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Aims Patients who have undergone some forms of bariatric surgery have increased risk of developing alcohol use disorder (AUD). In the present observational study, we compared patients with AUD who themselves reported to having undergone bariatric surgery with other patients in treatment for AUD. Materials One-hundred-and-six consecutively enrolled patients in residential treatment for AUD were asked if they had undergone bariatric surgery. Sociodemographics, mental health-related, and alcohol use-related parameters were compared between those who had and those who had not undergone bariatric surgery. Results Of the 106 patients with AUD, seven (6.6%; 95% confidence interval, 2.7%–13.1%) had undergone bariatric surgery. Six of seven patients had undergone such surgery were women (P  < .001). The patients with AUD who had undergone bariatric surgery were similar to other patients with AUD on most other parameters, the exception being a larger number of alcohol units ingested to feel an effect of alcohol (adjusted odds ratio 7.1; 95% confidence interval 2.0–12.2; P  = .007). Conclusion The high number of patients with AUD that reported having undergone bariatric surgery emphasizes the risks following such a procedure. The overrepresentation of women may reflect than more women undergo such procedures. The unexpected finding that patients with AUD having undergone bariatric surgery seemed to need more alcohol to feel intoxicated warrants further research. [ABSTRACT FROM AUTHOR]

Background and Aims: Little is known about long‐term consequences of delirium tremens (DT). This study aimed to compare all‐cause and cause‐specific mortality and alcohol‐related morbidity between patients with: (i) DT, (ii) alcohol withdrawal state (AWS) and (iii) alcohol dependence (AD). Design: A national longitudinal health registry study with linked data from the Norwegian Patient Registry and the Norwegian Cause of Death Registry. Setting: Norway. Participants: All patients registered in the Norwegian Patient Registry between 2009 and 2015 with a diagnosis of AD (ICD‐10 code F10.2), AWS (F10.3) or DT (F10.4) and aged 20–79 years were included (n = 36 287). Measurements: Patients were categorized into three mutually exclusive groups; those with DT diagnosis were categorized as DT patients regardless of whether or not they had received another alcohol use disorder diagnosis during the observation period or not. Outcome measures were: annual mortality rate, standardized mortality ratios (SMR) for all‐cause and cause‐specific mortality and proportion of alcohol‐related morbidities which were registered in the period from 2 years before to 1 year after the index diagnosis. Findings DT patients had higher annual mortality rate (8.0%) than AWS (5.0%) and AD (3.6%) patients, respectively. DT patients had higher mortality [SMR = 9.8, 95% confidence interval (CI) = 8.9–10.7] than AD patients (SMR = 7.0, 95% CI = 6.8–7.2) and AWS patients (SMR = 7.8, 95% CI = 7.2–8.4). SMR was particularly elevated for unnatural causes of death, and more so for DT patients (SMR = 26.9, 95% CI = 21.7–33.4) than for AD patients (SMR = 15.2, 95% CI = 14.2–16.3) or AWS patients (SMR = 20.1, 95% CI = 16.9–23.9). For all comorbidities, we observed a higher proportion among DT patients than among AWS or AD patients (P < 0.001). Conclusions: People treated for delirium tremens appear to have higher rates of mortality and comorbidity than people with other alcohol use disorders. [ABSTRACT FROM AUTHOR]

Background: Patients with alcohol use disorder (AUD) have an increased risk of suicide. Neuroimmunological measures, such as cytokines, are shown to deviate in people with attempted suicide. Few studies have investigated this among AUD patients.Patients and Methods: One-hundred and fourteen patients undergoing residential treatment for AUD were interviewed on lifetime suicide attempts (SA) along with several other background variables and clinical characteristics. Serum blood samples were drawn for analysis of cytokines.Results: Thirty-one patients (27%) reported at least one SA. These patients had more symptoms of current affective disorders and more severe dependence. In bivariate analysis only IL-6 and IL-10 appeared to be associated with lifetime SA but without reaching statistical significance. In multivariate linear regression, adjusting for sex, nicotine use, somatic illness, and the use of anti-inflammatory drugs, IL-6 was associated to SA (p = 0.033).Conclusion: The cytokine IL-6 has repeatedly been found to be associated with suicidality. The present study concurs with this role of IL-6 in a naturalistic observational study of AUD patients. [ABSTRACT FROM AUTHOR]

Introduction: Training in addiction medicine and addiction psychology is essential to ensure the quality of treatment for patients with substance use disorders. Some earlier research has shown varying training between countries, but no comprehensive study of addiction training across Europe has been performed. The present study by the European Federation for Addiction Societies (EUFAS) aimed to fill this gap. Methods: A Delphi process was used to develop a questionnaire on specialist training in addiction treatment in 24 European countries. The final questionnaire consisted of 14 questions on either addiction medicine or addiction psychology, covering the nature and content of the training and institutional approval, the number of academic professorial positions, and the estimated number of specialists in each country. Results: Information was not received from all countries, but six (Belgium, Denmark, Ireland, Italy, Poland, and Romania) reported no specialized addiction medicine training, while 17 countries did. Seven countries (Belgium, France, Ireland, Italy, Russia, Switzerland, and the Netherlands) reported no specialized addiction psychology training, while 14 countries did. Training content and evaluation methods varied. Approval was given either by governments, universities, or professional societies. Eighteen countries reported having professorships in addiction medicine and 12 in addiction psychology. The number of specialists in addiction medicine or psychology varied considerably across the countries. Discussion: The survey revealed a large heterogeneity in training in addiction medicine and addiction psychology across Europe. Several countries lacked formal training, and where formal training was present, there was a large variation in the length of the training. Harmonization of training, as is currently the case for other medical and psychology specializations, is warranted to ensure optimal treatment for this under-served patient group. [ABSTRACT FROM AUTHOR]

Aims A high number of alcohol units required to feel a subjective effect of alcohol predicts future alcohol use disorders (AUDs). The subjective response to alcohol can be measured using the validated retrospective self-rated effects of alcohol (SRE) questionnaire. Few studies have investigated the specific relationship between SRE and blood alcohol concentration (BAC) in an experimental setting. Methods Twenty healthy young adult male volunteers who had experience with binge drinking, but did not have AUD, filled out the SRE-questionnaire and were served with a fixed amount of alcohol per body weight. BACs were measured throughout a 12-hour period, reaching a maximum BAC of ~0.13%. Median split of SRE-scores was utilized to compare BACs among participants with relatively high effects (low SRE) and relatively low effects (high SRE) of alcohol. Results Participants reporting a relatively low SRE-score had a statistically significant higher measured BAC at all time points until alcohol was eliminated. This was especially pronounced during the first 2 hours after alcohol (P  = 0.015) without a significant difference in the alcohol elimination rate being detected. Conclusion The study indicates that a self-ated SRE-score is related to BACs after the ingestion of a standardized amount of alcohol per body weight. Reporting a higher number of alcohol units before feeling an effect was related to a lower BAC. As the differences in BAC between relatively high and low self-rated effects appeared rapidly after intake, this could be interpreted as an effect of presystemic metabolism of alcohol. [ABSTRACT FROM AUTHOR]

• The relationship between blood phosphate and alcohol metabolism is not much studied. • This experimental study related blood phosphate levels to with blood alcohol levels. • Higher blood phosphate level was related to lower blood alcohol maximum. • Blood phosphate levels could be related to levels of gastric alcohol metabolism. The role of blood phosphate in alcohol metabolism has not been studied. In this explorative experimental study, the relationship between blood phosphate levels and metabolism of alcohol was investigated. Twenty young male volunteers were given alcohol relative to body weight to make them reach a theoretical blood alcohol concentration (BAC) of 0.12%. Ten measurements of BAC were taken across the time from intake, to peak and total elimination. The results indicated that individuals with high blood phosphate levels achieved a lower BAC maximum than those with low blood phosphate levels. The difference between the highest and lowest maximum BAC was as much as 30–40% and correlated negatively to physiological blood phosphate levels. The results suggest that phosphate plays a role in prehepatic, possibly gastric, alcohol metabolism. The Alcohol Dehydrogenase enzyme 7 (ADH7) is represented in the upper gastrointestinal tract and may be the enzyme responsible for this variation in the blood alcohol concentration reached. [ABSTRACT FROM AUTHOR]

Women with alcohol use disorder (AUD) might be particularly vulnerable to psychiatric comorbidities. However, population surveys have yielded disparate findings. We used data from the French Mental Health in the General Population survey to investigate gender-related risks of psychiatric comorbidities associated with AUD. A cross-sectional survey based on face-to-face interviews, including the Mini International Neuropsychiatric Interview, was conducted among 38,717 subjects. Logistic regression models were used to assess risks of psychiatric comorbidities associated with AUD. After adjustment for socio-demographics and other psychiatric disorders, both women and men with AUD were at higher risk of comorbid depressive disorder (odds ratio [OR] = 2.6, 95% confidence interval [CI]: 2.0–3.4 in women, and OR = 2.0, 95% CI: 1.7–2.4 in men), bipolar I disorder (2.5; 1.4–4.4 in women vs. 2.6; 1.9–3.4 in men), and psychotic disorder (1.6; 1.01–2.5 in women vs. 1.8; 1.4–2.3 in men). Women with AUD exhibited an increased risk of comorbid panic disorder (OR = 1.6, 95% CI: 1.1–2.2) while the increased risk of post-traumatic stress disorder (PTSD) was significant in men only (OR = 2.6, 95% CI: 1.6–4.2). The increased risk of comorbid substance use disorder (SUD) was more elevated in women, compared to men (12.9; 8.1–18.1 vs. 4.8; 4.0–5.8 in men). Most of psychiatric conditions were over-represented in both women and men with AUD, relative to controls. Gender-specific findings were that women with AUD had an increased risk of comorbid SUD or panic disorder, while men had a significantly higher risk of comorbid PTSD. [ABSTRACT FROM AUTHOR]

Background: Patients with combined depression symptoms and post-traumatic stress disorder (PTSD) often exhibit high levels of circulating inflammatory biomarkers as either a cause or consequence of their disease. We aimed to investigate how cytokines and depression symptoms develop with one-year follow-up and compare them with non-PTSD patients. Methods: The study had a longitudinal design with one-year follow-up measurements in an inpatient treatment setting at a psychiatric center in Norway. PTSD diagnoses were set using the Mini International Neuropsychiatric Interview (MINI). The first three measurements were at baseline (T0), halfway (T1) and at discharge (T2) from a 12-week main stay, followed by a final measurement one year after discharge (T3). Serum blood samples were collected on all four occasions. The Beck Depression Inventory-II (BDI-II) was administered at T0, T2 and T3. Results: Levels of interleukin-6 (IL-6) and interleukin-10 (IL-10) in PTSD patients were higher than in patients without PTSD at T0 (p = 0.005 and 0.042). The PTSD patients had a higher average level of IL-10 across all four measurements (B = 1.62, Standard Error (SE) = 0.78, p = 0.037). The IL-10 levels in PTSD patients declined from T0 to T3 (p = 0.039). The PTSD patients were more depressed than non-PTSD patients at T3 (p = 0.019). Conclusions: The levels of IL-10 and IL-6 in PTSD patients more closely resembled the levels in non-PTSD patients at one-year follow-up, despite level of depression being unchanged in the PTSD patients. This calls into question the close relationship between level of circulating cytokines and depressive symptoms, at least in PTSD patients. Further research is needed to investigate what appears to be a complex relationship between immune markers and depression in patients with PTSD. [ABSTRACT FROM AUTHOR]

Some ecological studies have shown that areas with higher use of cannabis may have lower opioid use and fewer opioid‐related problems. Newer studies are questioning this finding. Few individually based studies have been performed. Using data from the Norwegian Prescription Database, this study investigated the individual level effect of prescribed cannabis extract (Sativex®) in prescription opioid users on their opioid use in the following year. Looking at all those filling a prescription for Sativex®, opioid use was only marginally lowered in the follow‐up period. Some Sativex® users, however, filled more prescriptions for Sativex® and were able to reduce their opioid use substantially. Further studies are needed to elucidate more details on these patients, so as to know who can benefit from such cannabis‐based extracts in reducing their opioid use. [ABSTRACT FROM AUTHOR]

As previously indicated an association may exist between early sleep problems in infants and toddlers, and a diagnosis of attention deficit hyperactivity disorder (ADHD). The aim of this study was to study if this association could be replicated in a complete nationwide cohort of children. Prospective cohort study using national registries. All children born in Norway from January 2004 to December 2010 were included (N = 410,555). Information on hypnotic drugs dispensed to children 0–3 years of age outside of institutions was collected from the Norwegian Prescription Database and used as a proxy for sleep problems. The outcome ADHD (ICD-10), as diagnosed by specialists in the Child Mental Health Service, was obtained from the Norwegian Patient Registry. Data were analysed using weighted estimation in Cox regression. The unadjusted weighted hazard ratio (wHR) for a later diagnosis of ADHD in children dispensed two or more prescriptions for any hypnotic drug, compared to zero prescriptions, was 2.30 [95% confidence interval (CI) 1.63–3.23] for girls and 1.75 (95% CI 1.48–2.07) for boys. For the sedative antihistamine trimeprazine the corresponding wHR was 3.71 (95% CI 1.83–7.52) for girls and 2.78 (95% CI 2.04–3.80) for boys. After adjusting for parental ADHD and parental education the wHR for trimeprazine users was 2.81 (95% CI 1.34–5.88) for girls and 2.33 (95% CI 1.70–3.20) for boys. Infants and toddlers who were dispensed hypnotics had an increased risk of ADHD at school age. This association was most pronounced with the use of trimeprazine, a drug traditionally prescribed to toddlers for sleep problems in Norway. After adjusting for parental ADHD and educational level the risk for ADHD among the trimeprazine users was still more than twice the risk among controls. [ABSTRACT FROM AUTHOR]

Background: In Europe, the COVID-19 pandemic triggered a range of restrictive measures, which may have impacted alcohol consumption. Objectives: We explored perceived changes in alcohol consumption, their association with sociodemographic characteristics and past year alcohol consumption, and self-reported reasons for change after CO-VID-19 restrictions in Norway. Method: A web-based survey was sent to Norwegians aged 18 years and older in June–July 2020. Respondents reporting any past year alcohol use (n = 1,200) were asked whether they drank less, approximately the same, or more after the COVID-19 restrictions compared to before and reasons for drinking less or more. Results: Almost a third (29.9%) reported they drank less, whereas 13.3% reported they drank more. Females, younger respondents, and Oslo residents were more likely to report both less and more drinking (p values between 0.001 and 0.029). Past year alcohol use was associated with less drinking (OR = 0.93; p < 0.001) and more drinking (OR = 1.07; p < 0.001). More drinking was also associated with living with child(ren) (p = 0.023) and high educational level (p = 0.029). The most frequently reported reasons for drinking less pertained to fewer social occasions and less on-premise drinking, whereas reasons for drinking more pertained to treating oneself to something good and fewer consequences of drinking more. Conclusions: After the COVID-19 restrictions were implemented, a substantial proportion of Norwegians changed their drinking behaviour. [ABSTRACT FROM AUTHOR]

Purpose: Most people were affected by the COVID-19 pandemic. Persons with co-occurring substance use disorder (SUD) and mental illness (MI) are already a marginalized group, with above average mortality. Thus, the study aim was to investigate SARS-CoV-2 incidence and mortality among persons with SUD/MI during the first two years of the pandemic.This historical cohort study merged data from the Norwegian Patient Register, the Norwegian Surveillance System for Communicable Diseases and census data from Statistics Norway. We calculated crude mortality rates for persons with SUD and mild/moderate vs. severe MI and compared them to persons with physical illnesses or healthy controls. The incidence rate ratios for SARS-CoV-2 infection and mortality were estimated using Poisson regression models.Compared to healthy controls, the SARS-Cov-2-infection rate was marginally lower in persons with SUD and mild/moderate MI (IRR,1.19 [95%CI,1.09–1.30]) as in persons with physical illness (IRR,1.35 [95%CI, 1.23–1.47]), whereas persons with SUD and severe MI showed a lower rate compared to healthy controls. Crude mortality rates for persons with SUD/MI were substantially higher and increased much more during the pandemic than for persons with physical illnesses or healthy controls. The IRR for mortality in persons with SUD and mild/moderate MI was 10.61 (95%CI,7.19–15.67) and 11.44 (95%CI,7.50-17.45) for SUD and severe MI, compared to 5.03 (3.34–7.57]) for persons with physical illnesses only.The analysis showed excess mortality during COVID-19-pandemic for SUD/MI, but without higher SARS-CoV-2 infection rates in this group. Consequently, excess mortality among persons with SUD/MI was not due to SARS-CoV-2 infection.Methods: Most people were affected by the COVID-19 pandemic. Persons with co-occurring substance use disorder (SUD) and mental illness (MI) are already a marginalized group, with above average mortality. Thus, the study aim was to investigate SARS-CoV-2 incidence and mortality among persons with SUD/MI during the first two years of the pandemic.This historical cohort study merged data from the Norwegian Patient Register, the Norwegian Surveillance System for Communicable Diseases and census data from Statistics Norway. We calculated crude mortality rates for persons with SUD and mild/moderate vs. severe MI and compared them to persons with physical illnesses or healthy controls. The incidence rate ratios for SARS-CoV-2 infection and mortality were estimated using Poisson regression models.Compared to healthy controls, the SARS-Cov-2-infection rate was marginally lower in persons with SUD and mild/moderate MI (IRR,1.19 [95%CI,1.09–1.30]) as in persons with physical illness (IRR,1.35 [95%CI, 1.23–1.47]), whereas persons with SUD and severe MI showed a lower rate compared to healthy controls. Crude mortality rates for persons with SUD/MI were substantially higher and increased much more during the pandemic than for persons with physical illnesses or healthy controls. The IRR for mortality in persons with SUD and mild/moderate MI was 10.61 (95%CI,7.19–15.67) and 11.44 (95%CI,7.50-17.45) for SUD and severe MI, compared to 5.03 (3.34–7.57]) for persons with physical illnesses only.The analysis showed excess mortality during COVID-19-pandemic for SUD/MI, but without higher SARS-CoV-2 infection rates in this group. Consequently, excess mortality among persons with SUD/MI was not due to SARS-CoV-2 infection.Results: Most people were affected by the COVID-19 pandemic. Persons with co-occurring substance use disorder (SUD) and mental illness (MI) are already a marginalized group, with above average mortality. Thus, the study aim was to investigate SARS-CoV-2 incidence and mortality among persons with SUD/MI during the first two years of the pandemic.This historical cohort study merged data from the Norwegian Patient Register, the Norwegian Surveillance System for Communicable Diseases and census data from Statistics Norway. We calculated crude mortality rates for persons with SUD and mild/moderate vs. severe MI and compared them to persons with physical illnesses or healthy controls. The incidence rate ratios for SARS-CoV-2 infection and mortality were estimated using Poisson regression models.Compared to healthy controls, the SARS-Cov-2-infection rate was marginally lower in persons with SUD and mild/moderate MI (IRR,1.19 [95%CI,1.09–1.30]) as in persons with physical illness (IRR,1.35 [95%CI, 1.23–1.47]), whereas persons with SUD and severe MI showed a lower rate compared to healthy controls. Crude mortality rates for persons with SUD/MI were substantially higher and increased much more during the pandemic than for persons with physical illnesses or healthy controls. The IRR for mortality in persons with SUD and mild/moderate MI was 10.61 (95%CI,7.19–15.67) and 11.44 (95%CI,7.50-17.45) for SUD and severe MI, compared to 5.03 (3.34–7.57]) for persons with physical illnesses only.The analysis showed excess mortality during COVID-19-pandemic for SUD/MI, but without higher SARS-CoV-2 infection rates in this group. Consequently, excess mortality among persons with SUD/MI was not due to SARS-CoV-2 infection.Conclusion: Most people were affected by the COVID-19 pandemic. Persons with co-occurring substance use disorder (SUD) and mental illness (MI) are already a marginalized group, with above average mortality. Thus, the study aim was to investigate SARS-CoV-2 incidence and mortality among persons with SUD/MI during the first two years of the pandemic.This historical cohort study merged data from the Norwegian Patient Register, the Norwegian Surveillance System for Communicable Diseases and census data from Statistics Norway. We calculated crude mortality rates for persons with SUD and mild/moderate vs. severe MI and compared them to persons with physical illnesses or healthy controls. The incidence rate ratios for SARS-CoV-2 infection and mortality were estimated using Poisson regression models.Compared to healthy controls, the SARS-Cov-2-infection rate was marginally lower in persons with SUD and mild/moderate MI (IRR,1.19 [95%CI,1.09–1.30]) as in persons with physical illness (IRR,1.35 [95%CI, 1.23–1.47]), whereas persons with SUD and severe MI showed a lower rate compared to healthy controls. Crude mortality rates for persons with SUD/MI were substantially higher and increased much more during the pandemic than for persons with physical illnesses or healthy controls. The IRR for mortality in persons with SUD and mild/moderate MI was 10.61 (95%CI,7.19–15.67) and 11.44 (95%CI,7.50-17.45) for SUD and severe MI, compared to 5.03 (3.34–7.57]) for persons with physical illnesses only.The analysis showed excess mortality during COVID-19-pandemic for SUD/MI, but without higher SARS-CoV-2 infection rates in this group. Consequently, excess mortality among persons with SUD/MI was not due to SARS-CoV-2 infection. [ABSTRACT FROM AUTHOR]

Aim: This study was aimed at investigating the availability and prescription of different medicinal variants of cannabis and their status in European countries.Methods: A -web-based survey was sent to all member societies of the -European Federation of Addiction Societies (EUFAS) in 2 waves during the summer of 2017. All 34 member societies in 19 different European countries were invited to participate.Results: We received 28 responses from 17 European countries. The cannabis extract nabiximol (Sativex®) is the most prevalent cannabis-based medicinal product marketed in Europe. Synthetic cannabinoids and standardized cannabis are less prevalent, and no country allows the growing of cannabis for personal medical use. The bringing of medical cannabis products from across borders to countries where the drug is not marketed is quite limited. The use of medical cannabis is restricted to some central medical conditions, but off-label use is prevalent in some countries.Conclusion: The use of medical cannabis in Europe seems to be restricted mostly to the use of the cannabis extract, nabiximol. There is only limited use of the cannabis plant as such for medical purposes, possibly indicating a different scenario in Europe as compared to the USA. Position Statement: EUFAS as an umbrella association of European addiction societies stresses the need for further studies on the efficacy of medical cannabis and warrants for possible dangers associated with the increasing popularity of medical cannabis. We need regulations at European level concerning registration and medical indications, development of uniform compounds and strength of products, and rules concerning sales and marketing. [ABSTRACT FROM AUTHOR]

This study aimed to identify trajectories of service use during the last year before suicide death and the characteristics associated with the trajectories in patients with substance use disorders. This study used a national registry data linkage, which included all patients with substance use disorders who died by suicide in Norway between 2010 and 2018. In- and outpatient contacts with mental health or substance use services during the last year before suicide death was analyzed by week using Sequence State Analysis and cluster analysis to identify trajectories. Logistic regression was used to measure the association between the characteristics and the trajectories. We identified four trajectories of service contact. A brief contact trajectory (n = 366) with a low proportion of weeks in contact (M weeks = 8.3), associated with less psychosis or bipolar disorder (aOR = 0.13 (0.08–0.22)) and higher age. A regular contact trajectory (n = 160), with a higher proportion of contact (M weeks = 47.9), associated with psychosis or bipolar disorder (aOR = 3.66 (2.10–6.47)) and depressive or anxiety disorder (aOR = 3.11 (1.93–5.13)). An intermittent contact trajectory (n = 195) with most contacts with outpatient substance use disorder services (M weeks = 9.7). A continuous contact trajectory (n = 109) with a high proportion of inpatient contact (M weeks = 44.5), strongly associated with psychosis or bipolar disorder (aOR = 6.08 (3.26–11.80)). Longitudinal descriptions of service use reveal different trajectories that are important to consider when developing policies or interventions to reduce the risk of suicide death in patients with substance use disorders. [ABSTRACT FROM AUTHOR]

Background: A reciprocal relationship between activated innate immune system and changes in mood and behavior has been established. There is still a paucity of knowledge on how the immune system responds during psychiatric treatment. We aimed to explore circulating cytokines and assess psychiatric symptom severity scores during 12 weeks of inpatient psychiatric treatment. Methods: The study was a longitudinal assessment of 124 patients (88 women and 36 men) in treatment at Modum Psychiatric Center, Norway. The patient sample comprised a mixed psychiatric population of whom 39 were diagnosed with posttraumatic stress disorder (PTSD). Serum blood samples for cytokine analysis and measures of mental distress using Global Severity Index were collected at admission (T0), halfway (T1), and before discharge (T2). Other factors assessed were age, gender, and the use of antidepressants and anti-inflammatory drugs. Multilevel modeling was used for longitudinal analyses to assess the repeated cytokine samples within each patient. Results: Overall level of IL-1RA was higher in PTSD patients when compared to those without PTSD (P=0.021). The level of IL-1β, MCP-1, and TNF-α increased over time in PTSD compared to non-PTSD patients (P=0.025, P=0.011 and P=0.008, respectively). All patients experienced reduced mental distress as measured by self-reported Global Severity Index scores. Stratified analysis showed that PTSD patients who used anti-inflammatory drugs had higher levels of IL-1β (P=0.007) and TNF-α (P=0.049) than PTSD patients who did not use such drugs. Conclusion: The study indicates that traumatized patients may have a distinct neuroimmune development during recovery. Their activated immune system shows even further activation during their rehabilitation despite symptom reduction. [ABSTRACT FROM AUTHOR]

Background Antipsychotic drug use among children and adolescents is increasing, and there is growing concern about off-label use and adverse effects. The present study aims to investigate the incidence, psychiatric co-morbidity and pharmacological treatment of severe mental disorder in Norwegian children and adolescents. Methods We obtained data on mental disorders from the Norwegian Patient Registry on 0–18 year olds who during 2009–2011 were diagnosed for the first time with schizophrenia-like disorder (International Classification of Diseases, 10th revision codes F20-F29), bipolar disorder (F30-F31), or severe depressive episode with psychotic symptoms (F32.3 or F33.3). Data on filled prescriptions for psychotropic drugs were obtained from the Norwegian Prescription Database. Results A total of 884 children and adolescents (25.1 per 100 000 person years) were first time diagnosed with schizophrenia-like disorder (12.6 per 100 000 person years), bipolar disorder (9.2 per 100 000 person years), or severe depressive episode with psychotic symptoms (3.3 per 100 000 person years) during 2009–2011. The most common co-morbid mental disorders were depressive (38.1%) and anxiety disorders (31.2%). Antipsychotic drugs were prescribed to 62.4% of the patients, 72.0% of the schizophrenia-like disorder patients, 51.7% of the bipolar disorder patients, and 55.4% of the patients with psychotic depression. The most commonly prescribed drugs were quetiapine (29.5%), aripiprazole (19.6%), olanzapine (17.3%), and risperidone (16.6%). Conclusions When a severe mental disorder was diagnosed in children and adolescents, the patient was usually also prescribed antipsychotic medication. Clinicians must be aware of the high prevalence of depressive and anxiety disorders among early psychosis patients. [ABSTRACT FROM AUTHOR]

Background: Different methods in pharmacoepidemiology can be used to study hypnotic use in children. But neither questionnaire-based data nor prescription records can be considered a "gold standard". This study aimed to investigate the agreement between mother-reported questionnaire-based data and prescription record data for hypnotic drugs in children aged 0-18 months. The agreement was compared to the agreement for a group of antiepileptic drugs. Methods: Prescription record data were collected from the Norwegian prescription database for 47,413 children also surveyed in the Norwegian mother and child cohort between 2005 and 2009. Agreement between in the two data sources was calculated using Cohens Kappa. Multinomial logistic regression was used to calculate the effect of sociodemographic variables on discrepancies in data sources. Results: The agreement between mother-reported and dispensed hypnotics was less than 50% for all hypnotics. Sensitivity of reporting increased with number of filled prescriptions. The agreement of antiepileptic drugs was 92.9% in the same population. Of several sociodemographic factors only paternal educational level and maternal work situation was significantly related to agreement between prescription record and survey data. Conclusion: There was a moderate agreement between reported use and dispensed hypnotic drugs for infants and toddlers. Results indicate that sociodemographic factors play only a minor role in explaining discrepancy. [ABSTRACT FROM AUTHOR]

Background: This study examined how alcohol use disorder (AUD) patients with post-traumatic stress disorder (PTSD) differed from those without PTSD in terms of demography, drinking patterns and C-reactive protein, inflammatory cytokines, tryptophan metabolism parameters, and brain-derived neurotrophic factor (BDNF). Methods: A consecutive sample (N = 187) of treatment-receiving AUD individuals were recruited from Nepalese facilities. They underwent fully structured psychiatric interviews. Serum levels of inflammatory cytokines [interleukin (IL)-6, IL-1 Receptor antagonist (IL-1Ra), IL-10, tumor necrosis factor-alpha (TNF-α), and interferon-gamma (IFN-γ)] were determined by a multiplex assay, kynurenine and tryptophan levels by high-performance liquid chromatography, and BDNF by enzyme-linked immunosorbent assay (ELISA). Results: The prevalence of exposure to severe trauma and PTSD was 74% and 17%, respectively. PTSD comorbidity was not associated with age, gender, or socioeconomic status, but with co-occurring major depression, history of attempted suicide, earlier peak of drinking problems, higher drinking quantity and withdrawal symptoms, experiencing alcoholic blackouts, and drinking problems among parents. None of the assessed neuroimmune parameters was related to comorbid PTSD. Conclusions: The findings support routine trauma screening in AUD treatment samples and screening for risky drinking in trauma populations to help guide interventions. The expected aberrations in neuroimmune functioning may not be found when examined in a sample with multiple psychiatric morbidities. [ABSTRACT FROM AUTHOR]

Introduction: Psychotic experiences (PE) are relatively common in the general population. PE is associated with mental health impairment and may be predictive of clinical psychosis. Substance use predicts PE, but the association is insufficiently understood, particularly the role of illicit substances. The purpose of this study was to describe PE (visual and auditory hallucinations and delusions of reference and persecution) in a population characterized by high levels of substance use and to investigate substance use and sociodemographic background characteristics as risk factors for PE.Methods: We used data from the Norwegian Offender Mental Health and Addiction Study (NorMA), a cross-sectional survey of 1499 individuals from Norwegian prisons. The outcome was one, two, three or four types of PE during the lifetime. The association between different variables and PE was investigated using multinomial logistic regression with three outcome categories: 0 PE, 1-2 PE and 3-4 PE.Results: The prevalence of lifetime PE was 53.7%. Several substances were strongly associated with PE: For cannabis, the adjusted relative risk ratio (RRR) of 1-2 PE was 2.78 (95% CI 1.89-4.10) and of 3-4 PE it was 4.36 (2.58-7.36). For amphetamine, the RRR of 1-2 PE was 3.26 (2.11-5.05) and of 3-4 PE it was 5.93 (3.72-9.46). For all variables, the association to PE was stronger with more types of PE.Conclusions: High levels of alcohol use, and lifetime use of cannabis, amphetamine and heroin were associated with PE. These effects were robust even when the substance use variables were adjusted against each other. This research received no specific grant from any funding agency, commercial or not-for-profit sectors. [ABSTRACT FROM AUTHOR]

A correction to the article "Exploring functional data analysis and wavelet principal component analysis on ecstasy (MDMA) wastewater data" that was published in the previous issue of February, 2017 issue is presented.

Background and Aims: There is limited data on hepatitis C (HCV) treatment uptake among people who inject drugs including individuals receiving opioid substitution treatment (OST). We aimed to calculate cumulative HCV treatment uptake, estimate annual treatment rates, and identify factors associated with HCV treatment among individuals who have received OST in Norway. Methods: This observational study was based on linked data from The Norwegian Prescription Database and The Norwegian Surveillance System for Communicable Diseases between 2004 and 2013. Both registries have national coverage. From a total of 9919 individuals who had been dispensed OST (methadone, buprenorphine or buprenorphine-naloxone), we included 3755 individuals who had been notified with HCV infection. In this population, dispensions of HCV treatment (pegylated interferon and ribavirin), benzodiazepines, selective serotonin reuptake inhibitors and antipsychotics were studied. Results: Among 3755 OST patients notified with HCV infection, 539 (14%) had received HCV treatment during the study period. Annual HCV treatment rates during OST ranged between 1.3% (95% confidence interval [CI] 0.7–2.2) in 2005 and 2.6% (95% CI 1.9–3.5) in 2008 with no significant changes over time. HCV treatment uptake was not associated with age or gender, but associated with duration of active OST (adjusted odds ratio [aOR] 1.11 per year; 95% CI 1.07–1.15), high (> 80%) OST continuity (aOR 1.62; 95% CI 1.17–2.25), and heavy benzodiazepine use (aOR 0.65; 95% CI 0.49–0.87). Conclusions: Cumulative HCV treatment uptake among OST patients notified with HCV infection in Norway between 2004 and 2013 was 14%. Annual treatment rates during OST remained unchanged below 3% per year. High continuity of OST over time and absence of heavy benzodiazepine use predicted HCV treatment uptake. Increased awareness for HCV among OST patients is needed as tolerable and efficient directly acting antiviral treatment is being introduced. [ABSTRACT FROM AUTHOR]

Background: Acamprosate, disulfiram (DIS), naltrexone and nalmefene can be used in treating alcohol use disorders. The drugs are, however, underutilized.Methods: In this survey of marketing status and perceived efficacy, member societies of the European federation for addiction societies were asked to report on the status of these drugs in their country. Results were obtained from 20 European countries showing that the drugs were registered in most countries.Results and Conclusion: The drugs were mentioned in guidelines in approximately half and were partially or fully reimbursed in half to two-thirds countries. DIS was perceived as the most efficacious drug. These results are discussed. [ABSTRACT FROM AUTHOR]

Background: Wastewater-based epidemiology (WBE) is a novel approach in drug use epidemiology which aims to monitor the extent of use of various drugs in a community. In this study, we investigate functional principal component analysis (FPCA) as a tool for analysing WBE data and compare it to traditional principal component analysis (PCA) and to wavelet principal component analysis (WPCA) which is more flexible temporally.Methods: We analysed temporal wastewater data from 42 European cities collected daily over one week in March 2013. The main temporal features of ecstasy (MDMA) were extracted using FPCA using both Fourier and B-spline basis functions with three different smoothing parameters, along with PCA and WPCA with different mother wavelets and shrinkage rules. The stability of FPCA was explored through bootstrapping and analysis of sensitivity to missing data.Results: The first three principal components (PCs), functional principal components (FPCs) and wavelet principal components (WPCs) explained 87.5-99.6 % of the temporal variation between cities, depending on the choice of basis and smoothing. The extracted temporal features from PCA, FPCA and WPCA were consistent. FPCA using Fourier basis and common-optimal smoothing was the most stable and least sensitive to missing data.Conclusion: FPCA is a flexible and analytically tractable method for analysing temporal changes in wastewater data, and is robust to missing data. WPCA did not reveal any rapid temporal changes in the data not captured by FPCA. Overall the results suggest FPCA with Fourier basis functions and common-optimal smoothing parameter as the most accurate approach when analysing WBE data. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the article "Psychedelics not linked to mental health problems or suicidal behavior: a population study" by P-Ø Johansen and T.S. Krebs in a 2015 issue. [ABSTRACT FROM AUTHOR]

Seasonal variation in the number of suicides has long been acknowledged. It has been suggested that this seasonality has declined in recent years, but studies have generally used statistical methods incapable of confirming this. We examined all suicides occurring in Norway during 1969-2007 (more than 20,000 suicides in total) to establish whether seasonality decreased over time. Fitting of additive Fourier Poisson time-series regression models allowed for formal testing of a possible linear decrease in seasonality, or a reduction at a specific point in time, while adjusting for a possible smooth nonlinear long-term change without having to categorize time into discrete yearly units. The models were compared using Akaike’s Information Criterion and analysis of variance. A model with a seasonal pattern was significantly superior to a model without one. There was a reduction in seasonality during the period. Both the model assuming a linear decrease in seasonality and the model assuming a change at a specific point in time were both superior to a model assuming constant seasonality, thus confirming by formal statistical testing that the magnitude of the seasonality in suicides has diminished. The additive Fourier Poisson time-series regression model would also be useful for studying other temporal phenomena with seasonal components. [ABSTRACT FROM AUTHOR]

Background: Prescription drug sales may vary considerably across regions and over time. This study aimed to assess whether there is an association between mean drug sales and prevalence of excessive use in a range of psychotropic prescription drugs with an abuse potential, and if so, whether the variation in mean drug sales mostly reflects variation in the prevalence of excessive use or mostly reflects variation in non-excessive use. Methods: Data on all filled prescriptions taken from the Norwegian prescription database for 10 drugs with an abuse potential (pain relievers, anxiolytics, and hypnotics) during one calendar year (2005) in Norway (n = 4 053 624) included number of defined daily doses (DDD). These were aggregated to individual level (n = 815 836) and county level (n = 19). Results: Analyses of individual level data showed that the distribution of drug use was skewed; those who used more than 365 DDD per year accounted for almost half of the sales of both anxiolytics and hypnotics. At the county level, the mean sales per inhabitant and the prevalence of excessive users were closely correlated, but both prevalence of non-excessive use and prevalence of excessive drug use were associated with the county-wise variation in mean drug sales. Conclusion: Despite a strong individual control of access to psychotropic drugs through health personnel' prescribing, a small proportion of users account for a large fraction of the sales of these drugs. The sales vary significantly between regions and this variation is closely associated with the prevalence of excessive users. This suggests that sales figures as such may be used as an indicator to monitor variations in excessive use between regions and over time, and to evaluate interventions targeting over-prescription and excessive use. [ABSTRACT FROM AUTHOR]

Background: To compare the publication and citation rate within the areas of drug abuse and dependence research in Europe with that in the USA. Methods: This is a bibliometric study using the Thomson Reuters Web of Knowledge as data source, 40 key words were used as search terms, but certain scientific publications not concerning the issue were excluded. Scientific publications from Denmark, England, Finland, France, Germany, Italy, the Netherlands, Norway, Spain, Sweden, and the USA were studied. The number of publications in each country and in each year in addition to the citation indices for these publications was retrieved. Results: Approximately two thirds of the publications came from the USA. Both in absolute and relative figures, Europe lagged behind. The trend over the last decade was a greater gap between the amount of research performed in Europe versus the USA. There were thematic differences. Smaller European countries had a greater relative publication rate. The citations were relatively evenly distributed. Conclusions: It has been claimed that 85% of the world's research within the field of drug abuse and dependence is carried out in the USA. This study challenges this figure, but European research within this field is lagging behind. Copyright © 2013 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Introduction and Aims This study investigated the prevalence of major depression ( MD) and its sociodemographic and alcohol-related correlates among Nepalese patients receiving treatment for an alcohol-use disorder ( AUD). Design and Methods A cross-sectional survey was carried out among 188 consecutively admitted AUD patients in eight residential alcohol treatment units in Kathmandu. We recorded sociodemographic data and administered the alcohol use and depression modules of the World Health Organization Composite International Diagnostic Interview 2.1 and the Alcohol Use Disorder Identification Test. Analyses were performed with χ2-tests, Student's t-tests, Mann- Whitney U-tests and logistic regression analyses. Results The lifetime and 12-month prevalence of MD among AUD patients were found to be 45% and 36% respectively. Living with a spouse and low-frequency drinking (2-3 days/week) showed negative associations with reporting MD in the preceding 12-month period, whereas a history of alcohol-induced blackout and problem drinking in the individual's parents were independently predictive of having a comorbid MD. Discussion and Conclusion MD is common among patients with AUDs in Nepal. Among AUD patients who sought treatment, a few factors, such as marital status, history of alcohol-induced blackout and drinking frequency, seem to correlate well with comorbid MD. Study results suggest that transgenerational underpinning of AUD-MD comorbidity may exist in those sections of the population who have strong taboos about the use of alcohol. [ABSTRACT FROM AUTHOR]

Introduction: Alcohol, tobacco and coffee are commonly used substances and use in adolescence has previously been linked to mood disorders. However, few large prospective studies have investigated adolescent use in relation to mental health outcomes in adulthood. The main aim of this study was to examine the prospective associations between alcohol use, cigarette smoking and coffee consumption at age 16 and subsequent mood disorders up to 33 years of age. Methods: Data from The Northern Finland Birth Cohort 1986 Study were used and a total of 7660 participants (49.9% male) were included. Associations between alcohol use, cigarette smoking and coffee consumption at age 16 and later diagnoses of major depression and bipolar disorder were examined using multinomial logistic regression analyses. Results: Mean number of cigarettes/day (OR, 1.23 [95% CI 1.01–1.50]) and mean volume of alcohol consumption (OR, 1.22 [95% CI 1.01–1.47]), but not frequency of excessive drinking, in adolescence were associated with increased risk for subsequent bipolar disorder after adjustment for sex, parental psychiatric disorders, family structure, illicit substance use, and emotional and behavioral problems at age 16. An association between cigarette smoking and major depression attenuated to statistically non‐significant when adjusted for emotional and behavioral problems. No associations were observed between adolescent coffee consumption and subsequent mood disorders. Conclusions: This is the first study to report an association of adolescent cigarette smoking and subsequent bipolar disorder diagnosis providing grounds for further research and pointing to a place for preventive measures among adolescents. [ABSTRACT FROM AUTHOR]

ABSTRACT Aims To investigate whether exposure to methadone affects the risk of motor vehicle accident with personal injury. Design Cohort study linking three Norwegian administrative registries using unique person identifiers. Setting Information was retrieved from the Norwegian Prescription Database on any prescriptions ever received by the individuals for methadone and all prescriptions for benzodiazepines. The Norwegian Road Accident Registry provided information about motor vehicle accidents involving personal injuries on Norwegian roads. The Central Population Registry provided demographic information on all residents in Norway. Participants All Norwegian adults aged 18-69 years were observed for 2.5 years. Measurements Standardized incidence ratio (SIR) was calculated by comparing the incidence of traffic accidents with personal injuries in patients exposed to methadone with the incidence in those not exposed. Findings During the 4626 person-years observed in patients exposed to methadone, there were 26 motor vehicle accidents. There were very few accidents among the females who received methadone and they had no increased risk of being involved in motor vehicle accidents (SIR 1.1; 95% CI 0.2-3.1). We observed an increased risk of involvement in accidents among males (SIR 2.4; 95% CI 1.5-3.6). This figure did not change significantly when exposure to benzodiazepines was excluded. Conclusions Men exposed to methadone appear to have an increased risk of being involved in motor vehicle accidents involving personal injuries. This increased risk could not be explained by exposure of benzodiazepines. [ABSTRACT FROM AUTHOR]

Background and aims: Depression and anxiety are commonly reported among patients in opioid maintenance treatment (OMT). The aim of the present study was to describe aspects of prescription of antidepresant drug therapy among patients on OMT. Our research questions were: 1) What is the prevalence of antidepressant use according to age and gender? 2) Which antidepressants are used? 3) How are antidepressants used in terms of reimbursement codes, dispensed dose and duration of therapy? Methods: Pharmacoepidemiological data were retrieved from the complete national Norwegian Prescription Database which contains information on all prescription drugs (such as Anatomical Theraputical Chemical (ATC)-code, Defined Daily Dose (DDDs)), dispensed at pharmacies to individual patients. Norwegian OMT-patients (N=4374, 3035 men and 1339 women) who received methadone mixture, buprenorphine capsules or combined buprenorphine-naloxone capsules for at least 6 months in 2009 were included. Prevalence of antidepressant use in the studied patients was measured in terms of retrieval of prescriptions. Results: During 2009 21.7% of the studied patients filled at least one prescription for an antidepressant drugs (men: 21.2%; women: 22.9%). The subgroup of antidepressants most frequently dispensed was selective serotonin reuptake inhibitors (SSRIs) (33%), followed by the sedative antidepressants mianserin and mirtazapin (22%) and tricyclic antidepressants (TCAs) (20%). Except for TCAs, prescriptions of all antidepressant subgroups were reimbursed for either anxiety or depression in 90% of the cases. Overall, 46.9% of the antidepressant users were prescribed antidepressants in the category < 1 DDD per day and/or treatment < 3 months, with no gender difference. Conclusions: About one out of five OMT-patients filled a prescription for an antidepressant drug in 2009. Above 90% had their prescriptions reimbursed for either depression or anxiety. Use at low doses and/or sporadic use among half of the antidepressant users may reflect poor compliance or use for other maladies than the reimbursed disease code. Drug therapy for depression and anxiety among OMT-patients seems to be in line with recommendations for use; the SSRIs constitute the recommended drugs of choice due to their better effect/side effect profile, compared to the older antidepressants such as the TCAs. / [ABSTRACT FROM AUTHOR]

Objectives: Benzodiazepines are effective and safe drugs for treatment of insomnia, anxiety, epilepsy and muscle spasm, but there is also a potential for harmful use, abuse and addiction. Even though these drugs are used extensively, have been on the market for 50 years, and quite a few reports have been published on risk factors and patterns of use, the basic epidemiological parameters of use, such as incidence, prevalence, mean volume used and duration of use have not been documented in Norway. The aim of this study was to describe these basic pharmacoepidemiological parameters of benzodiazepine use. Methods: Data were drawn from the Norwegian prescription database with an observation period of 5 years and 10 months between January 2004 and October 2009. Results: Around 61 per 1000 Norwegians filled at least one prescription each year in the observation period. The annual incidence rate of new users was 15 per 1000 in 2007, falling to 12 per 1000 in 2009. Of the users of benzodiazepines 65% were female, and they used a lower mean volume than men did. The mean volume used was often very low and for the most part was quite stable. The average length of use was estimated to be between 9 and 15 years. In addition to fewer incident users, the mean volume used also seemed to be declining. Conclusion: Most benzodiazepine use in Norway lasted a short period or at a very low level. Some individuals, however, carried on using benzodiazepines for years. [ABSTRACT FROM AUTHOR]

BSTRACT [ABSTRACT FROM AUTHOR]

Pregabalin (Lyrica®) may have an anxiolytic effect. It has also been reported that the use of this drug helps prevent excessive use of benzodiazepines. The aim of the present study was to examine if pregabalin reduced the intake of benzodiazepines. In a pharmacoepidemiological study, we compared pregabalin to the older drug gabapentin (Neurontin®) in the Norwegian Prescription Database. The database has total capture of all prescribed drugs outside institutions. We identified all prescriptions for the two drugs for patients aged 18-69 years between 2004 and 2007. Patients were grouped as psychiatric patients, patients with epilepsy, patients with neuropathic pain or non-specified users. We measured the use of benzodiazepines 182 days before and after the initiation of treatment with pregabalin and gabapentin. Between 15% and 29% of the patients were able to stop using benzodiazepines after starting pregabalin or gabapentin treatment. Psychiatric patients who started pregabalin were able to reduce the amount of benzodiazepines used by 48%, compared to only 14% among starters of gabapentin. This study shows that some patients reduced their use of benzodiazepines substantially after starting pregabalin. [ABSTRACT FROM AUTHOR]

Studies of clinical cohorts and retrospective reports have identified psychiatric disorders as paramount risk factors for suicide. Much less is known about how self-reported mental health is related to completed suicide. To study the relation between self-reported mental health and risk of completed suicide, the authors prospectively followed a population-based Norwegian cohort of 61,588 men and 69,774 women aged 39–44 years for an average of 10.4 years between 1994 and 2007. Self-reported mental health was measured using an instrument based on the Hopkins Symptom Checklist and the General Health Questionnaire. Completed suicides were registered in the official Norwegian Cause of Death Registry. Females reported higher levels of mental distress than males. In comparison with persons reporting the fewest mental health symptoms, the adjusted hazard ratio for suicide increased from 1.8 (95% confidence interval (CI): 1.1, 2.9) in the moderately depressed group to 8.9 (95% CI: 4.4, 18.2) in the most depressed group. The risk difference was greatest in males. At each level of the mental health index, males had double the risk of suicide of females (hazard ratio = 2.3, 95% CI: 1.5, 3.3). This study shows a dose-response effect of self-reported mental health problems on completed suicide and replicates the gender paradox observed in the general population with prospective data. [ABSTRACT FROM PUBLISHER]

Aims Studies have shown that the impairing effects of Δ-9-tetrahydrocannabinol (THC) are dose-related. Cannabis intake increases the risk of traffic accidents. The purpose of this study was to see how different clinical tests and observations were related to blood THC concentrations and to determine whether the combined influence of THC and ethanol was different from either drug alone. Design A retrospective cross-sectional forensic database study. Setting Drivers apprehended by the police suspected of driving under the influence of alcohol other drugs. Participants We investigated 589 cases positive for THC only. In addition, 894 cases with THC and ethanol were included. A comparison was made with 3480 drivers with only ethanol in their blood and 79 drivers who tested negative. Measurements Data were analytical results of blood samples and the 27 clinical tests and observations included in the Norwegian clinical test for impairment (CTI). Findings No relationship was found between blood THC concentration and most of the CTI tests. Blood THC concentration was, however, related to conjunctival injection, pupil dilation and reaction to light and to the overall risk of being judged impaired. When THC and ethanol were detected together the risk of being judged impaired was increased markedly. Conclusions This study demonstrates that cannabis impairs driving ability in a concentration-related manner. The effect is smaller than for ethanol. The effect of ethanol and cannabis taken simultaneously is additive. Conjunctival injection, dilated pupils and slow pupil reaction are among the few signs to reveal THC influence. [ABSTRACT FROM AUTHOR]

Background: The total consumption model implies a close relationship between the population mean of a health variable and prevalence of individuals at high risk concerning this variable in a population. The model applies well to alcohol consumption and prevalence of heavy drinkers, but has so far not been tested for prescription drugs with abuse potential. Carisoprodol is such a drug. Aim: To explore whether the total consumption model applies to the overall sales and prevalence of excessive use of the prescription drug carisoprodol. Data and measures: Norwegian wholesale statistics for carisoprodol were compared to data from the Norwegian prescription database on individuals’ use of the drug in 2004. Three different indicators of excessive use of carisoprodol were applied. County was the unit of analysis. Findings: Log transformed data of total annual amount of carisoprodol use showed a close to normal distribution. There was a close relationship between the sales figures and each of the three indicators of excessive use of carisoprodol. Conclusions: The total consumption model fits well for the excessive use of carisoprodol. This may be an important contribution to our understanding of excessive prescription drug use and may also have consequences for the regulatory actions concerning carisoprodol. [ABSTRACT FROM AUTHOR]

Abstract: Background: Lithium is an important drug in the treatment of bipolar disorder. Earlier epidemiological studies of lithium use have depended on sales statistics, clinical surveys or population surveys. The national prescription databases in Denmark, Norway and Sweden may help provide more reliable information on the epidemiology of lithium use. Methods: Data were taken from the three national prescription databases in Denmark, Norway and Sweden from July 2005 until June 2006, encompassing 1 year of prescription data. Similar methods were used to identify a number of different pharmacoepidemiological measures and data were collected for adults aged 18–69 at the time of prescription. Results: Norway and Sweden had higher sales and more prevalent use than Denmark. In all three countries, more female than males were treated and the prevalence of use increased linearly with age. In all, 0.17, 0.21, and 0.25% of the populations in Denmark, Norway and Sweden respectively redeemed at least 1 prescription for lithium in the period studied. The amount prescribed per user per year varied with age, increasing to maximum doses at 40 years of age and then decreasing. Conclusion: This study is the first attempt to use prescription databases in all three Scandinavian countries to describe in detail the epidemiology of a drug''s use. The analysis revealed subtle differences in the clinical use of lithium that cannot be explained by differences in the epidemiology of bipolar disorder. [Copyright &y& Elsevier]

Abstract: Background : There is an increasing awareness of bipolar disorder in children and adolescents. Our study aimed to explore how common the use of lithium, valproate and lamotrigine in psychiatric conditions in children and adolescents in Norway and to describe concomitant use of other psychotropic drugs. Methods : The Norwegian Prescription Database (NorPD) captures all prescriptions given to individuals in ambulatory care. We investigated prescriptions for lithium, and for valproate and lamotrigine given for psychiatric conditions to children and adolescents under the age of 18 years from 2004 till 2007. We also studied other prescriptions for psychotropic drugs given to the same patients during the period. A comparison was made with the users of ADHD medication. Results : The number below 18 years treated with lithium, valproate or lamotrigine rose from 323 (0.03%) in 2004 till 454 (0.04%) in 2007. Lamotrigine increased most rapidly and lithium was most infrequently used. The users of the three drugs had often also tried antidepressants (14–42%) and atypical antipsychotics (21–51%), but true concomitant use was rarer (7–20% and 16–43% respectively). The users of ADHD medication had a much lower use of other psychotropic drugs, but quite a few users of lithium, valproate and lamotrigine had tried ADHD medication (20–26%) and even used these drugs concomitantly (15–21%). Limitations : NorPD does not include diagnoses, and we do not know if the drugs dispensed were actually used. Conclusion : Overall there has been a slight increase in the use of lamotrigine in Norway during the last four years, most likely prescribed as a mood stabilizer in bipolar disorders. Still the use among the under 14-year-olds is rare in Norway. [Copyright &y& Elsevier]

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • Anticholinergic antiparkinson drugs are used to ameliorate extrapyramidal symptoms caused by either Parkinson's disease or antipsychotic drugs, but their use in the treatment of Parkinson's disease is assumed to be in decline. • Patients with psychotic conditions have a high prevalence of abuse of drugs, including anticholinergic antiparkinson drugs. WHAT THIS STUDY ADDS • Anticholinergic 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. AIMS The use of anticholinergic antiparkinson drugs is assumed to have shifted from the therapy of Parkinson's 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. METHODS Data 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 Parkinson's 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. RESULTS Anticholinergic antiparkinson drugs were prescribed to 4.5% of all outpatients who used antipsychotic drugs. This outnumbered sales to patients with Parkinson's 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. CONCLUSIONS Anticholinergic 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Carisoprodol is a centrally acting muscle relaxant that has been marketed in Europe for more than 45 years. In November 2007 the European Medicines Association recommended suspension of all carisoprodol containing products in all EU countries. During recent years, several observational studies on carisoprodol have been published by our group, which works in the field of traffic medicine and pharmacoepidemiological research in general. In this paper, we review the role pharmacoepidemiological studies on carisoprodol played in providing evidence for the risk of psychomotor impairment and traffic accidents, intoxications and abuse. These issues have been important for decisions about the regulation of carisoprodol. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study was to examine the risk of being involved in road traffic accidents as drivers among persons using prescribed medicines by utilizing data from population-based registries. The aim of the present paper was to focus on the methodology used in the study. Methods: All Norwegians aged 18-69 in April 2004 to September 2006 (3.1 million), were included in the study. Information on prescriptions, road accidents and emigrations/deaths was obtained from three different population-based registries. A total of 22,000 accidents were observed. The incidence of accidents in exposed and unexposed person-time was compared, by the standardized incidence ratio (SIR). Results: The risk of being involved in an accident was increased in persons exposed for prescribed medicines. The risk was markedly increased in persons exposed for natural opium alkaloids, benzodiazepine tranquillizers, benzodiazepine hypnotics and carisoprodol. A marginal increase or unchanged SIRs were found for NSAIDs, selective beta-2-adrenoreceptor agonists (anti-asthmatics), calcium receptor antagonists and penicillin. Conclusions: We have tested a method using different reference groups and different exposure periods to explore the association between drug use and involvement in traffic accidents. Using these methods, we have shown that exposure for prescribed opiates, benzodiazepines and carisoprodol increased the risk of being involved in an accident as driver. The findings confirm results from other studies. Further steps should be taken to reduce car driving under the influence of these drugs. [ABSTRACT FROM AUTHOR]

Abstract: Background: Despite 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. Method: All 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. Results: During 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. Conclusions: This study found that users of hypnotics had a clearly increased risk of road traffic accidents. The SIR for flunitrazepam was particularly high. [Copyright &y& Elsevier]

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • Mothers 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). WHAT THIS STUDY ADDS • In 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. AIMS The primary aim of this study was to describe the use of prescribed drugs in both mothers and fathers before and during pregnancy in Norway. METHODS This 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. RESULTS Among 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). CONCLUSION Large 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. [ABSTRACT FROM AUTHOR]

Abstract: Objective: To use laboratory based analyses of blood and urine to determine the prevalence and influence of drugs of abuse among acute psychiatric and medical admissions. Method: In 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. Results: Legal 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. Conclusion: This study shows widespread use of substances among psychiatric and medical inpatients and that many are under the influence of drugs on admission. [Copyright &y& Elsevier]

Abstract: Background: Opioid maintained patients report high levels of anxiety, but the use of benzodiazepines among these patients has been associated with negative outcomes such as increased risk of overdose and death and poorer retention in programmes. Previous research has used interview or urine analysis to assess benzodiazepine use. In this study a prescription database was applied. Methods: The Norwegian Prescription Database covers all prescriptions for the entire population from 1 January 2004. Benzodiazepine prescriptions to patients receiving methadone (N =1364) or buprenorphine (N =805) in 2004 and 2005 were studied. Type and amount of drugs received were investigated. Results: Overall 40% of the patients received at least one prescription for a benzodiazepine drug. Oxazepam was the most frequently prescribed drug. Female patients, methadone-maintained patients and patients in the liberal programmes received a prescription more often. Prescribed doses were high and highest in the liberal programmes. Older patients received more hypnotics. Dose of maintenance drug was positively related to amount of anxiolytics prescribed. Conclusions: This study showed that more benzodiazepines were prescribed to opioid maintenance treatment patients than previously shown by investigations using interview or urine analysis. The doses prescribed were generally high. In light of the negative outcomes following benzodiazepine use in these patients, Norwegian doctors need to review their prescription practices. [Copyright &y& Elsevier]

Abstract: Objective: Carisoprodol, a drug used for acute lower back pain, may cause psychomotor impairment. We wanted to investigate if patients using carisoprodol had increased risk of being involved in a traffic accident. Methods: Data were retrieved from three population-based registries for the period April 2004–September 2005. The Norwegian Prescription Database contained individual information on all dispensed drugs at all pharmacies outside hospitals. The Norwegian Road Accident Registry contained information on all drivers involved in motor vehicle accidents with person injury. The Norwegian Central Population Registry was used to control for emigration or death. The accident incidence among carisoprodol exposed and unexposed subjects was compared by standardized incidence ratio. Results: Having a prescription for carisoprodol dispensed increased the standardized incidence ratio for being involved in an accident with person injury to 3.7 (95% CI 2.9–4.8) the first week after the date of dispensing. This was similar to diazepam (2.8; 2.2–3.6), but higher than for salbutamol (1.1; 0.6–1.8). Conclusions: Patients receiving carisoprodol seem to have an increased risk of being involved in traffic accidents involving person injury. The study gives support to earlier work published on the impairing effects of carisoprodol. [Copyright &y& Elsevier]

Abstract: Background: Suicide is a major public health problem and depression is among the most important risk factors for suicide. Treatment of depression might prevent suicide. To study this hypothesis further we conducted an ecological study. Methods: An ecological study using sales data for antidepressants and numbers of suicides in Norway and Norwegian counties 1980–2004 was performed. Data on alcohol consumption and unemployment rates were registered and taken into account. Data were analyzed using Cochrane-Orcutt time series for the country as a whole. The county specific data were analyzed with a random coefficient model with county as subject and intercept and time (slope) as random variables using an unstructured covariance matrix. Results: Sales of non-tricyclic antidepressants (non-TCAs) and suicide were clearly negatively related, even when controlling for alcohol and unemployment (adjusted r2: 0.57). There was an effect modification between time and level of sales of non-TCAs. Studying the relationship between the sales of non-TCAs and the suicide rate, we found that it was significant and stronger for the low sales figures, but non-existent for the high sales figures. Limitations: Ecological studies cannot infer causality. Conclusions: The fall in suicide rates in Norway and its counties was related to the increased sales of non-TCAs. The effect was mostly a result of a sales increase in the lower sales segment, indicating that a change from the more toxic TCAs, or heightened awareness of depression and its treatment, could explain the relationship found between sales of newer antidepressants and a decrease in suicide rate. [Copyright &y& Elsevier]

What is already known about this subject • Carisoprodol was developed to create a drug with less abuse potential than meprobamate. • Case reports have established carisoprodol as a drug of abuse, but no systematic studies have been published about the extent of abuse. What this study adds • A large number of patients used more carisoprodol than recommended. • High use of carisoprodol was associated with high use of benzodiazepines and opiates. • Compared with other medicinal drugs, carisoprodol showed many prescription database signals of being a potential drug of abuse. Aim Carisoprodol was developed to create a drug with less potential for abuse than meprobamate. However, case reports have established carisoprodol as a drug of abuse. This paper explores the extent of potential abuse of this drug in Norway. Methods The Norwegian Prescription Database contains information on prescription drugs dispensed to individuals in Norway. Patients can be followed over time. High levels of carisoprodol use could indicate use for pleasurable effects or development of tolerance. Concomitant use of other potential drugs of abuse was also studied. We studied drug-seeking behaviour by looking at patients who received carisoprodol from many different pharmacies and doctors or from high-prescribing doctors. Carisoprodol was compared with a series of other medicinal drugs with or without known potential for abuse. Results Some 53 889 Norwegian women (2.4%) and 29 824 men (1.3%) ≥18 years old received carisoprodol at least once in 2004. Prescribing of carisoprodol was skewed. As many as 32% of the patients received more than 15 defined daily doses (DDDs) of carisoprodol and >11 000 patients (15%) received ≥75 DDDs in 2004. High users of carisoprodol also received more benzodiazepines and opioids. Few patients used three or more doctors for prescriptions, but carisoprodol-abusing patients more often received their prescription from high-prescribing doctors. Conclusions Carisoprodol was widely used and the skewedness in use indicated that it is a potential drug of abuse. A large number of patients used more carisoprodol than recommended in the guidelines. The high level of use and abuse of carisoprodol should be of concern in Norway. [ABSTRACT FROM AUTHOR]