Mortality in patients with incident rheumatoid arthritis and depression: a Danish cohort study of 11 071 patients and 55 355 comparators.

OBJECTIVES: In patients with RA, the association between mortality and depression has been investigated only in patients with prevalent RA. In this study, we estimated the mortality risk associated with depression, defined as the first filling of a prescription for antidepressants, in patients with incident RA and background population comparators. METHODS: From 2008 to 2018, we identified patients with incident RA in the nationwide Danish rheumatologic database, DANBIO. For each patient, we randomly selected five comparators. Participants were not treated with antidepressants or diagnosed with depression 3 years prior to the index date. From other registers we collected data on socioeconomic status, mortality and cause of death using unique personal identifiers. Using Cox models, we calculated hazard rate ratios (HRR) with 95% CI. RESULTS: In depressed patients with RA vs patients without depression, adjusted HRR for all-cause mortality was 5.34 (95% CI 3.02, 9.45) during 0-2 years and 3.15 (95% CI 2.62, 3.79) during the total follow-up period, and highest in patients <55 years with HRR 8.13 (95% CI 3.89, 17.02). In comparators with depression vs comparators without depression, the association with mortality was similar to that in patients with RA. There were no unnatural causes of death among depressed patients with RA. The most frequent natural causes of death were cancer, cardiovascular disease, stroke and pneumonia. CONCLUSION: In patients with RA, depression was a predictor of death but with a strength similar to that in matched comparators.

A target trial emulation comparing the antidepressant effectiveness of selective serotonin reuptake inhibitors (SSRIs) highlighting the importance of patent-related confounding by indication.

BACKGROUND: The comparative effectiveness of selective serotonin reuptake inhibitors (SSRIs) has been subjected to relatively little research. However, a recent study based on target trial emulation suggested that sertraline may be more effective than escitalopram. AIMS: To investigate whether sertraline, citalopram, and escitalopram differ in their effectiveness-assessed via the risk of psychiatric hospital admission and suicide following treatment initiation. The choice to focus on sertraline, citalopram, and escitalopram was made to limit confounding by indication, as the Danish depression treatment guideline from 2007 specifically listed these three SSRIs as first choice. METHOD: We conducted a target trial emulation based on data from Danish registers. We identified all individuals that initiated treatment for depression with sertraline, citalopram, or escitalopram in the period from January 1, 2007, to March 1, 2019. These individuals were followed until psychiatric hospital admission or suicide (separate analyses), death, 1 year after treatment initiation or end of data. Cox proportional hazards regression adjusted for relevant baseline covariates was performed to emulate randomized treatment allocation, comparing the rate of psychiatric hospital admission and suicide for individuals treated with sertraline (used as reference), citalopram or escitalopram, respectively. For escitalopram, we conducted a sensitivity analysis excluding data from the period during which the drug was sold under patent, as the price of the drug during that time likely entailed a different prescription pattern, increasing the risk of ("patent-related") confounding by indication. RESULTS: We identified 56,865, 118,145, and 31,083 individuals initiating treatment with sertraline, citalopram, and escitalopram, respectively. Using sertraline as reference, the adjusted hazard rate ratio (aHRR) for psychiatric admission was 0.98 (95% CI = 0.91-1.05) for citalopram and 1.21 (95% CI = 1.10-1.32) for escitalopram. Notably, in the sensitivity analysis only including patients initiating treatment after the escitalopram patent had expired, the increased risk of psychiatric hospital admission associated with escitalopram treatment was no longer present (aHRR = 0.98, 95% CI = 0.82-1.18). The results of the analyses of suicide were inconclusive, due to few outcome events. CONCLUSIONS: Sertraline, citalopram, and escitalopram do not seem to have differential effectiveness in the treatment of depression. Taking potential patent-related, time varying, confounding by indication (via severity) into account is critical for pharmacoepidemiological studies, including those employing target trial emulation.

Impact of the COVID-19 pandemic on antidepressant consumption in the Central region of Portugal: interrupted time series.

PURPOSE: To evaluate the impact of the pandemic on the consumption of antidepressive agents in Central Portugal. METHODS: To estimate the causal effect of the pandemic an interrupted time series analysis was conducted. Data of antidepressant drugs monthly dispensed in community pharmacies between Jan-2010 and Dec-2021 were provided by the regional Health Administration. Anti-Parkinson dopaminergic agents and statins, theoretically not influenced by COVID-19 pandemics, were used as comparator series. The number of packages was converted into defined daily doses and presented as defined daily doses/1000 inhabitants/day. A Bayesian structural time-series model with CausalImpact on R/RStudio was used to predict the counterfactual. Analyses with different geographical granularity (9 sub-regions and 78 municipalities) were performed. RESULTS: When compared to counterfactual, regional consumption non-significantly increased after the pandemic declaration, with a relative effect of + 1.30% [95%CI -1.6%:4.2%]. When increasing the granularity, differences appeared between sub-region with significant increases in Baixo Mondego + 6.5% [1.4%:11.0%], Guarda + 4.4% [1.1%:7.7%] or Cova da Beira + 4.1% [0.17%:8.3%], but non-significant variation in the remaining 6 sub-regions. Differences are more obvious at municipality level, ranging from increases of + 37.00% [32.00%:42.00%] to decreases of -11.00% [-17.00%:-4.20%]. Relative impact positively correlated with percentage of elderly in the municipality (r = 0.301; p = 0.007), and negatively with population density (r=-0.243; p = 0.032). No other predicting variables were found. CONCLUSION: Antidepressant consumption suffered very slight variations at regional level after the COVID-19 pandemic declaration. Analysis with higher granularity allowed identifying municipalities with higher impact (increase or decrease). The absence of clear association patterns suggests other causal hypotheses of the differences.

A retrospective analysis of iv ketamine outcome on hospitalisations in an unselected psychiatric sample.

OBJECTIVE: This study aims to explore the outcome with iv ketamine treatment in a real-world clinical setting, primarily measured as posttreatment days hospitalised. METHODS: The psychiatric medical records of 46 patients having received iv ketamine on a psychiatric treatment indication between 2015 and 2018 were retrospectively examined. Analysis comparing the number and duration of hospital admissions before and after ketamine treatment as well as logistic regression analysis to investigate clinical predictors of effectiveness, were performed. To assess patients' severity of depressed symptoms records were screened for MADRS-S scores. RESULTS: No significant difference between pre- and posttreatment hospital days (p = 0.170), or number of hospitalisations (p = 0.740) were found. The response rate was 31% and remission rate 21%. None of the predictors showed statistical significance in the logistic model. CONCLUSION: Iv ketamine treatment showed effectiveness in reducing depressive symptoms even with complex patients in a real-world clinical setting. However, this did not translate to a reduction in hospitalisation. Highlighting the multifaceted challenges posed when implementing iv ketamine treatment in clinical practice.

[Safe discontinuation of psychotropic drugs in older people? : New evidence and practical approach]. / Sicheres Absetzen von Psychopharmaka bei älteren Menschen? : Neue Evidenz und praktisches Vorgehen.

BACKGROUND: Many older patients are permanently prescribed one or more psychotropic drugs for treatment of symptoms, such as behavioral and psychological symptoms in dementia, depressive symptoms, anxiety, and insomnia. They therefore contribute to the risk of polypharmacy. Recently, deprescribing studies have been published in order to clarify if inadequate medications can be safely discontinued. This mini-review summarizes the study results and derives practical recommendations for routine use. METHOD: A literature search was carried out in PubMed for clinical studies on deprescribing in association with psychotropic substances. RESULTS: After removal of duplications, 12 heterogeneous clinical studies were identified and reduction of psychotropic substances could be successfully achieved in 8 studies. In four of these studies psychological, behavioral and functional endpoints were reported. Criteria for successful deprescribing of sedatives were in particular motivation, information and sufficient cooperation of the patients and for antipsychotic drugs in people with dementia, the sustainable establishment of nonpharmaceutical treatment strategies. Deprescribing was not attempted in cases of a history of severe chronic mental illness and in cases of severe behavioral symptoms in dementia. Evidence for antidepressants was not sufficient to extract practical recommendations. CONCLUSION: Safe deprescribing of antipsychotic drugs in patients with dementia is justified if non-pharmacological treatment options are sustainably implemented, and for sedative drugs in well-informed, highly motivated and cooperative patients.

Risk of repeated suicide attempt after redeeming prescriptions for antidepressants: a register-based study in Denmark.

BACKGROUND: It remains unclear how SSRIs and other antidepressants are associated with the risk of repeated suicide attempts. We aimed to analyse the association between redeemed antidepressant prescriptions and the risk of repeated suicide attempts, hypothesising that antidepressant treatment is associated with increased risk of repeated suicide attempts. METHODS: The study was based on Danish register data and a validated cohort of 1842 suicide attempts. We used three Cox regression models (crude, adjusted and propensity score matched) to analyse the data; these models included both static and dynamic time-dependent factors. RESULTS: 1842 individuals attempted suicide in the study period, with a total of 210 repeated attempts. Individuals redeeming antidepressant prescriptions were more likely to repeat a suicide attempt. All crude models showed all antidepressants to be significant risk factors (HR around 1.39), whereas all adjusted models showed all antidepressants to be insignificant risk factors. CONCLUSION: We found no significant increased risk of repeated suicide attempts in individuals redeeming a prescription for any antidepressant (or only SSRIs) when considering the individuals' baseline risk of repetition. This study is based on validated suicide attempts, register data, and strong epidemiology designs, but it still has some limitations, and the results should be replicated and confirmed in other studies.

Safety outcomes of selective serotonin reuptake inhibitors in adolescent attention-deficit/hyperactivity disorder with comorbid depression: the ASSURE study.

BACKGROUND: Attention deficit-hyperactivity disorder (ADHD) is related to depressive disorder, and adolescents with both present poor outcomes. However, evidence for the safety of concomitantly using a methylphenidate (MPH) and a selective serotonin reuptake inhibitor (SSRI) among adolescent ADHD patients is limited, a literature gap aimed to address through this investigation. METHODS: We conducted a new-user cohort study using a nationwide claims database in South Korea. We identified a study population as adolescents who were diagnosed both ADHD and depressive disorder. MPH-only users were compared with patients who prescribed both a SSRI and a MPH. Fluoxetine and escitalopram users were also compared to find a preferable treatment option. Thirteen outcomes including neuropsychiatric, gastrointestinal, and other events were assessed, taking respiratory tract infection as a negative control outcome. We matched the study groups using a propensity score and used the Cox proportional hazard model to calculate the hazard ratio. Subgroup and sensitivity analyses were conducted in various epidemiologic settings. RESULTS: The risks of all the outcomes between the MPH-only and SSRI groups were not significantly different. Regarding SSRI ingredients, the risk of tic disorder was significantly lower in the fluoxetine group than the escitalopram group [HR 0.43 (0.25-0.71)]. However, there was no significant difference in other outcomes between the fluoxetine and escitalopram groups. CONCLUSION: The concomitant use of MPHs and SSRIs showed generally safe profiles in adolescent ADHD patients with depression. Most of the differences between fluoxetine and escitalopram, except those concerning tic disorder, were not significant.

"Addressing the core trait of bipolar disorder": A concept analysis of mood-stabilizing drugs.

OBJECTIVE: The term "mood stabilizer" is controversial in the literature and criticized for being imprecise and overly inclusive, having its retirement suggested to avoid misuse. Nevertheless, it continues to be employed as it may still carry important meaning. METHODS: We employed document analysis for reviewing relevant definitions of mood stabilizer employed in the literature. Then, we clarify the meanings associated with the term by employing evolutionary concept analysis. Based on its results, we present a theoretical model for a mood stabilizer and further match it with evidence gathered from published meta-analyses and other sources for drugs used in the treatment of bipolar disorder. RESULTS: Concept analysis unearthed four attributes of a mood stabilizer that were nested into the following ascending hierarchy: "not worsening," "acute effects," "prophylactic effects," and "advanced effects." "Prophylactic effects" were often considered the core aspect of a legitimate mood stabilizer. CONCLUSION: The proposed model uses a hierarchy of attributes that take into account the complexity of the term and help to determine whether a drug is a mood stabilizer. Prophylaxis is pivotal to the concept, whose utility lies in implying a drug able to truly treat bipolar disorder, as opposed to merely targeting symptoms. Consistent use of the term could encourage investigation of drugs that modify long-term outcomes and illness trajectory, instead of simply approaching symptom clusters.

Shared and unique imaging-derived endo-phenotypes of two typical antidepressant-applicative depressive patients.

OBJECTIVES: Determining the clinical homogeneous and heterogeneous sets among depressive patients is the key to facilitate individual-level treatment decision. METHODS: The diffusion tensor imaging (DTI) data of 62 patients with major depressive disorder (MDD) and 39 healthy controls were used to construct a Latent Dirichlet Allocation (LDA) Bayesian model. Another 48 MDD patients were used to verify the robustness. The LDA model was employed to identify both shared and unique imaging-derived factors of two typically antidepressant-targeted depressive patients, selective serotonin reuptake inhibitors (SSRIs) and serotonin norepinephrine reuptake inhibitors (SNRIs). Furthermore, we applied canonical correlation analysis (CCA) between each factor loading and Hamilton depression rating scale (HAMD) sub-score, to explore the potential neurophysiological significance of each factor. RESULTS: The results revealed the imaging-derived connectional fingerprint of all patients could be situated along three latent factor dimensions; such results were also verified by the out-of-sample dataset. Factor 1, uniquely expressed by SNRI-targeted patients, was associated with retardation (r = 0.4, p = 0.037) and characterized by coupling patterns between default mode network and cognitive control network. Factor 3, uniquely expressed by SSRI-targeted patients, was associated with cognitive impairment (r = 0.36, p = 0.047) and characterized by coupling patterns within cognitive control and attention network, and the connectivity between threat and reward network. Shared factor 2, characterized by coupling patterns within default mode network, was associated with anxiety (r = 0.54, p = 0.005) and sleep disturbance (r = 0.37, p = 0.032). CONCLUSIONS: Our findings suggested that quantification of both homogeneity and heterogeneity within MDD may have the potential to inform rational design of pharmacological therapies. KEY POINTS: • The shared and unique manifestations guiding pharmacotherapy of depressive patients are caused by the homogeneity and heterogeneity of underlying structural connections of the brain. • Both shared and unique factor loadings were found in different antidepressant-targeted patients. • Significant correlations between factor loading and HAMD sub-scores were found.

Psychotropic consumption before and during COVID-19 in Asturias, Spain.

BACKGROUND: Spain as multiple other countries has been experiencing an increasing and sustained trend in the use of psychotropic medications since the mid 90s. Recent studies show public health measures implemented to control SARS-Cov2, such as mobility restrictions and the shutdown of nonessential activities increased mental suffering, even contributing to a higher number of anxiety, depression and insomnia disorders that could lead to an increase in the consumption of psychotropics. The aims were: 1) Evaluate the temporal trend in psychotropic consumption by pharmacological subgroup, sex, and age group 2) Estimate the effect of the COVID-19 pandemic in the use of psychotropic drugs. METHODS: We conducted a retrospective observational study, retrieving all prescriptions of anxiolytics, hypnotics and sedatives, and antidepressants dispensed in pharmacies of Asturias (Northern Spain) for Primary Care patients for the period 2018-2021. We presented the data expressed in Daily Defined Doses (DDDs) for 1000 persons/day (DHD). To estimate changes in DHDs by year and age group we conducted two multiple linear regressions (one for males and one for females) for every pharmacological subgroup studied. Changes were considered statistically significant when the regression coefficient was p < 0.05. We used the Software R 4.1.0. RESULTS: For the studied period, the highest DHDs are for antidepressants, although all of the subgroups experienced an increase in consumption rates. Women consumed more psychotropic drugs than men. In 2021, 372 out of every 1000 women were taking daily 1 DDD of these drugs versus 184 out of every 1000 men. Consumption rates for all psychotropic drugs progressively increases with age. Conversely, the biggest increases in consumption were among the youngest age groups (0-14 and 15-29 years) for women, while for men there is more variability. The regression models suggest an upward trend in psychotropic consumption during all the period, especially remarkable from 2020, for both genders and all age groups. CONCLUSIONS: - The consumption of psychotropic drugs has gradually increased over the last 4 years, with a significant boost starting in 2020 for both sexes, matching the start of the SARS-COV2 pandemic and the implementation of strict Public Health measures to contain it. - The increase observed on children and adolescents is a matter of concern.

Long-term stability in obsessive thoughts and compulsive behavior in the general population: a longitudinal study in Sweden.

OBJECTIVE: Obsessive thoughts and compulsive behavior and their related disorder Obsessive-Compulsive Disorder (OCD) commonly occur in the general population. Clinical populations indicate a high level of stability, although there are few longitudinal studies in the general population. The recommended drug treatments are SSRIs/TCAs. However, there are few long-term follow up studies. The goal of this study was to 1) examine the occurrence and stability of obsessions, compulsions, and OCD in a longitudinal population-based survey, 2) investigate the use of SSRI and TCA and the potential effect on symptoms. METHODS: A ten-year longitudinal general population in Stockholm was used (2000 and 2010, n = 5650) Obsessional washing, checking, intrusive unpleasant thoughts and the level of suffering due to these symptoms were measured by self-report. Information on use of SSRIs and TCAs by these individuals was obtained from registers. Stability was examined using contingency tables and multinomial logistic regression. RESULTS: At baseline, 2.1, 11.7 and 11.9% reported obsessional washing, checking and intrusive thoughts. A total of 5% reported considerable suffering from these (i.e. OCD). Based on psychiatric interview only 0.4% had OCD. Ten years later a quarter of OCD cases were still classified as having OCD, one quarter reported any obsessive or compulsive symptom and half were classified as symptom-free. Treatment receipt was low and controlling for medication did not change the stability. CONCLUSION: Obsessive thoughts and compulsive behavior are common and stable. While this group is potentially undertreated, there is no indication that those treated display a different pattern of recovery.

[Safe discontinuation of psychotropic drugs in older people? : New evidence and practical approach]. / Sicheres Absetzen von Psychopharmaka bei älteren Menschen? : Neue Evidenz und praktisches Vorgehen.

BACKGROUND: Many older patients are permanently prescribed one or more psychotropic drugs for treatment of symptoms, such as behavioral and psychological symptoms in dementia, depressive symptoms, anxiety, and insomnia. They therefore contribute to the risk of polypharmacy. Recently, deprescribing studies have been published in order to clarify if inadequate medications can be safely discontinued. This mini-review summarizes the study results and derives practical recommendations for routine use. METHOD: A literature search was carried out in PubMed for clinical studies on deprescribing in association with psychotropic substances. RESULTS: After removal of duplications, 12 heterogeneous clinical studies were identified and reduction of psychotropic substances could be successfully achieved in 8 studies. In four of these studies psychological, behavioral and functional endpoints were reported. Criteria for successful deprescribing of sedatives were in particular motivation, information and sufficient cooperation of the patients and for antipsychotic drugs in people with dementia, the sustainable establishment of nonpharmaceutical treatment strategies. Deprescribing was not attempted in cases of a history of severe chronic mental illness and in cases of severe behavioral symptoms in dementia. Evidence for antidepressants was not sufficient to extract practical recommendations. CONCLUSION: Safe deprescribing of antipsychotic drugs in patients with dementia is justified if non-pharmacological treatment options are sustainably implemented, and for sedative drugs in well-informed, highly motivated and cooperative patients.

Prevalence of the use of antidepressants in patients with venous thromboembolism / Prevalencia del uso de antidepresivos en pacientes con enfermedad tromboembólica venosa.

OBJECTIVE: To estimate the prevalence of Antidepressant use in patients with a history of venous thromboembolism (VTE). Describe the patient's characteristics and which drugs are the most prescribed. METHODS: A cross-sectional study involving a consecutive sample of patients included in the Registro de Enfermedad Tromboembólica (RIET) from the Hospital Italiano de Buenos Aires in a period between 01/01/2014 to 01/09/2018. All patients presented symptomatic VTE and confirmed diagnosis. Drugs considered included in this study were: Selective Serotonin Reuptake Inhibitors (SSRI), Dopamine and Norepinephrine Reuptake Inhibitors (NDRI), Serotonin and Norepinephrine Reuptake Inhibitors (SNRI) and Tricyclic antidepressants (TCA). RESULTS: From a total of 2373 patients with VTE, 472 were active users of antidepressants, showing a prevalence of antidepressant use of 19.9% (CI 95%). The most frequently prescribed drugs by drug classification were: SSRI 83.9%, TCA 20.5%, ISRN 14.6%, and NDRI 2.5%. Patients presented a median age of 76 years, predominantly women (71.4%), with several comorbidities: 52.24% arterial hypertension, 37.29% overweight, and 34.75% history of smoking. Concerning relevant history, we observed: 29.03% active oncologic disease, 26.27% major surgery before the VTE, and 21.61% previous VTE. CONCLUSION: The prevalence of antidepressant use in patients with VTE is 19.9%, superior by far to that of the general population. Depression is a major cause of morbidity worldwide, and its prevalence is increasing over the years.

OBJETIVOS: Estimar la prevalencia de consumo de fármacos antidepresivos en pacientes que hayan sufrido un evento tromboembólico venoso (TEV), describir esta población y las drogas más utilizadas. MATERIAL Y MÉTODOS: Corte transversal que incluyó una muestra consecutiva de adultos incluidos en el Registro de Enfermedad Tromboembólica (RIET) del Hospital Italiano de Buenos Aires entre el 01/01/2014 y el 1/09/2018. Se consideraron los siguientes fármacos: Inhibidores Selectivos de la Recaptación de Serotonina (IRSS), Inhibidores de la Recaptación de Dopamina y Noradrenalina (IRDN), Inhibidores de la Recaptación de Serotonina y Noradrenalina (IRSN), y Antidepresivos Tricíclicos (ATC). RESULTADOS: De un total de 2373 pacientes, 472 se identificaron como usuarios activos de antidepresivos, arrojando una prevalencia de 19,9% (IC95% de 18,3-21,6). Según familia farmacológica, en orden de mayor a menor frecuencia, se indicaron: IRSS 83,9%, ATC 20,5%, IRS 14,6% e IRDN y IRDN 2,5%. Los pacientes bajo tratamiento con antidepresivos presentaron una mediana de edad de 76 años, mayoritariamente mujeres (71,4%), con alta carga de comorbilidad: 52,24% hipertensión arterial, 37,29% sobrepeso, 34,75% ex tabaquismo. Los antecedentes de mayor frecuencia resultaron enfermedad oncológica activa (29,03%), cirugía mayor en último mes (26,27%), y el 21,61% presentaba ETV previa. CONCLUSIONES: La prevalencia de uso de antidepresivos en pacientes con ETV resultó 19,9%, superior a la población general. La depresión es una causa principal de enfermedad y discapacidad en todo el mundo, cuya prevalencia aumentó durante los últimos años.

Neonatal Hypotonia Following in Utero Exposure to Antidepressant Drugs.

Associations between fetal exposure to antidepressants and neonatal hypotonia were studied using VigiBase and the French PharmacoVigilance Database. We identified significant associations between neonatal hypotonia and clomipramine, venlafaxine, and imipramine. Reports from the French database implicated prolonged fetal exposure. Neonatal hypotonia may be associated with in utero exposure to antidepressants.

Antidepressant use and stroke or mortality risk in the elderly.

BACKGROUND AND PURPOSE: Current evidence on antidepressant-related stroke or mortality risk is inconsistent. Because the elderly have the highest exposure to antidepressants, the aim was to quantify their association with stroke and mortality risks in this vulnerable population. METHODS: Persons over 65 years old and registered in the Information System for Research in Primary Care of Catalonia during 2010-2015 comprised the study population. Antidepressant exposure was categorized into current-users, recent-users, past-users and antidepressant non-users (controls). The effect of antidepressant exposure on stroke or death, whichever came first, was analyzed by Cox regression adjusted for established risk factors. RESULTS: Of the 1,068,117 participants included, 20% had antidepressant reimbursements during follow-up, 17% had a stroke and 3% died. The risk of experiencing stroke or death was higher in antidepressant current-users (hazard ratio [HR] 1.04; 95% confidence interval [CI] 1.02-1.06), recent-users (HR 3.34; 95% CI 3.27-3.41) and past-users (HR 2.06; 95% CI 2.02-2.10) compared to antidepressant non-users. Antidepressant current-use was associated with increased stroke (HR 1.56; 95% CI 1.50-1.61) but decreased mortality risk (HR 0.93; 95% CI 0.91-0.94). During antidepressant recent-use and past-use, both stroke and mortality risks were significantly increased compared to no antidepressant use. CONCLUSIONS: Antidepressant use may be associated with increased stroke risk in the elderly. When using antidepressants in this population, the potential risks should be considered.

Anti-cholinergic drug burden in patients with dementia increases after hospital admission: a multicentre cross-sectional study.

BACKGROUND: Anticholinergic medications are drugs that block cholinergic transmission, either as their primary therapeutic action or as a secondary effect. Patients with dementia may be particularly sensitive to the central effects of anticholinergic drugs. Anticholinergics also antagonise the effects of the main dementia treatment, cholinesterase inhibitors. Our study aimed to investigate anticholinergic prescribing for dementia patients in UK acute hospitals before and after admission. METHODS: We included 352 patients with dementia from 17 UK hospital sites in 2019. They were all inpatients on surgical, medical or Care of the Elderly wards. Information about each patient's medications were collected using a standardised form, and the anticholinergic drug burden of each patient was calculated with an evidence-based online calculator. Wilcoxon's rank test was used to look at the correlation between two subgroups upon admission and discharge. RESULTS: On admission to hospital, 37.8% of patients had an anticholinergic burden score ≥ 1 and 5.68% ≥3. On discharge, 43.2% of patients with an anticholinergic burden score ≥ 1 and 9.1% ≥3. The increase in scores was statistically significant (p = 0.001). Psychotropics were the most common group of anticholinergic medications prescribed at discharge. Of those patients taking cholinesterase inhibitors, 44.9% were also prescribed anticholinergic medications. CONCLUSIONS: Our cross-sectional, multicentre study found that people with dementia are commonly prescribed anticholinergic medications, even if concurrently taking cholinesterase inhibitors, and are significantly more likely to be discharged from hospital with a higher anticholinergic burden than on admission.

Comparison of depression care provided in general practice in Norway and the Netherlands: registry-based cohort study (The Norwegian GP-DEP study).

BACKGROUND: Depression is highly prevalent in general practice, and organisation of primary health care probably affects the provision of depression care. General practitioners (GPs) in Norway and the Netherlands fulfil comparable roles. However, primary care teams with a mental health nurse (MHN) supplementing the GP have been established in the Netherlands, but not yet in Norway. In order to explore how the organisation of primary mental care affects care delivery, we aimed to examine the provision of GP depression care across the two countries. METHODS: Registry-based cohort study comprising new depression episodes in patients aged ≥ 18 years, 2011-2015. The Norwegian sample was drawn from the entire population (national health registries); 297,409 episodes. A representative Dutch sample (Nivel Primary Care Database) was included; 27,362 episodes. Outcomes were follow-up consultation(s) with GP, with GP and/or MHN, and antidepressant prescriptions during 12 months from the start of the depression episode. Differences between countries were estimated using negative binomial and Cox regression models, adjusted for patient gender, age and comorbidity. RESULTS: Patients in the Netherlands compared to Norway were less likely to receive GP follow-up consultations, IRR (incidence rate ratio) = 0.73 (95% confidence interval (CI) 0.71-0.74). Differences were greatest among patients aged 18-39 years (adj IRR = 0.64, 0.63-0.66) and 40-59 years (adj IRR = 0.71, 0.69-0.73). When comparing follow-up consultations in GP practices, including MHN consultations in the Netherlands, no cross-national differences were found (IRR = 1.00, 0.98-1.01). But in age-stratified analyses, Dutch patients 60 years and older were more likely to be followed up than their Norwegian counterparts (adj IRR = 1.21, 1.16-1.26). Patients in the Netherlands compared to Norway were more likely to receive antidepressant drugs, adj HR (hazard ratio) = 1.32 (1.30-1.34). CONCLUSIONS: The observed differences indicate that the organisation of primary mental health care affects the provision of follow-up consultations in Norway and the Netherlands. Clinical studies are needed to explore the impact of team-based care and GP-based care on the quality of depression care and patient outcomes.

What is the effectiveness and safety of mirtazapine versus escitalopram in alleviating cancer-associated poly-symptomatology (the MIR-P study)? A mixed-method randomized controlled trial protocol.

BACKGROUND: Advanced cancer patients often experience multiple symptoms at a same time. This might lead to polypharmacy and increase adverse events representing major threats to the quality of health care, especially in palliative care situations. Mirtazapine, an antidepressant agent, has been suggested as a potential relevant drug to alleviate multiple cancer-related symptoms at a same time. Therefore, the present study aims to assess the effectiveness of mirtazapine in alleviating multiple symptoms at a same time in advanced cancer patients suffering from a major depressive episode compared to a group receiving escitalopram, another antidepressant agent. METHODS: Multicentre, prospective, randomized, controlled trial in 12 palliative care services in France. The study will be based on a mixed-method methodology using parallel groups, of oral mirtazapine compared with oral escitalopram, with a 56 day follow-up. The primary outcome will be an improvement of the Global health Status (issued from the EORTC-QLQ-C30) on day 56. 418 participants will be clinically followed-up on day 7 and 56 and will have a telephonic assessment on days 14 and 28. A sub-sample of participants will be invited to take part in semi-structured qualitative interviews at baseline and day 56. For the qualitative part, purposeful sampling will be used. DISCUSSION: This study will provide evidence for the pharmaceutics management of poly-symptomatology in advanced cancer patients. This could lead to important changes in the management of those patients by using a single molecule to alleviate multiple symptoms at a same time, potentially improving medication adherence, symptoms' control, and reducing the risk of medications adverse events. TRIAL REGISTRATION: Trial registration: NCT04763135 . Registered 18 March 2021.

A systematic review and meta-analysis of maintenance treatment for psychotic depression.

PURPOSE: To perform a systematic review on the use of maintenance treatment to prevent relapse and recurrence in patients with psychotic unipolar or bipolar depression. METHODS: We conducted an electronic search in December 2019 (and an updated search in July 2021) of four databases (PubMed, Embase, PsycINFO, and Cochrane) to identify controlled studies comparing the relapse rates of patients receiving maintenance treatment for psychotic unipolar depression and psychotic bipolar depression. A meta-analysis was made that included three studies comparing antidepressant (AD) and antipsychotic (AP) combination therapy with AD monotherapy. We used the GRADE tool to assess the quality of evidence. RESULTS: We included five randomized controlled trials fulfilling the inclusion criteria, making three comparisons: (a) AD + AP versus AD monotherapy; (b) AD + AP versus AP monotherapy; (c) AD + electroconvulsive therapy versus AD monotherapy. The included studies only examined patients with psychotic unipolar depression. The largest included study reported a statistically significant advantage of AD + AP compared with AD monotherapy. We made a meta-analysis of the three studies comparing AD + AP combination therapy with AD monotherapy, which included 195 patients and 56 events. The meta-analysis did not show a statistically significant difference between these treatments. CONCLUSIONS: Contrary to the finding of the largest study, we did not find a statistically significant difference between AD + AP combination therapy and AD monotherapy in the meta-analysis. There is insufficient evidence to support the superiority of any treatment modality as maintenance treatment for psychotic depression. Further studies are required.

Association between sleep bruxism, use of antidepressants, and obstructive sleep apnea syndrome: A cross-sectional study.

BACKGROUND: Sleep bruxism (SB) is a condition regulated centrally, with a multifactorial etiology, which can occur secondary to systemic disorders and the use of certain medications. OBJECTIVE: The aim of this study was to identify associations between SB, obstructive sleep apnea, and hypopnea syndrome (OSAHS) and the use of antidepressants. MATERIAL AND METHODS: In this cross-sectional study, 240 individuals underwent full-night polysomnography for medical reasons. Anamnesis was performed to collect data about the use of antidepressants and general health conditions. Polysomnography was performed to analyse sleep data and assess respiratory-related events and apnea and hypopnea index (AHI). The polysomnographic assessment of SB was performed, from electrodes placed on masseter muscles and chin. SB was defined by the presence of more than two events of rhythmic masticatory muscles activity per hour of sleep. Statistical analyses were performed to compare the presence of SB and AHI, the severity of OSAHS, and the use of antidepressants. RESULTS: There were statistically significant differences between bruxers and non-bruxers when comparing AHI (48.28 ± 25.84; p = .001) and severity of OSAHS (p = .015). Regarding the use of antidepressants, comparative analyses did not show correlations with bruxism (p = .072). However, logistic regression suggests that the use of these medications may represent increased odds for SB development (OR =2.387; p = .005). CONCLUSION: The relationship between the use of antidepressants and SB remains inconclusive. SB is associated with OSAHS, mainly in its severe form. Therefore, identifying SB can raise the suspicion of the occurrence of other systemic disturbances.