Search

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., 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.

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.

Kasper Bruun Kristensen,1 Lars Christian Lund,1 Peter Bjødstrup Jensen,1 Anne Broe,1 Emelie Rotbain,2 Per Damkier,1,3,4 Anton Pottegård,1 Jacob Harbo Andersen,1 Mikkel Højlund,1,5 Morten Olesen,1 Lotte Rasmussen,1 Morten Rix Hansen,1,3,4 Martin Thomsen Ernst,1 Rikke Wesselhoeft,1,6 Daniel Pilsgaard Henriksen,3 Mette Reilev,1 Mette Bliddal,1,7 Jesper Hallas1 1Clinical Pharmacology, Pharmacy and Environmental Medicine, Department of Public Health, University of Southern Denmark, Odense, Denmark; 2Department of Hematology, Odense University Hospital, Odense, Denmark; 3Department of Clinical Pharmacology, Odense University Hospital, Odense, Denmark; 4Department of Clinical Research, University of Southern Denmark, Odense, Denmark; 5Department of Psychiatry Aabenraa, Mental Health Services in the Region of Southern Denmark, Aabenraa, Denmark; 6Child and Adolescent Psychiatry Odense, Mental Health Services in the Region of Southern Denmark, Odense, Denmark; 7Research Unit OPEN, Department of Clinical Research, University of Southern Denmark, Odense, DenmarkCorrespondence: Jesper Hallas, Clinical Pharmacology, Pharmacy and Environmental Medicine, Department of Public Health, University of Southern Denmark, J.B. Winsløws Vej 19, 2, Odense, 5000, Denmark, Tel +4565503010, Email jhallas@health.sdu.dkPurpose: 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 resid

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.

Objective: Anorexia nervosa (AN) has been associated with cognitive impairment. While re-nutrition is one of the main treatment targets, the effect on cognitive impairments is unclear. The aim of this review was to examine whether cognitive functions improve after weight gain in patients with AN. Method: A systematic review was performed following Preferred Reporting Items for Systematic Reviews and Meta-analyses statement guidelines (PROSPERO CRD42019081993). Literature searches were conducted May 20th , 2019 in PubMed, EMBASE, PsychINFO and Cochrane Library. Pairs of reviewers screened reports independently based on titles/abstracts (N = 6539) and full texts (N = 378). Furthermore, they assessed the quality of reports, including whether practice effects were accounted for. Results: Twenty-four longitudinal reports were included featuring 757 patients and 419 healthy controls. Six studies examined children and adolescents. Four out of four studies found processing speed to improve above and beyond what could be assigned to practice effects and three out of four studies found that cognitive flexibility was unaffected after weight gain in children and adolescents. Results from studies of adults were inconclusive. Discussion: The literature on cognitive change in patients with AN following weight gain is sparse. Preliminary conclusions can be made only for children and adolescents, where weight gain appeared to be associated with improved processing speed., Part of Special Issue: Value of Treatment.

Objective Anorexia nervosa (AN) has been associated with cognitive impairment. While re‐nutrition is one of the main treatment targets, the effect on cognitive impairments is unclear. The aim of this review was to examine whether cognitive functions improve after weight gain in patients with AN. Method A systematic review was performed following Preferred Reporting Items for Systematic Reviews and Meta‐analyses statement guidelines (PROSPERO CRD42019081993). Literature searches were conducted May 20th, 2019 in PubMed, EMBASE, PsychINFO and Cochrane Library. Pairs of reviewers screened reports independently based on titles/abstracts (N = 6539) and full texts (N = 378). Furthermore, they assessed the quality of reports, including whether practice effects were accounted for. Results Twenty‐four longitudinal reports were included featuring 757 patients and 419 healthy controls. Six studies examined children and adolescents. Four out of four studies found processing speed to improve above and beyond what could be assigned to practice effects and three out of four studies found that cognitive flexibility was unaffected after weight gain in children and adolescents. Results from studies of adults were inconclusive. Discussion The literature on cognitive change in patients with AN following weight gain is sparse. Preliminary conclusions can be made only for children and adolescents, where weight gain appeared to be associated with improved processing speed.

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.

OBJECTIVE This study examined the validity of childhood depression diagnoses in the Danish Psychiatric Central Research Register (DPCRR) and identified predictors of validity. METHODS A nationwide random sample of 500 children (6-17 years) diagnosed with depression between 1996 and 2016 was identified in the DPCRR. Psychiatric hospital records were reviewed and rated using an online checklist. The primary outcome was, whether depressive symptoms and functional impairment documented in hospital records justified a depressive disorder diagnosis based on ICD-10 or DSM-5 diagnostic criteria. Diagnostic validity was calculated as the positive predictive value. Binary logistic regression analysis was used to identify potential predictors of diagnostic validity and these were included in a multiple logistic regression. RESULTS Psychiatric hospital records were available for 393 patients (78.6%). The documentation in the records justified an ICD-10 depressive episode diagnosis in 72.8%, and DSM-5 major depressive disorder in 73.3% of the patients registered with a depression diagnosis. We identified three predictors of diagnostic validity; 1) The validity increased almost linearly from 2000-2016 (OR 1.14, 95% CI 1.07-1.20, p<0.001), 2) antidepressant use was associated with increased diagnostic validity (OR 2.27, 95% CI 1.35-3.82, p=0.002), and 3) emergency department admission predicted low diagnostic validity (OR 0.33, 95% CI 0.12-0.93, p=0.036). CONCLUSION Childhood depression diagnoses registered in the DPCRR show a satisfactory validity according to both ICD-10 and DSM-5 diagnostic criteria. Diagnostic validity increased steadily from 2000-2016 and was positively correlated to antidepressant use. Depression diagnoses assigned in emergency departments had low diagnostic validity.