Swedish Drug Research Articles

Is there an increased risk for drug treated attention deficit/hyperactivity disorder in children born after in vitro fertilization?

Background There is mounting evidence that children born after in vitro fertilization (IVF) run an increased risk of neurological complications and notably cerebral palsy. Whether developmental disturbances occur more often than expected is debated. Aim To investigate the risk for ADHD in children conceived after IVF. Methods Children conceived after IVF and born between 1982 and 2005 were identified from all IVF clinics in Sweden. Children who developed attention deficit/hyperactivity disorder (ADHD) were identified with the use of a register over all prescribed drugs in Sweden, using prescriptions for methylphenidate or atomixetine as indicators of ADHD. Maternal and neonatal characteristics were obtained by linkage with the Medical Birth Register and relevant confounders were adjusted for using Mantel–Haenszel procedures. We studied 28 158 children born after IVF and compared them with 2 417 886 children in the population. Results After adjustment for year of birth, maternal age, parity, smoking, BMI, and maternal education and after exclusion of women who did not cohabit, a weak but statistically significant association was found with an odds ratio = 1.18, 95% confidence interval 1.03–1.36. The effect was stronger in girls (OR = 1.40) than boys (OR = 1.11) but this difference could be random. After adjustment for length of involuntary childlessness, the OR decreased slightly and lost statistical significance. Conclusions The study suggests a weak association between IVF and drug treated ADHD.

Causes of premature mortality in Swedish drug abusers: A prospective longitudinal study 1970–2006

Aims To evaluate premature mortality and causes of death from young adulthood to middle age in a cohort of drug users followed during almost four decades Design Follow-up study of a consecutive cohort of patients with drug abuse/dependence. Methods A cohort of 561 drug abusers, admitted to a detoxification and short-term rehabilitation unit 1970–1978 was followed to December 31st, 2006. Standardized interviews and hospital records with toxicological analyses were used for demographic data, substance use and psychiatric diagnoses at admission. For Follow-up analyses, autopsy protocols including toxicology tests and death certificates were obtained for assessment of causes of death which were coded according to ICD-10. Age-group standardized mortality ratios were calculated independently for both sexes. Results 204 persons (36.4%) were deceased by 2006. SMR was 5.94 for the cohort. Compared to an age- and gender-matched population, the risk of premature death was about eighteen times higher between the ages of 20–44 and about five times higher from 45 up to the age of 69. Of 120 (59%) drug-related deaths, 43 were opiate overdoses, and 3 were overdose from amphetamine. A total of 53 (26%) persons died violent deaths: 39 suicides, of which 25 were drug-related, 3 homicides and 12 accidents. The Swedish national causes of death register underestimated drug-related death by 37% and suicide by 85% compared to the results from this study. Conclusions The cohort of drug abusers had an increased risk of premature often drug-related and violent death well into middle age, and to a great extent the drug addicts died from the same drug they had abused when they were first admitted for treatment. The underestimation of drug-related death and suicide in some national death cause registers could be reduced if the doctor routinely records ICD codes when issuing death certificates and autopsy protocols.

Cost-effectiveness of atazanavir/ritonavir compared with lopinavir/ritonavir in treatment-naïve human immunodeficiency virus-1 patients in Sweden

The aim of this study was to estimate the cost-effectiveness of atazanavir/ritonavir (atazanavir/r) versus lopinavir/ritonavir (lopinavir/r) in treatment-naïve human immunodeficiency virus-1 (HIV-1) patients in Sweden for whom efavirenz is not suitable. A Markov model was developed to predict the lifetime outcomes of atazanavir/r and lopinavir/r in terms of quality-adjusted life years (QALYs) and total costs. The model was structured to focus on treatment lines--how patients progress from first- to second-, and then to third-line treatment. Model inputs were derived directly from clinical trials, such as the CASTLE study (a 96-week head-to-head trial in first-line therapy), and from the Framingham risk-equation. The analysis was conducted from a payer perspective and included extensive scenario and probabilistic sensitivity analyses. The model predicted atazanavir/r to save 0.16 (95% confidence interval (CI) 0.00 to 0.33) QALYs and reduce total costs by -202,896 SEK (95% CI -332,156 to -81,644 SEK) over a lifetime horizon. Probabilistic sensitivity analyses showed that atazanavir/r had a 100% probability to be cost-effective at a willingness to pay of 200,000 SEK per QALY. The results indicate that atazanavir/r is cost-saving and more effective compared to lopinavir/r for patients who have previously not been exposed to antiretroviral drugs in Sweden.

Nationwide prevalence of rheumatoid arthritis and penetration of disease-modifying drugs in Sweden

ObjectiveTo provide Swedish nationwide data on the prevalence of rheumatoid arthritis (RA), including variations by age, sex, geography, demography and education level, and assess antirheumatic treatment penetration.MethodsPatients ≥16 years assigned...

Have recent evolutions in European governance brought harmonisation in the field of illicit drugs any closer?

With the long awaited ratification of the Lisbon Treaty on 1 December 2009, it appears that plans within Europe to achieve an ‘ever closer union’ are back on track, yet, in the field of illicit drug policy, harmonisation remains as elusive a goal as ever. Sweden and the Netherlands have long provided examples of the different paradigms of drug policy operating within Europe and this article seeks to examine whether, as European Union harmonisation moves forward, recent developments bring the two any closer to convergence on this contentious issue. In addition to changes in Swedish and Dutch drug policy, the progress of the drug policy of other European countries has been evaluated. The article concludes that the Swedes and the Dutch remain ultimately wedded to their national policies and that movement both towards increased repression of drug use and increased liberalisation of drug use can be observed among other European countries. Harmonisation of European drug policy therefore remains in a state of stalemate.

Were the changes to Sweden's maintenance treatment policy 2000–06 related to changes in opiate‐related mortality and morbidity?

To analyse whether changes in maintenance treatment of opiate-dependent subjects in Sweden were related to changes in opiate-related mortality and inpatient care from 1998 to 2006. We collected data from surveys of methadone maintenance treatment units, of buprenorphine and methadone sales, and of mortality and inpatient care in Sweden. Sweden. Patients in maintenance treatment. Survey data of treatment policy to all units in 2003 and 2005. Trend tests and correlation analyses of data on sales, mortality, inpatient care and forensic investigations. The surveys showed a marked change to a less restrictive policy, with increased use of 'take-away doses' and a reduction of discharges due to side misuse. The one-year retention rate stayed high. Sales of buprenorphine and methadone and the number of patients in treatment increased more than threefold from 2000 to 2006, with the greatest increase for buprenoprphine, introduced in year 2000. There was a significant 20-30% reduction in opiate-related mortality and inpatient care between 2000-2002 and 2004-2006 but not of other drug-related mortality and inpatient care. This decline was larger in Stockholm County, which had a less restricted treatment policy. However, a significant increase in buprenorphine- and methadone-related mortality occurred. For the study period 1998-2006, statistically significant declines occurred only in Stockholm County. The liberalization of Sweden's drug policy correlated with an increase in maintenance treatment, a decrease in opiate-related mortality and inpatient care and an increase in deaths with methadone and buprenorphine in the tissues.

A signal for an abuse liability for pregabalin—results from the Swedish spontaneous adverse drug reaction reporting system

Pregabalin is a gamma-aminobutyric acid (GABA) analogue approved for the treatment of epilepsy, neuropathic pain and generalised anxiety disorder. As a GABA analogue, there has been some concern about an abuse liability. We aimed to investigate the possible abuse liability of pregabalin. By applying a Bayesian data-mining algorithm to reports of possible drug abuse or addiction in the Swedish national register of adverse drug reactions (SWEDIS), we calculated the information component (IC) for pregabalin and reports of abuse and addiction. Out of 198 reports indicative of abuse or addiction to any drug, 16 concerned pregabalin. The IC became significantly elevated in the fourth quarter of 2008, rising to 3.99 (95% confidence interval 3.21-4.59) at the end of 2009. Based on the signal from the present study, we conclude that pregabalin is likely to be associated with an abuse potential.

Performing Cannabis in the Light of the Backpacker Discourse

The aim of this article is to discuss how we theoretically can understand the relationship between a specific intoxicating drug and a specific holiday discourse, in this case the relationship between the drug cannabis and the backpackers' discourse. Starting from the term performance, which is divided into different forms of performance—directed, identity-oriented, and nonconforming—I try to grasp the process of materialization: how matters or substances ascribe meaning. In this article I discuss how the backpacker discourse is historically formed by the 1960s/70s hippie discourse, and further, how the drug cannabis is a part of this picture. Cannabis is used as a marketing instrument when the backpackers' discourse is promoted. There is a link between an ideology described in the hippie discourse and different forms of performance, such as identity-oriented, where cannabis is referred to as “natural,” and intoxication as a happy, nonviolent alternative, connected to solidarity, and the nonconforming performance, which can be a performance showing shame in relation to travelling and illicit drug experiences, or a resistance performance which aligns with the official Swedish drug discourse in order to present Swedish backpackers positively.

Muscle toxicity with statins

Statins rarely cause serious muscle toxicity and rhabdomyolysis. The aim of our investigation was to identify and quantify potential risk factors for statin-induced rhabdomyolysis. All cases of suspected adverse reactions to statins reported to the Swedish Adverse Drug Reactions Advisory Committee until 15 September 2006 containing the codes myalgia, myopathy, increased serum creatine kinase (CK), myoglobinuria or rhabdomyolysis were included in the study. Cases were classified into different CK categories, where cases with CK levels >10 times the upper limit of normal (ULN) laboratory range were compared with cases with normal CK levels (in some analyses cases with CK not measured were also included as controls). Fisher's test and multiple logistic regression were used to test the degree of association. A total of 338 cases with muscle toxicity were identified. CK had not been measured in 148 cases. Of the remaining 190 cases, 59 were classified as rhabdomyolysis, 62 had CK increases below the level of rhabdomyolysis, 69 had normal CK and 2 contained insufficient information to classify the degree of CK increase. A high statin dose and concomitant interacting drug treatment were over-represented among cases with rhabdomyolysis compared with cases with normal CK. Renal disease and unusual strenuous muscular activity were also associated with an increased risk of rhabdomyolysis when the control group included cases with CK not measured. Results from our study support previous studies indicating that the risk of rhabdomyolysis with statin treatment increases with increase in systemic exposure to the statin. Renal disease and unusual strenuous muscular activity may also contribute to an increased risk of rhabdomyolysis.

Vem tvångsvårdas? Utmärkande drag för tvångsvårdade respektive frivilligt vårdade personer med alkohol- och narkotikaproblem

J. Storbjörk: Who is in compulsory treatment? Charasteristics for compulsory treated and voluntary treated persons misusing alcohol and drugs The article studies what characterized those committed to compulsory treatment (CT) according to the Care of Alcoholics, Drug abusers and Abusers of Volatile Solvents (Special Provision) Act as compared to those in voluntary treatment in Stockholm County 2001–2002. The aim is to analyze who is in CT by studying which client characteristics (sex, age, drug of choice, consumption, route of administration, social situation, physical health, incl. municipality) are associated with CT. Responses from 361 CT-clients who were interviewed with DOK (Documentation of Clients) are compared to comparable responses from 1772 clients in voluntary treatment from the study Women and Men in Swedish Alcohol and Drug Treatment. Bivariate and multivariate analyses show that the two groups differ significantly in many respects. Clients in CT are younger, report more frequent consumption of their main drug of choice and an inferior social situation (housing, livelihood). An analysis of interaction terms shows that old alcohol misusers are less likely to be in CT than young drug misusers. Women are not more likely to be in CT than men. However, CT was more often used for women, but not for men, with children under the age of 18 or who were living with another misuser.

Hair analysis for drugs in driver's license regranting. A Swedish pilot study

When being convicted for petty drug offence or driving under the influence of drugs in Sweden, the driving license may be suspended. To regain the license, the person has to prove that he or she has been drug free during an observation period. This is controlled by urine samples taken at several occasions. However, the risk of manipulation and the risk of false negative urine samples are high. In addition, many people find it difficult or embarrassing to urinate when observed. Hair sampling might therefore be a welcome option to this procedure, with its easy sampling and minimal risk of manipulation. The longer detection window may also provide better information to the physician. The aim of this work was to evaluate if clients preferred hair samples to urine and to investigate practical and interpretive problems or advantages with hair samples. Ninety-nine hair samples and 198 urine samples were collected from 84 clients during the 12 month study period. Hair samples were divided into either one segment (0–3 cm) or two segments (0–3 and 3–6 cm) depending on the length. The hair samples were screened with LC–MS–MS for 20 drugs and confirmation of positive results were performed with GC–MS or LC–MS–MS. The results were compared to urine samples taken at two occasions during the observation period. To cover the timeframe of the urine samples hair was collected 2 weeks after the second sample. The urine samples were analysed with immunochemical screening and positive results confirmed with GC–MS or LC–MS–MS. Seventy-four clients presented with negative results in both urine and hair. Hair analysis identified illegal drugs at seven different occasions whereas urine failed to identify any illegal drugs. However the thresholds used may still be too high to find sporadic use as clients that admitted to use drugs sporadically presented with drug concentrations lower than the agreed thresholds but above the limit of detection. This implicates that the physician must have an understanding and knowledge of the limitations of the screening methods used. Another important outcome was that the clients approved of hair sampling considering it a better means to prove their drug abstinence. In addition, both the clients and the clinicians thought hair sampling easier than urine sampling. We believe that hair analysis can offer several advantages compared to urine analysis for clinicians working with driving license regranting.

Using pharmacy information in a decision support system to improve efficient delivery of primary health care. A study focusing on the Swedish national drug register

The aim of the project was to apply the John Hopkins ACG case-mix system, Rx-PM model, to the Swedish National Drug Register (period 2006-2008). Its intention was to analyze and compare results between different county councils, and analyze if drug use in the population can be employed to approximate the need for care, and as a tool to adjust the capitation payment system in the county councils. This paper focuses on the comparisons between the different county councils. Practical examples and usage of data are presented.

Regional variation and adherence to guidelines for drug treatment of asthma

To describe the utilization of antiasthmatic drugs in Sweden and to explore regional variations in drug utilization and adherence to guidelines for rational drug prescribing of antiasthmatics and their rationale. Data on antiasthmatic drugs dispensed between July 2005 and December 2008 to all Swedish citizens aged between 18 and 44 years were obtained from the Swedish National Prescribed Drug Register. The period prevalence was determined by analyzing the number of users/1000 inhabitants, and the incidence by analyzing the number of new users after an 18-month drug-free wash-out period. Three drug-related indicators were used to assess the adherence to guidelines. All measures were analyzed by gender and region. A total of 161,000 patients were dispensed antiasthmatics in 2007, corresponding to a prevalence of 4 and 6% among men and women, respectively; the incidence rates were 2 and 3%, respectively. The total drug utilization and adherence to guidelines varied between regions. The total drug expenditures of antiastmatics were 258 million SEK (28 million euro), with fixed dose combinations accounting for 46% of the expenditure. No relation was found between models for allocating prescribing budgets or clear Drug and Therapeutics Committee recommendations and adherence to guidelines. There are large regional variations in the utilization of antiasthmatics between Swedish regions, with substantial room for improvement in the adherence to guidelines. New methods of influencing physician behavior may be needed in the future to enhance adherence.

Tramadol dependence: a survey of spontaneously reported cases in Sweden

Tramadol is a weak opioid analgesic, which is generally considered to be safe. However, conflicting data exist on the dependence potential of tramadol. The aim of this study was to investigate occurrence of tramadol dependence and associated risk factors using spontaneously reported adverse drug reactions. The Swedish database for spontaneously reported adverse drug reactions, Swedish Drug Information System (SweDIS), was searched for reports on tramadol dependence from 1 January 1995 until 31 December 2006. Selection was conducted based on the DSM-IV definition of dependence. Available information was scrutinised and registered and then presented descriptively. A total of 104 reports of tramadol dependence were identified, of which 60 (58%) concerned women. The median age (range) was 45 (15-84) years. Information on a history of substance abuse was present in 31 patients (30%) and 41 patients (39%) had a documented past or current use of a drug of abuse. Prescribed doses of tramadol ranged between 50-800 mg/day, and ingested doses between 50-4000 mg/day. Time of onset ranged from some weeks up to 4 years. In 72 (69%) cases the reaction was classified as serious, mainly due to hospitalisations for detoxification or discontinuation of tramadol. There is an occurrence of tramadol dependence in association with analgesic treatment within the recommended dose range. In susceptible patients a severe and serious dependence syndrome may develop. A history of abuse or use of a drug of abuse seems to be an important risk factor.

Association between the use of serotonin receptor 2A–blocking antidepressants and joint disorders

There are case reports about antidepressants causing arthritis and arthralgia, and the majority of these reports deal with atypical antidepressants, which are serotonin receptor 2A (5-HT(2A))-blocking substances. The aim of this study was to examine a possible association between joint disorders and the use of 5-HT(2A)-blocking atypical antidepressants. We performed a retrospective study using reports of adverse drug reactions (ADRs) of 5-HT(2A)-blocking atypical antidepressant substances concerning joint disorders reported to the Swedish Adverse Drug Reactions Committee and the World Health Organization (WHO) Adverse Reactions Database during the period January 1, 1990 to December 31, 2006. The reports of joint disorders were related to sales figures measured as defined daily doses and to the total number of ADR reports. In the Swedish material, the 5-HT(2A) antagonists were 45 times more often reported to give joint ADRs when related to sales figures and compared with the selective serotonin reuptake inhibitors (SSRIs; P < 0.001). Joint disorders constituted 6.6% of the total number of reports of possible ADRs for the three 5-HT(2A)-blocking substances mianserin, mirtazapine, and nefazodone compared with 0.5% for the SSRIs (P < 0.001). In the WHO material, the joint disorders constituted 1.3% of all ADRs for the 5-HT(2A)-blocking antidepressants and 0.6% for the SSRIs (P < 0.001). In this study, joint disorders were considerably more frequently reported ADRs of 5-HT(2A)-blocking antidepressants than of other comparable drugs, suggesting a possible association between the use of 5-HT(2A)-blocking antidepressants and joint disorders.

Events as Precipitators to Treatment: Important for Both Well-Integrated and Marginalized Alcohol and Drug Users of a Swedish Treatment System

“Women and Men in Swedish Alcohol and Drug Treatment” studies how people with alcohol and drug problems come to treatment. The focus is on different alcohol- and drug-related life events in the year prior to treatment and whether or not these events contributed to treatment entry. The importance of these events is also studied in relation to level of marginalization. The representative cross-sectional sample includes 1865 clients (71% men) interviewed inperson when entering inpatient and outpatient treatment facilities. Most respondents reported events in the year prior to treatment and these were also perceived as contributors to treatment. Events related to significant others and health workers seem to be of greatest importance for treatment entry. These events happen to a lot of the problematic alcohol and drug users and are viewed as strong contributing factors by the respondents. More marginalized people and misusers with more severe addiction problems experience more events. A curvilinear relationship (somewhat U-shaped) was found between level of marginalization and events as contributors to treatment: the least marginalized people are most likely to report events as contributors, people in between are the least likely and the most marginalized people are likely to report events as contributors to treatment, given that they have experienced the event.

A Swedish county with unexpectedly high utilization of anti-parkinsonian drugs.

This report is based on the use of L-dopa-containing drugs within 24 Swedish counties in the period 1977-1984. The mean utilization of these drugs in Sweden in 1984 was 1.46 defined daily doses (DDD)/day X 10(3) inhabitants (inh). As Parkinson's disease is virtually the only condition for which these drugs are prescribed, it seems highly probable that the determining factor for their use today is the prevalence of the disease. The exceptionally high utilization (2.34 DDD/day X 10(3) inh) of L-dopa-containing drugs in the county of Gävleborg, warranted further analyses of subareas in this particular county. The use is discussed in relation to environmental factors.

Epidemiology of adverse reactions to carbamazepine as seen in a spontaneous reporting system

A survey was made of 505 reports on 713 adverse reactions to carbamazepine submitted to the Swedish Adverse Drug Reactions Advisory Committee from 1965-1987. For the period after 1972, the relation between the reports and sales statistics could be investigated. The total incidence of reported adverse reactions to carbamazepine was 4.5 per million defined daily doses (DDD), corresponding to 2.7 per million prescribed daily doses (PDD). Most often reported were skin reactions (48%), but reports on haematological (12%) and hepatic disorders (10%) were also frequent. Virtually all hepatic disorders and severe skin reactions, as well as the majority (60%) of the haematological reactions, occurred within the first 2 months of treatment. In view of the very low incidence of reported serious blood dyscrasias, such as pancytopenia (0.04/million PDD) and agranulocytosis (0.06/million PDD), continuous haematological monitoring seems to be of little value. The elderly appear to be at increased risk of developing blood dyscrasias and liver reactions, and alcohol abusers seem to represent a high-risk group for developing serious skin reactions.

Costs and outcomes for patients with rheumatoid arthritis treated with biological drugs in Sweden: a model based on registry data

Objective: To design an economic model describing the costs and outcomes for patients treated with tumour necrosis factor alpha (TNFα) inhibitors for rheumatoid arthritis (RA) in current clinical practice in Sweden, to be used as a tool to estimate cost-effectiveness of the next generation of treatments.Methods: The model was constructed as a discrete event simulation (DES) model analysed at patient level. It contains treatment and outcome data for 1903 patients followed in the RA registry for biological drugs in southern Sweden between 1999 and 2007 [the Southern Swedish Arthritis Treatment Group (SSATG) Register]. Resource consumption was based on a survey of 1027 patients in the same region. Costs and quality-adjusted life years (QALYs) are presented for 10 (5) years, for patients with the mean characteristics at treatment start in SSATG [Health Assessment Questionnaire (HAQ) score 1.33, disease duration 12.1 years, age 55 years], but also for patients with more or less severe disease. Cost and outcomes (QALYs) are discounted with 3%.Results: The 10-year costs in the base case amount to USD336 000 (SD USD 64 000) or EUR 223 000, with a total of 4.4 QALYs. Over 5 years, the costs amount to USD 208 000 or EUR 138 000 and QALYs to 2.5. The results were most sensitive to HAQ level at treatment start, but also to underlying disease progression, age, and disease duration. Starting treatment at a lower HAQ level (0.85) reduces costs by 10% and increase QALYs by 20%.Conclusion: This analysis is based on the longest available follow-up for patients treated with TNFα inhibitors and provides an opportunity to explore treatment strategies when new therapies become available using actual clinical practice data.

Costs and outcomes for patients with rheumatoid arthritis treated with biological drugs in Sweden: a model based on registry data

Costs and outcomes for patients with rheumatoid arthritis treated with biological drugs in Sweden: a model based on registry data