Psychological burden associated with incident persistent symptoms and their evolution during the COVID-19 pandemic: a prospective population-based study.

BACKGROUND: Identifying factors that predict the course of persistent symptoms that occurred during the COVID-19 pandemic is a public health issue. Modifiable factors could be targeted in therapeutic interventions. OBJECTIVE: This prospective study based on the population-based CONSTANCES cohort examined whether the psychological burden associated with incident persistent symptoms (ie, that first occurred from March 2020) would predict having ≥1 persistent symptom 6-10 months later. METHODS: A total of 8424 participants (mean age=54.6 years (SD=12.6), 57.2% women) having ≥1 incident persistent symptom at baseline (ie, between December 2020 and February 2021) were included. The psychological burden associated with these persistent symptoms was assessed with the Somatic Symptom Disorder-B Criteria Scale (SSD-12). The outcome was having ≥1 persistent symptom at follow-up. Adjusted binary logistic regression models examined the association between the SSD-12 score and the outcome. FINDINGS: At follow-up, 1124 participants (13.3%) still had ≥1 persistent symptom. The SSD-12 score at baseline was associated with persistent symptoms at follow-up in both participants with (OR (95% CI) for one IQR increase: 1.42 (1.09 to 1.84)) and without SARS-CoV-2 infection prior to baseline (1.39 (1.25 to 1.55)). Female gender, older age, poorer self-rated health and infection prior to baseline were also associated with persistent symptoms at follow-up. CONCLUSIONS: The psychological burden associated with persistent symptoms at baseline predicted the presence of ≥1 persistent symptom at follow-up regardless of infection prior to baseline. CLINICAL IMPLICATIONS: Intervention studies should test whether reducing the psychological burden associated with persistent symptoms could improve the course of these symptoms.

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.

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.

Acculturation and Disparities in Telemedicine Readiness: A National Study.

Telemedicine provided older adults the ability to safely seek care during the coronavirus disease (COVID-19) pandemic. This study aimed to evaluate the potential impact of acculturation factors in telemedicine uptake between ethnic groups. As part of the National Health and Aging Trends Study 2018 survey, 303 participants (≥65 years) were interviewed. We assessed the impact of acculturation on telemedicine readiness by race and ethnicity. Compared to the white non-Hispanic immigrant population, Hispanic and Asian/Pacific Islander (API) populations had significantly lower telemedicine readiness and uptake. Limited English proficiency or older age at the time of migration was associated with telemedicine unreadiness and uptake in the Hispanic and API populations. Our findings suggested that acculturation factors play a substantial role in telemedicine uptake among older adult immigrants in the United States. Therefore, acculturation factors should be considered when promoting and adopting telemedicine technologies in older adults.

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.

Comorbidity patterns and mortality among hospitalized patients with psychiatric disorders and COVID-19

Objectives: To examine the association between psychiatric and non-psychiatric comorbidity and 28-day mortality among patients with psychiatric disorders and COVID-19. Methods: 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 five 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. Conclusion: 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 may help identify at-risk patients with psychiatric disorders who should benefit from vaccine booster prioritization and other prevention measures.

Depression and anxiety before and at the beginning of the COVID-19 pandemic and incident persistent symptoms: a prospective population-based cohort study.

Many patients affected by COVID-19 suffer from debilitating persistent symptoms whose risk factors remained poorly understood. This prospective study examined the association of depression and anxiety symptoms measured before and at the beginning of the COVID-19 pandemic with the incidence of persistent symptoms. Among 25,114 participants [mean (SD) age, 48.72 years (12.82); 51.1% women] from the SAPRIS and SAPRIS-Sérologie surveys nested in the French CONSTANCES population-based cohort, depression and anxiety symptoms were measured with the Center for Epidemiologic Studies-Depression scale and the 12-item General Health Questionnaire before the pandemic, and with the 9-item Patient Health Questionnaire and the 7-Item Generalized Anxiety Disorder scale at the beginning of the pandemic (i.e., between April 6, 2020 and May 4, 2020). Incident persistent symptoms were self-reported between December 2020 and January 2021. The following variables were also considered: gender, age, educational level, household income, smoking status, BMI, hypertension, diabetes, self-rated health, and SARS-CoV-2 infection according to serology/PCR test results. After a follow-up of seven to ten months, 2329 participants (9.3%) had been infected with SARS-CoV-2 and 4262 (17.0%) reported at least one incident persistent symptom that emerged from March 2020, regardless of SARS-CoV-2 infection. In multi-adjusted logistic regression models, participants in the highest (versus the lowest) quartile of depressive or anxiety symptom levels before or at the beginning of the pandemic were more likely to have at least one incident persistent symptom (versus none) at follow-up [OR (95%CI) ranging from 2.10 (1.89-2.32) to 3.01 (2.68-3.37)], with dose-response relationships (p for linear trend <0.001). Overall, these associations were significantly stronger in non-infected versus infected participants, except for depressive symptoms at the beginning of the pandemic. Depressive symptoms at the beginning of the pandemic were the strongest predictor of incident persistent symptoms in both infected and non-infected participants [OR (95%CI): 2.88 (2.01-4.14) and 3.03 (2.69-3.42), respectively]. In exploratory analyses, similar associations were found for each symptom taken separately in different models. Depression and anxiety symptoms should be tested as a potential target for preventive interventions against persistent symptoms after an infection with SARS-CoV-2.

Cardiovascular burden and unemployment: A retrospective study in a large population-based French cohort.

The specific effect of unemployment on cardiovascular health relatively to the effects of social position and work environment is still unclear. To clarify this effect, the associations between current or past unemployment and the prevalence of common cardiovascular risk factor and events were tested using multiple logistic regression models with adjustment for both social position and prior work environment. The analyses were performed in a population-based French cohort (CONSTANCES) that included 131,186 adults enrolled between 2012 and 2021. Participants who were unemployed at inclusion (n = 8278) were overexposed to non-moderate alcohol consumption, smoking, leisure-time physical inactivity and depression (odds ratios (ORs) from 1.19 to 1.58) whereas those who have been unemployed at least once in the past (n = 19,015) were additionally overexposed not only to the previous risk factors but also to obesity, diabetes and sleep disorders (ORs from 1.10 to 1.35). These latter were also more exposed to non-fatal myocardial infarction and peripheral arterial disease (ORs of 1.44 and 1.47 respectively), overexposures that persisted after further adjustment for cardiovascular risk factors (ORs of 1.36 and 1.33). The overexposures to risk factors and cardiovascular events were both dependent on the duration of past unemployment. They were equally observed in participants with low social position or bad work environment. These results suggest that unemployment increases cardiovascular risk independently from social position and work environment with a cumulative effect over time. The effect of unemployment could add up to those of low social position and bad work environment during lifetime to further increase cardiovascular risk. They also suggest that long-term unemployment increases the prevalence of cardiovascular events through pathways including but not limited to overexposure to common risk factors.

[Depression in older adults. What are the differences in clinical practice?] / Dépression du sujet âgé. Quelles différences de prise en charge en pratique ?

BACKGROUND: Management of depression in the elderly is a growing public health issue in France. The objective of this study was to compare practitioners' perception of depression severity (i.e., intensity and suicidal risk) and clinical practice (i.e., clinical assessment and medication choice) in elderly versus younger adult patients with major depression. MATERIALS AND METHOD: The method consisted of an online questionnaire completed by general practitioners and psychiatrists. Respondents'answers to a fictive case of a patient with major depression were randomized according to the patient's age, if the patient'age was either 40 or 70 years old. We assessed the perceived intensity of the depression, the perceived suicidal risk, the prescription of biological tests and cerebral imaging, and of antidepressive or other psychotropic medications. 102 completed forms were included. Data indicate that there were no significant differences in terms of perceived depression intensity and suicidal risk according to the patients'age. The prescription of biological tests was systematic in both groups, but a significant difference was observed in terms of prescription of brain imaging (71% of respondents for the 70-year-old patient versus 43% for the 40-year-old patient, p < 0.005), use of tetracyclic antidepressant (33% if aged 70 years versus 2% if aged 40 years, p < 0.001) and other psychotropic non-antidepressant medications (69% if aged 70 years versus 85% if aged 40 years, p < 0.05). This study did not show any significant difference in the perception of depression according to age. However, it highlights differences in terms of practical care according to age. These results suggest a partial gap between clinical practice and guidelines for the management of major depression in older adults, reflecting the need to favor the dissemination of guidelines and strengthen research for this population.

Distinct cardiovascular and cancer burdens associated with social position, work environment and unemployment: a cross-sectional and retrospective study in a large population-based French cohort.

OBJECTIVES: Distinguish the respective effects of social position, work environment and unemployment on cardiovascular and cancer risks. DESIGN: A cross-sectional and retrospective observational study. SETTING: A population-based French cohort (CONSTANCES). PARTICIPANTS: 130 197 adults enrolled between 2012 and 2021 without missing values. PRIMARY OUTCOME MEASURES: The associations of social position, work environment and unemployment exposure with the prevalence of cardiovascular events and cancers simultaneously tested using logistic regression models adjusting for common risk factors. RESULTS: While social position, work environment and unemployment exposure are strongly inter-related with each other, they are not linked to the same cardiovascular and cancer outcomes. Low social position and long unemployment duration are significantly associated with an increased prevalence of angina pectoris, myocardial infarction and peripheral arterial disease (OR=1.22 to 1.90, p<0.04 to p<0.0001) but not of stroke. In contrast, a bad work environment is associated with an increased prevalence of stroke (OR=1.29, p<0.01) but not of angina pectoris, myocardial infarction and peripheral arterial disease. Low social position is associated with an increased prevalence of cervical and lung cancers (OR=1.73 and 1.95, p<0.002 and p<0.03) and a decreased prevalence of skin cancer (OR=0.70, p<0.0001) while a bad work environment is associated with an increased prevalence of breast, skin, prostate and colon cancers (OR=1.31 to 2.91, p<0.0002 to p<0.0001). Unemployment exposure is not associated with the prevalence of any type of cancers. CONCLUSIONS: Social position, work environment and unemployment are associated with distinct cardiovascular and cancerous diseases that could add up during lifetime, they should therefore be considered all together in any preventive strategy.

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.

Trust in sources of information on COVID-19 at the beginning of the pandemic's first wave and incident persistent symptoms in the population-based CONSTANCES cohort: A prospective study.

OBJECTIVE: To examine the association between trust in different sources of information on COVID-19 at the beginning of the pandemic and the burden of incident persistent symptoms. METHODS: This prospective study used data from the SAPRIS and SAPRIS-Sérologie surveys nested in the French CONSTANCES population-based cohort. Trust in different information sources was measured between April 6 and May 4, 2020. Persistent symptoms that emerged afterwards were self-reported between December 2020 and January 2021. The associated psychological burden was measured with the somatic symptom disorder B criteria scale (SSD-12). The analyses were adjusted for gender, age, education, income, self-rated health, SARS-CoV-2 serology tests, and self-reported COVID-19. RESULTS: Among 20,985 participants [mean age (SD), 49.0 years (12.7); 50.2% women], those with higher trust in government/journalists at baseline had fewer incident persistent symptoms at follow-up (estimate (SE) for one IQR increase: -0.21 (0.03), p < 0.001). Participants with higher trust in government/journalists and medical doctors/scientists were less likely to have ≥1 symptom (odds ratio (95% confidence interval) for one IQR increase: 0.87 (0.82-0.91) and 0.91 (0.85-0.98), respectively). Among 3372 participants (16.1%) who reported ≥1 symptom, higher trust in government/journalists and medical doctors/scientists predicted lower SSD-12 scores (-0.39 (0.17), p = 0.02 and - 0.85 (0.24), p < 0.001, respectively), whereas higher trust in social media predicted higher scores in those with lower trust in government/journalists (0.90 (0.34), p = 0.008). These associations did not depend upon surrogate markers of infection with SARS-CoV-2. CONCLUSIONS: Trust in information sources on COVID-19 may be associated with incident persistent symptoms and associated psychological burden, regardless of infection with SARS-CoV-2.

Associations Between Early Life Adversity, Reproduction-Oriented Life Strategy, and Borderline Personality Disorder.

Importance: Borderline personality disorder (BPD) is often accompanied by a history of high-risk sexual behavior and somatic comorbidities. Yet, these features are most often considered in isolation and little is known about their underlying developmental pathways. Life history theory, a leading framework in evolutionary developmental biology, can help make sense of the wide range of behaviors and health issues found in BPD. Objective: To examine whether the emergence of BPD is associated with the prioritization of immediate reproductive goals over longer-term somatic maintenance goals, a life strategy that can be viewed as a developmental response to adverse early life experiences, providing rapid reproductive benefits despite costs to health and well-being. Design, Setting, and Participants: This study used cross-sectional data from the second wave of the National Epidemiologic Survey on Alcohol and Related Conditions in 2004-2005 (n = 34 653). Civilian, noninstitutionalized individuals in the US, 18 years or older, and those with and without a DSM-IV diagnosis of BPD were included. Analysis took place between August 2020 and June 2021. Main Outcomes and Measures: Structural equation models were used to examine whether early life adversity was associated with the likelihood of a BPD diagnosis, either directly or indirectly through a life strategy whereby individuals trade somatic maintenance for immediate reproduction. Results: Analyses were performed on a sample of 30 149 participants (females: 17 042 [52%]; mean [SE] age, 48.5 [0.09]; males: 12 747 [48%]; mean [SE] age, 47 [0.08]). Of these, 892 (2.7%) had a diagnosis of BPD and 29 257 (97.3%) did not have BPD. Mean early life adversity, metabolic disorder score, and body mass index were significantly higher among participants with a diagnosis of BPD. In an analysis adjusted for age, individuals with BPD reported having significantly more children than those without BPD (b =0.06; SE, 0.01; t = 4.09; P < .001). Having experienced greater levels of adversity in early life was significantly associated with a greater risk of being diagnosed with BPD later in life (direct relative risk = 0.268; SE, 0.067; P < .001). Importantly, this risk was further increased by 56.5% among respondents who prioritized short-term reproductive goals over somatic maintenance (indirect relative risk = 0.565; SE, 0.056; P < .001). Similar patterns of associations were found in male and female individuals. Conclusions and Relevance: The hypothesis of a reproduction/maintenance life history trade-off mediating the association between early life adversity and BPD helps make sense of the high dimensionality that characterizes the physiological and behavioral correlates of BPD. Additional studies are needed to confirm these results using longitudinal data.

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 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.

Using filled prescription sequences to rank antidepressants: A nationwide replication study.

Ranking antidepressants according to their acceptability (i.e., a combination of both efficacy and tolerability) in the general population may help choosing the best first-line medication. This study aimed to replicate the results of a proof-of-concept study ranking anti-depressants according to the proportion of filled prescription sequences consistent with a continuation of the first treatment versus those consistent with a change. We used a nationwide cohort from the French national health data system (SNDS) to support the use of this method as a widely available tool to rank antidepressant treatments in real life settings. About 1.2 million people were identified as new antidepressant users in the SNDS in 2011. The outcome was clinical acceptability as measured by the continuation/failure ratio over the six-month period following the introduction of the first-line treatment. Continuation was defined as at least two refills of the same treatment. Failure was defined as a psychiatric hospitalization, death or at least one filled prescription of another antidepressant, an antipsychotic medication, or a mood-stabilizer. Adjusted Odds Ratios (aOR) and 95% Confidence Interval (CI) were computed through multivariable binary logistic regressions. We ranked antidepressant medications according to clinical acceptability. Escitalopram again was the most acceptable option, and the five following antidepressants were the same as in the replication sample of the proof-of-concept study, in order Fluoxetine, Paroxetine, Sertraline, Citalopram and Venlafaxine with aOR (95% CI) for continuation ranging from 0.79 (0.77-0.81) to 0.66 (0.64-0.67). The present study provides evidence that filled prescription sequences is a widely available, robust and reproductible tool to rank antidepressant treatments in real life settings.

Risk of Death in Individuals Hospitalized for COVID-19 With and Without Psychiatric Disorders: An Observational Multicenter Study in France.

Background: Prior research suggests that psychiatric disorders could be linked to increased mortality among patients with COVID-19. However, whether all or specific psychiatric disorders are intrinsic risk factors of death in COVID-19 or whether these associations reflect the greater prevalence of medical risk factors in people with psychiatric disorders has yet to be evaluated. Methods: We performed an observational, multicenter, retrospective cohort study to examine the association between psychiatric disorders and mortality among patients hospitalized for laboratory-confirmed COVID-19 at 36 Greater Paris University hospitals. Results: Of 15,168 adult patients, 857 (5.7%) had an ICD-10 diagnosis of psychiatric disorder. Over a mean follow-up period of 14.6 days (SD = 17.9), 326 of 857 (38.0%) patients with a diagnosis of psychiatric disorder died compared with 1276 of 14,311 (8.9%) patients without such a diagnosis (odds ratio 6.27, 95% CI 5.40-7.28, p < .01). When adjusting for age, sex, hospital, current smoking status, and medications according to compassionate use or as part of a clinical trial, this association remained significant (adjusted odds ratio 3.27, 95% CI 2.78-3.85, p < .01). However, additional adjustments for obesity and number of medical conditions resulted in a nonsignificant association (adjusted odds ratio 1.02, 95% CI 0.84-1.23, p = .86). Exploratory analyses after the same adjustments suggested that a diagnosis of mood disorders was significantly associated with reduced mortality, which might be explained by the use of antidepressants. Conclusions: These findings suggest that the increased risk of COVID-19-related mortality in individuals with psychiatric disorders hospitalized for COVID-19 might be explained by the greater number of medical conditions and the higher prevalence of obesity in this population and not by the underlying psychiatric disease.

Toward a generalized developmental model of psychopathological liabilities and psychiatric disorders.

BACKGROUND: Most psychiatric disorders are associated with several risk factors, but a few underlying psychopathological dimensions account for the common co-occurrence of disorders. If these underlying psychopathological dimensions mediate associations of the risk factors with psychiatric disorders, it would support a trans-diagnostic orientation to etiological research and treatment development. METHOD: An analysis was performed of the 2012-2013 National Epidemiologic Survey on Alcohol and Related Conditions III (NESARC-III), a US nationally representative sample of non-institutionalized civilian adults, focusing on respondents who were aged ⩾21 (n = 34 712). Structural equation modeling was used to identify the psychopathological dimensions underlying psychiatric disorders; to examine associations between risk factors, psychopathological dimensions and individual disorders; and to test whether associations of risk factors occurring earlier in life were mediated by risk factors occurring later in life. RESULTS: A bifactor model of 13 axis I disorders provided a good fit (CFI = 0.987, TLI = 0.982, and RMSEA = 0.011) including an overall psychopathology factor as measured by all 13 disorders and 2 specific factors, one for externalizing disorders and one for fear-related disorders. A substantial proportion of the total effects of the risk factors occurring early in life were indirectly mediated through factors occurring later in life. All risk factors showed a significant total effect on the general psychopathology, externalizing and fear-related factors. Only 23 of 325 direct associations of risk factors with psychiatric disorders achieved statistical significance. CONCLUSION: Most risk factors for psychiatric disorders are mediated through broad psychopathological dimensions. The central role of these dimensions supports trans-diagnostic etiological and intervention research.