Mirtazapine exposure in pregnancy and fetal safety: A nationwide cohort study.

OBJECTIVE: To investigate the association between mirtazapine exposure in pregnancy and risk of specific adverse pregnancy outcomes. METHODS: A register-based nationwide cohort study was conducted including all registered pregnancies in Denmark from 1997 to 2016. Mirtazapine-exposed pregnancies were compared with mirtazapine unexposed pregnancies in a 1:4 ratio matched according to propensity scores. Outcomes were major congenital malformations analyzed using log binomial models, and spontaneous abortion, stillbirth and neonatal death analyzed using Cox proportional hazard regression. RESULTS: From a source population of 1,650,649 pregnancies, the propensity score-matched cohort included 4475 pregnancies (895 mirtazapine exposed) in the analysis of major congenital malformations. The analyses of spontaneous abortion included 9 500 pregnancies (1900 mirtazapine exposed), and for the analyses of stillbirths and neonatal deaths 9725 (1 945 mirtazapine-exposed) and 4485 pregnancies (897 mirtazapine-exposed) were included, respectively. Thirty-one (3.5%) children were diagnosed with major congenital malformation among the mirtazapine exposed compared with 152 (4.3%) among the unexposed pregnancies (OR=0.81, 95% CI 0.55-1.20). Spontaneous abortion occurred in 237 (12.5%) of the mirtazapine exposed compared with 931 (12.3%) of the unexposed pregnancies (HR = 1.04%, 95% CI 0.91-1.20). The analyses revealed no increased risk of stillbirth (HR = 0.88%, 95% CI 0.34-2.29) or neonatal death (HR = 0.60%, 95% CI 0.18-2.02). CONCLUSIONS: In this nationwide Danish register study, mirtazapine exposure in pregnancy was not associated with major congenital malformations, spontaneous abortion, stillbirth, or neonatal death. Clinicians and patients can be reassured that mirtazapine is safe in pregnancy.

Psychiatric morbidity among men using anabolic steroids.

OBJECTIVE: The purpose of this study was to investigate the psychiatric morbidity among men with abuse of anabolic steroids. METHODS: The design is a retrospectively matched cohort study. Five hundred and fourty-five males, who tested positive for anabolic steroids in Danish fitness centers during the period January 3, 2006 to March 1, 2018, were matched with 5450 randomly chosen male controls. Data was cross-referenced with seven national registers pertaining to information about education, employment status, and psychiatric comorbidity. Main outcomes and measures were prescription of psychopharmacological treatment. RESULTS: The incidence of treatment with anxiolytics (HR: 2.34, 95% CI: 1.62-3.38) and antipsychotics (HR: 2.69, 95% CI: 1.99-3.63) displayed a remarkable increase in the years following doping sanction, compared to the control group. The prevalence of antidepressant use was already markedly elevated several years before doping sanction, but also displayed a higher incidence in the years following sanction (HR: 1.65, 95% CI: 1.28-2.13). The associations remained highly significant after controlling for socioeconomic factors. CONCLUSION: Anabolic steroids use is strongly associated with psychiatric morbidity.

Ciprofloxacin exposure and adverse pregnancy outcomes: A Danish nationwide cohort study.

OBJECTIVE: To examine the association between maternal exposure to ciprofloxacin and the risk of miscarriage and major malformations. DESIGN: A nationwide register-based cohort study. SETTING: Data were obtained from the Medical Birth Registry, the National Hospital Registry, the Danish National Prescription Registry and Statistics Denmark. POPULATION: Data were collected in the period between 1997 and 2016 and included all registered pregnancies that ended in an elective termination, miscarriage, stillbirth or a live birth. Exposure was defined as redeeming one or more prescriptions of ciprofloxacin. METHODS: Miscarriage was defined as a diagnosis given before 22 weeks without any medical intervention. Major malformations were classified according to EUROCAT 1.4. We matched ciprofloxacin-exposed pregnancies to unexposed pregnancies on the propensity score in a ratio 1:4. To estimate the hazard ratio (HR) of miscarriage a Cox proportional hazard regression model was used. A log binomial model was used to estimate the relative risk ratio (RR) of major malformations. MAIN OUTCOME MEASURES: HR of miscarriage and the RR of major malformations. RESULTS: A total of 1 650 649 pregnancies were identified. Of these, 10 250 (2050 ciprofloxacin-exposed) and 6100 (1220 ciprofloxacin-exposed) were included in the miscarriage and major malformation analysis, respectively. The HR of miscarriage was 0.99 (95% confidence interval [CI] 0.84-1.17). For major malformation, the RR was 1.01 (95% CI 0.72-1.40). For the organ-specific major malformations and the sensitivity analyses, no significant increased risks were identified. CONCLUSION: We demonstrated no association between miscarriage and maternal ciprofloxacin exposure within the first 22 weeks of pregnancy, or between major malformations and maternal exposure during the first trimester. TWEETABLE ABSTRACT: No association between maternal ciprofloxacin exposure and adverse pregnancy outcomes.

Exposure to duloxetine during pregnancy and risk of congenital malformations and stillbirth: A nationwide cohort study in Denmark and Sweden.

BACKGROUND: The prevalence of depression and the exposure to antidepressants are high among women of reproductive age and during pregnancy. Duloxetine is a selective serotonin-norepinephrine reuptake inhibitor (SNRI) approved in the United States and Europe in 2004 for the treatment of depression. Fetal safety of duloxetine is not well established. The present study evaluates the association of exposure to duloxetine during pregnancy and the risk of major and minor congenital malformations and the risk of stillbirths. METHODS AND FINDINGS: A population-based observational study was conducted based on data from registers in Sweden and Denmark. All registered births and stillbirths in the medical birth registers between 2004 and 2016 were included. Malformation diagnoses were identified up to 1 year after birth. Logistic regression analyses were used. Potential confounding was addressed through multiple regression, propensity score (PS) matching, and sensitivity analyses. Confounder variables included sociodemographic information (income, education, age, year of birth, and country), comorbidity and comedication, previous psychiatric contacts, and birth-related information (smoking during pregnancy and previous spontaneous abortions and stillbirths). Duloxetine-exposed women were compared with 4 comparators: (1) duloxetine-nonexposed women; (2) selective serotonin reuptake inhibitor (SSRI)-exposed women; (3) venlafaxine-exposed women; and (4) women exposed to duloxetine prior to, but not during, pregnancy. Exposure was defined as redemption of a prescription during the first trimester and throughout pregnancy for the analyses of malformations and stillbirths, respectively. Outcomes were major and minor malformations and stillbirths gathered from the national patient registers. The cohorts consisted of more than 2 million births with 1,512 duloxetine-exposed pregnancies. No increased risk for major malformations, minor malformations, or stillbirth was found across comparison groups in adjusted and PS-matched analyses. Duloxetine-exposed versus duloxetine-nonexposed PS-matched analyses showed odds ratio (OR) 0.98 (95% confidence interval [CI] 0.74 to 1.30, p = 0.909) for major malformations, OR 1.09 (95% CI 0.82 to 1.45, p = 0.570) for minor malformation, and 1.18 (95% CI 0.43 to 3.19, p = 0.749) for stillbirths. For the individual malformation subtypes, some findings were statistically significant but were associated with large statistical uncertainty due to the extremely small number of events. The main limitations for the study were that the indication for duloxetine and a direct measurement of depression severity were not available to include as covariates. CONCLUSIONS: Based on this observational register-based nationwide study with data from Sweden and Denmark, no increased risk of major or minor congenital malformations or stillbirth was associated with exposure to duloxetine during pregnancy.

Fetal safety of chloroquine and hydroxychloroquine use during pregnancy: a nationwide cohort study.

OBJECTIVE: The antimalaria 4-aminoquinoline drugs chloroquine and HCQ are used in the treatment of a wide range of CTDs. Data to inform on the safety of their use in pregnancy are limited. METHODS: In a Danish nationwide cohort study from 1996 through 2016, we identified 4-aminoquinoline-exposed pregnancies from a cohort of 1 240 875 pregnancies to investigate the associated risks of major birth defects, preterm birth, and small size for gestational age (SGA). Distinct study cohorts of propensity-score-matched 4-aminoquinoline-exposed and unexposed pregnancies (in a 1:1 ratio) were established for each outcome analysis. The association with the outcomes was assessed by prevalence odds ratios (ORs) estimated through logistic regression. The associated risks for chloroquine and HCQ were individually assessed through additional analyses. RESULTS: A total of 1487 pregnancies exposed to 4-aminoquinolines (1184 chloroquine- and 303 HCQ-exposed) were identified. Among the 983 pregnancies exposed to 4-aminoquinolines in the first trimester, 34 infants (3.5%) were diagnosed with major birth defects as compared with 36 (3.7%) among the matched unexposed pregnancies (prevalence OR, 0.94; 95% CI: 0.59, 1.52). Exposure to 4-aminoquinolines in pregnancy was neither associated with an increased risk of preterm birth (prevalence OR, 0.97; 95% CI: 0.73, 1.28) or SGA (prevalence OR, 1.18; 95% CI: 0.93, 1.50), compared with unexposed pregnancies. No significant associations between exposure to chloroquine or HCQ individually and risk of the outcomes were identified. CONCLUSION: Among pregnancies exposed to 4-aminoquinolines (chloroquine and HCQ), no increased risk of major birth defects, preterm birth, or SGA was identified.

Mortality Among Users of Anabolic Steroids.

This cohort study investigates mortality and cause of death among a large cohort of androgenic anabolic steroid users, compared with a control group, in Denmark from January 3, 2006, to March 1, 2018.

Clarithromycin, trimethoprim, and penicillin and oxidative nucleic acid modifications in humans: randomised, controlled trials.

AIMS: In vitro studies have demonstrated that formation of reactive oxygen species (ROS) contributes to the effect of bactericidal antibiotics. The formation of ROS is not restricted to bacteria, but also occurs in mammalian cells. Oxidative stress is linked to several diseases. This study investigates whether antibiotic drugs induce oxidative stress in healthy humans as a possible mechanism for adverse reactions to the antibiotic drugs. METHODS: This study contains information from two randomised, controlled trials. Participants underwent 1 week treatment with clarithromycin, trimethoprim, phenoxymethylpenicillin (penicillin V), or placebo. Oxidative modifications were measured as 24-h urinary excretion of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) and 8-oxo-7,8-dihydroguanosine (8-oxoGuo), and plasma levels of malondialdehyde before and after treatment as a measurement of DNA oxidation, RNA oxidation, and lipid peroxidation, respectively. RESULTS: Clarithromycin significantly increased urinary excretion of 8-oxodG by 22.0% (95% confidence interval (CI): 3.6-40.4%) and 8-oxoGuo by 14.9% (95% CI: 3.7-26.1%). Further, we demonstrated that trimethoprim significantly lowered urinary excretion of 8-oxodG by 21.7% (95% CI: 5.8-37.6%), but did not influence urinary excretion of 8-oxoGuo. Penicillin V did not influence urinary excretion of 8-oxodG or 8-oxoGuo. None of the antibiotic drugs influenced plasma levels of malondialdehyde. CONCLUSION: Clarithromycin significantly increases oxidative nucleic acid modifications. Increased oxidative modifications might explain some of clarithromycin's known adverse reactions. Trimethoprim significantly lowers DNA oxidation but not RNA oxidation. Penicillin V had no effect on oxidative nucleic acid modifications.

Use of thyroid hormones in relation to pregnancy: a Danish nationwide cohort study.

OBJECTIVE: To determine the rate of exposure of pregnant women to levothyroxine and to assess changes in these rates before, during and after pregnancy. DESIGN: Register-based cohort study. SETTING: Danish nationwide registers. POPULATION: All women having a live birth in Denmark between 1 January 1997 and 31 December 2010 (n = 912 342). METHODS: All pregnant women in the study period were identified from the Danish Medical Birth Register. Exposed women were identified from the Danish National Prescription Register, based on redemption of levothyroxine prescriptions before, during or after pregnancy. MAIN OUTCOME MEASURES: The rate of pregnant women redeeming levothyroxine prescriptions and maternal characteristics. RESULTS: We identified a fourfold increase in levothyroxine prescription redemption during the study period, from 0.34% in 1997 to 1.39% by 2010. A mean of 0.79% of our cohort received levothyroxine. Most of the women who were using levothyroxine before pregnancy continued the therapy during their pregnancy, but 9.4% stopped redeeming their prescriptions. Overall, 0.28% of our cohort received a levothyroxine prescription for the first time within 9 months after pregnancy. CONCLUSIONS: Fewer women than expected received levothyroxine treatment during pregnancy even though a fourfold increase was observed during the study period. Furthermore, one of 10 discontinued treatments during pregnancy. These findings all indicate that too few women are treated for hypothyroidism during pregnancy. Further research is needed to determine whether hypothyroid pregnant women are suboptimally treated and the possible consequences for the mother and fetus.

Extensive androgen exposure and meningioma risk - A matched cohort study.

INTRODUCTION: Meningiomas frequently occur within the field of neuro-oncology, but it is unclear whether exogenous or imbalanced endogenous hormones are involved in the pathophysiology. A previous case-control study found an almost 20-fold increase in the risk of developing meningioma among users of androgenic anabolic steroids. We, therefore, investigated this hypothesis. METHODS: We compared the incidence rate of meningioma in a cohort of males sanctioned for the use of androgenic anabolic steroids with age- and sex-matched controls with an identical enrollment date. RESULTS: We followed 1189 males sanctioned for using androgenic anabolic steroids for a total of 13,305 person-years and found 0 cases of meningioma. The control cohort of 59,450 males was followed for a total of 654,938 person-years, and 16 were diagnosed with meningioma. Thus, the incidence rate ratio was 0 (95% CI: 0-12.8). CONCLUSION: We did not find any evidence supporting the hypothesis of an increased risk of meningioma development with the use of androgenic anabolic steroids. Due to the limited sample size, we cannot exclude androgenic anabolic steroids as a potential risk factor for meningioma development, despite the lack of apparent evidence in this study.

Adverse drug reactions in neonates: a brief analysis of the FDA adverse event reporting system.

Introduction: Drug trials in neonates are scarce, and the neonates may consequently be at risk of adverse drug reactions (ADRs). Spontaneous ADR reporting is an important tool for expanding the knowledge on drug safety in neonates. This study explores the quality of current neonatal ADR reports and the ADR reports of the most common drugs used in neonatal departments. Methods: An observational cross-sectional study focused on neonates was conducted using data on spontaneous reports extracted from the U.S. Food and Drug Administration Adverse Events Reporting System (FAERS) from the third quarter of 2014 up to December 2022. Only the primary suspect drugs given to neonates or subjects aged <30 days were included in the analysis. Results: Spontaneous reports from 13 million patients of all ages, totaling 50 million ADRs, were evaluated. Information regarding the age was missing in 40% of the reports, and data on 43,737 neonates with 948 different suspected drugs were identified and included in the analysis. We report the frequency of spontaneous ADR reports in the FAERS database for the ten most frequently administered drugs in neonatal intensive care units in the USA. Conclusion: Overall, neonatal ADRs are still underreported. The FAERS database in its current form discriminates insufficiently between prenatal and postnatal drug exposures. Hence, improved neonatal pharmacovigilance systems are urgently needed.

Healthcare professionals' experiences with the use of antipsychotics in dementia.

Background: Antipsychotics are commonly administered to nursing home residents with dementia, despite the associated risk of severe adverse events. Objective: This study aimed to explore healthcare professionals' experiences in caring for nursing home residents with dementia, with a focus on rationales behind the use of antipsychotics. Method: Twelve semi-structured interviews with healthcare professionals' from Danish nursing homes were conducted and analyzed using the method Systematic Text Condensation. Results: Nonpharmacological interventions were reported as the primary approach to care and the first-choice treatment for behavioral and psychological symptoms of dementia (BPSD). Use of antipsychotics was considered to serve as a last resort, reserved for residents with severe symptoms. However, most informants preferred a more limited use. The study identified four main barriers to reduce the use of antipsychotics: "Scarcity of resources", "Perceiving antipsychotic use to provide relieve", "Reluctance towards deprescribing" and "Limited access to medical counseling", and three potential enablers: "Updating knowledge and nonpharmacological competencies", "Management support and clear procedures" and "Regularity in interdisciplinary collaboration". Conclusion: The treatment and care were reported as primarily following guidelines in BPSD. Several barriers were perceived to challenge the healthcare professionals' preference of limited use of antipsychotics. To further reduce the use, this study highlights the importance of understanding the adverse effects caused by limited resources, enhancing employee knowledge and competencies and ensuring regular interprofessional collaboration for assessing and reassessing the need to use antipsychotics.

Health care use by patients with somatoform disorders: a register-based follow-up study.

OBJECTIVE: Studies have shown a greater use of medical than mental health services in patients with somatoform disorders. However, not many studies are based on structured interviews and include the entire somatoform spectrum of diagnoses. We conducted a register-based case-control study to investigate medical care use prior to and three years after diagnosis in patients with somatoform disorders. METHODS: We included 380 patients with somatoform diagnoses (SCID-NP for DSM-IIIR) in a case-control study and compared them with 174 patients with anxiety disorders and 5540 controls from the background population. Data from the Danish National Registers were used to assess health care use in both primary and secondary care. RESULTS: Somatoform patients incurred 2.11 (2.09-2.12) times the primary care visits of controls. They had 3.12 (3.08-3.16) times as many somatic bed-days than controls and 3.94 (3.91-3.97) as many psychiatric bed-days. Primary care use remained stable 3 years after diagnosis (p = 0.14) and the award of disability pension (p = 0.82). However, the number of somatic admissions decreased from 5.64 to 2.76 (p = 0.0004) 3 years after diagnosis. Somatization had an independent effect on health care use when controlling for psychiatric comorbidity. CONCLUSIONS: Patients with somatoform disorders make significantly greater use of health care services than do controls and patients with anxiety. Somatoform patients made more use of psychiatric services than expected. The use of somatic health care was independent of psychiatric comorbidity. Primary care use and disability pension award were not influenced by proper diagnosing of somatoform disorders whereas number of somatic admissions were halved.

Interferon-beta exposure in-utero and the risk of infections in early childhood.

BACKGROUND: Knowledge within the field of multiple sclerosis treatment during pregnancy is vital to ensure the most optimal clinical practice. Immunomodulatory treatment in pregnancy could in theory affect the normal development and maturation of the immune system of the fetus with a potential increased risk of infections, consequently. We therefore set out to investigate whether exposure to interferon-beta in utero affected the risk of acquiring infections in early childhood. METHODS: This retrospective matched cohort study utilized data from the Danish Multiple Sclerosis Registry linked with national Danish registries to identify all children born of mothers with MS in Denmark from 1998 to 2018. The study included 510 children exposed to interferon-beta in utero. The children were matched 1:1 on various of demographic characteristics with children born to mothers with untreated MS and 1:3 with children born to mothers without MS. Each child was followed for up to five years. Using individual-level data, we investigated all-cause mortality, rate of hospital admissions due to infections, and redeemed prescriptions of antibiotics. The primary statistical model applied was a negative binomial regression analysis. RESULTS: We found no differences in childhood mortality, for hospital admissions the rate ratio compared to healthy controls was 0.79 (0.62-1.00). Regarding antibiotic prescriptions, the results were similar (RR 1.00 (0.90-1.11). Furthermore, we found no certain dose-response relationship between interferon-beta exposure duration and hospital admission rate (P = 0.47) or redeemed antibiotic prescription (P = 0.71). CONCLUSION: Exposure to interferon-beta during gestation has little to no impact on the risk of acquiring significant infections during the first five years of childhood.

Duloxetine Exposure During Pregnancy and the Risk of Offspring Being Born Small for Gestational Age or Prematurely: A Nationwide Danish and Swedish Safety Study.

BACKGROUND: Depression or depressive symptoms are common among pregnant women. The use of antidepressants during pregnancy has grown steadily. The risk of offspring being born small for gestational age or prematurely when exposed to duloxetine during pregnancy is not established. OBJECTIVE: We aimed to investigate the association between duloxetine exposure during pregnancy and offspring being born small for gestational age or prematurely. METHODS: We conducted an observational study including live births in Sweden and Denmark (2004-2016). Duloxetine exposure during early (0-140 days) or late (141 to delivery) pregnancy compared with duloxetine-non-exposed, selective serotonin reuptake inhibitor-exposed, venlafaxine-exposed, and duloxetine discontinuers. RESULTS: In total, 2,083,467 pregnancies were identified, where 1589 and 450 were duloxetine exposed in early and late pregnancy, respectively. For small for gestational age, no increased risk was seen for duloxetine across comparators. In the early and late exposure windows, propensity score-matched odds ratios for small for gestational age ranged between 0.64 (95% confidence interval 0.44-0.95) and 1.48 (95% confidence interval 0.85-2.57). For preterm birth, the findings differed across comparators and exposure-time windows, but trended towards an increased risk for duloxetine-exposed when compared with duloxetine-non-exposed, selective serotonin reuptake inhibitor-exposed, and duloxetine discontinuers in both early exposure and late exposure. The odds ratios ranged between 1.17 and 2.04, of which some did not reach statistical significance. No clear association was observed when compared with venlafaxine exposed, 0.91 (95% confidence interval 0.73-1.14) for early exposure and 1.26 (95% confidence interval 0.86-1.86) for late exposure. Most preterm births (79.2%) occurred in weeks 33-36 of gestation. CONCLUSIONS: Duloxetine exposure during pregnancy is unlikely to increase the risk of small for gestational age. Although not consequently statistically significant across comparisons, a trend towards an increased risk of preterm birth was observed for duloxetine exposed. Therefore, an increased risk of preterm birth cannot be excluded, especially for women exposed to duloxetine throughout pregnancy.

Protocol for DEprescribing and Care to reduce Antipsychotics in Dementia (DECADE)-A hybrid effectiveness-implementation pilot study.

INTRODUCTION: Behavioural and psychological symptoms of dementia (BPSD) should only rarely and briefly be treated with antipsychotics. Despite recommendations to the contrary, the use of antipsychotics in nursing home residents with dementia is widespread and followed by serious adverse effects. Intervention studies on methods to reduce the use of antipsychotics in persons with dementia are few and needed. The aim of this protocol is to describe the rationale and content of the intervention DEprescribing and Care to reduce Antipsychotics in DEmentia (DECADE)-a hybrid effectiveness-implementation pilot study. MATERIALS AND METHODS: This is a protocol of a prospective hybrid effectiveness-implementation pilot study. The primary aim of DECADE is to reduce the use of antipsychotic drugs by 50% in 50% of nursing home residents with dementia while maintaining or improving BPSD. The intervention is implemented in six nursing homes including approximately 190 residents with dementia and consists of Academic Detailing, medication review, education of nursing home staff, and care plans. The evaluation of feasibility and potential effectiveness is an overall assessment of all clinical and process outcomes. Logistic regression analyses will be used to investigate factors characterizing situations with prescription of antipsychotics. BPSD is analysed with a before- and after design using self-controlled case series methods and the use of antipsychotics is analysed as interrupted time series. DISCUSSION: This protocol describes a study that will provide an indication of DECADE effectiveness and a model for upscaling and further evaluation in a controlled design.

The Blind Spot of Pharmacology: A Scoping Review of Drug Metabolism in Prematurely Born Children.

The limit for possible survival after extremely preterm birth has steadily improved and consequently, more premature neonates with increasingly lower gestational age at birth now require care. This specialized care often include intensive pharmacological treatment, yet there is currently insufficient knowledge of gestational age dependent differences in drug metabolism. This potentially puts the preterm neonates at risk of receiving sub-optimal drug doses with a subsequent increased risk of adverse or insufficient drug effects, and often pediatricians are forced to prescribe medication as off-label or even off-science. In this review, we present some of the particularities of drug disposition and metabolism in preterm neonates. We highlight the challenges in pharmacometrics studies on hepatic drug metabolism in preterm and particularly extremely (less than 28 weeks of gestation) preterm neonates by conducting a scoping review of published literature. We find that >40% of included studies failed to report a clear distinction between term and preterm children in the presentation of results making direct interpretation for preterm neonates difficult. We present summarized findings of pharmacokinetic studies done on the major CYP sub-systems, but formal meta analyses were not possible due the overall heterogeneous approaches to measuring the phase I and II pathways metabolism in preterm neonates, often with use of opportunistic sampling. We find this to be a testament to the practical and ethical challenges in measuring pharmacokinetic activity in preterm neonates. The future calls for optimized designs in pharmacometrics studies, including PK/PD modeling-methods and other sample reducing techniques. Future studies should also preferably be a collaboration between neonatologists and clinical pharmacologists.

Short-term mortality following tramadol poisonings in Denmark.

Tramadol is a commonly used opioid with a potential of addiction and abuse. Using Danish nationwide registers, we aimed to (1) characterise opioid poisonings; (2) assess the 30-day mortality following morphine, oxycodone, and mixed poisonings compared to tramadol poisonings; and (3) assess the development in tramadol poisonings during a 12-year period. Poisonings were identified from 2006 to 2017. A Cox proportional hazards regression model was used to estimate adjusted hazard ratios (aHRs) along with 95% confidence intervals (CIs) for 30-day mortality following morphine, oxycodone or mixed poisonings compared to tramadol poisonings. We identified 7718 opioid poisonings among 6365 patients. The patients with a tramadol poisoning were younger and had less comorbidities than the patients with a morphine, oxycodone or mixed poisoning. Within 30 days, a total of 205 patients died. The 30-day mortality risk was higher following morphine (aHR 3.2, 95% CI 2.0-5.1), oxycodone (aHR 2.1, 95% CI 1.2-3.6) and mixed poisonings (aHR 1.6, 95% CI 1.0-2.7) compared to tramadol poisonings. The annual number of tramadol poisonings increased from 233 in 2006 to 501 in 2013 and declined to 348 in 2017. In conclusion, despite a lower mortality risk compared to other opioid poisonings, physicians should consider the poisoning and abuse risks when prescribing tramadol.