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Objective: The authors investigated the clinical outcomes of commonly used antidepressants among older adults who initiated first-time antidepressants for depression by analyzing the 1-year risk of selected clinically relevant outcomes. Methods: This cohort study used nationwide Danish registry data and included all older adults who redeemed a first-time (since 1995) antidepressant prescription with an indication of depression between 2006 and 2017. Only the 10 most frequently redeemed antidepressants were included in the analyses. Outcomes included discontinuation, switching, augmentation, psychiatric hospital contacts, suicide attempt or self-harm, fall-related injuries, cardiovascular events, and all-cause mortality. Incidence rate ratios (IRRs) and 95% confidence intervals were estimated using Poisson regression models, controlling for potential confounders. Results: The study sample included 93,883 older adults (mean age, 78.0 years, SD=7.5 years; 56% female). The most frequently prescribed antidepressants were selective serotonin reuptake inhibitors (citalopram, 47.04%; escitalopram, 11.81%; fluoxetine, 0.55%; paroxetine, 0.52%; sertraline, 11.17%), serotonin-norepinephrine reuptake inhibitors (duloxetine, 0.71%; venlafaxine, 1.54%), a tricyclic antidepressant (amitriptyline, 1.86%), and two atypical antidepressants (mianserin, 1.93%; mirtazapine, 22.87%). Compared with users of sertraline (the reference drug in this analysis, as Danish guidelines recommend it as the first-choice treatment for depression), users of most of the other nine antidepressants had a significantly higher risk of discontinuation (e.g., mirtazapine: IRR=1.55, 95% CI=1.50–1.61; venlafaxine: IRR=1.22, 95% CI=1.12–1.32), switching (amitriptyline: IRR=1.45, 95% CI=1.15–1.81; venlafaxine: IRR=1.47, 95% CI=1.20–1.80), augmentation, cardiovascular events, and mortality. Overall, mirtazapine and venlafaxine users had the most adverse outcomes compared with sertrali, OBJECTIVE: The authors investigated the clinical outcomes of commonly used antidepressants among older adults who initiated first-time antidepressants for depression by analyzing the 1-year risk of selected clinically relevant outcomes.METHODS: This cohort study used nationwide Danish registry data and included all older adults who redeemed a first-time (since 1995) antidepressant prescription with an indication of depression between 2006 and 2017. Only the 10 most frequently redeemed antidepressants were included in the analyses. Outcomes included discontinuation, switching, augmentation, psychiatric hospital contacts, suicide attempt or self-harm, fall-related injuries, cardiovascular events, and all-cause mortality. Incidence rate ratios (IRRs) and 95% confidence intervals were estimated using Poisson regression models, controlling for potential confounders.RESULTS: The study sample included 93,883 older adults (mean age, 78.0 years, SD=7.5 years; 56% female). The most frequently prescribed antidepressants were selective serotonin reuptake inhibitors (citalopram, 47.04%; escitalopram, 11.81%; fluoxetine, 0.55%; paroxetine, 0.52%; sertraline, 11.17%), serotonin-norepinephrine reuptake inhibitors (duloxetine, 0.71%; venlafaxine, 1.54%), a tricyclic antidepressant (amitriptyline, 1.86%), and two atypical antidepressants (mianserin, 1.93%; mirtazapine, 22.87%). Compared with users of sertraline (the reference drug in this analysis, as Danish guidelines recommend it as the first-choice treatment for depression), users of most of the other nine antidepressants had a significantly higher risk of discontinuation (e.g., mirtazapine: IRR=1.55, 95% CI=1.50-1.61; venlafaxine: IRR=1.22, 95% CI=1.12-1.32), switching (amitriptyline: IRR=1.45, 95% CI=1.15-1.81; venlafaxine: IRR=1.47, 95% CI=1.20-1.80), augmentation, cardiovascular events, and mortality. Overall, mirtazapine and venlafaxine users had the most adverse outcomes compared with sertraline users. These

INTRODUCTION: Proton pump inhibitors (PPIs) may increase dementia risk. However, it is currently unknown whether timing of exposure or age at dementia diagnosis influence the risk. METHODS: We assessed associations between cumulative PPI use and dementia at different ages in a nationwide Danish cohort of 1,983,785 individuals aged 60 to 75 years between 2000 and 2018. RESULTS: During follow-up, there were 99,384 all-cause dementia incidences. Incidence rate ratio (IRR) of dementia with PPI ever-use compared with never-use was 1.36 (95% CI, 1.29 to 1.43) for age 60 to 69 years at diagnosis, 1.12 (1.09 to 1.15) for 70 to 79 years, 1.06 (1.03 to 1.09) for 80 to 89 years, and 1.03 (0.91 to 1.17) for 90+ years. Longer treatment duration yielded increasing IRRs. For cases below 90 years, increased dementia rate was observed regardless of treatment initiation up to >15 years before diagnosis. DISCUSSION: Regardless of timing of treatment initiation, PPI use was associated with increased dementia rate before age 90 years. Dementia rates increased with younger age at diagnosis. Highlights: After following 1,983,785 individuals for a median of 10 years, 99,384 developed dementia PPIs were used by 21.2% of cases and 18.9% of controls PPI use was associated with increased dementia rate regardless of time of treatment onset Magnitude of associations increased with younger age at diagnosis PPI use was not associated with dementia occurring after age 90 years.

We appreciate the interest from Lu et al. suggesting a possible influence on dementia risk owing to the use of aluminum-containing drugs for acid-related disorders among users of proton pump inhibitors (PPIs).1, 2 The association between exposure to aluminum and dementia risk is important to investigate where, as also pointed out by Lu et al., evidence is inconclusive to date.3 However, whether this biases the reported association in our study between PPI users and dementia risk is unlikely. Experimental studies have revealed various neurotoxic effects attributed to aluminum exposure.4 Although the use of aluminum is widespread in food production, drinking water purification, medications, and vaccines, the absorption of aluminum in humans is typically low and renal elimination is efficient.5, 6 While the association between aluminum exposure and dementia risk has been a subject for research and discussion for a century, the question remains unresolved.3, 7 Since aluminum-containing antacids do not require a prescription, individual-level data on the use of these drugs were not available in our nationwide registry-based study.

Objective Concurrent polypharmacy and potentially-inappropriate-medication (PIMs) use with antidepressants in older adults is understudied. We investigated the prevalence and associated user characteristics of concurrent polypharmacy (≥5 drugs) and PIMs with antidepressants in all older adults (≥65 years) in Denmark based on prescriptions filled at community pharmacies during 2015–2019. Method We applied a cross-sectional and cohort study design using socio-demographic and clinical data from Danish registers. Results A total of 261,479 older adults (mean age 76 years, females 63%) redeemed at least one prescription of antidepressants during 2015–2019. The prevalence of polypharmacy was 73%, and PIMs was 56%, with over 80% using at least one other nervous system drug or cardiovascular system drug concomitantly with antidepressants. Characteristics associated with higher concurrent use of polypharmacy and PIM with antidepressants were older age, marital status as widow/widower/separated/single, place of residence predominantly in the rural regions, non-western origin, and having somatic diagnoses. Some characteristics showed opposite directions of the associations with the two outcomes, including previous antidepressant use and psychiatric diagnoses being associated with higher use of polypharmacy but lower use of PIM. Conclusion High polypharmacy and PIM use with antidepressants underline the importance of regularly reviewing pharmacological treatments in older adults with depression., Objective: Concurrent polypharmacy and potentially-inappropriate-medication (PIMs) use with antidepressants in older adults is understudied. We investigated the prevalence and associated user characteristics of concurrent polypharmacy (≥5 drugs) and PIMs with antidepressants in all older adults (≥65 years) in Denmark based on prescriptions filled at community pharmacies during 2015–2019. Method: We applied a cross-sectional and cohort study design using socio-demographic and clinical data from Danish registers. Results: A total of 261,479 older adults (mean age 76 years, females 63%) redeemed at least one prescription of antidepressants during 2015–2019. The prevalence of polypharmacy was 73%, and PIMs was 56%, with over 80% using at least one other nervous system drug or cardiovascular system drug concomitantly with antidepressants. Characteristics associated with higher concurrent use of polypharmacy and PIM with antidepressants were older age, marital status as widow/widower/separated/single, place of residence predominantly in the rural regions, non-western origin, and having somatic diagnoses. Some characteristics showed opposite directions of the associations with the two outcomes, including previous antidepressant use and psychiatric diagnoses being associated with higher use of polypharmacy but lower use of PIM. Conclusion: High polypharmacy and PIM use with antidepressants underline the importance of regularly reviewing pharmacological treatments in older adults with depression.

Background and Objective Antidepressant use in older adults (≥ 65 years) is understudied in large population-based samples, particularly in recent years and regarding user characteristics. We aimed to describe the trends, patterns, and associated user characteristics of all antidepressant prescriptions redeemed by older adults at community pharmacies in Denmark during 2015–2019. Methods This register-based study used a cross-sectional design to characterize antidepressant prescription trends and patterns, and a cohort design to describe user characteristics associated with antidepressant prescription initiation. We used descriptive statistics to characterize trends and patterns, and Poisson regression for analyzing user characteristics. Results During the years 2015–2019, 17.9% of 1.2 million older adults redeemed 4.84 million antidepressant prescriptions, where 48.5% were selective serotonin reuptake inhibitors, followed by noradrenergic and specific serotonergic antidepressants (26.2%), serotonin-norepinephrine reuptake inhibitors (12.7%), tricyclic antidepressants (11.2%), and others (1.4%). Amitriptyline and nortriptyline, considered potentially inappropriate medications, were among the 10 most frequently redeemed antidepressants. Only 60.5% of prescriptions had a treatment indication of depression. Prescription-proportion trends by drug classes and individual antidepressants remained consistent. A higher incidence rate ratio (IRR) and 95% confidence interval (CI) of initiating antidepressants was associated with female sex (IRR 1.20, 95% CI 1.07–1.34), older age (e.g., 81–85 years vs. 65–70 years: IRR 1.74, 95% CI 1.44–2.11), living in rural areas (North Denmark vs. Capital Region: IRR 1.31, 95% CI 1.09–1.58), and having somatic and psychiatric diagnoses (e.g., per one psychiatric diagnosis: IRR 1.10, 95% CI 1.05–1.15), while a lower ratio was associated with being non-Western (vs. Danish: IRR 0.50, 95% CI 0.28–0.89) and having hos, Background and ObjectiveAntidepressant use in older adults (>= 65 years) is understudied in large population-based samples, particularly in recent years and regarding user characteristics. We aimed to describe the trends, patterns, and associated user characteristics of all antidepressant prescriptions redeemed by older adults at community pharmacies in Denmark during 2015-2019.MethodsThis register-based study used a cross-sectional design to characterize antidepressant prescription trends and patterns, and a cohort design to describe user characteristics associated with antidepressant prescription initiation. We used descriptive statistics to characterize trends and patterns, and Poisson regression for analyzing user characteristics.ResultsDuring the years 2015-2019, 17.9% of 1.2 million older adults redeemed 4.84 million antidepressant prescriptions, where 48.5% were selective serotonin reuptake inhibitors, followed by noradrenergic and specific serotonergic antidepressants (26.2%), serotonin-norepinephrine reuptake inhibitors (12.7%), tricyclic antidepressants (11.2%), and others (1.4%). Amitriptyline and nortriptyline, considered potentially inappropriate medications, were among the 10 most frequently redeemed antidepressants. Only 60.5% of prescriptions had a treatment indication of depression. Prescription-proportion trends by drug classes and individual antidepressants remained consistent. A higher incidence rate ratio (IRR) and 95% confidence interval (CI) of initiating antidepressants was associated with female sex (IRR 1.20, 95% CI 1.07-1.34), older age (e.g., 81-85 years vs. 65-70 years: IRR 1.74, 95% CI 1.44-2.11), living in rural areas (North Denmark vs. Capital Region: IRR 1.31, 95% CI 1.09-1.58), and having somatic and psychiatric diagnoses (e.g., per one psychiatric diagnosis: IRR 1.10, 95% CI 1.05-1.15), while a lower ratio was associated with being non-Western (vs. Danish: IRR 0.50, 95% CI 0.28-0.89) and having hospital contacts for psychiatr

und Older adults with dementia are at an increased risk of hospitalizations with respiratory infections and death. This emphasizes the need for increased focus on preventive measures, such as influenza vaccination, in this vulnerable group. The aim of our study was to investigate whether dementia, along with other factors, is associated with likelihood of influenza vaccination among older adults as well as to estimate time trends of vaccine uptake for older adults with dementia. Method We conducted a nationwide cross-sectional study with data from national registries on the entire Danish population aged ≥65 years. We mapped the time trends of vaccination for each vaccination season (September to August) from 2002/2003 to 2018/2019. Using multivariable logistic regression, we estimated the likelihood of vaccination in 2018/2019 for a combined measure of dementia status and living situation (home living vs. nursing home). In the same model, we estimated the effect of other potential predictors of influenza vaccination. Result The study population was 801,710 individuals in 2002/2003, and 1,122,489 in 2018/2019. In the entire elderly population vaccine uptake increased steadily from 6% in 2002/2003 to 51% in 2009/2010 and then plateaued but was 10% higher among people with dementia. Compared to home living without dementia, the likelihood of vaccination in 2018/2019 was lower for home living with dementia (OR: 0·80; 95% CI: 0·78-0·82), while it was higher for nursing home residents both with (1·36; 95% CI:1·31-1·41) and without dementia (1·21; 95% CI: 1·17-1·25). Higher age, more GP contacts, higher number of drugs and CCI score were associated with higher vaccination likelihood, while lower educational level, lower residential urbanization and being unmarried were associated with lower vaccination likelihood. Conclusion Influenza vaccination coverage has remained below 60% among older adults regardless of dementia status, not

Background Opioids have been associated with an increased excess mortality-risk in the general population. Older people with dementia have been prescribed opioids more frequent and the use of strong opioids has increased considerably over the past decade among older people with dementia. Whether opioids are associated with an excess mortality risk in older people with dementia is unknown. Method Matched cohort study using nationwide registries. All Danish residents aged 65 years and older diagnosed with dementia between 01.01.2008-31.12.2018 were included. Exposure was defined as first opioid prescription after dementia diagnosis (1 year washout before diagnosis). Persons exposed to opioids were matched with up to two unexposed persons on age and sex. Cox proportional hazards models were used to compare rates of death within 180 days after the initiation of opioid treatment and adjusted for potential confounders (time since diagnosis, nursing home residency, comorbidity, admission within 30 days, number of medications). Result Forty-two percent (31,619/75,471) of older people with dementia redeemed a prescription for an opioid after their diagnosis of dementia. We matched 31,619 exposed persons to 63,235 unexposed. Among the exposed, 10,642 (33.7%) died within 180 days after initiating their first opioid prescription compared with 3980 (6.4%) of the unexposed, yielding a 4-fold increased excess mortality risk (adjusted Hazard ratio (95% CI): 4.13 (3.98-4.30)). Strong opioids were associated with a 6-fold increased mortality risk (6.34 (6.00-6.69)), whereas the risk was lower for weak opioids (2.52 (2.38-2.67). Among those who had redeemed transdermal fentanyl as their first prescription, 65.3% died within the first 180 days compared with 6.7% in the unexposed with a risk of 8.03 (7.02-9.18). The risk was greatest within the first 14 days, where the mortality (for all opioids) was increased 11-fold (10.95 (9.87-12.15)), but there was sti

Background: Many patients with schizophrenia experience psychiatric symptoms long before being diagnosed. We investigated patterns of pre-diagnostic psychopharmacological treatment in individuals diagnosed with first-episode schizophrenia during the last two decades. Design: Using Danish nationwide healthcare registers, we identified all individuals aged ≥10 years registered with their first ICD-10 schizophrenia diagnosis between January 1999 and March 2019. For each calendar year from 1999 to 2019, we calculated the proportion of patients – among those having received their first schizophrenia diagnosis in the respective calendar year – who redeemed prescriptions for various psychotropics in the two years preceding the schizophrenia diagnosis. We calculated proportions of all pre-diagnostic prescriptions since 1995 for a sub-population diagnosed 2011–2019 and for an age- and sex-matched reference group without schizophrenia. Results: Among 33,361 individuals with schizophrenia (58 % males), the schizophrenia incidence rate was stable during the study period but the mean age at diagnosis decreased by >10 years. In the two pre-diagnostic years, 69 % received psychopharmacological treatment (52 % antipsychotics, 40 % antidepressants). This was stable between 1999 and 2019. Among 14,425 individuals diagnosed 2011–2019, psychotropic drug use was observed among 14–20 % between 24 and 10 years before the diagnosis, being four times higher than the reference group. Particularly antipsychotic and antidepressant drug use increased steadily during the ten pre-diagnostic years. Conclusions: Pre-diagnostic psychotropic drug use in schizophrenia was frequent but stable between 1999 and 2019 despite an earlier identification of schizophrenia patients. Our findings emphasize the continued importance of thorough diagnostic interviews, particularly among patients in need of antipsychotic treatment.

Background We investigated the mortality risk associated with the initiation of antipsychotic treatment among patients with dementia and whether comorbidities related to the cardiovascular system and diabetes interact with antipsychotic treatment to increase the mortality risk beyond the risk of death independently associated with antipsychotics and comorbidity alone. Methods We designed a matched cohort study using nationwide registry data. All Danish residents aged 65-95 years diagnosed with dementia between 2009 and 2014 were included. Dementia was assessed as a first-time registered dementia diagnosis in the Danish National Patient Register or the Danish Psychiatric Central Research Register and/or a first-time prescription for antidementia medication. Patients exposed to antipsychotics were matched with up to three unexposed patients. Cox proportional hazards models were used to compare rates of death within 180 days after the initiation of antipsychotic treatment. The models were adjusted for potential confounders. Analyses were stratified for diabetes, heart disease, and cerebrovascular disease, and we calculated the relative excess risk due to interaction (RERI). Results The study cohort included 8244 exposed patients and 24,730 unexposed patients. A total of 5938 patients died during the first 180 days of follow-up. Patients exposed to antipsychotics had a significantly higher adjusted risk of death (hazard ratio: 1.35, 95% confidence interval: 1.27-1.43) than unexposed patients. Crude mortality rates were higher among patients with heart disease and diabetes when antipsychotic treatment was initiated compared with patients without comorbidities. Relative risk estimates did not differ between patients with and without heart disease, cerebrovascular disease, and diabetes, and RERI suggested no positive additive interaction. Risk analysis suggested higher mortality in patients without cerebrovascular disease who initiated antipsychotics. Conclusion This na