Effect of the market withdrawal of dextropropoxyphene on use of other prescribed analgesics

Abstract Background and aims Dextropropoxyphene (DXP) is a synthetic opioid that was prescribed worldwide for mild to moderate pain. It was withdrawn from the European market in 2009. In this study we aim to investigate the effect of the market withdrawal of dextropropoxyphene in Norway on overall use of opioids and other analgesics at an individual level. Methods Data were collected from the nationwide Norwegian Prescription Database (NorPD). It covers all prescription of drugs from 01 January 2004 from Norwegian pharmacies dispensed to individuals outside institutions. The study period was divided in two 2-year periods from 01 September 2008 to 31 August 2010, and from the market withdrawal of DXP on 01 September 2010 to 31 August 2012. We included every individual that filled at least one prescription of dextropropoxyphene in the first 2-year period in our study population. In this study dextropropoxyphene, codeine and tramadol are defined as “weak opioids”, and all other opioids are termed “strong opioids”. Results Nine thousand one hundred and seventy-one individuals were included in our study population. Four thousand two hundred and ninety filled a prescription of DXP only once and were classified as “single users”, 2,990 were users with prescriptions of up to 200 defined daily doses (DDD) over the first 2-year period, or “sporadic users”, and 1,886 were classified high users with over 200 DDDs over a 2-year period. After the market withdrawal 8,392 continued to be prescribed analgesics or benzodiazepines. In the single user group, the proportion of users of weak opioids decreased from 69.5% to 57.6%, whereas the proportion of users of strong opioids was unchanged. Among the sporadic user group, the proportion of users of weak opioids went from 69.7% to 71.0%, the proportion using tramadol from 39.1% to 43.9%, and the users of strong opioids from 25.8% to 31.3%. In the high user group, there was an increase in the number of users of strong opioids from 37.8% to 51.4%. The amount of strong opioids prescribed in the high user group increased from a mean of 262.5 DDD to a mean of 398.3 DDD in the following 2 years. The amount of tramadol increased in all groups and was 3 times as high in the high user group after market withdrawal of DXP. Conclusions Our study showed that the withdrawal of DXP lead to an increase in prescription of other analgesics. The proportion of users increased in all three groups and so did the prescribed amount of other analgesics. Both the proportion of users of other opioids and the amount prescribed increased considerably. However, 1 in 10 earlier users of DXP stopped using prescribed analgesics altogether in the following 2 years. The increase in use among earlier high users of DXP was most striking. Implications This study documents markedly increased prescriptions of other opioids after withdrawal of dextropropoxyphene due to its high risk of serious complications. However, consequences of the increased use of opioids among earlier high users of DXP such as changes in risk of poisonings, accidental deaths and suicides remain to be investigated.

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Changes in the consumption of antiepileptics and psychotropic medicines after starting low dose naltrexone: A nation-wide register-based controlled before-after study

Scientific Reports ◽

10.1038/s41598-019-51569-z ◽

2019 ◽

Vol 9 (1) ◽

Author(s):

Guttorm Raknes ◽

Lars Småbrekke

Keyword(s):

Low Dose ◽

Prescription Database ◽

Cumulative Number ◽

Beneficial Effects ◽

Defined Daily Doses ◽

Psychotropic Medicines ◽

Significant Difference ◽

Norwegian Prescription Database ◽

One Year ◽

Low Dose Naltrexone

Abstract In this controlled before-after study based on data from the Norwegian Prescription Database, we examine whether starting off-label use of Low Dose Naltrexone (LDN) is followed by changes in the consumption of psychotropic medicines including antiepileptics. Patients that collected LDN for the first time in 2013 (N = 11247) were included and stratified into three groups based on LDN exposure. We compared differences in means of cumulative number of defined daily doses (DDD) as well as changes in the number of users one year before and one year after starting LDN. There was a dose-response association between increasing LDN exposure and reductions in the number of users of antiepileptics, antipsychotics and antidepressants. There were significant difference-in-differences in DDDs between the groups with the lowest and highest LDN exposure of antipsychotics (1.4 DDD, 95% CI 0.4 to 2.3, p = 0.007), and in number of users of antiepileptics (3.1% points, 95% CI 1.6% to 4.6%, p < 0.001), antipsychotics (2.1% points, 95% CI 1.2% to 3%, p < 0.001), and antidepressants (2.8% points, 95% CI 1.1% to 4.4%, p = 0.001). The findings show an association between the initiation of persistent LDN use and reduced consumption of several psychotropic medicines and antiepileptics. Beneficial effects of LDN in the treatment of psychiatric diseases cannot be ruled out.

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Dispensing of prescribed analgesics in Norway among young people with foreign-or Norwegian-born parents

Scandinavian Journal of Pain ◽

10.1016/j.sjpain.2010.11.001 ◽

2011 ◽

Vol 2 (1) ◽

pp. 36-44 ◽

Cited By ~ 2

Author(s):

Tomas Log ◽

Svetlana Skurtveit ◽

Aage Tverdal ◽

Kari Furu ◽

Ingeborg Hartz

Keyword(s):

Young People ◽

Health Surveys ◽

Prescription Database ◽

Youth Health ◽

Birth Country ◽

Norwegian Prescription Database ◽

Study Population ◽

Muslim Majority ◽

Males And Females

AbstractPurposeTo examine and compare dispensing of prescribed analgesics between young people with parents from countries with a Muslim majority and those with parents born in Norway.MethodsOur study-population constituted 11,542 adolescents from the Norwegian Youth Health Surveys conducted in 2000–2003. Users and non-users of prescribed analgesics at baseline were analysed separately. Self-reported information on their parents’ birth country was used to classify them into one of the three predefined groups: Norway, countries with a Muslim majority or others. To study and compare dispensing of prescribed analgesics, data from the youth surveys were linked to the Norwegian Prescription Database (NorPD) 2004–2007. Dispensed analgesics studied were antiinflammatory and antirheumatic products (non-steroid), opioids and other analgesics and antipyretics.ResultsAmong non-users of prescribed analgesics at baseline, 34% of all males with parents born in Norway received prescribed analgesics at least once during 2004–2007, compared to 36% in the group with parents from countries with a Muslim majority. The proportions of females receiving prescribed analgesics were about 44% in both of the two previously mentioned groups. Among users of prescribed analgesics at baseline, the proportion of individuals who were dispensed prescribed analgesics in 2004–2007 was generally higher than for those that were non-users at baseline. Both males and females with parents from countries with a Muslim majority reported more pain compared to those with parents born in Norway. No statistical differences were detected between participants with parents from countries with a Muslim majority compared to those with parents born in Norway in terms of prescribed analgesics dispensed or total amount of analgesics dispensed in 2004–2007. For the dispensing of all analgesics in 2004–2007 the adjusted OR for having parents from countries with a Muslim majority compared to parents born in Norway was 1.02 (0.87–1.21) among non-users of prescribed analgesics at baseline and 0.82 (0.57–1.16) among users.ConclusionsThere were no differences in the dispensing of prescribed analgesics between young people with parents born in countries with a Muslim majority and those with parents born in Norway. Nor did the amount of prescribed analgesics differ between these groups.

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A pharmacoepidemiological cohort study of subjects starting strong opioids for nonmalignant pain: A study from the Norwegian Prescription Database

Pain ◽

10.1016/j.pain.2013.07.033 ◽

2013 ◽

Vol 154 (11) ◽

pp. 2487-2493 ◽

Cited By ~ 25

Author(s):

Olav Magnus S. Fredheim ◽

Petter C. Borchgrevink ◽

Milada Mahic ◽

Svetlana Skurtveit

Keyword(s):

Cohort Study ◽

Prescription Database ◽

Nonmalignant Pain ◽

Norwegian Prescription Database ◽

Strong Opioids

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Social inequalities in use of potentially addictive drugs in Norway – use among disability pensioners

Norsk Epidemiologi ◽

10.5324/nje.v19i2.592 ◽

2010 ◽

Vol 19 (2) ◽

Author(s):

Ingeborg Hartz ◽

Aage Tverdal ◽

Svetlana Skurtveit

Keyword(s):

Social Inequalities ◽

Independent Effect ◽

Prescription Database ◽

Addictive Drugs ◽

Defined Daily Doses ◽

Norwegian Prescription Database ◽

Multivariable Analyses ◽

Use Pattern ◽

Annual Amount

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.

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Opioids for outpatients with cancer in their last year of life: A nationwide pharmacoepidemiological study

Journal of Opioid Management ◽

10.5055/jom.2016.0309 ◽

2016 ◽

Vol 12 (1) ◽

pp. 25 ◽

Cited By ~ 2

Author(s):

Siri Brelin, MD ◽

Olav M. Fredheim, MD, PhD ◽

Jon H. Loge, MD, PhD ◽

Svetlana Skurtveit, PhD ◽

Tom B. Johannesen, MD, PhD ◽

...

Keyword(s):

Odds Ratio ◽

Prescription Database ◽

Prescription Data ◽

Pharmacoepidemiological Study ◽

Patients With Cancer ◽

Sociodemographic Data ◽

Norwegian Prescription Database ◽

Study Population ◽

To Receive ◽

Cancer Diseases

Objective: Opioids are the main pharmacological treatment for moderate-to-severe cancer pain. Few longitudinal studies have examined the prescription prevalence (PP) of opioids to patients with cancer. The aims of the study were to examine 1) changes in the PP of opioids from 2005 to 2009 among outpatients with cancer who were in their last year of life and 2) associations between the PP of opioids and medical and sociodemographic factors.Design: Retrospective, registry-based, national study.Patients: This study used data on all patients with cancer who died 2005-2009, combining the following three complete nationwide registries; prescription data from the Norwegian Prescription Database, data on cancer diseases from the Cancer Registry of Norway, and sociodemographic data from Statistics Norway.Results: The study population consisted of 44,579 adults (mean age 72 years at death, 54 percent males). The opioid PP increased from 74 to 82 percent during the study period. Oxycodone had the highest PP, and increased from 39.8 to 48.5 percent during the period, whereas the PP of morphine declined from 29.0 to 27.3 percent. The PP for fentanyl remained stable at 17 percent. The PP of opioids increased toward death with higher PP during the last 3 months of life compared to previous 3-month periods. Older patients (>60) were less likely to receive opioids, while prostate or pancreatic cancer increased the odds for opioid prescriptions (p < 0.001, Odds ratio [OR] 2.60 and OR 1.98, respectively).Conclusion: The PP increased yearly during the study period. Use of oxycodone increased while that of morphine decreased.

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Repeated dispensing of codeine is associated with high consumption of benzodiazepines

Norsk Epidemiologi ◽

10.5324/nje.v18i2.33 ◽

2009 ◽

Vol 18 (2) ◽

Author(s):

Liliana C. Bachs ◽

Jørgen G. Bramness ◽

Anders Engeland ◽

Svetlana Skurtveit

Keyword(s):

Drugs Of Abuse ◽

Prescription Database ◽

Age And Gender ◽

High Consumption ◽

Defined Daily Doses ◽

Concurrent Use ◽

Norwegian Population ◽

Norwegian Prescription Database ◽

And Gender ◽

One Year

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. Key Words: Codeine analgesics, Norwegian Prescription Database, prevalence, dispensed quantity, concurrent use, high consumers, abuse.

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No change in the consumption of thyroid hormones after starting low dose naltrexone (LDN): a quasi-experimental before-after study

BMC Endocrine Disorders ◽

10.1186/s12902-020-00630-4 ◽

2020 ◽

Vol 20 (1) ◽

Author(s):

Guttorm Raknes ◽

Lars Småbrekke

Keyword(s):

Thyroid Hormones ◽

Low Dose ◽

Prescription Database ◽

Beneficial Effects ◽

Defined Daily Doses ◽

Before And After ◽

Quasi Experimental ◽

Norwegian Prescription Database ◽

Study Participants ◽

Low Dose Naltrexone

Abstract Background Low dose naltrexone (LDN) is reported to have beneficial effects in several autoimmune diseases. The purpose of this study was to examine whether starting LDN was followed by changes in the dispensing of thyroid hormones to patients with hypothyroidism. Methods We performed a quasi-experimental before-after study based on the Norwegian Prescription Database. Study participants were identified by using reimbursement codes for hypothyroidism. Cumulative dispensed Defined Daily Doses and the number of users of triiodothyronine (T3) and levothyroxine (LT4) 1 year before and after the first LDN prescription was compared in three groups based on LDN exposure. Results We identified 898 patients that met the inclusion criteria. There was no association between starting LDN and the subsequent dispensing of thyroid hormones. If anything, there was a tendency towards increasing LT4 consumption with increasing LDN exposure. Conclusion The results of this study do not support claims of efficacy of LDN in hypothyroidism.

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Manual occupations with high all-cause mortality: The contribution of socioeconomic and occupational characteristics

Scandinavian Journal of Public Health ◽

10.1177/1403494820960653 ◽

2020 ◽

pp. 140349482096065

Author(s):

Hanna Rinne ◽

Mikko Laaksonen

Keyword(s):

High Mortality ◽

Excess Mortality ◽

Proportional Hazard ◽

Individual Level ◽

Cox Proportional Hazard ◽

Occupational Characteristics ◽

Study Population ◽

Cox Proportional Hazard Regression ◽

Year 2000

Aims: Most high mortality-risk occupations are manual occupations. We examined to what extent high mortality of such occupations could be explained by education, income, unemployment or industry and whether there were differences in these effects among different manual occupations. Methods: We used longitudinal individual-level register-based data, the study population consisting of employees aged 30–64 at the end of the year 2000 with the follow-up period 2001–2015. We used Cox proportional hazard regression models in 31 male and 11 female occupations with high mortality. Results: There were considerable differences between manual occupations in how much adjusting for education, income, unemployment and industry explained the excess mortality. The variation was especially large among men: controlling for these variables explained over 50% of the excess mortality in 23 occupations. However, in some occupations the excess mortality even increased in relation to unadjusted mortality. Among women, these variables explained a varying proportion of the excess mortality in every occupation. After adjustment of all variables, mortality was no more statistically significantly higher than average in 14 occupations among men and 2 occupations among women. Conclusions: The high mortality in manual occupations was mainly explained by education, income, unemployment and industry. However, the degree of explanation varied widely between occupations, and considerable variation in mortality existed between manual occupations after controlling for these variables. More research is needed on other determinants of mortality in specific high-risk occupations.

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Is Suicidality Increased in Covid-19 Pandemic? A Scoping Review and Quality Assessment

10.47363/jmhc/2021(4)170 ◽

2021 ◽

pp. 1-8

Author(s):

Kimberly Virginin Cruz Correia da Silva ◽

Keyword(s):

Scoping Review ◽

Web Of Science ◽

Significant Risk ◽

Stressful Situation ◽

Confounding Variable ◽

Individual Level ◽

Level Data ◽

Study Population ◽

Coronavirus Infection ◽

Risk Of Exposure

Background: There are emerging concerns that the COVID-19 pandemic may specifically increase suicide. Methods: Scoping Review in the MEDLINE/PubMed, SCOPUS, Web of Science, PsycINFO, Science Direct databases and in the medRxiv, bioRxiv and PsyArXiv preprint servers, using the descriptors “Covid-19”, “coronavirus infection”, “coronavirus”, “2019-nCoV”, “2019 new coronavirus disease”, “SARS-CoV-2”, “Suicide”, “General Public” and “Mental Health”. Results: A total of 62 studies were included in this review, where 10 studies were reported to have been conducted between March and May 2021; 39 in 2020; 4 in 2019; 3 in 2018; 1 in 2015; 2 in 2014; 2 in 2010 and 1 in 2004, all were conducted via online platforms. Limitations: We have interpreted our study findings in the context of the overall significant risk of exposure to suicide in our study population, while recognizing that individual level data of exposure to COVID-19 is a significant confounding variable. Conclusions: Being one of the first reviews in this context, the findings are anticipated to be helpful to predict the possible solutions for reducing the number of suicides in and facilitate further studies on strategies of how to alleviate such a stressful situation in COVID-19.

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Flood Control and Water Management at Basin Level-at Orathur of Kanchipuram District

International Journal of Engineering and Advanced Technology - Regular Issue ◽

10.35940/ijeat.f1252.0986s319 ◽

2019 ◽

Vol 8 (6S3) ◽

pp. 1418-1421 ◽

Cited By ~ 4

Keyword(s):

Water Management ◽

Water Resources ◽

Water Resources Management ◽

Flood Control ◽

Gis Mapping ◽

User Group ◽

Basin Management ◽

Water Basin ◽

Resources Management ◽

Single User

The water resources management affords many solutions to manage water more holistically and optimally. In essence, they are a call to stop fragmentary approaches to water management and high-handed development decisions made for the benefit of a single user group of action.The Integrated Water Basin Management and its components are used to find a suitable flood mititgation measure. The study area is Orathur of Kancheepuram district. The data that are used in this work is been taken for the consecutive 20 years and it has been analysed. With the overall data the GIS mapping is done using ArcGIS software to locate the area precisely. Its tributaries and origin from Manimangalam tributary is located clearly to estimate the inflow and outflow of the water and the demand for water at the particular region is found and then analysed for the planning of water management and flood control..

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