RESUMEN
INTRO: Prenatal exposure to synthetic glucocorticoids may increase the risk of emotional symptoms in childhood partly by reducing fetal growth. We explored if physiological levels of prenatal maternal cortisol were associated with internalising problems in boys and girls and if this was mediated by birth weight. METHODS: Mother-child dyads from the prospective Odense Child Cohort (n=1162) were included if maternal serum cortisol (3rd trimester), offspring birth weight, and Child Behaviour Checklist (CBCL) assessments in preschool age were available. Crude and adjusted associations between cortisol and internalising problems were determined in linear mixed models stratified by offspring sex. Covariates included parental psychiatric history, parity, maternal age, education, smoking during pregnancy, and gestational age at birth. In the presence of significant associations, we evaluated the potential mediating role of birth weight. RESULTS: The study sample included 601 boys and 561 girls and internalising problems were assessed at mean ages 2.3 (±0.4) and 5 (±0.5) years. In the crude analysis, cortisol was positively associated with internalising problems in boys (p-value 0.017) and in girls (p-value < 0.0001). In the adjusted analyses, there was no statistically significant association between cortisol and offspring internalising problems in boys or girls (all p-values > 0.15). There was no mediation by birth weight. DISCUSSION: Maternal serum cortisol was positively associated with offspring internalising problems in boys and girls, but there was no association following adjustment for potential confounders and no mediation through birth weight. Maternal third-trimester cortisol levels do not predict preschool offspring internalising problems in our study.
Asunto(s)
Peso al Nacer , Hidrocortisona , Efectos Tardíos de la Exposición Prenatal , Humanos , Femenino , Hidrocortisona/sangre , Embarazo , Masculino , Preescolar , Efectos Tardíos de la Exposición Prenatal/sangre , Peso al Nacer/fisiología , Estudios Longitudinales , Adulto , Estudios Prospectivos , Madres/psicología , Trastornos de la Conducta Infantil/sangre , Trastornos de la Conducta Infantil/etiología , Conducta Infantil/fisiología , Conducta Infantil/psicologíaRESUMEN
PURPOSE: The healthcare systems in Scandinavia inform nationwide registers and the Scandinavian populations are increasingly combined in research. We aimed to compare Norway (NO), Sweden (SE), and Denmark (DK) regarding sociodemographic factors and healthcare. METHODS: In this cross-sectional study, we analyzed aggregated data from the nationwide Scandinavian registers. We calculated country-specific statistics on sociodemographic factors and healthcare use (general practitioner visits, admissions to somatic hospitals, and use of medicines). RESULTS: In 2018, population were 5295,619 (NO), 10,120,242 (SE), and 5781,190 (DK). The populations were comparable regarding sex, age, education, and income distribution. Overall, medication use was comparable, while there was more variation in hospital admissions and general practitioner visits. For example, per 1000 inhabitants, 703 (NO), 665 (SE), and 711 (DK) individuals redeemed a prescription, whereas there were 215 (NO), 134 (SE), and 228 (DK) somatic hospital admissions per 1000 inhabitants. General practitioner contacts per 1000 inhabitants were 7082 in DK and 5773 in NO (-data from SE). CONCLUSION: The Scandinavian countries are comparable regarding aggregate-level sociodemographic factors and medication use. Variations are noted in healthcare utilisation as measured by visits to general practitioners and admissions to hospitals. This variation should be considered when comparing data from the Scandinavian countries.
RESUMEN
The aim of this study was to examine variations in use of antidepressants among children and adolescents in the three Scandinavian countries (Sweden, Norway, and Denmark). We identified new users of antidepressants (5-17 years) during 2007-2018 and described the annual incidence rate, treatment duration, concomitant psychotropic drug use, and the clinical setting of the prescribing physician (in Sweden and Denmark). Incident use of antidepressants increased by a factor 1.9 in Sweden, 1.3 in Norway and decreased by a factor 0.6 in Denmark during the study period. In Sweden, 58% of antidepressant users were covered by a prescription 12 months after initiation compared to 40% in Norway and 49% in Denmark. Also, 34% of Swedish antidepressant users were in continuous treatment after 12 months compared to 26% in Norway and 31% in Denmark. Concomitant use of other psychotropics was more common in Sweden (57%) than in Norway (37%) and Denmark (27%). During 2007-2018, clinicians from psychiatry settings initiated 75% of antidepressant treatments in Sweden, while this was the case for 50% of prescriptions in Denmark, although the proportion increased over time. The number of new antidepressant users is high and still rising in Sweden compared to Norway and Denmark. Swedish antidepressant users are more likely to use other psychotropics and to be covered by an antidepressant prescription after one year. Most antidepressants in Sweden are prescribed by physicians within psychiatric settings suggesting that they are based on specialized psychiatric evaluation.
RESUMEN
Since the onset of the COVID-19 pandemic, there have been concerns over the mental health impact of COVID-19. This is a review of the utilization of antidepressants, anxiolytics, and hypnotics since the COVID-19 pandemic was declared on March the 11th 2020. A number of reports so far have been based on large prescription databases for administrative use at the national or regional level, but mainly in high-income countries. We found studies reporting increased prescription rates of antidepressants, anxiolytics, and hypnotics during March 2020, which has been interpreted as hoarding of such medications. In the following months, most studies of antidepressant prescription rates did not display a clear pattern of change compared with prepandemic trends. In later phases of the pandemic small increases in utilization of antidepressants, with higher than predicted prescription rates, have been the most consistent finding, especially in youth. In most high-income countries, there were increasing trends in utilization of antidepressants also before 2020, which needs to be considered when estimating utilization during the pandemic, whereas for anxiolytics and hypnotics, the prepandemic patterns of prescriptions were more varying. Overall, after March 2020 we could not find any distinct changes in the utilization of anxiolytics and hypnotics during the COVID-19 pandemic. Most studies did not contain information about the prevalence of indicated psychiatric disorders in the studied populations. More studies are needed about the long-term effects of COVID-19, particularly regarding utilization of antidepressants. Research relating antidepressant utilization with the prevalence of major depression and anxiety disorders would promote a better understanding of how well antidepressant prescription rates reflect the needs of the population.
Asunto(s)
Ansiolíticos , COVID-19 , Adolescente , Humanos , Ansiolíticos/uso terapéutico , Hipnóticos y Sedantes/uso terapéutico , Pandemias , Antidepresivos/uso terapéuticoRESUMEN
We have previously shown that the use of hypnotic drugs increased among young Scandinavians during 2012-2018. This study aimed to explore psychiatric and somatic morbidity among adolescent hypnotic drug users in a cohort study of 13-17-year-old individuals during 2008-2018 in Norway. Data sources were (i) prescription data from the Norwegian Prescription Database linked to specialist health care diagnoses from the Norwegian Patient Registry and (ii) sleep disorder diagnoses from the Primary Health Care Database. Hypnotic drugs were defined as the sedative antihistamine alimemazine and the ATC group "Hypnotics and Sedatives" (N05C), excluding midazolam. In 2017, 2519 girls (16.5/1000) and 1718 boys (10.7/1000) were incident (new) users of hypnotic drugs. Most of these new users (82% of girls, 77% of boys) were referred to secondary health care, where the most frequent diagnoses were mental and behavioral disorders (51.8% of girls, 46.2% of boys), while only 3.2% received a specific sleep disorder diagnosis. The most common mental and behavioral disorders were "Neurotic stress-related disorders" among girls (27.4%) and "Behavioral and emotional disorders" among boys (23.6%). In conclusion, the trend of increasing hypnotic drug use among adolescents reflects the initiation of hypnotic drugs in a subgroup of the population with a higher disease burden, mainly due to psychiatric disorders, than the general population.
RESUMEN
BACKGROUND: Conduct disorders (CD) are among the most frequent psychiatric disorders in children and adolescents, with an estimated worldwide prevalence in the community of 2-4%. Evidence-based psychological outpatient treatment leads to significant improvement in about two-thirds of cases. However, there seems to be considerable variation in rates of CD diagnoses and implementation of evidence-based interventions between nations. The aim of this study was to compare administrative prevalence and treatment patterns for CD in children and adolescents seen in health care systems across four Western countries (Denmark, Germany, Norway, and the USA). METHODS: Cross-sectional observational study using healthcare data to identify children and adolescents (aged 0-19 years) with an ICD-10 code for CD within the calendar year 2018. Within each country's study population, the prevalence of CD, psychiatric comorbidity, psychopharmacological treatment, and psychiatric hospitalisation was calculated. RESULTS: The prevalence of diagnosed CD differed 31-fold between countries: 0.1% (Denmark), 0.3% (Norway), 1.1% (USA) and 3.1% (Germany), with a male/female ratio of 2.0-2.5:1. The rate of psychiatric comorbidity ranged from 69.7 to 86.1%, with attention-deficit/hyperactivity disorder being most common. Between 4.0% (Germany) and 12.2% (USA) of youths with a CD diagnosis were prescribed antipsychotic medication, and 1.2% (Norway) to 12.5% (Germany) underwent psychiatric hospitalisation. CONCLUSION: Recognition and characteristics of youths diagnosed with CD varied greatly by country. In some countries, the administrative prevalence of diagnosed CD was markedly lower than the average estimated worldwide prevalence. This variation might reflect country-specific differences in CD prevalence, referral thresholds for mental health care, diagnostic tradition, and international variation in service organisation, CD recognition, and availability of treatment offers for youths with CD. The rather high rates of antipsychotic prescription and hospitalisation in some countries are remarkable, due to the lack of evidence for these therapeutic approaches. These findings stress the need of prioritising evidence-based treatment options in CD. Future research should focus on possible reasons for inter-country variation in recognition and management of CD, and also address possible differences in patient-level outcomes.
RESUMEN
BACKGROUND: Attention Deficit Hyperactivity Disorder (ADHD) is a common childhood psychiatric disorder with severe and lifelong impact on mental health and socioeconomic achievements. Environmental factors may play a role in the increasing incidens rates. Previous studies on associations between prenatal and childhood exposure to organophosphate and pyrethroid insecticides and ADHD symptoms have yielded mixed findings. OBJECTIVES: To investigate associations between prenatal and childhood exposure to chlorpyrifos and pyrethroids and ADHD symptoms in 5-year-old children from the Odense Child Cohort. METHODS: Spot urine samples from pregnant women in gestational week 28 (n = 614) and offspring at 5 years of age (n = 814) were collected and analyzed for the specific metabolite of chlorpyrifos, TCPY (3,5,6-trichloro-2-pyridinol), as well as the generic pyrethroid metabolite, 3-PBA (3-phenoxybenzoic acid). Offspring ADHD symptoms were assessed at age 5 years using the parent reported "ADHD scale" from the "Child Behavior Checklist 1½-5" (n = 1114). Associations between insecticide exposure variables and an ADHD score ≥90th percentile were analyzed using logistic regression for all children and stratified by sex. RESULTS: Most pregnant women had detectable concentrations of 3-PBA (93%) and TCPY (91%) with median concentrations of 0.20 µg/L and 1.62 µg/L, respectively. In children, 3-PBA and TCPY concentrations were detectable in 88% and 82% of the samples, and the median concentrations were 0.17 and 1.16 µg/L. No statistically significant associations were observed between insecticide metabolites and an ADHD score ≥90th percentile at age 5. CONCLUSION: In this relatively large Danish birth cohort study with mainly low dietary insecticide exposure, we found no statistically significant associations between prenatal or childhood exposure to chlorpyrifos or pyrethroids, and excess ADHD-symptom load, in 5-year-old children. Prospective studies with multiple urine samples across vulnerable windows of neurodevelopment is warranted to improve assessment of safe exposure levels, which is particularly relevant for pyrethroids, since their use is increasing.
Asunto(s)
Trastorno por Déficit de Atención con Hiperactividad , Cloropirifos , Insecticidas , Efectos Tardíos de la Exposición Prenatal , Piretrinas , Humanos , Femenino , Preescolar , Embarazo , Niño , Cloropirifos/toxicidad , Cloropirifos/orina , Insecticidas/toxicidad , Insecticidas/orina , Trastorno por Déficit de Atención con Hiperactividad/inducido químicamente , Trastorno por Déficit de Atención con Hiperactividad/epidemiología , Estudios de Cohortes , Estudios Prospectivos , Piretrinas/toxicidad , Piretrinas/orina , Efectos Tardíos de la Exposición Prenatal/inducido químicamente , Efectos Tardíos de la Exposición Prenatal/epidemiologíaRESUMEN
Dr. Wickersham et al.'s study linked educational and health records providing important knowledge on educational trajectories in youths with mental disorders. They found that youths diagnosed with depression prior to age 18 were more likely to have a decline in educational attainment over time than youths without depression. Furthermore, educational attainment trajectories showed some specificity with different patterns between youths with depression and youths with neurodevelopmental disorders. In this commentary, we highlight the clinical implications of these findings, showing that low or declining educational attainment in youths might serve as a marker for psychopathology, providing the opportunity to identify youths that could benefit from coordinated interventions across diagnostic boundaries.
Asunto(s)
Éxito Académico , Trastornos del Neurodesarrollo , Humanos , Adolescente , EscolaridadRESUMEN
BACKGROUND: Selective serotonin reuptake inhibitors (SSRIs) are the most frequently prescribed antidepressants in pregnancy. Animal and some clinical studies have suggested potential increases in depression and anxiety following prenatal SSRI exposure, but the extent to which these are driven by the medication remains unclear. We used Danish population data to test associations between maternal SSRI use during pregnancy and children outcomes up to age 22. METHODS: We prospectively followed 1,094,202 single-birth Danish children born 1997-2015. The primary exposure was ≥ 1 SSRI prescription filled during pregnancy; the primary outcome, first diagnosis of a depressive, anxiety, or adjustment disorder, or redeemed prescription for an antidepressant medication. We used propensity score weights to adjust potential confounders, and incorporated data from the Danish National Birth Cohort (1997-2003) to further quantify potential residual confounding by subclinical factors. RESULTS: The final dataset included 15,651 exposed and 896,818 unexposed, children. After adjustments, SSRI-exposed had higher rates of the primary outcome than those of mothers who either did not use an SSRI (HR = 1.55 [95%CI:1.44,1.67] or discontinued the SSRI use ≥ 3 months prior to conception (HR = 1.23 [1.13,1.34]). Age of onset was earlier among exposed (9 [IQR:7-13] years) versus unexposed (12 [IQR:12-17] years) children (p < 0.01). Paternal SSRI use in the absence of maternal use during the index pregnancy (HR = 1.46 [1.35,1.58]) and maternal SSRI use only after pregnancy (HR = 1.42 [1.35,1.49]) were each also associated with these outcomes. CONCLUSIONS: While SSRI exposure was associated with increased risk in the children, this risk may be driven at least partly by underlying severity of maternal illness or other confounding factors.
RESUMEN
Neurodevelopmental disorders - including attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorder, communication disorders, intellectual disability, motor disorders, specific learning disorders, and tic disorders - manifest themselves early in development. Valid, reliable and broadly usable biomarkers supporting a timely diagnosis of these disorders would be highly relevant from a clinical and public health standpoint. We conducted the first systematic review of studies on candidate diagnostic biomarkers for these disorders in children and adolescents. We searched Medline and Embase + Embase Classic with terms relating to biomarkers until April 6, 2022, and conducted additional targeted searches for genome-wide association studies (GWAS) and neuroimaging or neurophysiological studies carried out by international consortia. We considered a candidate biomarker as promising if it was reported in at least two independent studies providing evidence of sensitivity and specificity of at least 80%. After screening 10,625 references, we retained 780 studies (374 biochemical, 203 neuroimaging, 133 neurophysiological and 65 neuropsychological studies, and five GWAS), including a total of approximately 120,000 cases and 176,000 controls. While the majority of the studies focused simply on associations, we could not find any biomarker for which there was evidence - from two or more studies from independent research groups, with results going into the same direction - of specificity and sensitivity of at least 80%. Other important metrics to assess the validity of a candidate biomarker, such as positive predictive value and negative predictive value, were infrequently reported. Limitations of the currently available studies include mostly small sample size, heterogeneous approaches and candidate biomarker targets, undue focus on single instead of joint biomarker signatures, and incomplete accounting for potential confounding factors. Future multivariable and multi-level approaches may be best suited to find valid candidate biomarkers, which will then need to be validated in external, independent samples and then, importantly, tested in terms of feasibility and cost-effectiveness, before they can be implemented in daily clinical practice.
RESUMEN
The objective of the study was to compare the use of attention deficit hyperactivity disorder (ADHD) medication among children and adolescents in Scandinavia 2010-2020. Using aggregated prescription data for individuals aged 5-19 years, we calculated annual prevalence proportions of ADHD medication (users/1000 inhabitants) for each country, overall and stratified by age and sex. Overall, use of ADHD medication increased during 2010-2020 in all countries. The increase was pronounced in Sweden reaching 35 users/1000 inhabitants in 2020 (119% increase), whereas it reached 22/1000 in Denmark and Norway (equivalent to a 38% and 16% increase, respectively). Methylphenidate was the most frequently used drug and Sweden had the highest use reaching 25/1000 in 2020 compared to 16/1000 and 18/1000 in Denmark and Norway, respectively. Lisdexamfetamine use increased steadily and was also highest in Sweden (13/1000 in 2020). In 2020, atomoxetine use was higher in Sweden (4.6/1000) and Denmark (4.5/1000) compared to Norway (2.2/1000). From 2015, use of guanfacine increased in Sweden reaching 4.4/1000 in 2020 but remained low in Denmark (0.4/1000) and Norway (0.7/1000). Use of dexamphetamine was low (ranging from 0.47 to 0.75/1000 in 2020) in the three countries. ADHD medication use was highest in Sweden across all age groups. In all countries, the prevalence was higher in males compared to females. In conclusion, use of ADHD medication among children and adolescents in Scandinavia is increasing. The prevalence of use is higher in Sweden for all drug groups compared to Norway and Denmark.
Asunto(s)
Trastorno por Déficit de Atención con Hiperactividad , Estimulantes del Sistema Nervioso Central , Metilfenidato , Masculino , Femenino , Niño , Humanos , Adolescente , Trastorno por Déficit de Atención con Hiperactividad/tratamiento farmacológico , Trastorno por Déficit de Atención con Hiperactividad/epidemiología , Estimulantes del Sistema Nervioso Central/uso terapéutico , Metilfenidato/uso terapéutico , Clorhidrato de Atomoxetina/uso terapéutico , Países Escandinavos y Nórdicos/epidemiologíaRESUMEN
We aimed to provide a detailed description of the use of melatonin in Danish children, adolescents, and young adults during 2012-2019. We identified melatonin users 0-24 years of age (n = 43,652; median age 16 years) via the Danish nationwide health registers. Melatonin is a prescription drug in Denmark. The incidence of melatonin use increased from 2.4 to 3.9/1000 person-years during 2012 to 2019. Among 6,557 incident users in 2019, 53% filled only a single prescription within the first 6 months. Long-term use was most common among the younger age groups, with 17% of 5-9-year-olds and 14% of 10-13-year-olds being in continued treatment (no treatment breaks) 12 months after their first melatonin prescription. Disregarding treatment breaks, 3 in 10 were using melatonin 12 months after their first melatonin prescription and this proportion was also highest among 5-9-year-olds (63%) and 10-13-year-olds (51%). Psychopathology was common among melatonin users with 75% registered with either a psychiatric disorder diagnosis (54%), a filled prescription for another psychotropic (58%), or a contact to a private practice psychiatrist (15%) within ± 12 months of treatment initiation. General practitioners authorized melatonin prescriptions to almost half of all new users (48%), while psychiatric specialists authorized 37% of first prescriptions. In conclusion, the incidence of melatonin use increased in Denmark from 2012 to 2019. A substantial proportion of users had concurrent psychopathology most likely explaining their use of melatonin. Long-term melatonin use was more common among the youngest age groups, which should be a focus of interest due to limited safety data.
Asunto(s)
Melatonina , Medicamentos bajo Prescripción , Humanos , Niño , Adolescente , Adulto Joven , Lactante , Melatonina/uso terapéutico , Sistema de Registros , Utilización de Medicamentos , Dinamarca/epidemiología , Prescripciones de MedicamentosRESUMEN
OBJECTIVE: To study patterns of antidepressant, anxiolytic, and hypnotic drug utilization in Denmark, Norway, and Sweden during the first year of the COVID-19 pandemic. METHODS: The monthly observed number of prescription fills of antidepressants, benzodiazepines and benzodiazepine-related hypnotics (BZ), and other anxiolytics and hypnotics (OAH) per population in 2020 were compared with predicted numbers based on analysis of covariance of prescription fills during 2015-2019. RESULTS: In March 2020, there was an increased number of prescription fills for antidepressants, anxiolytics, and hypnotics in youths and adults aged 20-59 years in Denmark, Norway, and Sweden. Antidepressant prescription fills increased between 13.5 % and 31.3 % at the end of 2020 in all age groups in Denmark and 17.4 % in youths in Norway. BZ drug prescription fills increased by 20.8 % at the end of 2020 in the 20-59 year age group in Denmark and decreased by 16.7 % in youths in Sweden. A general increase of prescription fills of OAH at the end of 2020 was observed in all countries (range 24.0-80.0 % in Denmark, 11.5-30.8 % in Norway, and 9.1-12.1 % in Sweden). Increases of prescription fills of OAH occurred earlier in Denmark. LIMITATIONS: Aggregated data with lack of information on indications. CONCLUSIONS: Peaks of utilization of antidepressants, anxiolytics, and hypnotics observed in March 2020 may reflect medication stock piling. Increased antidepressant drug utilization in Denmark and in Norwegian youths together with the general increase in OAH utilization in the Scandinavian countries in late 2020 may indicate an increase of symptoms of depression and anxiety, as well as disturbed sleep.
Asunto(s)
Ansiolíticos , COVID-19 , Adulto , Adolescente , Humanos , Adulto Joven , Persona de Mediana Edad , Ansiolíticos/uso terapéutico , Hipnóticos y Sedantes/uso terapéutico , Pandemias , COVID-19/epidemiología , Antidepresivos/uso terapéutico , Países Escandinavos y Nórdicos/epidemiología , Benzodiazepinas/uso terapéutico , Prescripciones de Medicamentos , Utilización de MedicamentosRESUMEN
Importance: The direct and indirect implications of the COVID-19 pandemic have been associated with the mental health of children and adolescents, but it is uncertain whether these implications have been associated with changes in prescribing and diagnosis patterns. Objective: To examine psychotropic medication use and rates of psychiatric disorders in Danish children, adolescents, and young adults during the COVID-19 pandemic. Design, Setting, and Participants: This population-based, descriptive register-based cohort study included all Danish individuals aged 5 to 24 years from January 1, 2017, until June 30, 2022. Main Outcomes and Measures: Rates of filled prescriptions of psychotropic medications, including antipsychotics, anxiolytics, hypnotics, sedatives, antidepressants, and psychostimulants, and all inpatient and outpatient contacts with mental and behavioral disorders. Rates of new (incident) and total (prevalent) psychotropic medication use and psychiatric diagnoses were estimated. Rate ratios (RRs) were assessed between observed and expected numbers of incident psychotropic medication use or psychiatric diagnoses from March 2020 to June 30, 2022, comparing observed numbers with expected numbers predicted from the modeled prepandemic trend. Results: The study identified 108â¯840 (58â¯856 female individuals [54%]; median [IQR] age, 18 [14-22] years) incident psychotropic medication users. From March 2020 (first national lockdown) to June 2022, the rate of incident users of any psychotropic medication showed a relative increase of 18% (RR, 1.18; CI, 1.17-1.20) compared with expected numbers, which was primarily associated with an increase among those aged 12 to 17 years of 37% (RR, 1.37; 95% CI, 1.34-1.41). Similarly, there was an overall relative increase of incident psychiatric disorders of 5% (incidence rate, 1.05; CI, 1.04-1.07) (incident cases, 114â¯048 [58â¯708 female individuals (51%)]), which was associated with an increase in hyperkinetic disorders (RR, 1.13; CI, 1.09-1.18) and anxiety disorders (RR, 1.04; CI, 1.02-1.06). Prevalence patterns showed similar trends of an overall increase in psychotropic medication use and psychiatric disorders. One of 3 new users of an individual drug group had filled a prescription for a drug from another psychotropic medication group within the prior 6 months. Conclusions and Relevance: The results of this cohort study suggest that Danish youths experienced an increase in rates of psychotropic treatment and psychiatric disorder diagnoses during the COVID-19 pandemic, which was most pronounced among those aged 12 to 17 years. The increase was observed for children and adolescents with and without a psychiatric history within the last 5 years.
Asunto(s)
COVID-19 , Trastornos Mentales , Adolescente , Niño , Humanos , Femenino , Adulto Joven , Estudios de Cohortes , Pandemias , COVID-19/epidemiología , Control de Enfermedades Transmisibles , Psicotrópicos/uso terapéutico , Trastornos Mentales/tratamiento farmacológico , Trastornos Mentales/epidemiología , Dinamarca/epidemiologíaRESUMEN
Purpose: To develop the Nordic Multimorbidity Index (NMI), a multimorbidity measure specifically suited to the Nordic health and administrative registry data based on current diagnosis, treatment, and coding practices. Methods: The NMI was developed to predict 5-year mortality in a population-based cohort of randomly sampled Danish residents aged ≥40 years (n = 425,087) followed from 2013 to 2018. Included predictors were selected from hospital diagnoses and filled drug prescriptions based on a combination of subject matter knowledge and a data-driven approach using backwards elimination. The performance of the NMI was assessed in a temporal validation cohort of Danish residents followed from 2007 to 2012 and in six cohorts of new users of selected drugs. The discriminative performance of the NMI, Charlson Comorbidity Index (CCI) and the Elixhauser Comorbidity Index (ECI) was assessed using the c-statistic from logistic regression models with 5-year mortality as dependent variable and the multimorbidity index score, age, and sex as independent variables. Results: The NMI included 50 predictors. In the temporal validation cohort, the c-statistic of the NMI (0.887, 95% CI 0.883-0.890) exceeded that of the CCI (0.871, 95% CI 0.868-0.874) and ECI (0.866, 95% CI 0.863-0.870). In all new user cohorts, the NMI outperformed the other indices with c-statistics ranging from 0.781 (95% CI 0.779-0.784) to 0.838 (95% CI 0.834-0.842). Conclusion: The NMI predicted 5-year mortality in a general Danish population and six cohorts of new users of selected drugs and was superior to the CCI and ECI. The NMI could be preferred over these indices to quantify the level of multimorbidity for, eg, descriptive purposes or confounding control. The NMI should be validated in other patient populations and other Nordic countries.
RESUMEN
Chlorprothixene is commonly used off-label in low doses for sedative-hypnotic purposes although it might carry a risk of cardiometabolic adverse events due to its pharmacodynamic profile. We investigated the risk of diabetes and major adverse cardiovascular events (MACE) with use of low-dose chlorprothixene, compared with use of low-dose quetiapine in a nationwide cohort study, including all new users of low-dose chlorprothixene (n = 81 328) and low-dose quetiapine (n = 91 163) in Denmark 2000-2017. Main outcomes were diabetes and MACE (myocardial infarction, stroke and death from cardiovascular causes). The association between cumulative dose of chlorprothixene and the outcomes was tested in a case-control analysis. Low-dose chlorprothixene use was associated with increased risk of diabetes (intention-to-treat [ITT]-hazard ratio [HR]: 1.16; 95% CI: 1.08-1.25), compared with low-dose quetiapine use. This association strengthened when follow-up was restricted to time on treatment (as-treated [AT]-HR: 1.34; 95% CI: 1.14-1.56). Low-dose chlorprothixene use was also associated with increased risk of MACE (ITT-HR: 1.12; 95% CI: 1.04-1.21) and stroke (ITT-HR: 1.21; 95% CI: 1.06-1.37) but not with myocardial infarction (ITT-HR: 1.11; 95% CI: 0.95-1.30) nor death from cardiovascular causes (ITT-HR: 1.07; 95% CI: 0.96-1.20). Cumulative dose of chlorprothixene ≥6000 mg was associated with increased risk of diabetes (OR: 1.15-1.63; test for trend: p < 0.001), whereas cumulative dose of chlorprothixene ≥1500 mg was associated with increased risk of MACE (OR: 1.10-1.85; test for trend: p < 0.001). In conclusion, low-dose chlorprothixene use is associated with increased risk of cardiometabolic adverse events compared with low-dose quetiapine use.
Asunto(s)
Enfermedades Cardiovasculares , Diabetes Mellitus Tipo 2 , Infarto del Miocardio , Enfermedades Cardiovasculares/inducido químicamente , Enfermedades Cardiovasculares/complicaciones , Enfermedades Cardiovasculares/epidemiología , Clorprotixeno/uso terapéutico , Estudios de Cohortes , Diabetes Mellitus Tipo 2/inducido químicamente , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Humanos , Infarto del Miocardio/inducido químicamente , Infarto del Miocardio/epidemiología , Fumarato de Quetiapina/efectos adversos , Factores de RiesgoRESUMEN
BACKGROUND: Hypnotic use in children and adolescents is controversial. OBJECTIVE: To describe the use of hypnotic drugs (melatonin, z-drugs, and sedating antihistamines) among 5- to 24-year-old Scandinavians during 2012 to 2018. METHODS: Aggregate-level data were obtained from public data sources in Sweden, Norway, and Denmark. We calculated annual prevalence (users/1000 inhabitants) stratified by age group, sex, and country. Quantity of use (Defined Daily Dose (DDD)/user/day) was estimated for Norway and Denmark. RESULTS: Melatonin was the most commonly used hypnotic, and its use increased markedly from 2012 to 2018, particularly among females and 15- to 24-year-old individuals. Sweden had the highest increase in use (6.5 to 25/1000) compared with Norway (10-20/1000) and Denmark (5.7-12/1000). The annual prevalence of sedating antihistamine use was also highest in Sweden, reaching 13/1000 in 2018 in comparison to 7.5/1000 in Norway and 2.5/1000 in Denmark. Z-drug use decreased in all countries toward 2018, dropping to 3.5/1000 in Sweden, 4.4/1000 in Norway, and 1.7/1000 in Denmark. The quantity of hypnotic use in Norway and Denmark was 0.8-1.0 DDD/user/day for melatonin in 2018, as compared to 0.1-0.3 for z-drugs and antihistamines. CONCLUSION: The use of melatonin and sedating antihistamines increased among young Scandinavians during 2012-2018, and the increase was twice as high in Sweden compared with Norway and Denmark. In addition, Sweden had the highest use of sedating antihistamines. The Scandinavian variation of hypnotic use could reflect differences in frequency of sleep problems between populations or variation of healthcare access or clinical practice between countries.