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Use of benzodiazepines (BZ) and related drugs is subject to considerable debate due to problems with dependency and adverse events. We aimed to describe and compare their use across the Nordic countries. Data on the use of clonazepam, BZ-sedatives, BZ-hypnotics, and benzodiazepine-related drugs (BZRD) in adults (≥20 years) were obtained from nationwide registers in Denmark, Finland, Iceland, Norway, and Sweden, 2000-2020. Main measures were therapeutic intensity (TI:DDD/1000 inhabitants [inhab.]/day) and annual prevalence (users/1000 inhab./year). Overall, TI of BZ and related drugs decreased in all Nordic countries from 2004 to 2020. However, there were considerable differences between countries in TI. In 2020, the TI of BZ and related drugs ranged from 17 DDD/1000 inhab./day in Denmark to 93 DDD/1000 inhab./day in Iceland. BZRD accounted for 55-78% of BZ use in 2020, followed by BZ sedatives at 20-44%, BZ-hypnotics at <1-5%, and clonazepam at <1-2%. Annual prevalence of BZ use increased with age in all countries, and the highest annual prevalence was observed among people ≥80 years. Overall, the use of BZ and related drugs has decreased in all Nordic countries from 2004 to 2020, however, with considerable differences in their use between countries. The highest prevalence was observed among the oldest age groups-despite warnings against their use in this population., (© 2022 The Authors. Basic & Clinical Pharmacology & Toxicology published by John Wiley & Sons Ltd on behalf of Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).)

Importance: Understanding the safety profile of medications used in pregnancy is crucial for clinical decision-making. Few studies exist on the associations of exposure to benzodiazepines and benzodiazepine-like hypnotic drugs (z-hypnotics) in pregnancy with pregnancy outcomes., Objective: To determine whether exposure to benzodiazepines or z-hypnotics in pregnancy is associated with greater risk of negative immediate pregnancy outcomes compared with nonexposure., Design, Setting, and Participants: This questionnaire-based cohort study used data from the Norwegian Mother, Father and Child cohort study (MoBa), which also includes data from the Medical Birth Registry of Norway. Pregnant women were recruited from all over Norway from 1999 and 2008. The first child was born in October 1999 and the last in July 2009. This analysis included women who completed 3 questionnaires, twice during pregnancy and once 6 months after delivery. Data analyses were conducted from September to November 2019., Exposures: Self-reported exposure to benzodiazepines or z-hypnotics during pregnancy, characterized in terms of any exposure, timing (ie, early, middle, or late), and duration of exposure., Main Outcomes and Measures: The main outcomes were gestational age at delivery, risk of preterm delivery, birth weight, birth weight relative to gestational age and sex, risk of being small for gestational age, head circumference, Apgar score less than 7 at 5 minutes, and risk of neonatal respiratory distress. Continuous outcomes are reported using effect estimates as mean differences, and binary outcomes are reported using risk ratios., Results: The MoBa study included 114 234 mother-child dyads. This analysis of MoBa data includes 82 038 singleton pregnancies among 69 434 unique women. Mean (SD) maternal age was 30.2 (4.5) years, and 37 641 pregnancies (45.9%) were in primiparous women. Exposure to benzodiazepines or z-hypnotics was reported in 679 pregnancies (0.8%). After adjusting for all measured baseline and postbaseline confounders, benzodiazepine or z-hypnotic use during pregnancy was associated with lower birth weight (mean difference, -79.3 [95% CI, -126.7 to -31.9] g), lower gestational age at birth (mean difference, -2.1 [95% CI, -3.3 to -0.9] days), and higher risk of preterm birth (risk ratio, 1.41 [95% CI, 1.03 to 1.94]). We found no significant association of exposure to benzodiazepines or z-hypnotics with the child's birth weight relative to gestational age and sex (z score), or any of the other immediate birth outcomes., Conclusions and Relevance: These findings suggest that the magnitude of the association of exposure to benzodiazepines or z-hypnotics with gestational age is not necessarily clinically significant. The absence of an association of exposure to benzodiazepines or z-hypnotics with z score for birth weight relative to gestational age and sex suggests that association of exposure to benzodiazepines or z-hypnotics with birth weight could be explained by earlier delivery rather than impaired intrauterine growth.

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). A total of 10,371 OAT patients were included in the study period. The dispensation rates were defined as the number of patients who were dispensed at least one of the potentially addictive drugs divided among the number of patients who have dispensed an OAT opioid per calendar year. Mean daily doses were calculated, and for benzodiazepines and z-hypnotics, stated in diazepam equivalents. The association between dispensed potentially addictive drugs, and the number and the type of dispensed OAT opioids were calculated by using logistic regression models., Results: Half of the OAT patients received at least one dispensation of a benzodiazepine or z-hypnotic, and 11% were dispensed at least a gabapentinoid in 2017. For dispensed benzodiazepines or z-hypnotics, the mean daily dose was reduced from 21 mg (95% confidence interval (CI): 20-23) diazepam equivalents in 2013 to 17 mg (95% CI: 16-17) in 2017. The mean daily dose of pregabalin increased from 365 mg (95% CI: 309-421) in 2013 to 386 mg (95% CI: 349-423) in 2017. Being dispensed a gabapentinoid (adjusted odds ratio (aOR) = 2.5, 95% CI: 2.1-3.0) or a non-OAT opioid (aOR = 3.0, 95% CI: 2.6-3.5) was associated with being dispensed a benzodiazepine or z-hypnotic. Discontinuing OAT did not affect the number of dispensations and the doses of potentially addictive drugs., Conclusion: The dispensation rates of potentially addictive drugs are high in the OAT population. Treatment indications, as well as requirements for prescription authority, need to be debated and made explicit. Randomized controlled trials evaluating the benefits and risks of such co-prescription are required.

Importance: The reproductive safety of benzodiazepine/z-hypnotic exposure on child longer-term developmental risks remains unresolved., Objective: To quantify the association of motor, communication, and attention-deficit/hyperactivity disorder (ADHD) symptoms in preschoolers with gestational benzodiazepine/z-hypnotic exposure by timing and duration and coexposure to opioids or antidepressants., Design, Setting, and Participants: Nationwide, population-based Norwegian Mother and Child Cohort Study, recruiting pregnant women from 1999 to 2008, with child follow-up from ages 6, 18, and 36 months to ages 5, 7, and 8 years. Follow-up of teenagers is ongoing. The study included women with depressive/anxiety (n = 4195), sleeping (n = 5260), or pain-related (n = 26 631) disorders before and/or during pregnancy., Exposures: For the timing analyses, children exposed to benzodiazepines/z-hypnotics in midpregnancy (weeks 17-28) or late pregnancy (week 29 or later) vs those born to nonmedicated women. For the duration and coexposure analyses, benzodiazepine/z-hypnotic treatment for multiple 4-week intervals vs 1 and co-use of benzodiazepine/z-hypnotic with opioids or antidepressants vs sole benzodiazepine/z-hypnotic use., Main Outcomes and Measures: Parent-reported motor and communication skills (Ages and Stages Questionnaires) and ADHD symptoms (Conners' Parent Rating Scale-Revised) at child median age of 5.1 years (interquartile range, 5.0-5.3 years) as standardized mean scores. General linear propensity score-adjusted and marginal structural models were fitted. Analyses were stratified by maternal disorder., Results: Of 41 146 eligible pregnancy-child dyads, 36 086 children (18 330 boys and 17 756 girls) were included, of whom 283 (0.8%) were prenatally exposed to benzodiazepines/z-hypnotics (134 in the depressive/anxiety, 60 in the sleeping, and 89 in the pain-related disorders). There was no increased risk for greater ADHD symptoms or fine motor deficits after intrauterine benzodiazepine/z-hypnotic exposure at different time points. Children born to women with depressive/anxiety disorders who took benzodiazepines/z-hypnotics in late pregnancy had greater gross motor (weighted β, 0.67; 95% CI, 0.21-1.13) and communication (weighted β, 0.35; 95% CI, 0.04-0.65) deficits than unexposed children. There was no evidence for substantial duration or coexposure associations., Conclusions and Relevance: These findings suggest no substantial detrimental risk on child fine motor and ADHD symptoms after prenatal benzodiazepine/z-hypnotic exposure alone or in combination with opioids or antidepressants. Residual confounding by indication and/or a higher drug dose regimen among women with anxiety/depression may explain the moderate association of gross motor and communication deficits with late-pregnancy benzodiazepine/z-hypnotic use.

Chronic pain due to surgery, radiotherapy, or chemotherapy is prevalent in long-term cancer survivors. Chronic pain due to successful cancer treatment should be treated as chronic nonmalignant pain, primarily with nonpharmacological strategies. Based on complete national data from the Cancer Registry of Norway and the Norwegian prescription database, the aim of this study was to compare the use of nonopioid analgesics, opioids, and benzodiazepines 10 years after cancer diagnosis in long-term cancer survivors and the age- and sex-adjusted general population. The 1-year periodic prevalence of use was higher in long-term cancer survivors in all the studied drug classes: opioids (143.5 vs 129.6/1000), paracetamol (88.3 vs 80.7/1000), nonsteroidal anti-inflammatory drugs (229.1 vs 221.7), gabapentinoids (13.4 vs 10.0/1000), benzodiazepines (88.3 vs 77.9/1000), and benzodiazepine-like hypnotics (118.1 vs 97.4/1000). The prevalence of persistent and high-dose opioid use (>365 defined daily doses [DDDs] and >730 DDDs, respectively, during 365 days, and prescriptions all quarters of the year) was also higher in the cancer survivors than in the general population (6.5 vs 4.8/1000 for persistent use and 2.7 vs 1.3/1000 for high-dose use). Less than 10% of persistent and high-dose users received only long-acting opioid formulations. Furthermore, most long-term cancer survivors with persistent or high-dose opioid use were also high-dose users (>100 DDDs/year) of either benzodiazepines or benzodiazepine-like hypnotics. It is an issue of concern that most of those using opioids did not adhere to guidelines regarding opioid formulation and comedication with other drugs with addictive properties.

Background: During pregnancy, many women experience sleep problems and anxiety that require treatment. The long-term safety for the child of maternal benzodiazepine (BZD) and z-hypnotic use during pregnancy remains controversial., Method: We conducted a cohort and a sibling control study using data from the Norwegian Mother and Child Cohort Study. Data on use of BZD and z-hypnotics, internalizing and externalizing outcomes, and covariates were collected from mothers at gestational weeks 17 and 30 and when children were 0.5, 1.5, and 3 years of age. The total sample consisted of 71,996 children (19,297 siblings) at 1.5 years and 55,081 children (13,779 siblings) at 3 years. Short-term use was defined as use in one pregnancy period only. Long-term use was defined as use in two or more pregnancy periods. Linear full cohort random-effect and sibling-matched fixed-effect regression models were used to compare internalizing and externalizing behavior in children prenatally exposed compared to those unexposed in the full cohort of pregnancies accounting for family clusters, as well as within sibling clusters comparing pregnancies with discordant exposures. Propensity score (PS) adjustment included variables on indication for use (sleep problems, symptoms of anxiety and depression) and other potential confounding factors., Results: Long-term prenatal exposure to BZD or z-hypnotics was associated with increased internalizing behavior in crude cohort analyses and at age 1.5 years after PS adjustment in sibling-matched fixed-effect models [β 0.60, 95% confidence interval 0.17-0.95]. Analyses on specific drug groups showed that prenatal exposure to BZD-anxiolytics was associated with increased internalizing problems at both 1.5 years [β 0.25, 0.01-0.49] and 3 years [β 0.26, 0.002-0.52] while exposure to z-hypnotics was not associated with any adverse outcomes after adjustment., Conclusion: The findings suggest a moderate association between BZD-anxiolytic exposure and child internalizing problems that is not likely due to stable familial confounding factors.

Benzodiazepine-like drugs (z-hypnotics) are the most commonly used drugs for treatment of insomnia in Norway. Z-hypnotics are recommended for short-term treatment not exceeding 4 weeks. We aimed to study the use of z-hypnotics in the adult population in Norway with focus on recurrent use in new users, treatment intensity and co-medication with benzodiazepines and opioids in long-term users. Data were obtained from the Norwegian Prescription Database. New users in 2009 were followed through 2013. Recurrent z-hypnotic use was defined as new fillings at least once in each of the four 365-day follow-up periods. Age groups of 18-39, 40-64 and 65+ years were analysed separately for men and women. In 2013, 354,571 (8.9%) of the population filled at least one prescription of z-hypnotics and the prevalence was relatively stable over time. Among the 92,911 new users of z-hypnotics in 2009, 13,996 (16.8%) received z-hypnotics all four 365-day periods of follow-up. In these long-term recurrent users, the treatment intensity was high already the second year, with mean annual amounts of 199 and 169 DDDs per patient in men and women, respectively. The interquartile differences were greatest in the youngest age group. 27.9% of the long-term recurrent users of z-hypnotics used benzodiazepines the fourth year and 33.9% used opioids. The proportions with co-medication increased with level of z-hypnotic treatment intensity. Overall, many z-hypnotic users had medicines dispensed for longer periods than recommended, and co-medications with drugs that may reinforce the central depressing and intoxicating effects were common., (© 2016 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).)

Background: Benzodiazepines are frequently prescribed to patients with drug use disorders. However, it has previously been difficult to distinguish whether this frequent prescribing was due to underlying psychiatric disorders or inappropriate prescribing. In a nationwide cohort study, we investigated the prescribing of benzodiazepines to patients with drug use disorders in connection with treatment admission., Methods: Benzodiazepine prescriptions to patients (N = 33203) aged 18 to 67 years admitting for outpatient treatment for drug use disorders in Denmark, 2000 to 2010, were studied by using linked data from nationwide health registries. Factors associated with increasing amounts of benzodiazepine use within the first year after admission were assessed by multinomial logistic regression. Proportions of very long-term benzodiazepine prescription were calculated., Results: During the first year after admission to treatment, 26.2 % of patients were prescribed benzodiazepines. Of these, 35.5 % were prescribed benzodiazepines at dose levels that might indicate inappropriate use (>365 Defined Daily Dose per year), and 34.6 % were prescribed more than one type of benzodiazepines. Diazepam was the most commonly prescribed type. Among patients with opioid use, 43.2 % were prescribed benzodiazepines which were three times higher than for patients with cannabis (12.2 %) or central stimulating drugs (13.8 %) as their primary drug use. Admitting to treatment for a drug use disorder did not increase the specialized psychiatric treatment coverage of this patient group, disregarding use of prescribed benzodiazepines. 29.5 % were new users of prescribed benzodiazepines, and of these, 27.5 % continued into very long-term use (≥4 years after admission) during the study period., Conclusions: Benzodiazepines were commonly prescribed to patients admitting to treatment for drug use disorders, and included prescription of multiple and non-optimal types, high doses, and very long-term prescriptions. These findings point towards inappropriate prescribing of benzodiazepines in many cases more than treatment for psychiatric disorders.

Purpose: The study aimed to describe the dispensing of benzodiazepines and benzodiazepine-related drugs (z-hypnotics) to pregnant women and to study the characteristics of these women and the extent of co-medication., Methods: A population-based cohort study was conducted based on the linkage of nationwide registries: the Medical Birth Registry of Norway and the Norwegian Prescription Database. The data covers dispensed drugs to women 3 months prior to, during and after pregnancy. The study population consisted of 345,703 singleton pregnancies during a period starting 1 April 2004 or later and ending before 1 January 2011., Results: In 5,135 (1.5 %) of the pregnancies, the women were dispensed a benzodiazepine or z-hypnotic at least once. Of these, 68.5 % filled just one prescription for the duration of the pregnancy. Prevalence was lower in pregnancy than before and after pregnancy. The median total amount of benzodiazepines and/or z-hypnotics dispensed during pregnancy was 15 defined daily doses (DDDs), while the 25 % receiving the largest amounts got 40 DDDs or more. Five hundred eleven women, the 10 % that were prescribed the largest amounts during pregnancy, received a median amount of 220 DDDs. Women receiving these drugs were older, more often smokers, without a partner and suffering from chronic disease. Of the medicated pregnant women, 19.6 % and 19.3 % were also prescribed an opioid and antidepressant, respectively., Conclusions: The use of benzodiazepines and z-hypnotic drugs during pregnancy was not very prevalent in Norway. However, our findings imply that there is a substantial number of pregnancies where these drugs are dispensed often and/or in large quantities and where co-medication occurred.

In previous studies on prescription patterns of opioids, accurate data on pain are missing, and previous epidemiological studies of pain lack accurate data on opioid use. The present linkage study, which investigates the relationship between pain and opioid use, is based on accurate individual data from the complete national Norwegian prescription database and the Nord-Trøndelag health study 3, which includes about 46,000 people. Baseline data were collected in 2006 to 2008, and the cohort was followed up for 3 years. Of 14,477 people who reported chronic nonmalignant pain, 85% did not use opioids at all, 3% used opioids persistently, and 12% used opioids occasionally. Even in the group reporting severe or very severe chronic pain, the number not using opioids (2680) was far higher than the number who used opioids persistently (304). However, three quarters of people using opioids persistently reported strong or very strong pain in spite of the medication. Risk factors for the people with chronic pain who were not persistent opioid users at baseline to use opioids persistently 3 years later were occasional use of opioids, prescription of >100 defined daily doses per year of benzodiazepines, physical inactivity, reports of strong pain intensity, and prescription of drugs from 8 or more Anatomical Therapeutic Chemical groups. The study showed that most people having chronic nonmalignant pain are not using opioids, even if the pain is strong or very strong. However, the vast majority of patients with persistent opioid use report strong or very strong pain in spite of opioid treatment., (Copyright © 2014 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.)

Aims: This study describes the use of prescribed drugs among women in opioid maintenance treatment (OMT) prior to, and during, pregnancy., Design: This cohort study was based on data from two nationwide databases: the Medical Birth Registry of Norway and the Norwegian Prescription Database., Setting: Norway, 2004-2010., Participants: OMT drugs were dispensed to 138 women with 159 pregnancies., Measurements: All prescription drugs dispensed to women in OMT three months prior to, and during, pregnancy were studied. Amounts of benzodiazepines, z-hypnotics and opioid analgesics dispensed during pregnancy were studied and bivariate analysis was used to study neonatal outcomes of OMT pregnancies with and without such co-medication., Findings: The prevalence of prescription drug use by pregnant OMT women was high both during the three-month period prior to (69%), and during (81%), pregnancy. The proportion of pregnant women that was dispensed anti-infectives (48%) and/or drugs acting on the nervous system (45%) during any time in pregnancy was especially high. In 21%, 15% and 13% of the pregnancies the women were dispensed benzodiazepine anxiolytics, opioid analgesics or benzodiazepine hypnotics respectively. Only 5% of the OMT women were dispensed antidepressants. Malformations were significantly more common among children born to mothers in OMT that received co-medication with opioids, benzodiazepines or z-hypnotics., Conclusions: A higher proportion of women in opioid maintenance treatment in Norway use prescription drugs prior to, and during, pregnancy than pregnant women in the general population. Co-medication with drugs with abuse potential may increase the risk of adverse pregnancy outcomes and this need to be further addressed., (© 2012 The Authors, Addiction © 2012 Society for the Study of Addiction.)

Background: According to published guidelines regarding the use of benzodiazepines or z-hypnotics (BZD-Z), the elderly should avoid hypnotic BZD, and use anxiolytic BZD and z-hypnotics only at low doses and for a short time. Our objective is to quantify inappropriate BZD-Z use in the elderly., Methods: The study population consisted of people aged 70-89 who filled at least two prescriptions in 2008 within one of three subgroups: anxiolytic BZD, hypnotics BZD, or z-hypnotics. Inappropriate use criteria used for this study were (1) any hypnotic BZD, (2) exceeding 300 DDD, or a dosage exceeding 9 DDD/week, or anxiolytic BZD and z-hypnotics use exceeding 30 weeks., Results: 118,526 persons, or 25% of elderly Norwegians, filled at least two prescriptions for one of these medication subgroups. Inappropriate use was found for 25% of anxiolytic BZD users, 100% of hypnotic BZD users, and 65% of z-hypnotic users. Altogether 57,276 elderly Norwegians, or 12.3% of the elderly source population, used BZD-Z inappropriately as defined in this study., Conclusions: Clearly, inappropriate use of BZD-Z is widespread. An active response to such noncompliance with existing guidelines could consist of either (1) stricter enforcement of guidelines or (2) revamping guidelines through a fresh look at risks, benefits, and treatment practices. The implications of both options are discussed in some detail., (Copyright © 2012. Published by Elsevier B.V.)

Background: The various benzodiazepines have essentially the same mechanism of action and differ from one another primarily through differences in pharmacokinetics. There is no pharmacological basis for using more than one benzodiazepine for the same patient. The purpose of the study was to examine the occurence of co-medication with different types of benzodiazepines in Norway., Material and Method: Data were obtained from the Norwegian Prescription Database. Patients who received at least one benzodiazepine in 2008 were included (n = 299,185). The percentage of users who were co-medicated with at least two different benzodiazepines and the amounts prescribed were calculated and stratified by gender and age., Results: It is highly probably that 27,861 (14,6%) of patients who received at least two benzodiazepines in the course of 2008 used two different benzodiazepines simultaneously. 13,267 (6.9%) of the patients were prescribed at least two different benzodiazepines on the same prescription. A larger number of women were co-medicated with different benzodiazepines, but the proportion of comedication was higher in men than in women, and most frequent in the age group 18-49 years., Interpretation: There is an extensive and unfortunate prescription practice whereby the same patient is prescribed different benzodiazepines that are used concurrently. Patients who use different benzodiazepines concurrently are mainly prescribed these by one and the same doctor.

Purpose: The use of restricted medications, for example, opioids, benzodiazepines (BZD), and z-hypnotics, in the older persons continues to increase. Little is known about usage practices or about the extent of polypharmacy within this group. The objectives of this study were (i) to describe polypharmacy and (ii) to develop a medication usage index (MUI) to quantify usage patterns., Methods: Data for 2008 were obtained from the Norwegian Prescription Database containing all prescriptions filled in Norwegian pharmacies. The study population included people aged 70-89 years who filled prescriptions for weak opioids, strong opioids, anxiolytic BZD, hypnotic BZD, and/or z-hypnotics. A MUI was developed based on Anatomical Therapeutic Chemical codes, defined daily doses, Anatomical Therapeutic Chemical subgroups, and number of prescribers., Results: Forty-two percent of elderly Norwegians filled at least one prescription in one of the medication subgroups in 2008. MUI Level 1 (least) usage was shown by 56.6% of users (23.8% of the general population), Level 2 by 29.7% (12.5%), Level 3 by 11.3% (4.8%), and Level 4 (most) by 2.4% (1.0%). People using strong opioids were the most likely to use other restricted medications. In addition, female participants had a higher MUI than did male participants, and older users higher than younger users. Cancer or palliative care patients attained twice the MUI points than did the others., Conclusions: Polypharmacy was found to be common within these restricted drug categories for the older persons. MUI provides a convenient approach to summarizing drug usage and will be useful in detecting trends and regional differences and determining the impact of interventions., (Copyright © 2011 John Wiley & Sons, Ltd.)

Purpose: The aim of the study was to describe the use of prescribed opioid analgesics for noncancer pain and the degree of possible concurrent co-medication with benzodiazepines to women in Norway before, during, and after pregnancy., Methods: This was a population-based cohort study based on linkage of two nationwide registries: the Medical Birth Registry of Norway, and the Norwegian Prescription Database. Prescribed opioid analgesics and benzodiazepines issued to women 3 months prior to, during, and 3 months after pregnancies were identified. The study population consisted of 194,937 singleton pregnancies beginning in March 2004 or later and ending before January 2009., Results: About 6% of the women were dispensed opioid analgesics before, during, or after pregnancy. Almost all these women received weak opioids (99%) with short-acting codeine in combination with paracetamol (acetaminophen) as the most frequently dispensed drug. The dispensing of codeine was reduced from 24/1,000 women before pregnancy to 10/1,000 in the last trimester, increasing to 17/1,000 during the breastfeeding period. Most women were dispensed codeine once, and treatment was of short duration (about 1 week). A small group of women (n = 271) were dispensed opioids in all trimesters. Increasing benzodiazepine use was observed as the number of opioid prescriptions increased., Conclusions: The use of opioid analgesics in pregnant women in Norway was dominated by treatment of short duration of the weak opioid codeine. As pregnancy proceeded, opioid use was reduced. However, the increase in opioid use during the nursing period has the potential for serious adverse effects.

Pregabalin (Lyrica(®) ) may have an anxiolytic effect. It has also been reported that the use of this drug helps prevent excessive use of benzodiazepines. The aim of the present study was to examine if pregabalin reduced the intake of benzodiazepines. In a pharmacoepidemiological study, we compared pregabalin to the older drug gabapentin (Neurontin(®) ) in the Norwegian Prescription Database. The database has total capture of all prescribed drugs outside institutions. We identified all prescriptions for the two drugs for patients aged 18-69 years between 2004 and 2007. Patients were grouped as psychiatric patients, patients with epilepsy, patients with neuropathic pain or non-specified users. We measured the use of benzodiazepines 182 days before and after the initiation of treatment with pregabalin and gabapentin. Between 15% and 29% of the patients were able to stop using benzodiazepines after starting pregabalin or gabapentin treatment. Psychiatric patients who started pregabalin were able to reduce the amount of benzodiazepines used by 48%, compared to only 14% among starters of gabapentin. This study shows that some patients reduced their use of benzodiazepines substantially after starting pregabalin., (© 2010 The Authors. Basic & Clinical Pharmacology & Toxicology © 2010 Nordic Pharmacological Society.)

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.

Objective: To evaluate the effect of the use of benzodiazepines on prescription of opioids 4-7 years later in patients with noncancer pain., Design: A cohort of 7,991 men and 9,083 women aged 40, 45 and 60 years who reported no use of opioids in health surveys in 2000-2001 was linked to the nationwide Norwegian Prescription Database, and their prescriptions of opioids during 2004-2007 were analyzed. Moderate-high prescription frequency of opioids was defined as at least 12 prescriptions during the period January 2004-December 2007., Results: The unadjusted odds ratio for moderate-high prescription frequency of opioids for individuals who had previously used benzodiazepines was 7.7 (95% confidence interval 5.6-10.5) as compared with previous nonusers. After adjustment for musculoskeletal pain, alcohol, smoking habits, and socioeconomic variables, the odds ratio was lowered to 3.1 (2.1-4.6). The analysis of the effect of benzodiazepines and chronic pain individually and in combination suggest that use of benzodiazepines is an even stronger predictor of later opioid use than self-reported chronic pain., Conclusions: Our study suggests that earlier use of benzodiazepines may predict repeated use of opioids. Before starting pain treatment with opioids, clinicians should take into consideration the possibility of substance abuse and mental health disorders. A central issue when prescribing opioids for chronic noncancer pain is to balance the risk of problematic use of these drugs with the benefits of pain relief.

The proportion of Norwegians on disability pensions has doubled since the 1980s. The Norwegian Government wants action to stimulate the working capacity in those disability pensioners who have the potential to work. Information on factors that may impair rehabilitation efforts, including the unfavourable use of benzodiazepines, may be useful in this context. A longitudinal design, including data on 40-42 year old participants in Norwegian health surveys (year 1985-1989) linked to a prescription database (year 2004-2006), was used to describe risk of long-term use of benzodiazepines among disability pension recipients. The study population constituted benzodiazepine users at baseline. More than half of those on disability pensions, 57% of all men and 65% of all women, retrieved benzodiazepine prescriptions 20 years later, a span covering a large part of the potential active workforce period. Further, the observed amount of benzodiazepines dispensed over a three-year period indicated more than sporadic use e.g. half of the female disability pensioners were dispensed an amount of benzodiazepines corresponding to the use of a daily dose every second day over a three year period (median 450 daily doses). The majority of those who were dispensed benzodiazepines, were dispensed opioids as well: half of all men and 3 out of four women. And last, being on a disability pension was a predictor of benzodiazepine use 20 years later. Our study suggests that benzodiazepines are extensively and unfavourably used among disability pensioners, and that disability pension may have an independent effect on long-term use. Improved management of benzodiazepine use may be one alternative to get disability pensioners with the potential to work back into employment., (Copyright 2009 Elsevier Ltd. All rights reserved.)

Aim: The Norwegian government states that actions are needed to stimulate working capacity in disability pension (DP) recipients with such a potential. Identification of factors that may impair rehabilitation efforts, such as information on the start of benzodiazepines in DP recipients, may be useful in this context.Thus, the aim of the study was to describe the association between receipt of DP and later prescriptions of benzodiazepines among non-users at baseline., Methods: We followed a cohort reporting non-use of benzodiazepines, 6645 men and 6455 women aged 40-42 years who underwent health surveys in 1985-89 in two Norwegian counties, with respect to subsequent use of benzodiazepines by linkage to the Norwegian Prescription Database for 2004-2006. At baseline, 83 men and 163 women reported receiving DP., Results: In both genders, the proportion started on at least one prescription of a benzodiazepine was approximately doubled among those reporting being on a DP 20 years in the past, 21% of all men and 29% of all women, respectively. Univariate odds ratios for a benzodiazepine prescription for men and women on a DP were 2.6 (95% confidence interval (CI) = 1.5-4.4) and 2.1 (95% CI = 1.5-2.9), respectively, as compared with those not receiving a DP. After adjustment for alcohol use, smoking habits, physical activity, socioeconomic and health variables, the odds ratios were lowered for both genders, being 2.1 (95% CI = 1.2-3.7) (men) and 1.6 (95% CI = 1.1-2.3) (women)., Conclusions: For both men and women, the chance of being prescribed benzodiazepines was higher among those reporting being DP recipients 20 years in the past.

Purpose: Drugs prescribed for the treatment of insomnia can be either benzodiazepine hypnotics or the newer z-hypnotics, zopiclone and zolpidem. This paper explores possible explanations for the choice made., Methods: Data from the Norwegian Prescription Database covering the entire population was studied for incident users of hypnotics. Possible predictors were age, gender, previous psychotropic or analgesic drug use and prescriber speciality., Results: Of the 73,163 incident users of hypnotics, 3876 were prescribed benzodiazepine hypnotics in 2006. The strongest predictors for being prescribed benzodiazepines were previous use of anxiolytics [odds ratio (OR) 1.8, 95% confidence interval (CI) 1.7-2.0] and male gender (OR 1.5, 95% CI 1.4-1.6). Other significant predictors were antipsychotic or opioid drug use and the prescriber being a psychiatrist., Conclusions: Z-hypnotics were commonly prescribed. Norwegian drug therapy recommendations also suggest a preference for z-hypnotics. The clear predominance of the shorter acting z-hypnotics may be due to the fact that only longer acting benzodiazepines are available in Norway. Reasons for prescribing benzodiazepines may be co-morbid psychiatric illness, such as anxiety, or a belief that benzodiazepine hypnotics are more effective than z-hypnotics.

Purpose: To evaluate the effect of the consumption of benzodiazepines at age 40-42 years on prescription of opioids later in life., Methods: A cohort of 6707 men and 6683 women aged 40-42 years reported no use of analgesics in health surveys in 1985-1989. This cohort was linked to the Norwegian prescription database (NorPD) and their prescriptions of opioids during 2004-2006 were analysed. Low-high, moderate-high and high prescription frequency of opioids were defined as at least 6, 12 or 16 prescriptions during January 2004-December 2006. Non-steroid anti-inflammatory drugs (NSAIDs) were used as comparators., Results: The unadjusted odds ratios (ORs) for low-high prescription frequency of opioids for men and women using benzodiazepines were 3.8 (95%CI 2.5-5.7) and 3.4 (2.6-4.4), respectively, as compared with non-users. After adjustment for alcohol, smoking habits and socio-economic variables, the ORs were lowered for both sexes: 2.6 (1.7-4.0) in men and 2.5 (1.9-3.3) in women. The adjusted OR for those with high prescription of opioids was higher for both sexes: 4.5 (2.4-8.5) in men and 3.7 (2.4-5.7) in women. A stratified analysis revealed no relationship between benzodiazepine use and later low and moderate prescription frequency of opioids among teetotallers. The adjusted ORs for low-high prescription frequency NSAID use for men and women using benzodiazepines were 1.6 (1.1-2.4) and 1.6 (1.3-2.0), respectively., Conclusion: In this study population, a history of benzodiazepine use raised the chance of being prescribed opioids later in life among those who also used alcohol.

Purpose: The aim of this study was to examine the risk of a car driver being involved in a road traffic accident while using prescribed drugs. We used data from population-based registries., Methods: Information on prescriptions, road traffic accidents, and emigrations/deaths was obtained from population-based registries. The incidence of accidents in the exposed person-time was compared with the incidence in the unexposed person-time, by the standardized incidence ratio (SIR). All Norwegians ages 18-69 between April 2004 and September 2005 (3.1 million), were included in the study., Results: A total of 13,000 road traffic accidents with personal injuries were registered. The risk of being involved in an accident was somewhat increased in users of prescribed drugs in the first seven days after the date of dispensing (SIR for both sexes combined=1.4; 95% confidence interval: 1.3-1.5). The risk was markedly increased in users of natural opium alkaloids (2.0; 1.7-2.4), benzodiazepine tranquillizers (2.9; 2.5-3.5), and benzodiazepine hypnotics (3.3; 2.1-4.7). Somewhat increased or unchanged SIRs were found for nonsteroidal antiiflammatory drugs (1.5; 1.3-1.9), selective beta-2-adrenoreceptor agonists (i.e., antiasthmatics, 1.5; 1.0-2.1), calcium receptor antagonists (0.9; 0.5-1.5), and penicillin (1.1; 0.8-1.5)., Conclusions: The increased risk of being involved in a road accident as driver while receiving prescribed opiates and benzodiazepines supported the results from other studies.

Objective: To study how the various 25 subtests and observations of the Norwegian clinical test for impairment related to the blood benzodiazepine concentrations of apprehended drivers suspected of driving under the influence of benzodiazepines. The impact of single-dose intake in non-daily users of benzodiazepines on the clinical picture of inebriation was also studied., Methods: Included in the study were 818 drivers suspected of driving under the influence of non-alcoholic drugs with blood samples containing only one benzodiazepine. We determined which of the 25 subtests and observations of the clinical test for impairment related significantly to the blood benzodiazepine concentrations., Results: Significantly related to blood benzodiazepine concentrations were 13 subtests and observations. Of these, 9 withstood adjustment for a variety of background variables. Single dose intake in non-daily users only influenced 3 subtests and observations after adjustment for blood benzodiazepine concentration and background variables. Romberg's test, 1 observation concerning alertness (oriented for time and place), 4 tests on motor and coordination (walk and turn on line, finger-to-nose and finger-to-finger tests), 2 observations on speech (articulation and content) and 1 observation regarding appearance (general conduct) were related to blood benzodiazepine concentrations., Conclusion: Many of these simple clinical tests are included in the standardized field sobriety test and are of value in revealing benzodiazepine impairment. The present study offered some possible additions. Combinations of these robust tests can also be used to reveal benzodiazepine inebriation in other contexts.

Background: Acute intake of benzodiazepines is followed by concentration-dependent deterioration of performance in controlled experimental studies. Whether this is true in a population of benzodiazepine users is uncertain. We studied the relationship in a population of suspected drugged drivers., Methods: In Norway physicians examine and take blood samples from nearly all suspected drivers. Our material comprised 818 samples containing only one benzodiazepine and our reference group consisted of 10,759 cases containing only alcohol., Results: 159 drivers (19%) were considered as not impaired and 659 (81%) as impaired. None of the background factors, e.g. gender, age or time of day when apprehended, related significantly to either the physician's conclusion or to blood levels of benzodiazepines. Impaired subjects had significantly higher blood levels of diazepam (n=411) (P<0.001), oxazepam (n=73) (P<0.05) and flunitrazepam (n=211) (P<0.05) than those not impaired. The risk of being assessed as impaired did rise with increasing benzodiazepine blood level, with odds ratios (ORs) for being assessed as impaired of 1.61, 3.65 and 4.11 for the three supratherapeutic drug levels. The corresponding OR found for different elevated blood-alcohol concentrations were 1.49, 2.94 and 10.49., Conclusion: The blood concentration of benzodiazepines was the only characteristic which was related to impairment. This indicated a drug-concentration related effect of benzodiazepines on performance and paves the way for a discussion on legal limits for benzodiazepines in relation to driving.

Norwegian drugged drivers with benzodiazepine (BZD) detections have been studied with regard to drug use pattern and rearrest rate. During 1995, 3343 drivers were apprehended by the police in Norway due to the suspicion of influence by drugs. Blood samples from all drivers were sent to the National Institute of Forensic Toxicology (NIFT). The samples were analysed using a standard program covering the most commonly abused drugs on the marked in Norway. BZDs, representing some of the most frequently detected drugs, were found in approximately 30% (n = 1051) of the cases, represented by 14% (n = 150) female and 86% (n = 901) male drivers. In 8% of the cases, one BZD only was detected, half of these cases with one BZD could reflect therapeutic use. One or more BZDs were combined with illegal drug(s) (73%), other prescribed drugs (10%), and/or alcohol (24%). 62% of the drivers with BZD detections, had earlier been arrested for the same offence, or six cases per rearrested driver. The frequency of earlier arrests were lower for female (34%) than for male (67%) drivers. Alcohol was most frequently found for those arrested for the first time before 1992, while BZD or illegal drugs were most frequently found for those with their first arrest during 1992-1995. Our study shows that apprehended drivers using BZD are mainly represented by drug abusers due to frequent multi-drug use, blood concentrations representing doses above therapeutic levels and high rearrest rate for the same offence. A treatment program or other reactions, are thus necessary in addition to fines, prison penalty and suspension of driving licence.

Abstract\nKEY POINTSObjective Is the involvement of the regular general practitioner (GP) in the decision to initiate opioid treatment for chronic non-cancer pain (CNCP) associated with two main risk factors for serious adverse events: increased opioid dose and the concomitant use of prescribed benzodiazepines or benzodiazepine-related medications? Design and setting An anonymous web-based survey was conducted in the county of Rogaland, Norway, during the spring of 2021. Subjects GPs who self-reported applying at least once for reimbursement of opioids prescribed to treat CNCP. They were asked to answer the survey based on the last patient for whom they recalled submitting a reimbursement application. Main outcome measures 1) Total opioid dose in daily oral morphine equivalents (OMEQ). 2) Concurrent use of benzodiazepines and/or benzodiazepine-related drugs. Results The daily opioid dose was lower when the surveyed GPs initiated the opioid treatment (36 OMEQ, n = 25), than when others had initiated the treatment (108 OMEQ, n = 31, p = 0.001). For concurrent use of benzodiazepine or benzodiazepine-related drugs, no significant difference was found (33%, n = 9 with GP involvement vs. 47%, n = 16, p = 0.279 with no GP involvement). Conclusions GP involvement in the initiation of opioid medication for CNCP was associated with a lower opioid dose being prescribed. Implications GP involvement in the initiation of opioid prescriptions may facilitate safer prescribing.Opioid treatment against chronic non-cancer pain (CNCP) can be reimbursed in Norway. High opioid doses and the concomitant use of other medications with addictive properties, particularly benzodiazepines, increase the risk of serious adverse events. When the general practitioner (GP) in the survey had initiated the opioid treatment, this was associated with a lower opioid dose, but not with less concomitant use of benzodiazepines. [ABSTRACT FROM AUTHOR]

Purpose: Opioid analgesics (OA) and other pharmaceuticals have been associated with drug‐induced deaths. However, there is a lack of knowledge regarding patterns of use of these pharmaceuticals in the population and regarding such associations. We identify and describe subgroups of people with different patterns of filled prescriptions of OA and other relevant pharmaceuticals and examine associations with drug‐induced deaths. In addition, we estimate the proportion of drug‐induced deaths with a filled OA prescription and OA as cause of death. Methods: A Norwegian population‐based nested case‐control register study with cases (drug‐induced deaths 2010–2018, N = 2388) and population controls matched for age, gender and year of inclusion (N = 21 465). Patterns of filled prescriptions for opioid analgesics (OA), benzodiazepines and benzodiazepine‐related drugs, gabapentinoids, ADHD medication and antidepressants/antipsychotics were explored by k‐means cluster analysis. Associations with drug‐induced deaths were estimated by conditional logistic regression adjusted for sociodemographic characteristics. Overlap of filled OA prescriptions and OA as cause of death was estimated. Results: Five clusters were identified: 'few prescriptions', 'weak OA', 'ADHD medication', 'sedative/psychiatric morbidity' and 'strong OA'. The 'strong OA' cluster had higher socioeconomic status compared to the other groupings. The risk of drug‐induced death was also highest in this cluster (OR = 35.5; CI 25.6–49.3) and, for 68% (CI 64–73) of cases, filled prescriptions for OA was indicated as the underlying cause of death. Conclusions: The cluster analysis identified a subgroup with filled prescriptions of OA and other pharmaceuticals and a higher socioeconomic status than other subgroups. This subgroup had a high risk of drug‐induced death that needs to be addressed. [ABSTRACT FROM AUTHOR]

The ongoing opioid epidemic has been a global concern for years, increasingly due to its heavy toll on young people's lives and prospects. Few studies have investigated trends in use of the wider range of drugs prescribed to alleviate pain, psychological distress and insomnia in children, adolescents and young adults. Our aim was to study dispensation as a proxy for use of prescription analgesics, anxiolytics and hypnotics across age groups (0–29 years) and sex over the last 15 years in a large, representative general population. The study used data from a nationwide prescription database, which included information on all drugs dispensed from any pharmacy in Norway from 2004 through 2019. Age-specific trends revealed that the prevalence of use among children and adolescents up to age 14 was consistently low, with the exception of a substantial increase in use of melatonin from age 5. From age 15–29, adolescents and young adults used more prescription drugs with increasing age at all time points, especially analgesics and drugs with higher potential for misuse. Time trends also revealed that children from age 5 were increasingly dispensed melatonin over time, while adolescents from age 15 were increasingly dispensed analgesics, including opioids, gabapentinoids and paracetamol. In contrast, use of benzodiazepines and z-hypnotics slightly declined in young adults over time. Although trends were similar for both sexes, females used more prescription drugs than their male peers overall. The upsurge in use of prescription analgesics, anxiolytics and hypnotics among young people is alarming. Trial registration The study is part of the overarching Killing Pain project. The rationale behind the Killing Pain research was pre-registered through ClinicalTrials.gov on April 7, 2020. Registration number NCT04336605; https://clinicaltrials.gov/ct2/show/record/NCT04336605. [ABSTRACT FROM AUTHOR]

Increasing numbers survive cancers in childhood and adolescence. Long-term survivors of cancers in adulthood have increased prevalence of pain and consumption of analgesics. It is not established whether long-term survivors of cancers in childhood and adolescence also have an increased use of analgesics. However, based on increased use of antidepressants and anxiolytics in long-term survivors of cancers in childhood and adolescence, we hypothesized that this group also had increased use of analgesics. Based on data from the 2 nationwide registers, the Cancer Registry of Norway and the Norwegian Prescription Database, a cohort of 5585 (52% males) long-term survivors of cancers in childhood, adolescence, and early adult life was established. Age- and sex-adjusted comparisons were made to the general population. The age-adjusted one-year periodic prevalence of receiving prescriptions of opioids, benzodiazepines, and benzodiazepine-related hypnotics in the study population was increased by 20% to 50%, and the one-year periodic prevalence of receiving prescriptions of gabapentinoids was approximately increased 2-fold compared to the general population. For paracetamol and nonsteroidal anti-inflammatory drugs, no difference was found. For those survivors, who were persistent or high-dose users of opioids, comedication with high doses of benzodiazepines and/or benzodiazepine-related hypnotics was far more common than among persistent and high-dose opioid users in the general population. The high prevalence of gabapentinoids may indicate increased prevalence of neuropathic pain in this group. The high degree of comedication with benzodiazepines and/or benzodiazepine-related hypnotics in survivors on persistent and high-dose opioids might be an indication of problematic opioid use or addiction. [ABSTRACT FROM AUTHOR]

Background and Aims: There is limited data on hepatitis C (HCV) treatment uptake among people who inject drugs including individuals receiving opioid substitution treatment (OST). We aimed to calculate cumulative HCV treatment uptake, estimate annual treatment rates, and identify factors associated with HCV treatment among individuals who have received OST in Norway. Methods: This observational study was based on linked data from The Norwegian Prescription Database and The Norwegian Surveillance System for Communicable Diseases between 2004 and 2013. Both registries have national coverage. From a total of 9919 individuals who had been dispensed OST (methadone, buprenorphine or buprenorphine-naloxone), we included 3755 individuals who had been notified with HCV infection. In this population, dispensions of HCV treatment (pegylated interferon and ribavirin), benzodiazepines, selective serotonin reuptake inhibitors and antipsychotics were studied. Results: Among 3755 OST patients notified with HCV infection, 539 (14%) had received HCV treatment during the study period. Annual HCV treatment rates during OST ranged between 1.3% (95% confidence interval [CI] 0.7–2.2) in 2005 and 2.6% (95% CI 1.9–3.5) in 2008 with no significant changes over time. HCV treatment uptake was not associated with age or gender, but associated with duration of active OST (adjusted odds ratio [aOR] 1.11 per year; 95% CI 1.07–1.15), high (> 80%) OST continuity (aOR 1.62; 95% CI 1.17–2.25), and heavy benzodiazepine use (aOR 0.65; 95% CI 0.49–0.87). Conclusions: Cumulative HCV treatment uptake among OST patients notified with HCV infection in Norway between 2004 and 2013 was 14%. Annual treatment rates during OST remained unchanged below 3% per year. High continuity of OST over time and absence of heavy benzodiazepine use predicted HCV treatment uptake. Increased awareness for HCV among OST patients is needed as tolerable and efficient directly acting antiviral treatment is being introduced. [ABSTRACT FROM AUTHOR]

Aims. This study examined overdose deaths involving benzodiazepines and prescription opioids, and studied associated factors.Methods. In a retrospective registry study of drug-overdose deaths (n= 167) with post-mortem toxicological findings of benzodiazepines and/or opioids/carisoprodol (strong analgesics) in Oslo, Norway, from 2006 to 2008, prescribing and dispensing patterns were investigated, and factors associated with benzodiazepines and/or strong analgesics in post-mortem toxicology where these medications were not prescribed were identified.Results. Among deceased with toxicological findings of only benzodiazepines, 28.1% (20.7–36.9) had been dispensed benzodiazepines four weeks prior to death; only strong analgesics, 33.3% (13.0–61.3) had been dispensed strong analgesics; both benzodiazepines and strong analgesics, 58.3% (36.9–77.2) had been dispensed benzodiazepines and/or strong analgesics. Also, 33.0% of the deceased had five or more different prescribing physicians of either benzodiazepines or strong analgesics in the year prior to death. Doses of both dispensed benzodiazepines and strong analgesics were higher than recommended. Younger age and residing outside Oslo were associated with having benzodiazepines and/or strong analgesics in the toxicological findings when these medications had not been dispensed (p= 0.006 andp= 0.039, respectively).Conclusion. The majority of benzodiazepines and strong analgesics detected in overdose deaths were non-prescribed and/or associated with less than optimal prescribing practices by some treating physicians. [ABSTRACT FROM AUTHOR]

Background/aims: Increasing rates of overdose deaths involving opioid maintenance treatment (OMT) medications and particularly methadone have been observed concurrently with the implementation of liberal OMT strategies (i.e. minimum of control and high doses prescribed). This study examined methadone-related overdose deaths in a liberal OMT programme.Methods: Drug-overdose deaths (n = 130) with detection of methadone in Copenhagen, Aarhus, and Odense Municipality, Denmark, during the period 2008-2011 were identified from a registry. Cases with and without prescribed methadone as OMT were compared. Treatment delivery strategy among OMT-prescribed methadone cases was investigated.Results: Methadone was detected in 130 overdose deaths (71.4% of all overdose deaths). Among these, 63.1% were receiving methadone maintenance treatment. Of these, 79.3% had co-detection of benzodiazepines. Concomitant detection of heroin, non-prescribed benzodiazepines, and younger age were associated with having non-prescribed methadone in the toxicological findings (adjusted OR 3.1, 4.0 and 9.5, respectively). Of the decedents, 43.8% were prescribed a higher methadone dose than recommended (>120 mg daily), of which 80.0% did not have supervised intake of methadone.Conclusions: Liberal OMT access does not necessarily prevent overdose deaths overall. Prescription of higher doses of methadone combined with benzodiazepines may result in an increased risk of overdose for individuals in as well as outside OMT. [ABSTRACT FROM AUTHOR]

Purpose: Benzodiazepines/z-hypnotics (BZD-Z) guidelines suggest that elderly people ought to use anxiolytic benzodiazepines (BZD) and z-hypnotics only at low dose and only for a short time, and that hypnotic BZD not should be used at all. Since the elderly aged 65-79 tend to be recently retired but still in relatively good health, they may have different needs for BZD-Z than those older or younger. Our objective is to examine BZD-Z use in this age group. Methods: The study population consisted of Norwegians, aged 65-79, who filled prescriptions for anxiolytic BZD, hypnotic BZD and/or z-hypnotics in 2004-2009. The quantities prescribed were in daily defined doses (DDD), and 100 DDD/year was deemed excessive. Results: More than a quarter of the population received at least one BZD-Z prescription each year. Half of those received more than 100 DDD/year and a quarter received over 250 DDD/year, with these proportions increasing year by year. All three subgroups of BZD-Z showed increasing use with age and all except anxiolytic BZD showed increasing proportions of users using more than 100 DDD/year with age. Conclusions: Substantial numbers of elderly aged 65-79 receive prescriptions for BZD-Z, more with increasing age, and greater amounts per user. Guidelines are clearly ignored. While a rigid enforcement of guidelines/rules is not the answer, allowing the status quo to continue shows lack of respect for guidelines. [ABSTRACT FROM AUTHOR]

ABSTRACT Aims To investigate whether exposure to methadone affects the risk of motor vehicle accident with personal injury. Design Cohort study linking three Norwegian administrative registries using unique person identifiers. Setting Information was retrieved from the Norwegian Prescription Database on any prescriptions ever received by the individuals for methadone and all prescriptions for benzodiazepines. The Norwegian Road Accident Registry provided information about motor vehicle accidents involving personal injuries on Norwegian roads. The Central Population Registry provided demographic information on all residents in Norway. Participants All Norwegian adults aged 18-69 years were observed for 2.5 years. Measurements Standardized incidence ratio (SIR) was calculated by comparing the incidence of traffic accidents with personal injuries in patients exposed to methadone with the incidence in those not exposed. Findings During the 4626 person-years observed in patients exposed to methadone, there were 26 motor vehicle accidents. There were very few accidents among the females who received methadone and they had no increased risk of being involved in motor vehicle accidents (SIR 1.1; 95% CI 0.2-3.1). We observed an increased risk of involvement in accidents among males (SIR 2.4; 95% CI 1.5-3.6). This figure did not change significantly when exposure to benzodiazepines was excluded. Conclusions Men exposed to methadone appear to have an increased risk of being involved in motor vehicle accidents involving personal injuries. This increased risk could not be explained by exposure of benzodiazepines. [ABSTRACT FROM AUTHOR]

Abstract: When opioid therapy is initiated for a new pain condition, it may be unknown whether the pain will persist beyond the time of tissue healing. The aim of this study was to determine the prevalence of prescription patterns indicating persistent and/or problematic opioid use in a cohort of opioid-naive patients starting therapy with weak opioids. Data were drawn from the nationwide Norwegian Prescription Database. The study population was all new users of opioids receiving prescriptions of a weak opioid in 2005 for nonmalignant pain. This cohort was followed until December 2008. In order to be classified as having probable problematic opioid use, patients had to meet all of the following criteria: received opioids at least once every year from 2005 to 2008 and in 2008; (1) were dispensed more than 365 defined daily doses (DDDs) of opioids; (2) received opioid prescriptions from more than 3 doctors; and (3) were dispensed more than 100 DDDs of benzodiazepines. There were 245,006 persons who were new users of weak opioids in 2005 (216,902 codeine, 26,326 tramadol, 1778 dextropropoxyphene). There were 17,252 (7% of new users) who received a prescription for opioids at least once each of the 3 following years. Of these subjects, 686 patients were dispensed more than 365 DDDs of opioids in 2008 and are probably persistent users. There were 191 subjects who met our criteria for probable problematic opioid use. In a cohort of new opioid users who started treatment with weak opioids, only 0.3% and 0.08% developed prescription patterns indicating persistent opioid use and problematic opioid use, respectively. A national Norwegian cohort of new users of weak opioids was followed from 2005 until 2009; only 0.08% developed problematic opioid use. [Copyright &y& Elsevier]

Pregabalin (Lyrica®) may have an anxiolytic effect. It has also been reported that the use of this drug helps prevent excessive use of benzodiazepines. The aim of the present study was to examine if pregabalin reduced the intake of benzodiazepines. In a pharmacoepidemiological study, we compared pregabalin to the older drug gabapentin (Neurontin®) in the Norwegian Prescription Database. The database has total capture of all prescribed drugs outside institutions. We identified all prescriptions for the two drugs for patients aged 18-69 years between 2004 and 2007. Patients were grouped as psychiatric patients, patients with epilepsy, patients with neuropathic pain or non-specified users. We measured the use of benzodiazepines 182 days before and after the initiation of treatment with pregabalin and gabapentin. Between 15% and 29% of the patients were able to stop using benzodiazepines after starting pregabalin or gabapentin treatment. Psychiatric patients who started pregabalin were able to reduce the amount of benzodiazepines used by 48%, compared to only 14% among starters of gabapentin. This study shows that some patients reduced their use of benzodiazepines substantially after starting pregabalin. [ABSTRACT FROM AUTHOR]

Abstract: The aim was to study the introduction of the new low dose transdermal buprenorphine (LD-TD-BUP) in Norway, particularly with regard to former use and co-medication with other potentially addictive drugs. The nationwide Norwegian Prescription Database contains information on all prescription drugs dispensed to individual non-institutionalised patients, and we may follow all individuals who received LD-TD-BUP (Norspan®) after marketing on the Norwegian market on 15/11/05. We studied all prescriptions of opioids and other potentially addictive drugs to patients receiving at least two LD-TD-BUP prescriptions during 2004–2006. Poisson regressions were run with concomitant use of addictive drugs (yes, no) as the endpoint. Overall, 1884, non cancer individuals received at least two prescription of LD-TD-BUP. Of these 91.7% received prescriptions of other opioids and 58.6% of them had also been prescribed benzodiazepines/carisoprodol before the prescription of LD-TD-BUP. Of the LD-TD-BUP users who received more than one prescription, 60% co-medicated with at least one other potentially addictive drug, and 24% with at least two. In the multivariate analysis, the variables associated with a higher likelihood of using co-medicated drugs were: previous use of benzodiazepines/carisoprodol relative risk RR=16.7 (95% CI 10.4–26.9), previous use of opioids RR=4.0 (1.9–8.7) and younger age 20–40 years RR=1.9 (1.6–2.3). So far, it is questionable whether the introduction of LD-TD-BUP actually has stabilised opioids consumption or whether it has complicated and increased the consumption of potentially addictive drugs. [Copyright &y& Elsevier]

Abstract: Benzodiazepines are sedatives used for anxiolysis, hypnosis, muscle relaxation and the treatment of epilepsy. Paradoxical reactions including agitation, talkativeness, confusion, disinhibition, aggression, violent behavior and loss of impulse control may, however, occur in some subjects. It has been claimed that high doses of flunitrazepam may cause aggression on a more regular basis in all individuals. The present study makes use of a Norwegian forensic toxicological database containing analytical results from drivers suspected of driving under the influence and suspects of violent crime to analyze the relationship between behavior and blood flunitrazepam concentration. Four-hundred and fifteen cases of drivers suspected of driving under the influence and seven cases of suspects of violent crime were studied. These selected cases had flunitrazepam as the only drug in blood samples and had been evaluated by a clinical test for impairment (CTI) performed by a police physician at the time of blood sampling. The impaired drivers had higher blood flunitrazepam concentrations than the not impaired drivers. Multivariate analysis revealed that both blood flunitrazepam concentration and age of the suspected drivers had independent impact on impairment, indicating tolerance with age. Most of the effects measured were sedative effects of flunitrazepam and these effects were related to flunitrazepam level. Possible paradoxical reactions were observed in a subgroup of 23 individuals (6%), but these reactions did not relate to blood flunitrazepam concentration. The suspects of violent crime showed similar degree impairment and had not more paradoxical reactions than the suspected drugged drivers. The findings were in agreement with other research that claims paradoxical reactions should be viewed as a reaction in certain individuals, and does not support the notion that flunitrazepam in high concentration produces aggression in all individuals taking the drug. [Copyright &y& Elsevier]

The article discusses the study of prescription drug abuse in pregnant women. The author comments on the risk factors of substance abuse specifically benzodiazepines, reporting of diseases, and tranquilizing drugs. Other topics mentioned include mental illnesses and mental health of pregnant women as well as drug addiction.

Objective: To study patterns of antidepressant, anxiolytic, and hypnotic drug utilization in Denmark, Norway, and Sweden during the first year of the COVID-19 pandemic.Methods: The monthly observed number of prescription fills of antidepressants, benzodiazepines and benzodiazepine-related hypnotics (BZ), and other anxiolytics and hypnotics (OAH) per population in 2020 were compared with predicted numbers based on analysis of covariance of prescription fills during 2015-2019.Results: In March 2020, there was an increased number of prescription fills for antidepressants, anxiolytics, and hypnotics in youths and adults aged 20-59 years in Denmark, Norway, and Sweden. Antidepressant prescription fills increased between 13.5 % and 31.3 % at the end of 2020 in all age groups in Denmark and 17.4 % in youths in Norway. BZ drug prescription fills increased by 20.8 % at the end of 2020 in the 20-59 year age group in Denmark and decreased by 16.7 % in youths in Sweden. A general increase of prescription fills of OAH at the end of 2020 was observed in all countries (range 24.0-80.0 % in Denmark, 11.5-30.8 % in Norway, and 9.1-12.1 % in Sweden). Increases of prescription fills of OAH occurred earlier in Denmark.Limitations: Aggregated data with lack of information on indications.Conclusions: Peaks of utilization of antidepressants, anxiolytics, and hypnotics observed in March 2020 may reflect medication stock piling. Increased antidepressant drug utilization in Denmark and in Norwegian youths together with the general increase in OAH utilization in the Scandinavian countries in late 2020 may indicate an increase of symptoms of depression and anxiety, as well as disturbed sleep. [ABSTRACT FROM AUTHOR]

Objectives: The Norwegian Government urges that actions are needed to stimulate the working capacity in disability pensioners (DPs) with such a potential. Information on factors that may impair rehabilitation efforts, including use of potentially addictive drugs, may be useful in this context. Thus, the aim was to study the association between DP on initiation as well as long-term use of benzodiazepines (BZDs), and to describe aspects of problematic use of BZDs in terms of: long-term use pattern, including escalation of dose over time, and use of other potentially addictive drugs. Methods: We followed a cohort of 8,942 men and 10,578 women aged 40, 45, 60 years (non-users of BZDs at baseline), who participated in health surveys in 2000-01 in three Norwegian counties, with respect to use of BZDs, and other potentially addictive drugs, by linkage to the Norwegian Prescription Database (NorPD) for 2004-2007. Information on DP status was retrieved from Statistics Norway. Results: Incident BZD use was highest among female DPs; 18-20% compared to 5-8% of the non-DPs. Multivariable analyses revealed an independent effect of DP on incident (OR 1.6 (95% CI 1.4-2.0)) and long-term use (OR 2.47 (95% CI 1.90-3.20)) of BZDs. Among incident users, 51-60% of the DPs retrieved BZDs throughout the period 2004-07, as compared to 32-33% of the non-DPs. The annual median defined daily doses (DDDs) of BZDs among long-term users increased throughout the period 2004-07, most pronounced in the youngest DPs; from 50 (interquartile range (IQR) 14,140) DDD to 205 (IQR 25,352) DDD. Conclusions: The chance of being prescribed BZDs as well as becoming a long-term user was higher among DPs. High continuation rates, with a steadily increasing annual amount of use among the long-term users may reflect an unfavourable use pattern of potentially addictive drugs among DPs, most worrisome among the youngest. [ABSTRACT FROM AUTHOR]

Abstract: Clinical studies of short duration have demonstrated that strong opioids improve pain control in selected patients with chronic nonmalignant pain. However, high discontinuation rates and dose escalation during long-term treatment have been indicated. The aim of the present study was to determine discontinuation rates, dose escalation, and patterns of co-medication with benzodiazepines. The Norwegian Prescription Database provides complete national data at an individual level on dispensed drugs. A complete national cohort of new users of strong opioids was followed up for 5years after initiation of therapy with strong opioids. Of the 17,248 persons who were new users of strong opioids in 2005, 7229 were dispensed a second prescription within 70days and were assumed to be intended long-term users. A total of 1233 persons in the study cohort were still on opioid therapy 5years later. This equals 24% of the study cohort who were still alive. Of the participants, 21% decreased their annual opioid dose by 25% or more, whereas 21% kept a stable dose (±24%) and 34% more than doubled their opioid dose from the first to the fifth year. High annual doses of opioids were associated with high annual doses of benzodiazepines at the end of follow-up. It is an issue of major concern that large dose escalation is common during long-term treatment, and that that high doses of opioids are associated with high doses of benzodiazepines. These findings make it necessary to question whether the appropriate patient population receives long-term opioid treatment. [Copyright &y& Elsevier]

Aims: Our objective was to explore the use of codeine analgesics in individual patients in Norway, giving special attention to the 10% who consume the highest amounts. Methods: We retrieved data from the Norwegian Prescription Database on patients who were dispensed at least one codeine analgesic prescription during 2006. We looked at age and gender specific 1-year periodic prevalence. The 10% of codeine users who were prescribed the highest amounts of the drug that year were further characterized. Age and gender distribution and concurrent high consumption of other potential drugs of abuse were also considered. Results: In the year 2006, a total of 386,836 individuals filled at least one prescription for codeine analgesics from Norwegian pharmacies, excluding cancer patients. The crude prevalence for the use of codeine analgesics was 7.3% and 9.3% of the male and female Norwegian population, respectively. Twelve percent of women and 9% of men who filled a codeine prescription received 120 defined daily doses (DDD) or more of codeine analgesics in 2006 (moderate to high consumers). Fifty percent of those patients (21,759) were also dispensed large amounts of benzodiazepines or carisoprodol over the same period. In comparison, only ten percent of patients who received fewer than 120 DDD of codeine analgesics were dispensed large amounts of benzodiazepines or carisoprodol. Conclusions: A high percentage of the Norwegian population used codeine analgesics. One-year prevalence use of codeine increased with age and was higher for women at all ages. Our study showed that codeine use was mainly sporadic, but that a relatively large sub-group of users were dispensed repeated prescriptions of the drug in combination with other potential drugs of abuse. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study was to examine the risk of being involved in road traffic accidents as drivers among persons using prescribed medicines by utilizing data from population-based registries. The aim of the present paper was to focus on the methodology used in the study. Methods: All Norwegians aged 18-69 in April 2004 to September 2006 (3.1 million), were included in the study. Information on prescriptions, road accidents and emigrations/deaths was obtained from three different population-based registries. A total of 22,000 accidents were observed. The incidence of accidents in exposed and unexposed person-time was compared, by the standardized incidence ratio (SIR). Results: The risk of being involved in an accident was increased in persons exposed for prescribed medicines. The risk was markedly increased in persons exposed for natural opium alkaloids, benzodiazepine tranquillizers, benzodiazepine hypnotics and carisoprodol. A marginal increase or unchanged SIRs were found for NSAIDs, selective beta-2-adrenoreceptor agonists (anti-asthmatics), calcium receptor antagonists and penicillin. Conclusions: We have tested a method using different reference groups and different exposure periods to explore the association between drug use and involvement in traffic accidents. Using these methods, we have shown that exposure for prescribed opiates, benzodiazepines and carisoprodol increased the risk of being involved in an accident as driver. The findings confirm results from other studies. Further steps should be taken to reduce car driving under the influence of these drugs. [ABSTRACT FROM AUTHOR]