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.

Somatic Symptom Disorder-B criteria scale (SSD-12): Psychometric properties of the French version and associations with health outcomes in a population-based cross-sectional study.

OBJECTIVE: The 12-item Somatic Symptom Disorder-B Criteria Scale (SSD-12) is a self-reported questionnaire designed to assess the B criteria of the DSM-5 somatic symptom disorder. In this cross-sectional study, we aimed to examine the psychometric properties of the SSD-12 French version and associated health outcomes. METHODS: Participants were volunteers from the population-based CONSTANCES cohort who reported at least one new symptom that occurred between March 2020 and January 2021. Depressive symptoms were measured with the Center for Epidemiologic Studies-Depression scale (CES-D). RESULTS: A total of 18,796 participants completed the SSD-12. The scree plot was consistent with a 1-factor structure, while goodness-of-fit indices of the confirmatory factorial analyses and clinical interpretability were consistent with a 3-factor structure (excluding the item 7): 'Perceived severity', 'Perceived impairment', 'Negative expectations'. The Cronbach's α coefficients of the total and factors scores were 0.90, 0.88, 0.84 and 0.877, respectively. The total score was associated with depressive symptoms (Spearmann's rho: 0.32), self-rated health (-0.46), the number of persistent symptoms (0.32), and seeking medical consultation (odds ratio [95% confidence interval] for one interquartile range increase: 1.51 [1.48-1.54]). Among participants seeking medical consultation, those with higher SSD-12 scores were more likely to have their symptoms attributed to "stress/anxiety/depression" (1.32 [1.22-1.43]) and "psychosomatic origin" (1.25 [1.20-1.29]), and less to "COVID-19" (0.89 [0.85-0.93]). CONCLUSION: While the SSD-12 French version can be used as a unidimensional tool, it also has a 3-factor structure, somewhat different from the DSM-5 theoretical structure, with high internal consistency and clinically meaningful associations with other health outcomes.

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.

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.

Housing conditions and changes in professional activity during lockdown and the risk of prevalent and incident depression: Findings from the CONSTANCES cohort.

BACKGROUND: Material conditions of lockdown and changes in regular functioning may have played a role on depressive manifestations. We aimed to examine the association between housing conditions and changes in professional activity and depression during the first COVID-19 outbreak in France. METHOD: Participants of the CONSTANCES cohort were followed online. A first questionnaire covered the lockdown period (assessing housing conditions and changes in professional activity), and a second the post-lockdown period (assessing depression using the Center of Epidemiologic Studies Depression-Scale (CES-D)). Incident depression was also estimated (with a previous CES-D measure). Logistic regression models were applied. RESULTS: 22,042 participants (median age 46 years, 53.2 % women) were included and 20,534 had a previous CES-D measure. Depression was associated with female gender, lower household income and past history of depression. A negative gradient between the number of rooms and the likelihood of depression was consistently observed (OR = 1.55 95 % [1.19-2.00] for one room, OR = 0.76 [0.65-0.88] for seven rooms), while a U-shape relationship was observed with the number of people living together (OR = 1.62 [1.42-1.84] for living alone, OR = 1.44 [1.07-1.92] for six persons). These associations were also observed with incident depression. Changes in professional activity were associated with depression (Started distance working (OR = 1.33 [1.17-1.50]). Starting distance working was also associated with incident depression (OR = 1.27 [1.08-1.48]). LIMITATION: A cross-sectional design was used. CONCLUSION: The consequences of lockdown on depression may vary depending on living conditions and changes in professional activity, including distance working. These results could help to better identify vulnerable people to promote mental health.

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.

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.

Acceptability of Second-Line Antidepressant Medications Using Filled Prescription Sequences in a Nationwide Cohort Study.

Background: Although about half of patients do not respond to a first-line antidepressant medication, there is no consensus on the best second-line option. The aim of this nationwide population-based study was to rank antidepressants according to their relative acceptability (ie, efficacy and tolerability) using filled prescription sequences after failure of first treatment.Methods: About 1.2 million people were identified as new antidepressant users in the French national health data system in 2011. The inclusion criterion was having at least 2 filled prescriptions of a second-line treatment after a filled prescription of a first-line treatment, resulting in 63,726 participants. The outcome was clinical acceptability as measured by the continuation/change ratio for second-line treatment. Continuation sequence was defined as at least 2 refills of the same treatment. Change sequence was defined as at least 1 filled prescription of another antidepressant. Adjusted odds ratios (aORs) were computed through multivariable binary logistic regressions.Results: Intraclass switch had a better acceptability than interclass switch (aOR [95% CI]: 1.23 [1.20-1.28]). According to the first-line treatment, intraclass switch remained more acceptable for selective serotonin reuptake inhibitors only (1.37 [1.31-1.42]). For α2 blockers and tricyclic agents, combination antidepressant therapy was the most acceptable second-line option (1.59 [1.27-2.01] and 2.53 [1.53-4.04], respectively), whereas for serotonin-norepinephrine reuptake inhibitors there was no significant difference between the strategies. For other antidepressants, intraclass switch had lower acceptability than interclass switch (0.70 [0.51-0.95]).Conclusions: Administrative claim databases may help with ranking acceptability of second-line treatments in real world settings and complement randomized controlled trials in informing clinicians about the most acceptable second-line options according to the first-line treatment.

Outcomes associated with antidepressant treatment according to the number of prescriptions and treatment changes: 5-year follow-up of a nation-wide cohort study.

Background: Naturalistic studies regarding clinical outcomes associated with antidepressant treatment duration have yielded conflicting results, possibly because they did not consider the occurrence of treatment changes. This nation-wide population-based study examined the association between the number of filled prescriptions and treatment changes and long-term psychiatric outcomes after antidepressant treatment initiation. Methods: Based on the French national health insurance database, 842,175 adults who initiated an antidepressant treatment in 2011 were included. Cox proportional-hazard multi-adjusted regression models examined the association between the number of filled prescriptions and the occurrence of treatment changes 12 months after initiation and four outcomes during a 5-year follow-up: psychiatric hospitalizations, suicide attempts, sick leaves for a psychiatric diagnosis, new episodes of antidepressant treatment. Results: During a mean follow-up of 4.5 years, the incidence rates of the four above-mentioned outcomes were 13.49, 2.47, 4.57, and 92.76 per 1,000 person-years, respectively. The number of filled prescriptions was associated with each outcome (adjusted HRs [95% CI] for one additional prescription ranging from 1.01 [1.00-1.02] to 1.10 [1.09-1.11]), as was the occurrence of at least one treatment change vs. none (adjusted HRs [95% CI] ranging from 1.18 [1.16-1.21] to 1.57 [1.79-1.65]). Furthermore, the adjusted HRs [95% CI] of the number of filled prescriptions were greater in patients with (vs. without) a treatment change for psychiatric hospitalizations (1.12 [1.11-1.14] vs. 1.09 [1.08-1.10], p for interaction = 0.002) and suicide attempts (1.12 [1.09-1.15] vs. 1.06 [1.04-1.08], p for interaction = 0.006). Limitations: Lack of clinical data about the disorders warranting the prescriptions or their severity. Conclusion: Considering treatment changes is critical when using administrative claims database to examine the long-term psychiatric outcomes of antidepressant treatments in real-life settings.