Prescription opioids among older adults: ten years of data across five countries.

BACKGROUND: Opioid use has increased globally in the recent decade. Although pain remains a significant problem among older adults, susceptibility to opioid-related harms highlights the importance of careful opioid therapy monitoring on individual and societal levels. We aimed to describe the trends of prescription opioid utilisation among residents aged ≥65 in all Nordic countries during 2009-2018. METHODS: We conducted cross-sectional measurements of opioid utilisation in 2009-2018 from nationwide registers of dispensed drugs in Denmark, Finland, Iceland, Norway, and Sweden. The measures included annual opioid prevalence, defined daily doses (DDDs) per 1000 inhabitants per day (DIDs), and morphine milligram equivalents (MMEs) per user per day. RESULTS: From 2009 to 2018, an average of 808,584 of adults aged ≥65 used opioids yearly in all five countries; an average annual prevalence of 17.0%. During this time period, the prevalence decreased in Denmark, Norway, and Sweden due to declining codeine and/or tramadol use. Iceland had the highest opioid prevalence in 2009 (30.2%), increasing to 31.7% in 2018. In the same period, DIDs decreased in all five countries, and ranged from 28.3 in Finland to 58.5 in Denmark in 2009, and from 23.0 in Finland to 54.6 in Iceland in 2018. MMEs/user/day ranged from 4.4 in Iceland to 19.6 in Denmark in 2009, and from 4.6 in Iceland to 18.8 in Denmark in 2018. In Finland, Norway, and Sweden, MMEs/user/day increased from 2009 to 2018, mainly due to increasing oxycodone utilisation. CONCLUSIONS: The stable or decreasing opioid utilisation prevalence among a majority of older adults across the Nordic countries coincides with an increase in treatment intensity in 2009-2018. We found large cross-national differences despite similarities across the countries' cultures and healthcare systems. For the aged population, national efforts should be placed on improving pain management and monitoring future trends of especially oxycodone utilisation.

Proton pump inhibitors and fracture risk. The HUNT study, Norway.

Proton pump inhibitors (PPIs) have been linked to increased risk of fracture; the data have, however, been diverging. We did not find any increased risk of fractures among users of PPIs in a Norwegian population of 15,017 women and 13,241 men aged 50-85 years with detailed information about lifestyle and comorbidity. INTRODUCTION: Proton pump inhibitors (PPIs) are widely prescribed and have been linked to increased risk of fracture. METHODS: We used data from the Nord-Trøndelag Health Study (HUNT3), The Fracture registry in Nord-Trøndelag, and the Norwegian Prescription Database, including 15,017 women and 13,241 men aged 50-85 years. The study population was followed from the date of participating in HUNT3 (2006-2008) until the date of first fracture (forearm or hip), death, or end of study (31 December 2012). The Cox proportional hazards model with time-dependent exposure to PPIs was applied, and each individual was considered as unexposed until the first prescriptions was filled. To be included, the prescription of PPIs should minimum be equivalent to 90 defined daily doses (DDD) in the period. Individuals were defined as exposed until 6 months after end of drug supply. RESULTS: The proportion of women and men using PPIs was 17.9% and 15.5%, respectively. During a median of 5.2 years follow-up, 266 women and 134 men had a first hip fracture and 662 women and 127 men, a first forearm fracture. The combined rate/1000 patient-years for forearm and hip fractures in women was 49.2 for users of PPIs compared with 64.1 among non-users; for men 18.6 and 19.8, respectively. The hazard ratios with 95% confidence interval for the first forearm or hip fracture among users of PPIs in the age-adjusted analysis were 0.82 (0.67-1.01) for women and 1.05 (0.72-1.52) for men. Adjusting for age, use of anti-osteoporotic drugs, and FRAX, the HR declined to 0.80 (0.65-0.98) in women and 1.00 (0.69-1.45) in men. CONCLUSIONS: Use of PPIs was not associated with an increased risk of fractures.

Anti-osteoporosis drug use: too little, too much, or just right? The HUNT study, Norway.

Use of anti-osteoporotic drugs (AODs) was examined in a Norwegian population 50-85 years. Among them with Fracture Risk Assessment Tool (FRAX) score for major osteoporotic fracture ≥ 20, 25% of the women and 17% of the men received AODs. The strongest predictors for AODs were high age in women and use of glucocorticoids among men. INTRODUCTION: To examine the use of anti-osteoporotic drugs (AODs) and to identify predictors for prescriptions. METHODS: Data were obtained from the Nord-Trøndelag Health Study (HUNT3) performed in 2006-2008 and the Norwegian Prescription Database, including 15,075 women and 13,386 men aged 50-85 years. Bone mineral density (BMD) in the femoral neck was measured in a subgroup of 4538 women and 2322 men. High fracture risk was defined as a FRAX score for major osteoporotic fracture (MOF) ≥ 20%; in the subgroup with BMD, high risk was in addition defined as FRAXMOF ≥ 20% or T-score ≤ - 2.5. Hazard ratios (HRs) for predictors of incident use of AODs within 2 years after HUNT3 were estimated by Cox' proportional hazards model. RESULTS: Among individuals with FRAX MOF ≥ 20%, 25% of the women and 17% of the men were treated with AODs. Among those with FRAX MOF < 20%, 3% and 1% were treated, respectively. In the subgroup with BMD measurement, 24% of the women and 16% of the men at high risk of fractures were treated, compared to 3 and 1% in women and men not fulfilling the criteria. In women, high age was the strongest predictor for treatment (HR 3.84: 95% confidence interval 2.81-5.24), followed by use of glucocorticoids (GCs) (2.68:1.84-3.89). In men, predictors were use of GCs (5.28: 2.70-10.35) followed by multimorbidity (3.16:1.31-7.63). In the subgroup with BMD, T-score ≤ - 2.5 was the strongest predictor (women 3.98:2.67-5.89; men 13.31:6.17-28.74). CONCLUSIONS: This study suggests an undertreatment of AODs in individuals at high risk of fracture.

Increase in diagnosis of depressive disorders contributes to the increase in antidepressant use in adolescents.

OBJECTIVE: To study if the observed increase in use of antidepressants (AD) among adolescents may be explained by higher incidence of depressive disorder diagnosis, increasing treatment of other mental disorders or more liberal prescribing practice. METHODS: We used three different study populations of girls and boys aged 13-17 years in Norway: 1) individuals who were diagnosed with depressive disorders in primary health care, 2) individuals who were diagnosed with depressive disorders in secondary health care; 3) individuals who were dispensed ADs as recorded in the prescription database. Dataset 2) and 3) were linked. RESULTS: Incidence of depressive disorders increased from 2010 to 2015 both in primary and secondary health care, especially in girls. One in four girls with incident depressive disorders was prescribed ADs and this proportion was stable over time. Among girls treated with ADs the proportion with a diagnosis where AD treatment is indicated increased from 61.1% to 66.0%. Furthermore, the proportion with moderate or severe episodes of major depressive disorders was stable and high, 72.9% in 2014. CONCLUSION: The only issue studied that could explain increasing AD use in girls was increasing incidence of depressive disorders. Most adolescents with incident diagnosis of depressive disorders were not treated with ADs.

Validation of FRAX and the impact of self-reported falls among elderly in a general population: the HUNT study, Norway.

Fracture Risk Assessment Tool (FRAX) without bone mineral density (BMD) for hip fracture prediction was validated in a Norwegian population 50-90 years. Fracture risk increased with higher FRAX score, and the observed number of hip fractures agreed well with the predicted number, except for the youngest and oldest men. Self-reported fall was an independent risk factor for fracture in women. INTRODUCTION: The primary aim was to validate FRAX without BMD for hip fracture prediction in a Norwegian population of men and women 50-90 years. Secondary, to study whether information of falls could improve prediction of fractures in the subgroup aged 70-90 years. METHODS: Data were obtained from the third survey of the Nord-Trøndelag Health Study (HUNT3), the fracture registry in Nord-Trøndelag, and the Norwegian Prescription Database (NorPD), including 15,432 women and 13,585 men. FRAX hip without BMD was calculated, and hip fractures were registered for a median follow-up of 5.2 years. The number of estimated and observed fractures was assessed, ROC curves with area under the curve (AUC), and Cox regression analyses. For the group aged 70-90 years, self-reported falls the last year before HUNT3 were included in the Cox regression model. RESULTS: The risk of fracture increased with higher FRAX score. When FRAX groups were categorized in a 10-year percentage risk for hip fracture as follows, <4, 4-7.9, 8-11.9, and ≥12%, the hazard ratio (HR) for hip fracture between the lowest and the highest group was 17.80 (95% CI: 12.86-24.65) among women and 23.40 (13.93-39.30) in men. Observed number of hip fractures agreed quite well with the predicted number, except for the youngest and oldest men. AUC was 0.81 (0.78-0.83) for women and 0.79 (0.76-0.83) for men. Self-reported fall was an independent risk factor for fracture in women (HR 1.64, 1.20-2.24), and among men, this was not significant (1.09, 0.65-1.83). CONCLUSIONS: FRAX without BMD predicted hip fracture reasonably well. In the age group 70-90 years, falls seemed to imply an additional risk among women.

International trends in clozapine use: a study in 17 countries.

OBJECTIVE: There is some evidence that clozapine is significantly underutilised. Also, clozapine use is thought to vary by country, but so far no international study has assessed trends in clozapine prescribing. Therefore, this study aimed to assess clozapine use trends on an international scale, using standardised criteria for data analysis. METHOD: A repeated cross-sectional design was applied to data extracts (2005-2014) from 17 countries worldwide. RESULTS: In 2014, overall clozapine use prevalence was greatest in Finland (189.2/100 000 persons) and in New Zealand (116.3/100 000), and lowest in the Japanese cohort (0.6/100 000), and in the privately insured US cohort (14.0/100 000). From 2005 to 2014, clozapine use increased in almost all studied countries (relative increase: 7.8-197.2%). In most countries, clozapine use was highest in 40-59-year-olds (range: 0.6/100 000 (Japan) to 344.8/100 000 (Finland)). In youths (10-19 years), clozapine use was highest in Finland (24.7/100 000) and in the publicly insured US cohort (15.5/100 000). CONCLUSION: While clozapine use has increased in most studied countries over recent years, clozapine is still underutilised in many countries, with clozapine utilisation patterns differing significantly between countries. Future research should address the implementation of interventions designed to facilitate increased clozapine utilisation.

Antidepressant drug use among adolescents during 2004-2013: a population-based register linkage study.

OBJECTIVE: To study trends in use of antidepressants (ADs) by adolescents, and psychiatric morbidity and use of other psychotropic drugs as a measure of psychiatric comorbidity. METHODS: One-year prevalence of AD drug use was analyzed for 13- to 17-year-old Norwegians during 2004-2013. Use of other psychotropic drugs and specialist healthcare services was analyzed for incident AD users in 2012, using linked data from the Norwegian Prescription Database and the Norwegian Patient Register. RESULTS: The 1-year prevalence of AD drug use increased from 6.4/1000 to 9.1/1000 during 2004-2013, with the steepest increase from 2010, particularly among girls. The highest prevalence was found in 17-year-old girls (17.8/1000 in 2010, 27.5/1000 in 2013). Of incident AD drug users in 2012, 84.4% had been in contact with specialist health care. As the first drug, 78.4% were prescribed a selective serotonin reuptake inhibitor. The most common types of other psychotropic drugs were melatonin (24.6%), antipsychotic drugs (13.2%), stimulants (8.8%), and anxiolytics (6.0%). CONCLUSIONS: Use of ADs among adolescents has increased over the last 3-4 years, particularly among 16- to 17-year-old girls. A total of 85% of incident users had been in contact with specialist health care, which may indicate that drug-therapy is used by adolescents with more severe symptoms.

Motor development in children prenatally exposed to selective serotonin reuptake inhibitors: a large population-based pregnancy cohort study.

OBJECTIVES: To estimate the association between prenatal exposure to selective serotonin reuptake inhibitors (SSRIs) and motor development in children considering the effect of maternal symptoms of anxiety and depression before, during and after pregnancy. DESIGN: Population-based prospective pregnancy cohort study. SETTING: The Norwegian Mother and Child Cohort study (MoBa) (1999-2008). POPULATION: A total of 51 404 singleton pregnancies. METHODS: Self-reported use of SSRIs was collected for the 6 months before pregnancy and prospectively during pregnancy. We used ordinal logistic regression as the statistical analysis. MAIN OUTCOME MEASURES: Motor development was assessed by maternal reports of fine and gross motor development at child age 3 years by items from the Ages and Stages Questionnaire (ASQ). The maternal ASQ scores were compared with data from a MoBa sub-study where clinicians assessed motor development with the Gross and Fine Motor Mullen scales of early learning. RESULTS: In all 381 women (0.7%) reported use of SSRIs during pregnancy, of these 159 reported on at least two questionnaires (prolonged use). Prolonged SSRI exposure was associated with a delay in fine motor development, odds ratio 1.42 (95% CI 1.07-1.87) compared with no SSRI exposure, after adjusting for symptoms of anxiety and depression before and during pregnancy. Severity of maternal depression seemed to explain the association only partially. Stratifying on depression after pregnancy had no impact on the estimated effect of SSRIs. CONCLUSIONS: Prolonged prenatal exposure to SSRIs was weakly associated with a delayed motor development at age 3 years, but not to the extent that the delay was of clinical importance. TWEETABLE ABSTRACT: Long-term prenatal SSRI exposure is weakly associated with delayed motor development independent of depression.

The duration and course of opioid therapy in patients with chronic non-malignant pain.

BACKGROUND: Prescription databases provide the opportunity for investigating opioid treatment and co-medication within large populations. So far, few studies have investigated the duration of opioid therapy, and large differences in discontinuation rates have been reported. METHODS: Data from the Norwegian Prescription Database were used to follow the study population of all adult persistent opioid users with non-malignant pain in Norway in 2005 (n = 44,867) for 6 years. Persistent opioid use was defined as being dispensed ≥ 180 defined daily doses (DDD) or 4500 mg oral morphine equivalents (OMEQ) during a 365-day period. The study population was stratified according to previous opioid use into new persistent opioid users, without previous persistent opioid use, and previous low-dose or previous high-dose persistent opioid users, having earlier persistent opioid use and received less or more than 120 mg OMEQ/day in 2005, respectively. RESULTS: Twenty-seven percent of new, 59% of previous low-dose, and 55% of previous high-dose users met the criteria of persistent use of opioids each year. Exactly, 22%, 11%, and 3% increased their cumulative yearly opioid dose by 200% or more during the study period. With 80% still being regular users of either drugs, 6 years later, long-term persistent opioid users were more likely to continue concomitant use of benzodiazepines or z-hypnotics than other users, CONCLUSION: The findings confirm high discontinuation rates in patients receiving opioids for chronic non-malignant pain. However, a clinically significant number of patients increase their doses over 6 years and many patients combine long-term opioid treatment with benzodiazepines and z-hypnotics.

Consumption of and satisfaction with health care among opioid users with chronic non-malignant pain.

BACKGROUND: Although persons with chronic pain are frequent users of the health care system, they report poor satisfaction with health care services. Participants with persistent opioid use in Nord-Trøndelag Health Study (HUNT)3 report severe pain in spite of treatment. The aim of the study was to test the hypothesis that subjects with persistent opioid use have both a higher consumption of health care services and a poorer satisfaction than the remaining subjects reporting chronic pain. METHODS: This cross-sectional study was based on linkage of self-reported data from the substudy (10,238 were invited, 6927 met the inclusion criteria) of health care use in HUNT3; a population-based health survey during the years 2006-2008 and the complete national registers of the Norwegian Prescription Database and the Cancer Registry of Norway. Patients with chronic pain are stratified according to the level of opioid use as persistent users of opioids, intermittent users, and persons not using opioids. RESULTS: Persons with chronic non-malignant pain reported a higher consumption of all health care services compared to the control group. Consumption of health care services increased with increasing level of opioid use. Persons with persistent opioid use were highly satisfied with all health care services, although less satisfied than persons without chronic pain. CONCLUSIONS: Combined with previous findings of high levels of pain in spite of opioid treatment, the present findings indicate that symptomatic relief is not a prerequisite for patient satisfaction. The study shows higher patient satisfaction compared to previous studies.

Prenatal exposure to antidepressants and language competence at age three: results from a large population-based pregnancy cohort in Norway.

OBJECTIVE: To examine the association between maternal use of selective serotonin reuptake inhibitors (SSRI) in pregnancy and language competence in their children at age three taking into account maternal symptoms of anxiety and depression. DESIGN: Population-based prospective pregnancy cohort study. SETTING: The Norwegian Mother and Child Cohort Study; recruited pregnant women from 1999 through 2008. POPULATION: 45,266 women with 51,748 singleton pregnancies. METHODS: The association between short- or long-term use of SSRI during pregnancy and language competence in the child was investigated using multinomial logistic regression with three outcome categories: long, complicated sentences, fairly complete sentences and language delay. MAIN OUTCOME MEASURES: Children's language competence at age three measured by maternal report on a validated language grammar scale. RESULTS: Women reported use of SSRI in 386 (0.7%) pregnancies. Of these, 161 (42%) reported long-term use. Compared with children whose mothers took no SSRI, using the best language category as the reference, adjusted relative risk ratios (RRR) of having fairly complete sentences were 1.21 (95% CI 0.85-1.72) and 2.28 (1.54-3.38) for short- and long-term SSRI use, respectively. The adjusted RRRs of language delay were 0.86 (0.42-1.76) and 2.30 (1.21-4.37). Symptoms of anxiety and depression in pregnancy were independently related to language delay, adjusted RRR 1.25 (1.03-1.50) and 1.83 (1.40-2.40) for short- and long-term symptoms, respectively. CONCLUSIONS: Prolonged use of SSRI during pregnancy was associated with lower language competence in children by age three independently of depression. Having symptoms of depression throughout pregnancy had an independent effect.

Socioeconomic risk factors for long-term opioid use: A national registry-linkage study.

BACKGROUND: Opioid use has increased substantially as a treatment for chronic pain, although harms from long-term opioid therapy outweigh the benefits. More knowledge about factors associated with long-term opioid use is needed. We aimed to investigate the association between socioeconomic status and long-term opioid use in the period 2010-2019. METHODS: This was a nested case-control study in which the cases were all persons ≥18 years with long-term opioid use, that is use of opioids for more than 3 months (N = 215,642). Cases were matched on gender, age and index year (first long-term use period) with four controls who filled at least one opioid prescription, but never developed long-term opioid use in the study period (N = 862,568). We performed a logistic regression analysis adjusted for relevant confounders, stratified on age groups (18-67 years and 68 years and above). RESULTS: In the younger age group, long-term opioid use was associated with low education (adjusted odds ratio, aOR = 1.54; 95% confidence interval, CI [1.51-1.57]), low income (1.33 [1.31-1.36]), being unemployed (1.40 [1.38-1.42]) and receiving disability pension (1.36 [1.33-1.38]). Weaker associations were found for living in a single-person household or in a dense geographical area. Similar associations were found for the older age group. CONCLUSION: We found that low socioeconomic status was associated with long-term opioid use both among people in working age and older people. These results indicate a need for social and financial support for non-pharmacological treatment of chronic pain among people with lower socioeconomic status. SIGNIFICANCE: This study shows that people with low socioeconomic status are at higher risk of developing long-term opioid use. In the clinical setting, physicians should consider socioeconomic status when prescribing opioids for chronic pain. Non-pharmacological treatment options funded by public health services should be prioritized to those with low socioeconomic status as long-term opioid use in chronic pain patients is not recommended.

Mental disorder prevalence in chronic pain patients using opioid versus non-opioid analgesics: A registry-linkage study.

BACKGROUND: Chronic pain and mental disorders are leading causes of disability worldwide. Individuals with chronic pain are more likely to experience mental disorders compared to individuals without chronic pain, but large-scale estimates are lacking. We aimed to calculate overall prevalence of mental health diagnoses from primary and secondary care among individuals treated for chronic pain in 2019 and to compare prevalence among chronic pain patients receiving opioid versus non-opioid analgesics, according to age and gender. METHODS: It is a population-based cohort study. Linked data from nationwide health registers on dispensed drugs and diagnoses from primary (ICPC-2) and secondary (ICD-10) health care. Chronic pain patients were identified as all patients over 18 years of age filling at least one prescription of an analgesic reimbursed for non-malignant chronic pain in both 2018 and 2019 (N = 139,434, 69.3% women). RESULTS: Prevalence of any mental health diagnosis was 35.6% (95% confidence interval: 35.4%-35.9%) when sleep diagnoses were included and 29.0% (28.8%-29.3%) when excluded. The most prevalent diagnostic categories were sleep disorders (14% [13.8%-14.2%]), depressive and related disorders (10.1% [9.9%-10.2%]) and phobia and other anxiety disorders (5.7% [5.5%-5.8%]). Prevalence of most diagnostic categories was higher in the group using opioids compared to non-opioids. The group with the highest overall prevalence was young women (18-44 years) using opioids (50.1% [47.2%-53.0%]). CONCLUSIONS: Mental health diagnoses are common in chronic pain patients receiving analgesics, particularly among young individuals and opioid users. The combination of opioid use and high psychiatric comorbidity suggests that prescribers should attend to mental health in addition to somatic pain. SIGNIFICANCE: This large-scale study with nation-wide registry data supports previous findings of high psychiatric burden in chronic pain patients. Opioid users had significantly higher prevalence of mental health diagnoses, regardless of age and gender compared to users of non-opioid analgesics. Opioid users with chronic pain therefore stand out as a particularly vulnerable group and should be followed up closely by their physician to ensure they receive sufficient care for both their mental and somatic symptoms.

Concomitant medication among persistent opioid users with chronic non-malignant pain.

BACKGROUND: Recent guidelines for opioid treatment of chronic non-malignant pain discourage co-medication with benzodiazepines and benzodiazepine-related hypnotics, whereas co-medication with non-opioid analgesics and co-analgesics may offer a beneficial opioid sparing effect, and is recommended. The aim of this study was to describe 1-year periodic prevalence of co-medication with benzodiazepines, benzodiazepine-related hypnotics, non-opioid analgesics, co-analgesics and antidepressants in persistent opioid users with chronic non-malignant pain. METHODS: The study is based on data from the Norwegian Prescription Database, covering all drugs dispensed to outpatients in 2008. Concomitant medication levels were compared between users in two definitions of persistent opioid use, all Norwegian adults dispensed opioids in 2008 and the Norwegian background population. RESULTS: Of the Norwegian adult population studied, 1.2% met the criteria of persistent opioid use based on prescription pattern and prescription level. Sixty percent of persistent opioid users were dispensed a benzodiazepine or benzodiazepine-related hypnotic in amounts indicating regular use, with 15% dispensed a high amount of both classes. Sixty-two percent of persistent opioid users were dispensed one or more non-opioid analgesics, 47% an antidepressant and 33% were dispensed an antiepileptic drug. CONCLUSION: Approximately 60% of persistent opioid users also receive benzodiazepines or benzodiazepine-related hypnotics in amounts indicating regular use. This is in conflict with recent guidelines for the treatment of chronic non-malignant pain and may indicate that these users are at an increased risk of developing problematic opioid use.

Low-dose transdermal buprenorphine - long-term use and co-medication with other potentially addictive drugs.

INTRODUCTION: Recently, low-dose transdermal buprenorphine (LD-TD-BUP) was introduced for treatment of patients with chronic non-malignant pain. The primary aim of this study was to determine the proportion of patients who were prescribed LD-TD-BUP for non-malignant pain who became long-term users. The secondary aim was to determine the proportion of patients who co-medicated with other opioids or benzodiazepines during treatment with LD-TD-BUP. METHODS: Data were drawn from the Norwegian Prescription Database that covers all prescriptions dispensed at pharmacies to the entire Norwegian population (4.7 million inhabitants). The study population consisted of all patients who were dispensed at least one prescription of LD-TD-BUP from its introduction in November 2005 to 31 December 2008. Patients who were dispensed more than 24 patches (≥ 6 months) were defined as long-term users. Reimbursement codes were used to stratify patients as having cancer pain or non-malignant pain. RESULTS: Among new users of LD-TD-BUP for non-malignant pain (n = 13,451), only 22% became long-term users, while 44% were only dispensed one prescription. Among long-term users who were opioid naive when LD-TD-BUP was initiated, 43% co-medicated with other opioids or benzodiazepines, compared with 82% of those who previously had used opioids. CONCLUSION: Three years after introduction, 0.4% of the Norwegian population had been dispensed LD-TD-BUP. Only one-fifth had become long-term users. Those who used opioids before the first dispension of LD-TD-BUP co-medicated with other potentially addictive drugs to a much higher degree compared with those who were opioid naive.

Road traffic accident risk in patients with diabetes mellitus receiving blood glucose-lowering drugs. Prospective follow-up study.

AIM: To investigate, at a national level, whether patients using insulin or oral glucose-lowering agents had an increased risk of road traffic accidents compared with non-users. METHODS: All Norwegians aged 18-69 years (3.1 million) were followed from April 2004 until September 2006. Information on drug prescriptions, road traffic accidents and emigration/death was obtained from the following population-based registries: the Prescription Database, the Road Accident Registry and the Central Population Registry. The exposure period was the time from the first prescription of insulin or oral glucose-lowering agent during the study period. The incidence of accidents in the exposed person-time was compared with the incidence of accidents in the unexposed person-time by standardized incidence ratio (SIR). RESULTS: During the study period, 20 494 road traffic accidents with personal injuries were registered in Norway. One hundred and eighty-three accidents were registered for insulin users not taking oral glucose-lowering agents and 219 for users of oral blood glucose-lowering drugs without insulin. The SIR (95% confidence interval) for all ages and both genders combined were: insulin 1.4 (1.2-1.6), oral glucose-lowering agents 1.2 (1.0-1.3) and users of drugs for peptic ulcer and gastro-oesophageal reflux disease (negative comparators) 1.3 (1.2-1.4). The highest SIRs were found among the youngest insulin users (18-34 years old). CONCLUSIONS: A slightly increased risk of being involved in a road traffic accident was observed for drivers prescribed insulin, while no increased risk was observed for drivers prescribed oral glucose-lowering agents. The increased risk observed for insulin users was similar to that observed for users of drugs for peptic ulcer and gastro-oesophageal reflux disease.

Prescription pattern of codeine for non-malignant pain: a pharmacoepidemiological study from the Norwegian Prescription Database.

BACKGROUND: Opioid prescription for pain relief is increasing. Codeine is the dominating opioid in several European countries, with Norway being among the highest codeine users. AIM: To determine whether codeine is primarily used for acute pain or whether there is a prescription pattern indicating problematic opioid use. METHODS: All pharmacies in Norway are obliged to submit data electronically to the Norwegian Prescription Database at the Norwegian Institute of Public Health on all dispensed prescriptions. Because all prescriptions are identified with a unique person identifier, it is possible to identify all prescriptions to one subject. All subjects who had prescription(s) of codeine dispensed to them in 2004, 2005 or 2006 are included in the study. RESULTS: 385 190 Norwegian persons had at least one prescription of codeine dispensed to them due to non-cancer pain in 2005, corresponding to a 1-year periodic prevalence of 8.3%. 223 778 (58%) received only one prescription in 2005, 121 025 (31%) received more than one prescription but <120 defined daily doses (DDDs), 30 939 (8%) received between 120 and 365 DDDs, 7661 (2%) between 365 and 730 DDDs, while only 1787 (0.5%) exceeded the maximum recommended dose of 730 DDDs. In the latter group, co-medication with benzodiazepines (65%) and carisoprodol (45%) was prevalent. CONCLUSION: About one in 10 adult persons in Norway were dispensed codeine in 2005. A majority (58%) received codeine only once, most likely for acute pain, whereas a small minority (0.5%) had a prescription pattern indicating problematic opioid use.

Prescriptions of analgesics during complete disease trajectories in patients who are diagnosed with and die from cancer within the five-year period 2005-2009.

BACKGROUND: Even though validation studies of the WHO analgesic ladder have indicated that the simple approach of the analgesic ladder can provide adequate pain control in most patients, prevalence studies have documented a high prevalence of pain in cancer patients. Little is known about how analgesics are actually prescribed for cancer pain. The aim of the study was to study prescriptions of analgesics during the entire disease trajectory in patients dying from cancer within five years of diagnosis. METHODS: Complete national data from the Norwegian Cancer Registry, the Norwegian Prescription Database, the Cause of Death Registry and Statistics Norway were used to study prescriptions of analgesics in a complete study population of all patients dying from cancer within five years of diagnosis in Norway from 2005 to 2009. RESULTS: Of a total of 10,977 subjects who received prescriptions for analgesics between diagnosis and death, 56% started analgesic treatment at step I of the analgesic ladder, 29% started at step II and 14% started at step III. Of the patients starting at step I, 28% continued to step II, 37% bypassed step II and moved directly to step III whereas the remaining 35% remained at step I. Approximately 60% received one or more dispensed prescription of a step III analgesic during the disease trajectory, whereas nearly 20% remained at step I and 20% at step II respectively. CONCLUSION: The study indicates that clinicians seem to individually tailor analgesic treatment instead of applying the stepwise approach in the WHO analgesic ladder. SIGNIFICANCE: Complete national data covering the complete disease trajectory in cancer patients dying within five years of diagnosis. The majority of patients do not receive treatment in concordance with the stepwise approach suggested by the WHO analgesic ladder.

Use of prescribed opioids by children and adolescents: Differences between Denmark, Norway and Sweden.

BACKGROUND: There are few studies on the use of opioids among children and adolescents. The aim of this study was to determine the 1-year prevalence of prescribed opioid dispensing in Denmark, Norway and Sweden, and to compare gender and age differences in the use of weak and strong opioids between the three countries. METHODS: Data on the dispensing of opioids were collected from the websites of the complete national prescription databases in the three countries. All individuals aged 0-19 with at least one prescription of opioids during the study period were included. RESULTS: The 1-year prevalence of opioid use among young individuals aged 0-19 years increased during the study period (2006-2012) in Denmark from 2.5 to 3.4 per thousand, in Norway from 10.7 to 13.4 per thousand and in Sweden from 5.9 to 7.1 per thousand. In all three countries, more boys than girls used opioids between the ages of 0 and 10, whereas girls were the major users in the age range 11-19. Use of opioids in all three countries was dominated by weak opioids, codeine being the most dominant in Norway and Sweden and tramadol in Denmark. CONCLUSIONS: The 1-year prevalence of prescribed opioid use among children and adolescents in Norway was far higher than in Denmark and Sweden. During the study period, an increasing use of opioids among children and adolescents was observed in all three countries.