Association between antidepressant use and ED or hospital visits in outpatients with SARS-CoV-2

Antidepressants have previously been associated with better outcomes in patients hospitalized with COVID-19, but their effect on clinical deterioration among ambulatory patients has not been fully explored. The objective of this study was to assess whether antidepressant exposure was associated with reduced emergency department (ED) or hospital visits among ambulatory patients with SARS-CoV-2 infection. This retrospective cohort study included adult patients (N = 25 034) with a positive SARS-CoV-2 test performed in a non-hospital setting. Logistic regression analyses tested associations between home use of antidepressant medications and a composite outcome of ED visitation or hospital admission within 30 days. Secondary exposures included individual antidepressants and antidepressants with functional inhibition of acid sphingomyelinase (FIASMA) activity. Patients with antidepressant exposure were less likely to experience the primary composite outcome compared to patients without antidepressant exposure (adjusted odds ratio [aOR] 0.89, 95% CI 0.79-0.99, p = 0.04). This association was only observed with daily doses of at least 20 mg fluoxetine-equivalent (aOR 0.87, 95% CI 0.77-0.99, p = 0.04), but not with daily doses lower than 20 mg fluoxetine-equivalent (aOR 0.94, 95% CI 0.80-1.11, p = 0.48). In exploratory secondary analyses, the outcome incidence was also reduced with exposure to selective serotonin reuptake inhibitors (aOR 0.87, 95% CI 0.75-0.99, p = 0.04), bupropion (aOR 0.70, 95% CI 0.55-0.90, p = 0.005), and FIASMA antidepressant drugs (aOR 0.87, 95% CI 0.77-0.99, p = 0.03). Antidepressant exposure was associated with a reduced incidence of emergency department visitation or hospital admission among SARS-CoV-2 positive patients, in a dose-dependent manner. These data support the FIASMA model of antidepressants\u27 effects against COVID-19

Antidepressant use and its association with 28-day mortality in inpatients with SARS-CoV-2: Support for the FIASMA model against COVID-19

To reduce Coronavirus Disease 2019 (COVID-19)-related mortality and morbidity, widely available oral COVID-19 treatments are urgently needed. Certain antidepressants, such as fluvoxamine or fluoxetine, may be beneficial against COVID-19. We included 388,945 adult inpatients who tested positive for SARS-CoV-2 at 36 AP-HP (Assistance Publique-Hôpitaux de Paris) hospitals from 2 May 2020 to 2 November 2021. We compared the prevalence of antidepressant use at admission in a 1:1 ratio matched analytic sample with and without COVID-19 (N = 82,586), and assessed its association with 28-day all-cause mortality in a 1:1 ratio matched analytic sample of COVID-19 inpatients with and without antidepressant use at admission (N = 1482). Antidepressant use was significantly less prevalent in inpatients with COVID-19 than in a matched control group of inpatients without COVID-19 (1.9% versus 4.8%; Odds Ratio (OR) = 0.38; 95%CI = 0.35-0.41

Dexamethasone Use and Mortality in Hospitalized Patients with Coronavirus Disease 2019: a Multicenter Retrospective Observational Study

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Association of fluvoxamine with mortality and symptom resolution among inpatients with COVID-19 in Uganda : a prospective interventional open-label cohort study

Funding: We acknowledge the funding support from the Government of the Republic of Uganda through the Makerere University Research and Innovations Fund (Mak-RIF).Prior research suggests that fluvoxamine, a selective serotonin reuptake inhibitor (SSRI) used for the treatment of obsessive-compulsive disorder and major depressive disorder, could be repurposed against COVID-19. We undertook a prospective interventional open-label cohort study to evaluate the efficacy and tolerability of fluvoxamine among inpatients with laboratory-confirmed COVID-19 in Uganda. The main outcome was all-cause mortality. Secondary outcomes were hospital discharge and complete symptom resolution. We included 316 patients, of whom 94 received fluvoxamine in addition to standard care [median age, 60 years (IQR = 37.0); women, 52.2%]. Fluvoxamine use was significantly associated with reduced mortality [AHR = 0.32; 95% CI = 0.19–0.53; p < 0.001, NNT = 4.46] and with increased complete symptom resolution [AOR = 2.56; 95% CI = 1.53–5.51; p < 0.001, NNT = 4.44]. Sensitivity analyses yielded similar results. These effects did not significantly differ by clinical characteristic, including vaccination status. Among the 161 survivors, fluvoxamine was not significantly associated with time to hospital discharge [AHR 0.81, 95% CI (0.54–1.23), p = 0.32]. There was a trend toward greater side effects with fluvoxamine (7.45% versus 3.15%; SMD = 0.21; χ2 = 3.46, p = 0.06), most of which were light or mild in severity and none of which were serious. One hundred mg of fluvoxamine prescribed twice daily for 10 days was well tolerated and significantly associated with reduced mortality and with increased complete symptom resolution, without a significant increase in time to hospital discharge, among inpatients with COVID-19. Large-scale randomized trials are urgently needed to confirm these findings, especially for low- and middle-income countries, where access to vaccines and approved treatments against COVID-19 is limited.Publisher PDFPeer reviewe

Antiviral and Anti-Inflammatory Activities of Fluoxetine in a SARS-CoV-2 Infection Mouse Model

The coronavirus disease 2019 (COVID-19) pandemic continues to cause significant morbidity and mortality worldwide. Since a large portion of the world’s population is currently unvaccinated or incompletely vaccinated and has limited access to approved treatments against COVID-19, there is an urgent need to continue research on treatment options, especially those at low cost and which are immediately available to patients, particularly in low- and middle-income countries. Prior in vitro and observational studies have shown that fluoxetine, possibly through its inhibitory effect on the acid sphingomyelinase/ceramide system, could be a promising antiviral and anti-inflammatory treatment against COVID-19. In this report, we evaluated the potential antiviral and anti-inflammatory activities of fluoxetine in a K18-hACE2 mouse model of SARS-CoV-2 infection, and against variants of concern in vitro, i.e., SARS-CoV-2 ancestral strain, Alpha B.1.1.7, Gamma P1, Delta B1.617 and Omicron BA.5. Fluoxetine, administrated after SARS-CoV-2 infection, significantly reduced lung tissue viral titres and expression of several inflammatory markers (i.e., IL-6, TNFα, CCL2 and CXCL10). It also inhibited the replication of all variants of concern in vitro. A modulation of the ceramide system in the lung tissues, as reflected by the increase in the ratio HexCer 16:0/Cer 16:0 in fluoxetine-treated mice, may contribute to explain these effects. Our findings demonstrate the antiviral and anti-inflammatory properties of fluoxetine in a K18-hACE2 mouse model of SARS-CoV-2 infection, and its in vitro antiviral activity against variants of concern, establishing fluoxetine as a very promising candidate for the prevention and treatment of SARS-CoV-2 infection and disease pathogenesis

Effets des pathologies psychiatriques sur le risque de tentative de suicide : similitudes et différences selon l’âge au sein d’une cohorte en population générale

Les troubles mentaux sont associés à un risque accru de tentative de suicide. Or, la comorbidité entre les troubles psychiatriques est fréquente et peut être expliquée par des modèles où ces troubles sont appréhendés comme des manifestations de dimensions latentes de psychopathologie. Nous avons cherché à évaluer si le risque de tentative de suicide est dû à certains troubles psychiatriques ou à certaines dimensions de psychopathologie (internalisée ou externalisée) ou à un facteur de psychopathologie générale. Au sein d’une cohorte en population générale suivie sur une période de trois ans, nous avons utilisé des modèles d’équation structurelle afin de distinguer les effets spécifiques des effets partagés des différents troubles mentaux sur le risque de tentative de suicide. La structure dimensionnelle globale des troubles psychiatriques était invariante selon l'âge et leurs effets sur le risque de tentative de suicide étaient médiés principalement par une dimension de psychopathologie générale représentant un effet commun partagé, quel que soit le groupe d'âge. Cet effet était significativement plus faible chez les adultes d’au moins 50 ans comparativement aux sujets les plus jeunes. Les résultats étaient similaires en utilisant différentes approches de modélisation de la comorbidité psychiatrique, ainsi que dans un modèle incluant la plupart des facteurs de risque cliniques de tentative de suicide dans le sous-groupe de sujets présentant un épisode dépressif caractérisé. Nos résultats suggèrent que le facteur de psychopathologie générale a un rôle majeur et devrait être considéré comme une cible thérapeutique privilégiée afin de permettre une meilleure prévention du suicide.Pas de résum

Le trouble bipolaire subsyndromique (enjeux diagnostiques et thérapeutiques et impact sur la validité des essais cliniques)

Plusieurs études soutiennent la validité de distinguer, au sein de la catégorie diagnostique du trouble dépressif majeur récurrent (TDMR), le trouble dépressif majeur pur (TDMP) et le trouble bipolaire subsyndromique (TBS) dans les classifications psychiatriques. Nous avons mené une étude ayant pour but d'examiner l'impact potentiel de l inclusion de ces participants sur la validité externe et interne des essais cliniques évaluant l efficacité des traitements pour le TDMR et utilisant des critères d'exclusion traditionnels. Les données de l étude sont issues de la National Epidemiologic Survey on Alcohol and Related Conditions (NESARC), une enquête nationale représentative de la population adulte des États-Unis menée entre 2001 et 2002 (n = 43093).Le pourcentage des participants présentant un TBS qui auraient été éligibles dans ces essais cliniques variait de 7,98% à 22,59%, selon la définition d hypomanie subsyndromique adoptée. Le taux d'exclusion global des participants présentant un trouble dépressif caractérisé avec au moins 4 symptômes hypomaniaques concomitants au cours de leur vie différait significativement de celui des participants présentant un TDMP.La conception actuelle des essais cliniques évaluant l efficacité des traitements pour le TDMR souffre d un défaut de validité externe du fait de l'inclusion d'une proportion importante de sujets ayant un TBS. Ces personnes présentent des taux d'exclusion similaires à celles ayant un trouble bipolaire de type 2, à l origine d un biais d échantillonnage. De plus, l inclusion de ces patients dans les essais cliniques pourrait altérer la validité interne des méta-analyses.PARIS6-Bibl.Pitié-Salpêtrie (751132101) / SudocSudocFranceF

The acid sphingomyelinase/ceramide system in COVID-19

Acid sphingomyelinase (ASM) cleaves sphingomyelin into the highly lipophilic ceramide, which forms large gel-like rafts/platforms in the plasma membrane. We showed that SARS-CoV-2 uses these platforms for cell entry. Lowering the amount of ceramide or ceramide blockade due to inhibitors of ASM, genetic downregulation of ASM, anti-ceramide antibodies or degradation by neutral ceramidase protected against infection with SARS-CoV-2. The addition of ceramide restored infection with SARS-CoV-2. Many clinically approved medications functionally inhibit ASM and are called FIASMAs (functional inhibitors of acid sphingomyelinase). The FIASMA fluvoxamine showed beneficial effects on COVID-19 in a randomized prospective study and a prospective open-label real-world study. Retrospective and observational studies showed favorable effects of FIASMA antidepressants including fluoxetine, and the FIASMA hydroxyzine on the course of COVID-19. The ASM/ceramide system provides a framework for a better understanding of the infection of cells by SARS-CoV-2 and the clinical, antiviral, and anti-inflammatory effects of functional inhibitors of ASM. This framework also supports the development of new drugs or the repurposing of 'old' drugs against COVID-19

Telemedicine Readiness Across Medical Conditions in a US National Representative Sample of Older Adults.

Telemedicine has provided older adults the ability to seek care remotely during the coronavirus disease (COVID-19) pandemic. However, it is unclear how diverse medical conditions play a role in telemedicine uptake. A total of 3379 participants (≥65 years) were interviewed in 2018 as part of the National Health and Aging Trends Study. We assessed telemedicine readiness across multiple medical conditions. Most chronic medical conditions and mood symptoms were significantly associated with telemedicine unreadiness, for physical or technical reasons or both, while cancer, hypertension, and arthritis were significantly associated with telemedicine readiness. Our findings suggest that multiple medical conditions play a substantial role in telemedicine uptake among older adults in the US. Therefore, comorbidities should be taken into consideration when promoting and adopting telemedicine technologies among older adults