Pharmacological treatment of obesity in adults in Norway 2004-2022.

AIMS: To describe trends in the use of anti-obesity drugs in Norway during the period 2004-2022. MATERIALS AND METHODS: We assessed the annual utilization of any available drug indicated for obesity recorded in the nationwide Norwegian Prescribed Drug Register for adults (age 18-79 years) from 1 January 2004 to 31 December 2022. Prevalence was stratified by sex and age group (18-29 years and 10-year age groups thereafter). Additional analyses were performed in individuals initiating treatment with an anti-obesity drug and on the cost of the anti-obesity drugs since 2017. RESULTS: The prevalence of anti-obesity drug use decreased from 2009, when sibutramine and rimonabant were withdrawn from the market, and increased again after the approval of bupropion-naltrexone in 2017 and liraglutide in 2018. The use of the peripheral-acting anti-obesity drug orlistat decreased from 2004. In 2022, 1.04% of the adult Norwegian population (72.8% women) filled at least one prescription of bupropion-naltrexone, 0.91% used liraglutide (Saxenda; 74.2% women), and semaglutide without reimbursement was used by 0.68% (76.7% women). The prevalence increased with age, peaking in the age group 50 to 59 years, and decreased in older age groups. From 2017 to 2022, 2.8% of the adult residents initiated treatment with an anti-obesity drug. The total sale of those drugs increased from 1.1 million euros in 2017 to 91.8 million euros in 2022. CONCLUSIONS: The use of anti-obesity drugs in Norway has increased substantially in recent years, especially among women aged 40 to 59 years. Changes in availability and reimbursement have influenced the use of these drugs in recent years.

Methodology of the brodalumab assessment of hazards: a multicentre observational safety (BRAHMS) study.

INTRODUCTION: Safe and effective pharmacological treatment is of paramount importance for treating severe psoriasis. Brodalumab, a monoclonal antibody against interleukin (IL) 17 receptor A, was granted marketing authorisation in the EU in 2017. The European Medicines Agency requested a postauthorisation safety study of brodalumab to address potential safety issues raised during drug development regarding major adverse cardiovascular events, suicidal conduct, cancer and serious infections. METHODS AND ANALYSIS: BRodalumab Assessment of Hazards: A Multinational Safety is a multicentre observational safety study of brodalumab running from 2017 to 2029 using population-based healthcare databases from Denmark, Sweden, Norway, Netherlands, Germany and three different centres in Italy. A distributed database network approach is used, such that only aggregate data are exchanged between sites.Two types of designs are used: a case-time-control design to study acute effects of transient treatment and a variation of the new user active comparator design to study the effects of transient or chronic treatment. As comparators, inhibitors of TNF-α, inhibitors of IL-12 and IL-23, and other inhibitors of cytokine IL-17A are included.In the self-controlled case-time-control design, the risk of developing the outcome of interest during periods of brodalumab use is compared within individuals to the risk in periods without use.In the active comparator cohort design, new users of brodalumab are identified and matched to new users of active comparators. Potential baseline confounders are adjusted for by using propensity score modelling. For outcomes that potentially require large cumulative exposure, an adapted active comparator design has been developed. ETHICS AND DISSEMINATION: The study is approved by relevant authorities in Denmark, Norway, Sweden, the Netherlands, Germany and Italy in line with the relevant legislation at each site. Data confidentiality is secured by the distributed network approach. Results will be published in peer-reviewed journals. TRIAL REGISTRATION NUMBER: EUPAS30280.

ß-Blocker Use in Pregnancy and the Risk for Congenital Malformations: An International Cohort Study.

Background: ß-Blockers are a class of antihypertensive medications that are commonly used in pregnancy. Objective: To estimate the risks for major congenital malformations associated with first-trimester exposure to ß-blockers. Design: Cohort study. Setting: Health registries in the 5 Nordic countries and the U.S. Medicaid database. Patients: Pregnant women with a diagnosis of hypertension and their offspring. Measurements: First-trimester exposure to ß-blockers was assessed. Outcomes were any major congenital malformation, cardiac malformations, cleft lip or palate, and central nervous system (CNS) malformations. Propensity score stratification was used to control for potential confounders. Results: Of 3577 women with hypertensive pregnancies in the Nordic cohort and 14 900 in the U.S. cohort, 682 (19.1%) and 1668 (11.2%), respectively, were exposed to ß-blockers in the first trimester. The pooled adjusted relative risk (RR) and risk difference per 1000 persons exposed (RD1000) associated with ß-blockers were 1.07 (95% CI, 0.89 to 1.30) and 3.0 (CI, -6.6 to 12.6), respectively, for any major malformation; 1.12 (CI, 0.83 to 1.51) and 2.1 (CI, -4.3 to 8.4) for any cardiac malformation; and 1.97 (CI, 0.74 to 5.25) and 1.0 (CI, -0.9 to 3.0) for cleft lip or palate. For CNS malformations, the adjusted RR was 1.37 (CI, 0.58 to 3.25) and the RD1000 was 1.0 (CI, -2.0 to 4.0) (based on U.S. cohort data only). Limitation: Analysis was restricted to live births, exposure was based on dispensed medication, and cleft lip or palate and CNS malformations had few outcomes. Conclusion: The results suggest that maternal use of ß-blockers in the first trimester is not associated with a large increase in the risk for overall malformations or cardiac malformations, independent of measured confounders. Primary Funding Source: The Eunice Kennedy Shriver National Institute of Child Health and Human Development and the Söderström König Foundation.

Utilization of Stimulants and Atomoxetine for Attention-Deficit/Hyperactivity Disorder among 5.4 Million Children Using Population-Based Longitudinal Data.

Use of stimulants to treat attention-deficit/hyperactivity disorder (ADHD) has increased over the past two decades and varies substantially between countries. The objective of this multinational population-based study was to examine utilization of ADHD drugs (stimulants and atomoxetine) including comedication with other psychotropic drugs in the entire child population in the five Nordic countries. We included longitudinal data on dispensed ADHD drugs from five Nordic prescription registers during 2008-2012, which in 2012 comprised 48,296 individuals among 5.42 million inhabitants aged 0-17 years. Prevalence of filling ≥1 prescriptions of ADHD drugs among children aged 6-17 years increased during 2008-2012 from 5.9 to 11.2 and 19.4 to 31.0 per 1000 girls and boys, respectively. Prevalence by country showed that Iceland, Finland and Sweden had a steady increase during the study period, while in Norway the prevalence was quite stable and in Denmark it levelled off from 2010. Use in preschoolers (aged 0-5 years) was rare. Iceland had much higher prevalence and incidence than the other Nordic countries. The incidence of ADHD drug use increased during the study period, from 4.0 to 4.9 and from 1.5 to 2.3 per 1000 boys and girls, respectively. The increasing number of new users levelled off somewhat after 2010. Comedication with other psychotropic drugs was more common among girls (33.9%) than boys (27.0%) and was mainly melatonin, followed by antidepressants and antipsychotics. Overall prevalence of ADHD drug use increased among Nordic girls and boys aged 6-17 years, whereas the incidence increased slightly during 2008-2010 but levelled off through 2012. The substantial differences in ADHD drug use across the Nordic countries and high degree of comedication with other psychotropic drugs underscore the importance of close monitoring of treatment for ADHD among children.

Influence of socioeconomic factors on the adherence of alendronate treatment in incident users in Norway.

PURPOSE: To examine whether socioeconomic factors influence adherence to alendronate drug treatment among incident users in Norway during 2005-2009. METHODS: The study included 7610 incident alendronate users in 2005 (40-79 years), followed until 31 December 2009. Mean age was 66.6 years, and 86.7% of the patients were women. Data were drawn from the Norwegian Prescription Database and linked to marital status, education and income. Adherence was measured by the medication possession ratio (MPR). MPR was defined as the number of dispensed defined daily doses divided by the number of days each patient was included in the study. A patient was adherent if MPR ≥ 80%. ORs with 95%CI were estimated using logistic regression. RESULTS: Among all patients, 45.5% was adherent throughout 4.2 years. A slightly higher proportion of women than men were adherent. Adjusted for all covariates, women aged 70-79 years had an OR of 1.27 (95%CI 1.10-1.45) for adherence compared with those 40-59 years. In women, high household income predicted adherence of alendronate use. In men, a middle educational level compared with a low level, predicted adherence (adjusted OR = 1.47 (95%CI 1.10-1.96)). After adjustments, previous marriage reduced the odds of being adherent compared with present marriage, in both men and women. CONCLUSIONS: In women, the most important factors for being adherent were high age and high income. In men, a middle educational level predicted adherence. Previous marriage reduced the odds of being adherent in both women and men.

High validity of mother-reported use of antiasthmatics among children: a comparison with a population-based prescription database.

OBJECTIVES: To examine the validity of (1) maternal questionnaire report of children's use of antiasthmatics using a prescription database as the reference standard and (2) dispensed antiasthmatics as a measure of asthma using maternal report of children's asthma as the reference standard. STUDY DESIGN AND SETTING: A total of 3,394 children in the Norwegian Mother and Child Cohort Study aged 7 years were linked to the Norwegian Prescription Database. Maternal report of both children's use of antiasthmatics during the preceding year and the presence of asthma was compared with data on dispensed antiasthmatics. RESULTS: A total of 2,056 mothers responded and reported use of antiasthmatics during the previous year in 125 of 147 children who had been dispensed antiasthmatics (sensitivity 85.0%). Of the 1,909 children with no dispensed antiasthmatics, 1,848 had no maternal report of antiasthmatic use (specificity 96.8%). Mothers reported current asthma in 133 (6.5% of 2,056) children, including in 122 (5.9%) reported as verified by a doctor. Of these 122, 98 had been dispensed antiasthmatics during the preceding year (sensitivity 80.3%). Only 1.2% of the children without reported asthma were dispensed antiasthmatics. CONCLUSION: Mother-reported use of antiasthmatics during the previous year among 7-year-old children is highly valid. Dispensed antiasthmatics would be a useful proxy for the presence of current asthma when disease data are not available.

Generic substitution: micro evidence from register data in Norway.

The importance of prices, doctor and patient characteristics, and market institutions for the likelihood of choosing generic drugs instead of the more expensive original brand-name version are examined. Using an extensive dataset extracted from The Norwegian Prescription Database containing all prescriptions dispensed to individuals in February 2004 and 2006 on 23 different drugs (chemical substances) in Norway, we find strong evidence for the importance of both doctor and patient characteristics for the choice probabilities. The price difference between brand and generic versions and insurance coverage both affect generic substitution. Moreover, controlling for the retail chain affiliation of the dispensing pharmacy, we find that pharmacies play an important role in promoting generic substitution. In markets with more recent entry of generic drugs, brand-name loyalty proves to be much stronger, giving less explanatory power to our demand model.

Mental distress and subsequent use of anxiolytic drugs--a prospective population-based cohort study of 16,000 individuals.

AIMS: To study the relationship between mental distress and later use of anxiolytic drugs, taking into account potential confounders such as lifestyle and socioeconomic factors. METHODS: In a prospective cohort study, data from population-based health surveys from three Norwegian counties (2000-01) were linked to data from the Norwegian Prescription Database (NorPD) (2004-07). In the surveys, 9,386 men (43.1% of those invited) and 11,244 women (52.4%) participated. The two age cohorts were 40 and 45 years old (cohort 1) and 60 years old (cohort 2). Participants in each age group were divided into quartiles (Q1-Q4) separately for men and women according to the degree of mental distress, measured by increasing Hopkins Symptom Checklist-10 score (HSCL-10 score) at baseline. Multivariate logistic regression was performed to assess predictors of anxiolytic drug use. RESULTS: At baseline: Increasing HSCL-10 score was associated with: increasing use of specified prescribed drugs, poor health, ever having sought help because of mental distress, musculoskeletal pain, being married or in partnership, low educational level, receiving disability pension and current smoking (except for women 60 years old). Predictors found: There was a graded positive relationship between HSCL-10 score at baseline (2000-01) and the chance of a prescription of anxiolytics during follow-up (2004-07) in the 40 and 45 year olds. Predictors, regardless of age, were: female gender, reported use of hypnotics, having previously sought help because of mental distress and current smoking. CONCLUSIONS: HSCL-10 score was related to later use of anxiolytic drugs in a dose response manner.

Co-medication of statins and CYP3A4 inhibitors before and after introduction of new reimbursement policy.

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT: HMG-CoA reductase inhibitors (statins) are frequently used drugs in the treatment of dyslipidaemia. Co-medication with interacting drugs increases the risk of statin-induced muscular side-effects. Simvastatin exhibits particularly high interaction potential due to substantial metabolism via cytochrome P450 3A4 (CYP3A4). WHAT THIS STUDY ADDS: In June 2005, a new reimbursement policy was introduced by the Norwegian Medicines Agency stating that simvastatin should be prescribed as first-line lipid-lowering therapy. Following introduction of the new policy, the number of patients co-medicated with simvastatin and CYP3A4 inhibitors almost doubled. A potential consequence is increased incidence of muscular side-effects in the statin-treated population. AIMS: To assess the prevalence of co-medication of statins and CYP3A4 inhibitors before and after introduction of a new Norwegian reimbursement policy, which states that all patients should be prescribed simvastatin as first-line lipid-lowering therapy. METHODS: Data from patients receiving simvastatin, lovastatin, pravastatin, fluvastatin or atorvastatin in 2004 and 2006, including co-medication of potent CYP3A4 inhibitors, were retrieved from the Norwegian Prescription Database covering the total population of Norway. Key measurements were prevalence of continuous statin use (two or more prescriptions on one statin) and proportions of different statin types among all patients and those co-medicated with CYP3A4 inhibitors. RESULTS: In 2004, 5.9% (n= 272 342) of the Norwegian population received two or more prescriptions on one statin compared with 7.0% (n= 324 267) in 2006. The relative number of simvastatin users increased from 39.7% (n= 112 122) in 2004 to 63.1% (n= 226 672) in 2006. A parallel increase was observed within the subpopulation co-medicated with statins and CYP3A4 inhibitors, i.e. from 42.9% (n= 7706) in 2004 to 63.6% (n= 13 367) in 2006. For all other statins the number of overall users decreased to a similar extent to those co-medicated with CYP3A4 inhibitors. CONCLUSIONS: In both 2004 and 2006, the choice of statin type did not depend on whether the patient used a CYP3A4 inhibitor or not. Considering the pronounced interaction potential of simvastatin with CYP3A4 inhibitors, a negative influence of the new policy on overall statin safety seems likely.

The validity of self-reported prescription medication use among adolescents varied by therapeutic class.

OBJECTIVE: Validation studies of self-reported medication use in adolescents have been scarce. The objective of this study was to estimate the sensitivity and specificity of self-reported use of medication using a prescription database as reference standard. STUDY DESIGN AND SETTING: The study population consisted of a cohort of 2,613 adolescents aged 15-16 years from the Norwegian youth health survey in 2004 and 2005. Self-reported data on medication use were compared with data from the Norwegian Prescription Database which contains information from all prescription dispensed at Norwegian pharmacies. RESULTS: Sensitivity for self-reported questions on medication use was highest for contraceptive pills 99.2% (95% CI 97.7-100) compared to antiasthmatics 79.1% (66.9-91.2), painkillers 48.5% (36.7-60.4), and psychotropic drugs 75.0% (35.6-95.6). Specificity values of self-reported information of psychotropic drugs 89.6% (87.8-91.5) and antiasthmatics 87.4% (85.4-89.5) were higher than for painkillers 80.0% (77.5-82.4) and contraceptive pills 76.2% (72.3-80.1). CONCLUSION: Validity of self-reported previous medication use among adolescents differed by the therapeutic classes of medication. The highest sensitivity was observed for contraceptive pills and lowest for prescribed painkillers.

Switching statins in Norway after new reimbursement policy: a nationwide prescription study.

AIMS: To assess the changes in prescribing of statins in Norway after implementation of the new reimbursement regulations for statins in June 2005. METHODS: Data were retrieved from the Norwegian Prescription Database covering the total population in Norway (4.6 million). Outcome measures were the proportion of atorvastatin users switching to simvastatin and changes in the proportion of new statin users receiving simvastatin. Based on retail costs for all statin prescriptions dispensed in Norway, expenditure was measured in Norwegian currency. RESULTS: One-year prevalences of statin use increased from 6.3 to 6.8% for women and from 7.5 to 8.1% for men from the year before to the year after the new statin regulations. Of atorvastatin users (N = 131,222), 39% switched to simvastatin during the 13-month period after the implementation. The proportion of switching was higher in women (41%) than in men (36%). In May 2005, 48% of the new statin users received simvastatin. The proportion of new users receiving simvastatin increased rapidly after implementation of the new regulations to 68% in June 2005 and reached 92% in June 2006. Expenditure was reduced from 120 million to 95 million Euro when comparing the year before with the year after the new statin regulations. CONCLUSIONS: The new reimbursement policy for statins has had a great impact on physicians' prescribing of statins in Norway. Physicians in Norway acknowledge the importance of contributing to cost containment.

Why do sales of lipid-lowering drugs vary between counties in Norway? Evidence from the OPPHED Health Study 2000-2001.

OBJECTIVE: To study and compare plausible factors that might explain varying sales of lipid-lowering drugs (LLDs) in the two neighbouring counties of Hedmark and Oppland in Norway, with a similar age distribution, socioeconomic structure, and access to healthcare services. DESIGN, SETTING, SUBJECTS: Cross-sectional population study comprising 10 598 attendants aged 40, 45, 60, and 75 years in the OPPHED Health Study, 2000-2001 (attendance rate 61%). MAIN OUTCOME MEASURE: Treatment eligibility (cardiovascular morbidity and risk score), treatment frequency in treatment-eligible subgroups and treatment intensity in terms of achievement of total cholesterol (TC) goal. RESULTS: Proportions eligible for LLD treatment in Hedmark and Oppland were similar. There was no difference in prevalence of LLD use among participants with cardiovascular disease or diabetes (secondary prevention subgroup). However, LLD use among men in the primary prevention subgroup was higher in Hedmark compared with Oppland, 6.3% and 4.1%, respectively (p < 0.05). The same tendency was seen among women. In both sexes, more LLD users in the primary prevention subgroup achieved the TC goal in Hedmark compared with Oppland (p < 0.05). CONCLUSION AND IMPLICATIONS: The proportion of the population eligible for LLD treatment in the two counties should imply similar treatment rates in both. Higher LLD treatment frequency and intensity in the primary prevention subgroup in Hedmark are probably both contributing factors that explain the higher sales of LLDs in Hedmark compared with Oppland. Feasible intervention thresholds for primary prevention with concurrent reimbursement rules should be defined in guidelines to avoid unintentional variation in LLD use in the future.

[Changes in the sale and use of flunitrazepam in Norway after 1999]. / Endringer i salg og bruk av flunitrazepam etter 1999.

BACKGROUND: In Norway there has in later years been much discussion of misuse of flunitrazepam. From 1 January 2003 the drug was moved up one level in the schedule of controlled substances. On 1 August 2004 the manufacturer of the Rohypnol brand withdrew it from the Norwegian market. How did these two events influence the sales and use of drugs containing flunitrazepam? MATERIALS AND METHODS: Sales figures for drugs containing flunitrazepam from the statistics database at the Norwegian Institute of Public Health were studied. The Norwegian prescription database was used to describe new (incident) users of flunitrazepam and the two brands of this drug sold in Norway in 2004. RESULTS AND DISCUSSION: Restrictions on the prescription status of flunitrazepam lead to a decrease in sales from 7.2 defined daily doses (DDD) per 1000 inhabitants per day in 2002 to 3.0 DDD per 1000 inhabitants per day in 2003. This decrease was only partly compensated for by an increase in the sales of nitrazepam (from 5.0 to 6.0 DDD per 1000 inhabitants per day). During the years 1999 to 2004 there was a steady increase in the sales of benzodiazepine-related hypnotics (zopiclone and zolpidem). This shift could mean a change from flunitrazepam to zopiclone. The withdrawal of Rohypnol in August 2004 had only minor effects on the total sales of flunitrazepam. The decline in sales of Rohypnol was almost compensated for by the increase in the overall sales of Flunipam. This was reflected in the fact that in the later months of 2004 there were many new (incident) users of Flunipam, but few new users of flunitrazepam-containing drugs in total. It could be concluded that the restrictions on prescription status of flunitrazepam had a much higher impact than the withdrawal of the Rohypnol brand.

Use of psychotropic drugs in an urban adolescent population: the impact of health-related variables, lifestyle and sociodemographic factors--The Oslo Health Study 2000-2001.

AIMS: The aims of the study were to examine use of psychotropic drugs among 15-16 years old adolescents and to study the association between use of drugs and health-related, lifestyle and sociodemographic factors. MATERIAL AND METHODS: The youth part of the Oslo Health Study 2000-2001 included all individuals in 10th grade in Oslo County, Norway. A total of 3612 boys and 3695 girls, participated, giving a participation rate of 86.1% for boys and 90.6% for girls. All students filled in two self-administered questionnaires on various health behaviours, including use of medicines. Persons who reported use of hypnotics, anxiolytics and/or antidepressants during the last 4 weeks were defined as users. Data were analysed using bivariate and multivariate techniques. RESULTS: In all, 3.4% boys and 3.7% girls had used one or more psychotropic drugs during the last 4 weeks. Multivariate analyses revealed that mental disorders, seeing a psychologist/psychiatrist and use of prescription analgesics were significantly associated with the use of psychotropic drugs for both genders. Smoking, exposure to violence and lower education plans were registered as important factors for males only, whilst for females the factor 'one parent not working' was registered as significant. CONCLUSION: The proportion of psychotropic drug users in this young population was relatively low, under 4% and similar for males and females. Analyses of various factors associated with use of psychotropic drugs show that health, physical and mental, are the most important factors, and that lifestyle and socio-economic factors are of minor importance.