Sedative drug-use in Denmark, 2000 to 2019: a nationwide drug utilization study.

AIM: To describe trends in and characteristics of sedative drug use from 2000 through 2019 in relation to the introduction of central regulations and new drugs. METHODS: In this descriptive study, we used individual prescription data on the entire Danish population from the Danish National Prescription Registry to calculate yearly incidence and prevalence of use of benzodiazepines, benzodiazepine-related drugs (Z-drugs), melatonin, olanzapine, low-dose quetiapine, mianserin/mirtazapine, pregabalin, and promethazine from 2000 through 2019. From the Danish National Patient Registry, we obtained data on drug users' psychiatric and somatic comorbidity. RESULTS: The use of benzodiazepines and Z-drugs declined gradually from 2000 through 2019, whereas the newer alternatives, melatonin, low-dose quetiapine, pregabalin and promethazine, increased in use, while the use of olanzapine and mianserin/mirtazapine was relatively stable. This development was seen in both men and women and across all age groups except for hypnotic benzodiazepines which showed a steep increase in the oldest age group from 2010. For all sedative drugs depression, anxiety, alcohol and misuse disorder, pain and cancer were the most prevalent comorbidities. During our study period, the number of individuals without any of the selected diagnoses increased. CONCLUSION: In Denmark different central regulations have influenced prescription practice toward more restrictive use of Z-drugs and benzodiazepines, except for hypnotic benzodiazepine prescriptions increased after the introduction of special palliative care. An increase in use of newer sedative drugs, however, indicates that the regulations do not remove the need for sedative drugs in the population.

Use of GLP-1 receptor agonists and subsequent risk of alcohol-related events. A nationwide register-based cohort and self-controlled case series study.

Animal studies have related glucagon-like peptide 1 receptor agonists (GLP-1) to lower alcohol intake. We examined whether GLP-1 was associated with risk of alcohol-related events in a nationwide cohort study and a self-controlled case series analysis including all new users of GLP1 (n = 38 454) and dipeptidyl peptidase 4 inhibitors (DPP4) (n = 49 222) in Denmark 2009-2017. They were followed for hospital contacts with alcohol use disorder or purchase of drugs for treatment of alcohol dependence in nationwide registers from 2009 to 2018. Associations were examined using Cox proportional hazard and conditional Poisson regression. During follow-up of median 4.1 years, 649 (0.7%) of participants were registered with an alcohol-related event. Initiation of GLP-1 treatment was associated with lower risk of an alcohol-related event (Hazard ratio = 0.46 (95%CI: 0.24-0.86) compared with initiation of DPP4 during the first 3 months of follow-up. Self-controlled analysis showed the highest risk of alcohol-related events in the 3-month pretreatment period (incidence rate ratio [IRR] = 1.25 (1.00-1.58)), whereas the risk was lowest in the first 3-month treatment period (IRR = 0.74 (0.56-0.97). In conclusion, compared with DPP4 users, individuals who start treatment with GLP-1 had lower incidence of alcohol-related events both in cohort and self-controlled analyses. Thus, there might be a transient preventive effect of GLP1 on alcohol-related events the first months after treatment initiation.

An analysis of the relative and absolute incidence of somatic morbidity in patients with affective disorders-A nationwide cohort study.

BACKGROUND: Patients with affective disorder seem to experience higher risks of several somatic diseases, but no studies have provided estimates of both absolute and relative risks for these diseases in the same population. METHODS: A prospective cohort of all patients age ≥18 years old with a hospital contact with affective disorder between 1997-2014 (n=246,282) and a random sample from the background population (n=167,562) was followed for hospitalizations with cardiovascular disease, diabetes, cancers, chronic obstructive pulmonary disease (COPD), asthma, inflammatory bowel disease, hip fracture, psoriasis, migraine, or dementia. Adjusted absolute and relative risk estimates were calculated using multivariable adjusted Aalen's additive and Cox proportional hazard regression models. RESULTS: After adjustments, the absolute risk difference was 130.6 (95% confidence interval [CI] 125.5-135.7) additional cases per 10,000 person-years among affective disorder patients compared to the reference population. The corresponding hazard ratio for any somatic disease was 1.50 (95% CI 1.48-1.52). The strongest associations were found for dementia, hip fracture, COPD, and stroke on both the relative and absolute scale. The patients did not have higher risk of cancers except for lung cancer and brain tumors. Risk estimates tended to be slightly higher for individuals with depression or other affective disorder compared to bipolar disorder. LIMITATIONS: Limitations include use of register-based data, risk of reverse causation and Berkson's bias. CONCLUSIONS: Patients with affective disorder have both higher absolute and relative risk of most somatic diseases except for cancers. Further identification of the shared mechanisms will facilitate the development of targeted interventions.

Predictors of age at onset of tobacco and cannabis use in Danish adolescents.

INTRODUCTION: Early onset of tobacco and cannabis use predicts later substance abuse and risk behaviour and has large health consequences. OBJECTIVES: The aim of this study was to examine risk factors for the age at onset of smoking and cannabis use among a group of Danish children between 7 years and 18 years of age. METHODS: Four hundred and eighty randomly selected children and their parents participated in a study about the prevalence of asthma. The study included questions about alcohol, tobacco and cannabis use. The children were interviewed face-to-face while the parents answered a questionnaire. RESULTS: The age at onset of daily smoking was significantly associated with the adolescents' tendency to binge drink [hazard ratio 4.78, 95% confidence interval (CI) (1.85-12.34), P = 0.001) and to use hard drugs [hazard ratio 2.81, 95% CI (1.03-7.78), P = 0.047], whereas the age at onset of cannabis use was significantly associated with binge drinking [hazard ratio 3.29, 95% CI (1.51-7.20), P = 0.003] and cigarette smoking [hazard ratio 2.51, 95% CI (1.26-5.00), P = 0.009]. There were no significant effect of the parents' smoking and alcohol habits, their socioeconomic or marital status on the adolescent' age at onset of smoking or cannabis. CONCLUSION: This study shows a close connection between adolescent tobacco and cannabis use and alcohol habits. Knowledge of this is important when planning future prevention strategies.

[Onset of alcohol consumption in 7-18-year-old children and adolescents]. / Alkoholdebutalderen hos 7-18-årige unge.

INTRODUCTION: Early onset of alcohol consumption contributes to increased risk of subsequent heavy alcohol use, alcohol dependence and alcohol-related problems. The objective of this study was to examine the onset of alcohol consumption in a group of Danish children. METHODS: The study was part of an asthma study and was based on face-to-face interviews with 480 randomly chosen children and adolescents between seven and 18 years of age. Questionnaires were sent to their parents. Onset of alcohol was defined as consumption of at least one unit of alcohol. RESULTS: Age at onset of alcohol consumption was 13.4 years for boys and 13.9 years for girls (p = 0.020). There was a significant association between age at onset and smoking of the adolescent (hazard ratio 2.19; 95% confidence interval (CI 1.16-4.12, p = 0.015) and maternal smoking during pregnancy (hazard ratio 2.23; 95% CI 1.31-3.78, p = 0.003). We found no association between early onset of alcohol consumption and parents' smoking, drinking, socioeconomic or marital status. CONCLUSION: Further knowledge is needed to clarify the factors associated with early onset of alcohol consumption among Danish adolescents.