Jørgen G. Bramness

Prescription drug use among fathers and mothers before and during pregnancy. A population‐based cohort study of 106 000 pregnancies in Norway 2004–2006

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECTnMothers are using medicines during pregnancies; the extent varies across the world and is generally difficult to compare. In this registry-based study, we examined more than 100,000 Norwegian pregnancies and described the drug prescription pattern of both fathers and mothers around conception and during pregnancy (mothers).nnnWHAT THIS STUDY ADDSnIn every trimester of pregnancy, about 30% of the mothers was dispensed a drug. The total drug exposure did not seem to diminish throughout pregnancy. One-quarter of the fathers was dispensed drugs during the last 3 months prior to conception.nnnAIMSnThe primary aim of this study was to describe the use of prescribed drugs in both mothers and fathers before and during pregnancy in Norway.nnnMETHODSnThis population-based cohort study was based on data retrieved from the Medical Birth Registry of Norway and the Norwegian Prescription Database. These registries cover the entire population of Norway. Information on >100,000 births during 2004-2006 in the birth registry was linked to prescription data. Prescriptions issued to mothers just prior to, during and after the pregnancies as well as prescriptions to fathers just prior to conception were identified.nnnRESULTSnAmong mothers, 83% were prescribed drugs during the period 3 months prior to estimated conception until 3 months after giving birth. The mothers who received drugs were prescribed on average 3.3 different Anatomical Therapeutic Chemical (ATC) codes (range 1-38). During pregnancy, 57% were prescribed drugs. In the first trimester, 33% of mothers were dispensed drugs, while the figure was 29% for mothers in the last trimester. Among fathers, 25% used prescribed drugs during the 3 months prior to conception, with on average 1.9 different ATC codes (range 1-22).nnnCONCLUSIONnLarge proportions of both fathers and mothers were dispensed drugs prior to conception or during pregnancy. While there is a high awareness of the issues involved in maternal drug use in pregnancy, possible teratogenic effects of drug use in fathers shortly before conception should be further explored.

Road traffic accident risk related to prescriptions of the hypnotics zopiclone, zolpidem, flunitrazepam and nitrazepam

BACKGROUNDnDespite the high prescription rate of benzodiazepine-like hypnotics (z-hypnotics), there is limited information on the road traffic accident risk associated with the use of these drugs. We wanted to investigate whether filling a prescription for zopiclone or zolpidem was associated with increased risk of road traffic accidents at a national population level. Nitrazepam and flunitrazepam were used as comparator drugs.nnnMETHODnAll Norwegians 18-69 years (3.1 million) were followed-up from January 2004 until the end of September 2006. Information on prescriptions, road traffic accidents and emigration/death was obtained from three Norwegian population-based registries. The first week after the hypnotics had been dispensed was considered to be the exposure period. Standardized incidence ratios (SIRs) were calculated by comparing the incidence of accidents in the exposed person-time to the incidence of accidents in the unexposed person-time.nnnRESULTSnDuring exposure, 129 accidents were registered for zopiclone, 21 for zolpidem, 27 for nitrazepam and 18 for flunitrazepam. The SIRs were (SIR for all ages and both sexes combined; 95% CI): z-hypnotics (zopiclone+zolpidem) 2.3; 2.0-2.7, nitrazepam 2.7; 1.8-3.9 and flunitrazepam 4.0; 2.4-6.4. The highest SIRs were found among the youngest users for all hypnotics.nnnCONCLUSIONSnThis study found that users of hypnotics had a clearly increased risk of road traffic accidents. The SIR for flunitrazepam was particularly high.

Starting insomnia treatment: the use of benzodiazepines versus z-hypnotics. A prescription database study of predictors

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

Relationship Between THC Concentration in Blood and Impairment in Apprehended Drivers

Objective. The most important psychoactive ingredient in cannabis, Δ (9)-tetrahydrocannabinol (THC) is one of the most frequently detected substances in blood samples from suspected impaired drivers in Norway. There is growing concern over possible links between the use of cannabis and increased risk of motor-vehicle crashs. Experimental studies have provided useful information on the role of THC and dose-effect relations with respect to psychomotor performance. The main purpose of the present study was to investigate whether a physicians judgment on impairment in a real-life setting among suspected drugged drivers, was related to blood THC concentration. Methods. In Norway a police physician performs a clinical test for impairment (CTI) shortly after apprehension. The Norwegian Institute of Public Health analyze blood samples from all drivers suspected of driving under the influence of non-alcoholic drugs. In the present study 589 samples from approximately 30,000 cases of suspected drug impaired driving from the period 1997–99, contained THC as the only drug. In 456 of these cases a conclusion of the CTI was available. Results. 230 (54%) drivers were considered not impaired and 226 (46%) impaired. Impaired drivers had higher blood THC concentration than the drivers who were judged as not impaired (median; 2.5 ng/mL (range; 0.3–45.3 ng/mL) vs 1.9 ng/mL (range; 0.32–24.8 ng/mL), (p < 0.05). Furthermore, drivers with blood THC concentrations above 3 ng/mL had an increased risk for being judged impaired compared to drivers with lower concentration ranges. Conclusion. The relationship between the concentration of THC in blood and risk of being assessed impaired found in this cross-sectional study of suspected drugged drivers, supports findings from previous experimental studies of concentration related effects of THC on psychomotor performance and driving skills.

Testing for benzodiazepine inebriation—relationship between benzodiazepine concentration and simple clinical tests for impairment in a sample of drugged drivers

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

Carisoprodol intoxications: a retrospective study of forensic autopsy material from 1992–2003

Carisoprodol is commonly prescribed as a centrally acting muscle relaxant, but it is also subject to abuse. The literature describing fatal intoxications with the drug is limited to a relatively small number of cases, and there are inconsistencies with regard to which concentration levels that are toxic. We therefore investigated all forensic autopsies at the Norwegian Institute of Public Health during the period 1992–2003 where carisoprodol was detected. The median concentrations of carisoprodol in intoxication with carisoprodol only or with only minor other analytical findings was 36xa0mg/l (range 8–65xa0mg/l; n=5). In the rest of the intoxications, the relevance of carisoprodol relative to the other drugs detected was variable (n=93). When the number of intoxications with carisoprodol each year were divided by the number of defined daily doses (DDD) sold, a fatal toxicity index between 5.6 and 6.9 deaths/1 million DDD was obtained. The total number of cases where carisoprodol was detected increased during the period studied, which correlated to sales figures for the drug. We conclude that carisoprodol can be fatal in concentrations below those indicated in some of the previously published literature. There were, however, only a small number of cases where the cause of death can be attributed to use of carisoprodol alone.

The use and potential abuse of anticholinergic antiparkinson drugs in Norway: a pharmacoepidemiological study.

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECTnAnticholinergic antiparkinson drugs are used to ameliorate extrapyramidal symptoms caused by either Parkinsons disease or antipsychotic drugs, but their use in the treatment of Parkinsons disease is assumed to be in decline. Patients with psychotic conditions have a high prevalence of abuse of drugs, including anticholinergic antiparkinson drugs.nnnWHAT THIS STUDY ADDSnAnticholinergic antiparkinson drugs in Norway were primarily prescribed to patients using antipsychotic medication. The risk of abuse of this group of drugs was small, even among patients who probably abused other drugs.nnnAIMSnThe use of anticholinergic antiparkinson drugs is assumed to have shifted from the therapy of Parkinsons disease to the amelioration of extrapyramidal adverse effects induced by antipsychotic drugs. There is a considerable body of data suggesting that anticholinergic antiparkinson drugs have a potential for abuse. The aim was to investigate the use and potential abuse of this class of drugs in Norway.nnnMETHODSnData were drawn from the Norwegian Prescription Database on sales to a total of 73 964 patients in 2004 of biperiden and orphenadrine, and use in patients with Parkinsons disease or in patients who were also prescribed antipsychotic agents. Possible abuse of these drugs was assessed by the level of use, skewedness of use, indications of drug-seeking behaviour and concomitant use of benzodiazepine tranquillizers, a group of prescription drugs with a recognized potential for abuse.nnnRESULTSnAnticholinergic antiparkinson drugs were prescribed to 4.5% of all outpatients who used antipsychotic drugs. This outnumbered sales to patients with Parkinsons disease by >20 to 1. We found indications of abuse of benzodiazepine tranquillizers among patients using antipsychotics, but there were no clear indications of abuse of anticholinergics, even among patients who were strongly suspected of abuse of benzodiazepines.nnnCONCLUSIONSnAnticholinergic antiparkinson drugs were used primarily by patients with psychotic illnesses. These patients have a very high prevalence of legal and illegal drug abuse, but the risk of abuse of anticholinergic antiparkinson drugs seemed small.

Drugs of abuse among acute psychiatric and medical admissions: laboratory based identification of prevalence and drug influence

OBJECTIVEnTo use laboratory based analyses of blood and urine to determine the prevalence and influence of drugs of abuse among acute psychiatric and medical admissions.nnnMETHODnIn a cross sectional study, urine and blood samples were collected from 100 psychiatric and 106 medical admissions and extensively analysed for legal drugs with abuse potential, alcohol and illegal drugs. Drug influence at the time of admission was estimated on the basis of blood drug concentrations.nnnRESULTSnLegal drugs were found in 47% of the psychiatric and 42% of the medical admissions. Alcohol was detected in 8% of the psychiatric and 4% of medical admissions, and illegal drugs were detected in 36% of the psychiatric and 13% of the medical admissions. Drug influence was estimated in 26% of the psychiatric and 14% of the medical patients.nnnCONCLUSIONnThis study shows widespread use of substances among psychiatric and medical inpatients and that many are under the influence of drugs on admission.

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

Aimu2003 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.

Carisoprodol Intoxications and Serotonergic Features

The symptoms and signs of carisoprodol intoxications do not resemble those caused by its metabolite meprobamate. Meprobamate most probably produces its effects through the GABAergic neurotransmitter system. The signs and symptoms of carisoprodol intoxications, however, are not easily explained by interaction with this neurotransmitter system. In the present study, four cases of carisoprodol intoxications are presented with emphasis on the presence of serotonergic signs and symptoms. All four cases fulfilled three different sets of criteria for the diagnosis of serotonin syndrome. These findings could indicate that an increased serotonin level in the central nervous system could explain some of the symptoms and signs of carisoprodol intoxications. This may have implications for the clinical evaluation and treatment of such intoxications. Since few laboratories routinely screen for carisoprodol it is important to keep this drug in mind when encountering intoxications displaying serotonergic symptoms.