Nicotine dependence and incident psychiatric disorders: prospective evidence from US national study.

We examined the prospective associations between nicotine dependence and the likelihood of psychiatric and substance use disorders in the general adult population. Participants came from a nationally representative sample of US adults aged 18 years or older, who were interviewed 3 years apart in the National Epidemiologic Survey on Alcohol and Related Conditions (Wave 1, 2001-2002; Wave 2, 2004-2005). The primary analyses were limited to 32,671 respondents (13,751 male (47.9% weighted); mean age of 45 years (SD = 0.18)) who were interviewed in both waves. We used multiple regression and propensity score matching (PSM) to estimate the strength of independent associations between nicotine dependence related to the use of tobacco products at Wave 1 and incident psychiatric disorders at Wave 2. Psychiatric disorders were measured with a structured interview (Alcohol Use Disorder and Associated Disabilities Interview Schedule-DSM-IV). All analyses adjusted for multiple potential confounders, including childhood (family history of substance use disorders, parental loss, vulnerable family environment), early-adolescence (self-esteem, social deviance, conduct disorder), late-adolescence (education, personality and psychiatric disorders), adulthood (divorce, stressful life events, social deviance, quality of life, history of alcohol or other substance use disorder), and sociodemographic factors. Multiple regression analysis and PSM converged in indicating that nicotine dependence was associated with significantly increased incidence of any psychiatric disorder (OR = 1.39(95%CI:1.20;1.60)), including substance use disorders (OR = 1.91(95%CI:1.47;2.47)), and anxiety disorders (OR = 1.31(95%CI:1.06;1.62)). Population Attributable Risk Proportions were substantial, ranging from 12.5%(95%CI:8.10;17.0) for any psychiatric disorder to 33.3%(95%CI:18.7;48.0) for any other drug use disorder. Supplementary analyses also indicated significant associations between nicotine dependence and persistence of psychiatric and substance use disorders among patients having a disorder at Wave 1. In the general adult population, nicotine dependence is associated with an increased likelihood for several psychiatric and substance use disorders. Given its high prevalence, these findings have important public health implications.

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

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.

Excess mortality and its causes among older adults with schizophrenia versus those with bipolar disorder and major depressive disorder: a 5-year prospective multicenter study.

Excess mortality observed in people with schizophrenia may persist in later life. The specific causes of increased mortality observed in older adults with schizophrenia and the potential influence of psychotropic medications remain partly unknown. We compared 5-year mortality and its causes of older adults with schizophrenia to bipolar disorder (BD) or major depressive disorder (MDD). We used a 5-year prospective cohort, including 564 older inpatients and outpatients with schizophrenia, BD or MDD (mean age: 67.9 years, SD = 7.2 years). Causes of death were cardiovascular disorder (CVD) mortality, non-CVD disease-related mortality (e.g., infections), suicide, and unintentional injury. The primary analysis was a multivariable logistic model with inverse probability weighting (IPW) to reduce the effects of confounders, including sociodemographic factors, duration and severity of the disorder, and psychiatric and non-psychiatric comorbidity. Five-year all-cause mortality among older participants with schizophrenia and with BD or MDD were 29.4% (n = 89) and 18.4% (n = 45), respectively. Following adjustments, schizophrenia compared to MDD or BD was significantly associated with increased all-cause mortality (AOR = 1.35; 95%CI = 1.04-1.76; p = 0.024) and cardiovascular mortality (AOR = 1.50; 95%CI = 1.13-1.99; p = 0.005). These associations were significantly reduced among patients taking antidepressants [interaction odds ratio (IOR) = 0.42; 95%CI = 0.22-0.79; p = 0.008 and IOR = 0.39: 95%CI = 0.16-0.94; p = 0.035, respectively]. Schizophrenia was associated with higher mortality compared to BD or MDD. Cardiovascular diseases explained most of this excess mortality. Exploratory analyses suggested that psychotropic medications did not influence this excess mortality, except for antidepressants, which were associated with significantly reduced between-group difference in all-cause and cardiovascular mortality.

Psychiatric symptoms and mortality in older adults with major psychiatric disorders: results from a multicenter study.

Prior research suggests that certain psychiatric symptoms could be associated with increased risk of death. However, it remains unclear whether this association could rely on all or specific symptoms. In this report, we used data from a multicenter 5-year prospective study (N = 641) of older adults with an ICD-10 diagnosis of schizophrenia, bipolar disorder or major depressive disorder, recruited from French community psychiatric departments. We used a latent variable approach to disentangle the effects shared by all psychiatric symptoms (i.e., general psychopathology factor) and those specific to individual psychiatric symptoms, while adjusting for sociodemographic and clinical factors. Psychiatric symptoms were assessed face-to-face by psychiatrists trained to semi-structured interviews using the Brief Psychiatric Rating Scale (BPRS). Among older adults with major psychiatric disorders, we found that all psychiatric symptoms were associated with increased mortality, and that their effect on the 5-year mortality were exerted mostly through a general psychopathology dimension (ß = 0.13, SE = 0.05, p < 0.05). No BPRS item or lower order factor had a significant effect on mortality beyond and above the effect of the general psychopathology factor. Greater number of medical conditions, older age, male sex, and being hospitalized or institutionalized at baseline were significantly associated with this risk beyond the effect of the general psychopathology factor. Since psychiatric symptoms may affect mortality mainly through a general psychopathology dimension, biological and psychological mechanisms underlying this dimension should be considered as promising targets for interventions to decrease excess mortality of older individuals with psychiatric disorders.

Impact of lithium on mortality among older adults with major psychiatric disorders: A 5-year prospective multicenter study.

OBJECTIVE: Prior studies report conflicting results about the association between lithium use and all-cause mortality. In addition, data are scarce on this association among older adults with psychiatric disorders. In this report, we sought to examine the associations of lithium use with all-cause mortality and specific causes of death (i.e., due to cardiovascular disorder, non-cardiovascular disease, accident, or suicide) among older adults with psychiatric disorders during a 5-year follow-up period. METHODS: In this observational epidemiological study, we used data from 561 patients belonging to a Cohort of individuals with Schizophrenia or Affective disorders aged 55-years or more (CSA). Patients taking lithium at baseline were first compared to patients not taking lithium, and then to patients taking (i) antiepileptics and (ii) atypical antipsychotics in sensitivity analyses. Analyses were adjusted for socio-demographic (e.g., age, gender), clinical characteristics (e.g., psychiatric diagnosis, cognitive functioning), and other psychotropic medications (e.g. benzodiazepines). RESULTS: There was no significant association between lithium use and all-cause mortality [AOR=1.12; 95%CI=0.45-2.79; p=0.810] or disease-related mortality [AOR=1.37; 95%CI=0.51-3.65; p=0.530]. None of the 44 patients taking lithium died from suicide, whereas 4.0% (N=16) of patients not receiving lithium did. CONCLUSION: These findings suggest that lithium may not be associated with all-cause or disease-related mortality and might be associated with reduced risk of suicide in this population. They argue against the underuse of lithium as compared with antiepileptics and atypical antipsychotics among older adults with mood disorders.

Association between antidepressant use and reduced risk of intubation or death in hospitalized patients with COVID-19: results from an observational study.

A prior meta-analysis showed that antidepressant use in major depressive disorder was associated with reduced plasma levels of several pro-inflammatory mediators, which have been associated with severe COVID-19. Recent studies also suggest that several antidepressants may inhibit acid sphingomyelinase activity, which may prevent the infection of epithelial cells with SARS-CoV-2, and that the SSRI fluoxetine may exert in-vitro antiviral effects on SARS-CoV-2. We examined the potential usefulness of antidepressant use in patients hospitalized for COVID-19 in an observational multicenter retrospective cohort study conducted at AP-HP Greater Paris University hospitals. Of 7230 adults hospitalized for COVID-19, 345 patients (4.8%) received an antidepressant within 48 h of hospital admission. The primary endpoint was a composite of intubation or death. We compared this endpoint between patients who received antidepressants and those who did not in time-to-event analyses adjusted for patient characteristics, clinical and biological markers of disease severity, and other psychotropic medications. The primary analysis was a multivariable Cox model with inverse probability weighting. This analysis showed a significant association between antidepressant use and reduced risk of intubation or death (HR, 0.56; 95% CI, 0.43-0.73, p < 0.001). This association remained significant in multiple sensitivity analyses. Exploratory analyses suggest that this association was also significant for SSRI and non-SSRI antidepressants, and for fluoxetine, paroxetine, escitalopram, venlafaxine, and mirtazapine (all p < 0.05). These results suggest that antidepressant use could be associated with lower risk of death or intubation in patients hospitalized for COVID-19. Double-blind controlled randomized clinical trials of antidepressant medications for COVID-19 are needed.

Metabolic syndrome and risk of death in older adults with major psychiatric disorders: Results from a 5-year prospective multicenter study.

OBJECTIVES: No study has explored the association of individual components of metabolic syndrome with mortality in older patients with psychiatric disorders. In this report, we examined whether metabolic syndrome or any of its components predicted mortality in a cohort of older adults with psychiatric disorders. METHODS: We used data from a multicenter 5-year prospective cohort, including 634 in- and out-patients with schizophrenia, bipolar or major depressive disorder. Metabolic syndrome was assessed at baseline following NCEP-ATPIII criteria. Cause of death was categorized as cardiovascular disorder (CVD) mortality, non-CVD disease-related mortality (e.g., infections), suicide and accident. RESULTS: 122 participants (44.0%) were diagnosed with metabolic syndrome at baseline. In the full sample, there was no significant association between metabolic syndrome or any of its components with all-cause, CVD and non-CVD mortality. However, for the subpopulation of older adults with major depressive disorder, metabolic syndrome was significantly associated with increased all-cause and disease-related mortality after adjustment for age, sex and smoking status (p = 0.032 and p = 0.036, respectively). There was a significant interaction between metabolic syndrome and psychiatric diagnoses indicating that in participants with major depressive disorder, metabolic syndrome had a significantly greater effect on all-cause mortality (p = 0.025) and on disease-related mortality (p = 0.008) than in participants with either bipolar disorder or schizophrenia. CONCLUSIONS: Our findings do not support an association between metabolic syndrome and increased mortality in older patients with major psychiatric disorders. Several explanations are discussed, including a survival bias, a lack of sensitivity of the used cut-offs and a ceiling effect of metabolic syndrome on mortality in this very high-risk population. The latter hypothesis could also explain the significant association between metabolic syndrome and mortality in the depressive subgroup, where a ceiling effect is yet to be reached, given the less marked premature mortality in depressive patients compared to those with bipolar disorder or schizophrenia.

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.

Dexamethasone use and mortality in hospitalized patients with coronavirus disease 2019: A multicentre retrospective observational study.

AIMS: To examine the association between dexamethasone use and mortality among patients hospitalized for COVID-19. METHODS: We examined the association between dexamethasone use and mortality at AP-HP Greater Paris University hospitals. Study baseline was defined as the date of hospital admission. The primary endpoint was time to death. We compared this endpoint between patients who received dexamethasone and those who did not in time-to-event analyses adjusted for patient characteristics (such as age, sex and comorbidity) and clinical and biological markers of clinical severity of COVID-19, and stratified by the need for respiratory support, i.e. mechanical ventilation or oxygen. The primary analysis was a multivariable Cox regression model. RESULTS: Of 12 217 adult patients hospitalized with a positive COVID-19 reverse transcriptase-polymerase chain reaction test, 171 (1.4%) received dexamethasone orally or by intravenous perfusion during the visit. Among patients who required respiratory support, the end-point occurred in 10/63 (15.9%) patients who received dexamethasone and 298/1129 (26.4%) patients who did not. In this group, there was a significant association between dexamethasone use and reduced mortality in the primary analysis (hazard ratio, 0.46; 95% confidence interval 0.22-0.96, P = .039). Among patients who did not require respiratory support, there was no significant association between dexamethasone use and the endpoint. CONCLUSIONS: In this multicentre observational study, dexamethasone use administered either orally or by intravenous injection at a cumulative dose between 60 mg and 150 mg was associated with reduced mortality among patients with COVID-19 requiring respiratory support.

Late-onset and nonlate-onset schizophrenia: A comparison of clinical characteristics in a multicenter study.

OBJECTIVES: Data are scarce regarding the potential clinical differences between non-late onset schizophrenia (NLOS, i.e., disorder occurring before 40 years of age), late-onset schizophrenia (LOS, occurring between ages 40 and 60 years) and very-late-onset schizophrenia-like psychosis (VLOSLP, occurring after 60 years of age). Furthermore, previous research compared LOS patients with non-age matched NLOS patients. In this study, we sought to examine potential clinical differences between patients of similar age with LOS and NLOS. METHODS/DESIGN: This is a cross-sectional multicentre study that recruited in- and outpatients older adults (aged ≥55 years) with an ICD-10 diagnosis of schizophrenia or schizoaffective disorder with NLOS and LOS. Sociodemographic and clinical characteristics, comorbidity, psychotropic medications, quality of life, functioning, and mental health care utilization were drawn for comparison. RESULTS: Two hundred seventy-two participants (79.8%) had NLOS, 61 (17.9%) LOS, and 8 (2.3%) VLOSLP. LOS was significantly and independently associated with greater severity of emotional withdrawal and lower severity of depression (all p < 0.05). However, the magnitude of these associations was modest, with significant adjusted odds ratios ranging from 0.71 to 1.24, and there were no significant between-group differences in other characteristics. CONCLUSION: In an age-matched multicenter sample of elderly patients with schizophrenia, older adults with LOS were largely similar to older adults with NLOS in terms of clinical characteristics. The few differences observed may be at least partially related to symptom fluctuation with time. Implications of these findings for pharmacological and nonpharmacological management is yet to be determined.

Identifying Bridge Symptoms Between Borderline Personality Disorder and Posttraumatic Stress Disorder: A Network Analysis From a National Cohort.

Objective: Borderline personality disorder (BPD) and posttraumatic stress disorder (PTSD) share common risk factors, including exposure to traumatic events. We aim to estimate networks of DSM-IV BPD and PTSD to describe the interactions between the symptoms of these 2 disorders and identify bridging symptoms between the 2 diagnoses that may play critical roles in their co-occurrence.Methods: We performed a network analysis of data from the second wave of the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC 2004-2005), a nationally representative sample of the US adult population. We calculated network stability using a bootstrap method and centrality measures for each symptom across 3 different network estimations.Results: The networks were very stable. The symptom "chronic feelings of emptiness" was the most central in the BPD network. The symptoms "feeling of intense fear or horror" and "recurrent and intrusive memories of the traumatic event" were the most central in the PTSD network. The symptoms "self aggression," "severe dissociation," "chronic feelings of emptiness," and "feelings of detachment" had significantly higher bridge expected influence than most other symptoms in the network in both the full sample and the subsample of participants who responded to all PTSD and BPD symptoms.Conclusion: Self-aggression, chronic feelings of emptiness, dissociation symptoms, and feelings of detachment represent bridge symptoms between BPD and PTSD. These symptoms could potentially trigger and perpetuate the manifestations of one disorder in the presence of the other. Targeting these symptoms might allow better prevention and management of both disorders.

Sex differences in insomnia and hypersomnia complaints during major depressive episode: Results from a national sample.

BACKGROUND: Sex differences in sleep disturbances during major depressive episodes (MDE) have been suggested. This study compares the prevalence, sociodemographic characteristics, and psychiatric comorbidity associated with sleep complaints specific to each sex among adults with MDE. These findings are crucial for precise diagnosis, personalized treatment, and improved clinical outcomes. METHODS: In a large nationally representative prospective survey, we used multi-adjusted logistic regression models including sociodemographic characteristics, psychiatric comorbidity, and depression severity to examine whether associations differ between men and women. RESULTS: Among women, 93.3 % reported at least one type of sleep complaints (i.e., trouble falling asleep, early morning awakening or hypersomnia) while 91.0 % of men did, with respectively 78.3 % and 77.2 % of insomnia complaints, and 46.2 % and 41.3 % of hypersomnia complaints. Women with sleep complaints were more likely to be black, with lower individual incomes, have histrionic personality disorder or a specific phobia. Conversely, men with sleep complaints were more likely to have a lifetime diagnosis of mania spectrum disorder, generalized anxiety disorder, drug use disorder, as well as dependent and schizotypal personality disorders. Surprisingly, being "never married" has emerged as a protective factor against sleep complaints in women, while posing as a risk factor in men compared to other marital statuses. Differences and specificities were also noted concerning subtypes of insomnia and hypersomnia complaints. LIMITATIONS: The cross-sectional design means the associations found do not imply causality. CONCLUSIONS: These findings provide insights into the complex relationship between sleep and depression in men and women, highlighting the need for personalized interventions.

Parenthood and All-cause Mortality in Older Adults with Schizophrenia: A Multicenter 5-Year Prospective Study.

OBJECTIVE: The large body of literature examining the association between parenthood and mortality in the general population contrasts with a lack of studies among older adults with schizophrenia. Identifying potential protective factors of premature death in this population is important to help guide prevention measures. Here, we examined whether all-cause and cause-specific mortality rates significantly differ between older adults with schizophrenia with and without children, during a 5-year follow-up. METHODS: We used data from a 5-year prospective multicenter sample of older adults with an ICD-10 diagnosis of schizophrenia (aged 55 years or more) recruited in France. We performed a forward stepwise logistic regression to examine the association between parenthood and all-cause mortality, including only those independent variables that best explain outcome. RESULTS: Of 323 older adults with schizophrenia, 133 (41.2%) had children (mean age=67.0, SD=6.1), whereas 190 were without children (mean age=67.2, SD=6.6). Following adjustments, parenthood was significantly associated with lower all-cause mortality compared to patients without children in this population (21.1% (n=28) versus 35.8% (n=68); AOR=0.50; 95%CI=0.27-0.94; p=0.032), without significant sex differences in this association. CONCLUSIONS: Parenthood could be protective against mortality among older patients with schizophrenia who live in France. Further research is needed to understand the specific mechanisms underlying this association.

Lifetime exposure to unemployment and prior working conditions are associated with retiree's health: A retrospective study in a large population-based French cohort.

It is unclear whether unemployment exposure, as well as working conditions, can have sustained effects on the health of retirees who are no longer exposed. The aim of the present study is to investigate this issue in 29,281 French retirees from the CONSTANCES cohort in whom the prevalence of suboptimal self-rated health, disability for routine tasks, cardiovascular diseases and cancers is assessed according to lifetime exposure to unemployment and prior working conditions. The analyses are performed retrospectively using multivariable logistic regression models with adjustment for potential confounders such as sex, birth year, parental histories of cardiovascular disease and cancer, social position, retirement age and duration. High lifetime exposure to unemployment is associated with an increased prevalence of suboptimal self-rated health (adjusted odds ratio (95% CI), 1.39 (1.23-1.57)), disability for routine tasks (1.41 (1.26-1.57)) and several cardiovascular diseases including stroke (1.66 (1.19-2.31)), myocardial infarction (1.65 (1.18-2.31)) and peripheral arterial disease (2.38 (1.46-3.90)). Bad prior working conditions are associated with an increased prevalence of disability for routine tasks (1.17 (1.04-1.33)) and cancers (1.27 (1.04-1.54)), notably prostate cancer (1.60 (1.01-2.64)). These findings suggest that unemployment and working conditions have long-term health effects that may cumulate over lifetime, emphasizing that risk evaluation and preventive strategies in retirees, as in workers, should take into account the life-course of individuals in addition to traditional risk factors.

Comorbidity Patterns and Mortality Among Hospitalized Patients with Psychiatric Disorders and COVID-19.

OBJECTIVE: To examine the association between psychiatric and non-psychiatric comorbidity and 28-day mortality among patients with psychiatric disorders and COVID-19. METHODS: We performed a multicenter observational retrospective cohort study of adult patients with psychiatric disorders hospitalized with laboratory-confirmed COVID-19 at 36 Greater Paris University hospitals (January 2020-May 2021) (N=3,768). First, we searched for different subgroups of patients according to their psychiatric and non-psychiatric comorbidities through cluster analysis. Next, we compared 28-day all-cause mortality rates across the identified clusters, while taking into account sex, age, and the number of medical conditions. RESULTS: We found 5 clusters of patients with distinct psychiatric and non-psychiatric comorbidity patterns. Twenty-eight-day mortality in the cluster of patients with mood disorders was significantly lower than in other clusters. There were no significant differences in mortality across other clusters. CONCLUSIONS: All psychiatric and non-psychiatric conditions may be associated with increased mortality in patients with psychiatric disorders and COVID-19. The lower risk of death among patients with mood disorders might be in line with the potential beneficial effect of certain antidepressants in COVID-19, but requires further research. These findings help identify at-risk patients with psychiatric disorders who should benefit from vaccine booster prioritization and other prevention measures.

Antipsychotic use and 28-day mortality in patients hospitalized with COVID-19: A multicenter observational retrospective study.

Prior research has yielded conflicting results about the potential influence of antipsychotics in patients with COVID-19. In this multicenter retrospective study, we examined the association of antipsychotic use at admission with 28-day all-cause mortality in a sample of 59,021 adult patients hospitalized with COVID-19 from January 2020 to November 2021. In a 1:1 ratio matched analytic sample (N=1,454) accounting for age, sex, hospital, hospitalization period, the Elixhauser Comorbidity Index, other psychotropic medications, medications prescribed according to compassionate use or as part of a clinical trial, current diagnoses of psychiatric disorders, and clinical and biological markers of COVID-19 severity, antipsychotic use was not associated with 28-day mortality [23.5% (N=727) versus 18.6% (N=727); OR=1.16; 95%CI=0.89-1.51; p=0.280]. This association remained non-significant in exploratory analyses across all classes of antipsychotics and individual molecules, except for typical antipsychotics and loxapine, which were significantly linked to increased 28-day mortality, associations likely due to residual indication bias. Contrariwise, antipsychotics prescribed at daily doses higher than 200 mg of chlorpromazine-equivalents might be associated with reduced 28-day mortality when compared to patients not taking antipsychotics in the matched analytic sample [10.4% (N=154) versus 18.6% (N=727); AOR=0.56; 95%CI=0.31-0.96; p=0.040]. These results suggest that antipsychotic use, when prescribed at usual doses, are not be associated with 28-day mortality in patients hospitalized with COVID-19.

Medications Modulating the Acid Sphingomyelinase/Ceramide System and 28-Day Mortality among Patients with SARS-CoV-2: An Observational Study.

Prior evidence indicates the potential central role of the acid sphingomyelinase (ASM)/ceramide system in the infection of cells with SARS-CoV-2. We conducted a multicenter retrospective observational study including 72,105 adult patients with laboratory-confirmed SARS-CoV-2 infection who were admitted to 36 AP-HP (Assistance Publique-Hôpitaux de Paris) hospitals from 2 May 2020 to 31 August 2022. We examined the association between the ongoing use of medications functionally inhibiting acid sphingomyelinase (FIASMA), which reduces the infection of cells with SARS-CoV-2 in vitro, upon hospital admission with 28-day all-cause mortality in a 1:1 ratio matched analytic sample based on clinical characteristics, disease severity and other medications (N = 9714). The univariate Cox regression model of the matched analytic sample showed that FIASMA medication use at admission was associated with significantly lower risks of 28-day mortality (HR = 0.80; 95% CI = 0.72-0.88; p < 0.001). In this multicenter observational study, the use of FIASMA medications was significantly and substantially associated with reduced 28-day mortality among adult patients hospitalized with COVID-19. These findings support the continuation of these medications during the treatment of SARS-CoV-2 infections. Randomized clinical trials (RCTs) are needed to confirm these results, starting with the molecules with the greatest effect size in the study, e.g., fluoxetine, escitalopram, and amlodipine.