IMPORTANCEAntidepressant use is increasing worldwide. Yet, contrasting evidence on the safety of antidepressants is available from meta-analyses, and the credibility of these findings has not been quantified. OBJECTIVE To grade the evidence from published meta-analyses of observational studies that assessed the association between antidepressant use or exposure and adverse health outcomes.

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The aim of this study is to provide a more accurate representation of COVID-19's case fatality rate (CFR) by performing meta-analyses by continents and income, and by comparing the result with pooled estimates. We used multiple | ABOU GHAYDA ET AL.

Empirical evidence indicates a significant bidirectional association between mental disorders and physical diseases, but the prospective impact of men­tal disorders on clinical outcomes of physical diseases has not been comprehensively outlined. In this PRISMA‐ and COSMOS‐E‐compliant umbrella review, we searched PubMed, PsycINFO, Embase, and Joanna Briggs Institute Database of Systematic Reviews and Implementation Reports, up to March 15, 2022, to identify systematic reviews with meta‐analysis that examined the prospective association between any mental disorder and clinical outcomes of physical diseases. Primary outcomes were disease‐specific mortality and all‐cause mortality. Secondary outcomes were disease‐specific incidence, functioning and/or disability, symptom severity, quality of life, recurrence or progression, major cardiac events, and treatment‐related outcomes. Additional inclusion criteria were further applied to primary studies. Random effect models were employed, along with I2 statistic, 95% prediction intervals, small‐study effects test, excess significance bias test, and risk of bias (ROBIS) assessment. Associations were classified into five credibility classes of evidence (I to IV and non‐significant) according to established criteria, complemented by sensitivity and subgroup analyses to examine the robustness of the main analysis. Statistical analysis was performed using a new package for conducting umbrella reviews (https://metaumbrella.org/). Population attributable fraction (PAF) and generalized impact fraction (GIF) were then calculated for class I‐III associations. Forty‐seven systematic reviews with meta‐analysis, encompassing 251 non‐overlapping primary studies and reporting 74 associations, were included (68% were at low risk of bias at the ROBIS assessment). Altogether, 43 primary outcomes (disease‐specific mortality: n=17; all‐cause mortality: n=26) and 31 secondary outcomes were investigated. Although 72% of associations were statistically significant (p<0.05), only two showed convincing (class I) evidence: that between depressive disorders and all‐cause mortality in patients with heart failure (hazard ratio, HR=1.44, 95% CI: 1.26‐1.65), and that between schizophrenia and cardiovascular mortality in patients with cardiovascular diseases (risk ratio, RR=1.54, 95% CI: 1.36‐1.75). Six associations showed highly suggestive (class II) evidence: those between depressive disorders and all‐cause mortality in patients with diabetes mellitus (HR=2.84, 95% CI: 2.00‐4.03) and with kidney failure (HR=1.41, 95% CI: 1.31‐1.51); that between depressive disorders and major cardiac events in patients with myocardial infarction (odds ratio, OR=1.52, 95% CI: 1.36‐1.70); that between depressive disorders and dementia in patients with diabetes mellitus (HR=2.11, 95% CI: 1.77‐2.52); that between alcohol use disorder and decompensated liver cirrhosis in patients with hepatitis C (RR=3.15, 95% CI: 2.87‐3.46); and that between schizophrenia and cancer mortality in patients with cancer (standardized mean ratio...

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