета. Разработка обучающего материала для докторов и акушерок являлась одним из приоритетов проекта в течение последних двух лет. Ключевые участники проекта опубликовали брошюры о развитии грудного вскармливания на Северо-западе России и практическое руководство по перинатальному уходу для докторов и акушерок. Обмен знаниями посредством телемедицины также послужил звеном в отношениях между докторами и акушерками Северной Норвегии и Архангельской области.

Shows the questions concerning medication use from the Norwegian Mother and Child cohort study questionnaire Q4 (6 months of age) and Q5 (18 months of age). (DOCX 971 kb)

Shows the questions concerning medication use from the Norwegian Mother and Child cohort study questionnaire Q4 (6 months of age) and Q5 (18 months of age). (DOCX 971 kb)

Bakgrunn: I 2008 ble det gjort endringer i blåreseptordningen slik at pasienter med kroniske sterke smerter kunne få forskrevet smertestillende legemidler av spesialist gjennom blåreseptordningen med refusjonskode -71 (kroniske, sterke smerter). I 2016 ble blåreseptforskriften endret slik at også fastlegene kunne initiere søknad om individuell refusjon og forskrive opioider på blå resept til pasienter med kroniske sterke smerter. Fastleger kan nå søke om individuell refusjon for opioider for behandling med opptil 100 mg orale morfinekvivalenter (OMEQ) per døgn. Leger ved tverrfaglige smerte-klinikker kan søke om å forskrive daglige mengder over dette, med et øvre tak på 300 mg OMEQ. Hensikt: Studere om retningslinjer hos pasienter med kroniske, sterke smerter som bruker opioider på blå resept med refusjonskode -71 (kroniske, sterke smerter) blir fulgt. Metode: Reseptregisteret inneholder informasjon om alle legemidler som er forskrevet og utlevert fra apotek og mengde legemiddel utlevert registreres i definerte døgndoser (DDD). Personer i Reseptregisteret som i løpet av året fikk minst én opioidutlevering (ATC-gruppe N02A) på blå resept med refusjonskode -71 er definert som studiepopulasjon. Antall mg orale morfinekvivalenter (OMEQ) er beregnet ut fra antall definerte døgndoser (DDD) på ordinasjonsnivå for alle utleveringer (på varenummernivå) brukerne fikk i 2018. Morfin ekvianalgetisk ratio, som angitt i tabellen til Helfo er brukt i beregningene. Videre ble total mengde OMEQ utlevert per år aggregert på individnivå. Deretter ble antall pasienter som fikk doser på over 300 mg OMEQ per døgn i 2018 beregnet. Resultater: I denne studien var det totalt 17 383 pasienter ≥18 år som hentet ut minst ett opioid på blå resept med refusjonskode -71 (kroniske, sterke smerter) i 2018, som utgjør rundt 0,41 % av Norges befolkning. Av disse var 11 661 (67 %) kvinner og gjennomsnittsalderen for de 17 383 pasientene var på 62 år. Det var 331 pasienter som hadde en døgndose som var over 300 mg orale morfinekvivalenter per døgn på blå resept. 75 % av de 17 383 pasientene hadde også hentet ut minst ett opioid på hvit resept. Ved å legge til det som også var hentet ut av opioider på hvit resept, var det 631 pasienter som hadde en dose på over 300 mg orale morfinekvivalenter per døgn. 22,5 % av de 17 383 pasientene hentet ut sitt første opioid på blå resept med refusjonskode -71 i 2018. Konklusjon: Sett i forhold til hvor mange av Norges befolkning som oppgir å ha langvarige smerter, er det et lite antall personer som er del av blåreseptordningen ved bruk av opioider for kroniske, sterke smerter (-71). Det var en liten andel av disse pasientene som brukte en døgndose som var på mer enn det som dekkes i blåreseptordningen, men noen av pasientene brukte svært høye og urovekkende doser. Dette er pasienter som kan ha utviklet avhengighet og som kan ha behov for behandling av spesialister i rusmedisin. Background: In 2008, changes were made to the reimbursement regimen with reimbursement code -71 (strong, chronic pain), enabling patients with strong, chronic pain to get analgesic drugs prescribed by a specialist. In 2016, the reimbursement regulation was changed to also enable General Practitioners (GPs) to apply for individual reimbursement of opioids to patients with strong chronic pain. GPs can now apply for individual reimbursement for treatment up to 100 mg oral morphine equivalents (OMEQ) daily. Physicians at interdisciplinary pain clinics can apply for prescribing daily dosages above this, with a ceiling at 300 mg OMEQ. Purpose: To study whether the policies are followed in the use of reimbursed opioids with reimbursement code -71 (strong chronic pain) for patients with strong chronic pain. Method: The Norwegian Prescription Database (NorPD) contains information regarding all drugs prescribed and filled by pharmacies. The number of drugs filled is registered in defined daily dose (DDD). Individual registered in the Prescription Database who received reimbursed opioids with reimbursement code -71 at least once during the year (ATC group N02A), are defined as the population of this study. The amount of mg OMEQ is calculated based on the number of DDD at ordination level for all user prescriptions filled in 2018 (at article number level). Morphine equianalgesic dose ratios, specified in Helfo’s table, are used in the calculations. Next, the total amount of OMEQ filled each year was aggregated at individual level. Lastly, the number of patients receiving dosages above 300 mg OMEQ daily in 2018 was calculated. Results: A total of 17 383 patients ≥18 years old filled at least one reimbursed opioid with reimbursement code -71 in 2018. This makes up approximately 0.41 % of Norway’s population. Their mean age was 62 years. Of these, 11 661 (67 %) were women. 331 patients had a DDD above 300 mg OMEQ. 75 % of the patients also filled at least one non-reimbursed opioid prescription during the year. Adding both reimbursed and non-reimbursed opioids, it was found that 631 patients had a DDD above 300 mg OMEQ. Of the 17 383 patients, 22.5 % filled their first reimbursed opioid with reimbursement code -71 in 2018. Conclusion: Considering the proportion of Norway’s population that are stating that they experience prolonged pain, only a small number is part of the opioid reimbursement regimen for strong chronic pain. A small proportion of these patients had a DDD above what can be received through the reimbursement regimen, and some patients had disturbingly high dosages. These patients may have developed an addiction and could need treatment from addiction specialists.

Bakgrunn: I mange land ser man økt forbruk av opioidanalgetika de siste årene. Til nå har man hatt lite kunnskap om bruksmønstret hos pasienter under 18 år. Et økt forbruk kan skyldes at man er blitt flinkere til å behandle smerte hos barn og unge, eller det kan være snakk om et uønsket økt forbruk. Bruk av opioidanalgetika har gjerne vært forbundet med kreftbehandling, men man ser at en stadig større andel av forskrevet opioidanalgetika er til ikke-kreftrelaterte smerter. Materiale og Metode: Studien er basert på data fra Reseptregisteret (NorPD). Databasen inneholder data fra hele Norges befolkning på ca 4,7 millioner. Den studerte populasjonen var personer under 18 år som har mottatt minst en utlevering av opioidanalgetika i løpet av perioden 2004-2007. Resultater: Det har vært en økning i antall personer under 18 år som får forskrevet opioidanalgetika til ikke-kreft relaterte smerter i perioden 2004-2007. De aller fleste får kun forskrevet en resept på opioider i løpet av et kalenderår. Prevalens og insidens øker med økt alder. I de laveste aldersgruppene er det en tendens til at gutter har høyere forbruk enn jenter, men fra omkring 10-års-alderen er jentenes forbruk høyere enn guttenes. Det er hovedsakelig kodein i kombinasjon med paracetamol som brukes.

SAMMENDRAG BAKGRUNN Mange vestlige land rapporterer om økende bruk av psykofarmaka hos barn og ungdom. Kunnskap om bruk av anxiolytika og hypnotika/sedativa i Norge har frem til 2004 i all hovedsak basert seg på salgsstatistikk fra grossister til apotek. Slik statistikk gir imidlertid ingen informasjon om legemiddelbruk på individnivå. Ved hjelp av Reseptregisteret (opprettet i 2004) kan man kartlegge forbruk og belyse endringer over tid på individnivå. FORMÅL Studere bruk av anxiolytika og hypnotika hos barn og ungdom i aldersgruppen 0-17 år i Norge i perioden 2004-2007. MATERIALE OG METODE Studien er basert på data fra Reseptregisteret (Nor PD) som inneholder opplysninger over alle reseptpliktige legemidler utlevert fra alle landets apotek. Databasen dekker hele Norges befolkning (rundt 4,8 millioner). Studiepopulasjonen er barn og ungdom i aldersgruppen 0-17 år som har mottatt minst en utlevering av anxiolytika eller hypnotika/sedativa i løpet av perioden 2004-2007. Resultatene er presentert med ettårsprevalens og mengde utlevert i definerte døgndoser (DDD) per person per år. Analysene ble utført ved hjelp av statistikkprogrammet SPSS 15.0. RESULTATER/KONKLUSJON I perioden 2004-2007 har bruk av anxiolytika vært relativt stabilt, mens det har vært en betydelig økning i bruk av hypnotika/sedativa til barn og ungdom. Denne økningen skyldes i hovedsak økt bruk av melatonin som i gjennomsnitt utgjorde 77,2 % av det totale forbruket av sovemidler hos barn og ungdom i perioden (73,5 % i 2004, 77,2 % i 2005, 77,9 % i 2006 og 80,1 % i 2007). Guttene stod for over to tredeler (69,5 %) av forbruket av melatonin. Urovekkende mange barn og ungdom får utlevert høye doser DDD (over 200 DDD i året som da tilsvarer 1 DDD annen hver dag). ABSTRACT BACKGROUND Many Western countries report of increase in psychotropic drug use among children and adolescents. The Norwegian Prescription Database (NorPD) was established in 2004. The database gives the opportunity to describe drug use patterns and highlighting changes over time in individuals. Earlier (than 2004) one had to use sales statistics from the wholesome dealer in order to describe the use of anxiolytics and hypnotics/sedatives In Norway. AIM To study the use of anxiolytics and hypnotics among 0-17 years old children and adolescents in Norway in the period 2004-2007 MATERIAL AND METHODS Data were retrieved from the Norwegian Prescription Database (NorPD) which contains information of all reimbursement drugs prescriptions dispensed from Norwegian pharmacies. NorPD covers the entire nation (approximately 4,8 million). The study population is among 0-17 years old children and adolescent who received at least one dispensed anxiolytics or hypnotics/sedatives during the period 2004-2007. Outcome measures were one-year periodic prevalence and amount dispensed in defined daily doses (DDD) per person per year. SPSS 15.0 for Windows was applied for statistical analyses. RESULTS/ CONCLUSION During the period 2004-2007 use of anxiolytics has been relatively stable, while there has been a considerable increase in use of hypnotics/sedatives among children and adolescents. The increase is mainly due to use of melatonin, which accounted for 77,2 % of the total use of hypnotics among children and adolescents (73,5 % in 2004, 77,2 % in 2005, 77,9 % in 2006 and 80,1 % in 2007). Boys accounted for 69,5 % of the users of melatonin. A disturbing amount of children and adolescents were dispensed high numbers of DDD (over 200 DDD a year which means 1 DDD every second day).

Bakgrunn: Forekomst av bruk av opioidanalgetika er høy og ser ut til å være økende. Bruk av opioider ved behandling av ikke- kreftrelaterte smerter er omdiskutert. Kunnskap om bruk av opioider i Norge har til nå hovedsaklig vært basert på salgsstatistikk fra grossister til apotek. Ved bruk av Reseptregisteret (NorPD) har man mulighet til å beskrive bruk av opioider på individnivå. Formål: Studere bruk av opioidanalgetika hos personer som ikke har kreft i Norge i 2004- 2006. Studere bruk av kodein med fokus på prediktorer for høyt forbruk av kodein i 2006, samt prediktorer for komedikasjon med benzodiazepiner/ karisoprodol i 2006 blant brukere av kodein i 2005. Materiale og metoder: Studien er basert på data fra NorPD. Den studerte populasjonen var personer som har fått minst en utlevering av opioidanalgetika i løpet av 2004- 2006. Resultatene er presentert ved ettårsprevalens, insidens, mengde utlevert i definerte døgndoser (DDD) per person per år og andel pasienter med komedikasjon. I regresjonsanalysene er odds- ratio (OR) med tilhørende konfidensintervall (KI) brukt som effektmål. Analysene ble utført ved hjelp av statistikkprogrammet SPSS 15.0. Resultater: Ettårsprevalensen viser at 9,4 % av den norske befolkningen har fått minst en utlevering av opioidanalgetika mot ikke- kreftrelaterte sykdomstilstander i 2005 og i 2006. Antall nye brukere årlig lå på 5,9 % både i 2005 og i 2006. Prevalens og insidens øker med økende alder og er høyere blant kvinner sammenlignet med menn. I 2005 var ettårsprevalensen for svake opioider 9,3 % mot 0,3 % for sterke opioider. I 2005 har 8,3 % (n= 385 190) av den norske befolkningen hentet ut minst en forskrivning på kodein. En andel på 2,5 % (n= 9 448) av kodeinbrukerne har fått utlevert mer enn 365 DDD kodein i 2005, hvorav 19 % (n= 1 787) har fått utlevert mer enn 730 DDD. Blant de som har fått utlevert mer enn 365 DDD kodein i 2005 har 63,0 % brukt benzodiazepiner samtidig og 33,2 % har brukt karisoprodol. Justerte regresjonsanalyser for risikofaktorer for stort kodein forbruk (mer enn 365 DDD kodein utlevert) i 2006 viser at mer enn 365 DDD kodein utlevert i 2005 er den sterkeste prediktoren OR=285,5 (KI: 263,8-309,0). Å få utlevert mer enn 100 DDD benzodiazepiner OR=312,6 (290,1- 336,8) eller mer enn 15 DDD karisoprodol OR=85,4 (81,2- 89,8) i 2005 var den største prediktoren for komedikasjon med benzodiazepiner/ karisoprodol blant brukere av kodein i 2006. Konklusjon: Forbruket av opioidanalgetika blant ikke- kreft pasienter i Norge har vært stabilt i løpet av 2004- 2006. Svake opioidanalgetika, hovedsakelig kodein, brukes mest i Norge. Kodein brukes for det meste sporadisk, men en liten andel av brukerne har et høyt kodeinforbruk som kan være problematisk.

Sammendrag Bakgrunn På grunn av sitt smale terapeutiske vindu har warfarin et stort interaksjonspotensiale med både mat og andre legemidler, noe som kan øke risikoen for blødninger. Det er kjent at uselektive NSAIDs kan interagere med warfarin, men også tilfeller med økt INR og blødninger ved bruk av andre smertestillende legemidler som paracetamol og tramadol er observert. Formål: Beskrive warfarinpopulasjonen og hyppighet av samtidig bruk av smertestillende legemidler og warfarin ved hjelp av data fra Reseptregisteret (NorPd), og diskutere klinisk relevans av eventuelle interaksjoner mellom smertestillende legemidler og warfarin. Metoder og materiale: Data fra NorPd ble brukt. Analysene ble gjort av statistikk programmet SPSS. Resultater: Antall warfarinbrukere økte fra 72 755 i 2004 til 79 044 i 2006, og majoriteten av warfarinbrukerne var over 50 år. Omtrent 70% av warfarinbrukerne fikk warfarin som langtidsbehandling. Omtrent 20% av warfarinbrukerne hentet ut NSAIDs en eller flere ganger i løpet av warfarinbehandlingen i perioden 2004-2006. Andelen warfarinbrukere som hentet ut opioider (kodein og tramadol) og rene paracetamolpreparater var henholdsvis 25 og 15%. Konklusjon: Mange warfarinbrukere får også forskrevet analgetika, til tross for at klinisk relevante interaksjoner er kjente. På grunn av økt risiko for blødning ved bruk av warfarin og analgetika som NSAIDs, paracetamol og tramadol bør INR måles hyppig, og pasientene informeres nøye om bruk av reseptfri og reseptpliktige analgetika.

Background Anxiety is one of the most common symptoms one can find in general practice. At least every tenth Norwegian person suffers of anxiety once in their lifetime. The appearances of sleeping disorders are also high, and it increases with increasing age. More than half of the people over the age of 65 suffer from chronic sleep disturbance. The elderly is a big group in society, and it is assumed that the elderly over the age of 80 in the Nordic population will be twice as many until year 2050. This population diverse, amongst other things, from the normal population with higher morbidity, more polypharmcy, another body composition and changed metabolism. Much information about the utilization of anxiolytics and sedative-hypnotics amongst elderly people are still missing. Based on the Norwegian Prescription Database (NorPD) we have the opportunity to describe the use of anxiolytics and hypnotics at an individual-level. Aim To study the use of anxiolytics and hypnotics amongst elderly people from the age of 60 and older in Norway in 2004 and 2005. Material and methods Data were retrieved from the Norwegian Prescription Database covering the total population in Norway (4.6 million). Outcome measures were prevalence, incidence, amount dispensed in DDD per person per year, amount dispensed in DDD per prescription, the proportion of possibly concurrent use and the proportion of co-prescribing. The analysis were carried out with the statistics program SPSS. Results One in every five elderly Norwegian person ≥ 60 years old (198 642 persons) used sedative-hypnotics and 14, 4 % (135 015 persons) used anxiolytics in 2005. Despite that the prevalence was high in 2004 too; it is still many incident users in 2005. The prevalence for diazepam use was 7,9 %. The amounts used were also high. A mean equal to 1 months supply in DDD of diazepam per prescription and amounts equal to 3,5 months in DDD of diazepam per person per year were dispensed. As many as 8 out of 10 of the diazepam and the oxazepam users also used other substances in ATC-group N, several of them received the combination with the same substance in group N several times. Up till every tenth user combined the two types of benzodiazepine-anxiolytics. Conclusions It is recommended only limited and short-term use of both anxiolytics and sedative-hypnotics, especially amongst elderly people. Despite of this, the prevalence, the incidence and the amount dispensed per person per year and per prescription for the substances in the two groups is high. The high rate of co-medication between diazepam and other substances in ATC-group N is of high concern in terms of the potentially negative effects for the patients. Sammendrag Bakgrunn Angst er et av de hyppigste symptomene man møter i allmennpraksis. Minst hver 10. nordmann rammes en gang i livet av en angsttilstand. Også forekomsten av søvnproblemer er høy og den øker med alderen. Over halvparten av de eldre over 65 år lider av kroniske søvnvansker. Eldre er ei stor gruppe i samfunnet, og det forventes en fordobling av eldre over 80 år i den nordiske befolkningen fram til år 2050. Denne populasjonen skiller seg blant annet ut fra normalbefolkningen med økt sykelighet, polyfarmasi, ulik kroppssammensetning og endret metabolisme. På feltet eldres bruk av anxiolytika og hypnotika mangler det fortsatt informasjon om flere sider av området. Ved bruk av Reseptregisteret (NorPD) har vi muligheten til å beskrive bruken av anxiolytika og hypnotika på individnivå. Formål Studere bruken av anxiolytika og hypnotika blant eldre fra 60 år og oppover i Norge i 2004 og 2005. Materiale og metode Data ble hentet fra Reseptregisteret (NorPD), som dekker den totale befolkningen i Norge (4,6 millioner). Resultatene er presentert ved prevalens, insidens, mengde utlevert i DDD per person per år, mengde i DDD per forskrivning, andel ”possibly concurrent medication” og andel ”co-prescribing”. Analysene ble utført ved hjelp av statistikkprogrammet SPSS. Resultater Hver 5. eldre ≥ 60 år (198 642 personer) brukte hypnotika/sedativa og 14,4 % (135 015 personer) brukte anxiolytika i 2005, på tross av like høy prevalens i 2004 er det fortsatt mange nye brukere. Prevalensen for diazepambruk var på 7,9 %. I tillegg var mengden utlevert av de ulike substansene stor. Det ble utlevert gjennomsnittlig tilsvarende 1 måneds forbruk i DDD av diazepam per forskrivning og mengder tilsvarende over 3,5 måneder i DDD av diazepam per person per år. Så mange som 8 av 10 av henholdsvis diazepam- og oksazepambrukerne brukte også andre legemidler i ATC-gruppe N, flere fikk kombinasjonen med samme substans i gruppe N flere ganger. Oppimot hver 10. bruker kombinerte de to typene benzodiazepinanxiolytika. Konklusjon Til tross for anbefalinger om begrenset og kortvarig bruk, særlig hos eldre, av både anxiolytika og hypnotika/sedativa, er prevalensen, insidensen og mengden utlevert per person per år og per forskrivning for substansene i de to legemiddelgruppene høy. Den høye andelen komedikasjon mellom diazepam og andre legemidler i ATC-gruppe N er bekymringsfull med tanke på de potensielle negative følgene av slik bruk for pasienten.