Ingeborg Hartz

Detection of one single mutation predicts thiopurine S-methyltransferase activity in a population of Saami in northern Norway

Thiopurine S‐methyltransferase (TPMT) activity exhibits genetic polymorphism. The purpose of this investigation was to identify TPMT mutant alleles in the Saami population as a basis of developing genotyping tests for prediction of TPMT activity. The most predominant allele in Saamis (n = 194) was the TPMT*3C allele (A719G mutation) representing 92% of the mutant alleles, with an estimated allelic frequency of 3.3%. The most frequent allele in Caucasians (n = 66) living in the same geographic area was the TPMT*3A (A719G and G460A mutations) representing 91% of the mutant alleles, with an estimated allelic frequency of 3.4%. A test for one mutation, A719G, may prospectively identify more than 90% of the Saami individuals who require reduction in thiopurine dose to avoid hematopoietic toxicity. In a Norwegian population, comprising both the major Caucasian population and a minor Saami population, the same genotyping tests (eg, tests for the A719G and G460A mutations) may be used.

Aspects of statin prescribing in Norwegian counties with high, average and low statin consumption – an individual-level prescription database study

BackgroundA previous study has shown that variations in threshold and intensity (lipid goal attainment) of statins for primary prevention contribute to regional differences in overall consumption of statins in Norway. Our objective was to explore how differences in prevalences of use, dosing characteristics, choice of statin and continuity of therapy in individual patients adds new information to previous results.MethodsData were retrieved from The Norwegian Prescription Database. We included individuals from counties with high, average, and low statin consumption, who had at least one statin prescription dispensed during 2004 (N = 40 143).1-year prevalence, prescribed daily dose (PDD), statin of choice, and continuity of therapy assessed by mean number of tablets per day.ResultsThe high-consumption county had higher prevalence of statin use in all age groups.Atorvastatin and simvastatin were dispensed in 79–87% of all statin users, and the proportion was significantly higher in the high-consumption county.The estimated PDDs were higher than the DDDs, up to twice the DDD for atorvastatin. The high-consumption county had the highest PDD for simvastatin (25.9 mg) and atorvastatin (21.9 mg), and more users received tablets in the upper range of available strengths. Continuity of therapy was similar in the three counties.ConclusionAlthough differences in age-distribution seems to be an important source of variation in statin consumption, it cannot account for the total variation between counties in Norway. Variations in prevalences of use, and treatment intensity in terms of PDD and choice of statin also affect the total consumption. The results in this study seems to correspond to previous findings of more frequent statin use in primary prevention, and more statin users achieving lipid goal in the highest consuming county.

Hypnotic drug use among 0–17 year olds during 2004–2011: A nationwide prescription database study

Aims: To (a) describe the prevalence, trend, and amount of hypnotic drug use, (b) determine the prevalence of chronic diseases among hypnotic drug users, and (c) determine levels of recurrent hypnotic drug use (2007–2011), among 0–17 year old Norwegians. Methods: Data were obtained from the nationwide Norwegian Prescription Database (NorPD) in the period 2004–2011. Results: Hypnotic drug use in 0–17 year olds increased during the period, from 8.9 to 12.3 per 1000, mainly owing to doubling of melatonin use. Hypnotic drug use peaked at 15 per 1000 among those aged 1–2 years. Melatonin use increased steadily from 6 to 12 years of age, most pronounced in males. Among females, hypnotic drug use increased threefold from 13 to17 years of age. Melatonin was dispensed in the highest annual amount of all hypnotic drugs; accounting up to a median of 360 defined daily doses in 9–13 year old boys. A total of 62% and 52% of all male and female hypnotic drug users were co-medicated with reimbursable drugs for chronic diseases. Levels of recurrent use (2007–2011) were 12% in boys and 8% in girls, of whom 76–77% were co-medicated with drugs reimbursed for chronic diseases. Conclusions: There is a trend of increasing use of hypnotic drugs among 0–17 year olds, mainly owing to increasing use of melatonin, used in high amounts. Still, melatonin is not recommended in Norway for use in this age group because of insufficient data on safety and efficacy. A threefold increase in hypnotic drugs among females from 13 to 17 years of age warrants attention.

Increase in psychotropic drug use between 2006 and 2010 among adolescents in Norway: a nationwide prescription database study

Background The purposes of this study were to investigate the prevalence of psychotropic (hypnotic, antidepressant, and anxiolytic) drug use among adolescents aged 15–16 years during the period 2006–2010 according to gender and subcategories of psychotropics, and to study psychotropic drug use over the period 2007–2010 among incident users in 2007. Methods This was a one-year prevalence and follow-up study based on information retrieved from the nationwide Norwegian prescription database for the period 2006–2010. The study population consisted of adolescents aged 15–16 years who had filled at least one prescription for a psychotropic drug in the study period. The main outcome measures were filling of hypnotic, antidepressant, and/or anxiolytic drug prescriptions. Results Overall use of psychotropic drugs increased from 13.9 to 21.5 per 1000 among boys and from 19.7 to 24.7 per 1000 among girls during the 2006– 2010 period. Hypnotic drugs, and melatonin in particular, accounted for most of the increase. For melatonin, the annual median amount dispensed was 180 defined daily doses through the period until 2010, at which time it decreased to 90 defined daily doses. In total, 16.4% of all incident psychotropic drug users in 2007 were still having prescriptions dispensed in 2010. Conclusion This study shows an increase in hypnotic drugs dispensed for adolescents in Norway, mainly attributable to the increasing use of melatonin. The amount of melatonin dispensed indicates more than sporadic use over longer periods, despite melatonin only being licensed in Norway for use in insomnia for individuals aged 55 years or older.

The association between smoking and subsequent repeated use of prescribed opioids among adolescents and young adults--a population-based cohort study.

The use of prescribed opioids for chronic non‐cancer pain is increasing in many countries. It is, therefore, important to investigate predictors for repeated use of opioids in young non‐cancer patients.

Disability pension is associated with the use of benzodiazepines 20 years later: A prospective study

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.

Paediatric Off-Label Use of Melatonin – A Register Linkage Study between the Norwegian Prescription Database and Patient Register

The aims were, for the entire Norwegian population aged 4–17 years, to study the prevalence of melatonin use during 2004–2012, recurrent use in incident users and psychiatric and neurological morbidity in recurrent users. Data on dispensed melatonin were retrieved from the Norwegian Prescription Database and linked to diagnostic data from the Norwegian Patient Register. Outcome measures were the following: 1‐year prevalence of use, proportion of recurrent use (use over three consecutive 365‐day periods among incident users in 2009) and annual number of milligrams and number of prescriptions dispensed in recurrent users. The prevalence of registered ICD‐10 diagnoses during the period of 2008–2012 was given for the recurrent users. The prevalence of melatonin use increased annually in both genders during 2004–2012 (boys: 3.4–11.0 per 1000; girls: 1.5–7.7 per 1000). Twenty‐nine per cent of boys and 23% of girls were recurrent melatonin users, with highest level of recurrent use among the youngest (aged 4–8 years; boys: 47%, girls: 42%). In the third year, the median annual amount of melatonin dispensed was 1080 (IQR 586–1800) milligrams in boys and 900 (IQR 402–1620) milligrams in girls. Among recurrent users, 91% had a diagnosis of either psychiatric (84%) or neurological (32%) disorder. Off‐label recurrent use of melatonin seems to have acquired a role mainly in treating secondary sleep problems in children and adolescents with psychiatric and neurological disorders. Once melatonin has been started, a large proportion of patients continue for at least 3 years, in doses corresponding to daily use in the majority.

Mental Distress and Subsequent Use of Psychotropic Drugs Among Adolescents—A Prospective Register Linkage Study

PURPOSE To investigate the association between mental distress, other factors, and subsequent use of psychotropic drugs in adolescents aged 15-16 years. METHODS This study is based on information retrieved from the Norwegian Youth Health Surveys (2000-2003) and linked to prescription data from the Norwegian Prescription Database (2004-2009). The study population included 11,620 adolescents aged 15-16 (87% response rate) years. Self-reported mental distress (Hopkins Symptom Checklist-10 score 1.85) was recorded along with health and lifestyle habits, education plans, and family economics. Incident psychotropic drug use (outcome measure) was defined ≥1 prescriptions of one of the following psychotropic drugs: anxiolytics, hypnotics, antidepressants, or phenothiazines registered in the Norwegian Prescription Database. RESULTS Overall, 15.5% of the adolescents reported mental distress, 75% of them were girls. For both genders, incident psychotropic use was significantly higher among those reporting mental distresses at baseline, compared with the rest of the participants. The highest psychotropic drug use was observed among mentally distressed girls (27.7%). Mental distress was significantly associated with incident use of psychotropic drugs (odds ratio: 2.25, 95% confidence interval: 1.97-2.55). After adjustment for confounding factors and inclusion of potential mediating factors, the odds ratio attenuated to 1.59 (95% confidence interval: 1.35-1.86). CONCLUSIONS The prevalence of mental distress among adolescents may have consequences for health promotion. Public health nurses in Norway, working in health centers and schools, have a responsibility to promote health and prevent health problems. They have the opportunity and a responsibility to identify vulnerable young people.

Mental disorder diagnoses among children and adolescents who use antipsychotic drugs.

Antipsychotic drugs are used increasingly by children and adolescents and there is concern about off-label use. We aimed to study which substances, and for which mental disorder diagnoses, antipsychotic drugs were prescribed to 0-18-year-old boys and girls in Norway. Linked data from the national health registry for prescription drugs in 2010 and mental disorder diagnoses in 2008-2012 were used to study the prevalence of antipsychotic drug use, the type of antipsychotic drug substances used, mental disorder diagnoses in users and distribution of drugs per diagnostic category across gender. In total, 0.18% of Norwegian children and adolescents were prescribed antipsychotic drugs during 2010, of which there were more boys (0.23%) than girls (0.13%). Risperidone was the most frequently used substance among boys (57.4%) and girls (32.3%), followed by aripiprazole (19.4%) in boys and quetiapine (27.4%) in girls. The most common mental disorder diagnoses among male users were hyperkinetic (49.9%) and autism spectrum disorder (27.1%), while anxiety disorders (41.5%) and depressive illness (33.6%) were most common among female users. A schizophrenia-like psychosis diagnosis was given to 11.1% of the male and 18.2% of the female users. A hyperkinetic disorder was diagnosed among 56.9% and 52.4% of the male risperidone and aripiprazole users, respectively. Among female quetiapine users, 57.1% were diagnosed with anxiety disorders and 52.4% with depressive illness. These results demonstrate that children and adolescents who use antipsychotic drugs are predominantly diagnosed with non-psychotic mental disorders such as hyperkinetic disorder among boys and anxiety disorder or depressive illness among girls.

The association between prescribed opioid use for mothers and children: a record-linkage study

PurposeThe repeated use of prescription opioids may lead to serious side effects. It is therefore important to examine factors associated with such repeated use. The aim of this study was to investigate the association between the maternal use of prescription opioids and their use by offspring of these mothers.MethodsData were extracted from two nationwide registers linked by unique personal identity numbers: the 2001 Norwegian Population and Housing Census and the Norwegian Prescription Database 2004–2009. The study population consisted of 97,574 adolescents aged 15–16 years in 2001 and their mothers. The repeated use of opioids was defined as the issuing of >4 and >15 prescriptions to an adolescent and his/her mother, respectively, during the period 2004–2009. Non-steroidal anti-inflammatory drugs (NSAIDs) are not potentially addictive, and individuals issued prescriptions for NSAIDs were used as the reference analgesic drug group.ResultsThe proportion of repeated prescription opioid users was higher among adolescents whose mother was registered as a repeated user of prescription opioids (8.4 %) than among those whose mother did not repeatedly use prescription opioids (2.4 %). The odds ratio (OR) was 3.1 [95 % confidence interval (CI) 2.7–3.6] when adjusted for the mother’s socioeconomic characteristics and the gender of the offspring. A lower socioeconomic position of the mother increased the risk of repeated opioid use by her offspring. Maternal repeated use of NSAIDs was associated with repeated use of NSAIDs among offspring (OR 1.8, 95 % CI 1.7–2.0).ConclusionsAmong our study population, the maternal use of opioids was associated with the repeated use of prescription opioids among the respective offspring. The same association was seen with NSAIDs, but to a lesser extent.