Association between antidepressant use and reduced risk of intubation or death in hospitalized patients with COVID-19: results from an observational study.
Journal
Molecular psychiatry
ISSN: 1476-5578
Titre abrégé: Mol Psychiatry
Pays: England
ID NLM: 9607835
Informations de publication
Date de publication:
09 2021
09 2021
Historique:
received:
19
09
2020
accepted:
07
01
2021
revised:
18
12
2020
pubmed:
5
2
2021
medline:
19
11
2021
entrez:
4
2
2021
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 33536545
doi: 10.1038/s41380-021-01021-4
pii: 10.1038/s41380-021-01021-4
doi:
Substances chimiques
Antidepressive Agents
0
Types de publication
Journal Article
Meta-Analysis
Langues
eng
Sous-ensembles de citation
IM
Pagination
5199-5212Commentaires et corrections
Type : CommentIn
Type : CommentIn
Informations de copyright
© 2021. The Author(s), under exclusive licence to Springer Nature Limited part of Springer Nature.
Références
Hoertel N, Blachier M, Blanco C, Olfson M, Massetti M, Sánchez-Rico M, et al. A stochastic agent-based model of the SARS-CoV-2 epidemic in France. Nat Med. 2020;26:1417–21.
doi: 10.1038/s41591-020-1001-6
Hoertel N, Blachier M, Blanco C, Olfson M, Massetti M, Limosin F, et al. Facing the COVID-19 epidemic in NYC: a stochastic agent-based model of various intervention strategies. MedRxiv. 2020. 2020. https://doi.org/10.1101/2020.04.23.20076885 .
Gordon DE, Jang GM, Bouhaddou M, Xu J, Obernier K, White KM, et al. A SARS-CoV-2 protein interaction map reveals targets for drug repurposing. Nature. 2020;583:459–68.
doi: 10.1038/s41586-020-2286-9
Chevance A, Gourion D, Hoertel N, Llorca P-M, Thomas P, Bocher R, et al. Ensuring mental health care during the SARS-CoV-2 epidemic in France: a narrative review. L’Encephale. 2020;46:S3–S13.
doi: 10.1016/j.encep.2020.03.001
Stebbing J, Phelan A, Griffin I, Tucker C, Oechsle O, Smith D, et al. COVID-19: combining antiviral and anti-inflammatory treatments. Lancet Infect Dis. 2020;20:400–2.
doi: 10.1016/S1473-3099(20)30132-8
Liu Y, Yan L-M, Wan L, Xiang T-X, Le A, Liu J-M, et al. Viral dynamics in mild and severe cases of COVID-19. The Lancet Infectious Diseases. 2020;20:656–7.
doi: 10.1016/S1473-3099(20)30232-2
Hojyo S, Uchida M, Tanaka K, Hasebe R, Tanaka Y, Murakami M, et al. How COVID-19 induces cytokine storm with high mortality. Inflamm Regen. 2020;40:1–7.
doi: 10.1186/s41232-020-00146-3
Köhler CA, Freitas TH, Stubbs B, Maes M, Solmi M, Veronese N, et al. Peripheral alterations in cytokine and chemokine levels after antidepressant drug treatment for major depressive disorder: systematic review and meta-analysis. Mol Neurobiol. 2018;55:4195–206.
pubmed: 28612257
Ye Q, Wang B, Mao J. The pathogenesis and treatment of theCytokine Storm’in COVID-19. J Infect. 2020;80:607–13.
doi: 10.1016/j.jinf.2020.03.037
Gulbins E, Palmada M, Reichel M, Lüth A, Böhmer C, Amato D, et al. Acid sphingomyelinase–ceramide system mediates effects of antidepressant drugs. Nat Med. 2013;19:934–8.
doi: 10.1038/nm.3214
Carpinteiro A, Edwards MJ, Hoffmann M, Kochs G, Gripp B, Weigang S, et al. Pharmacological inhibition of acid sphingomyelinase prevents uptake of SARS-CoV-2 by epithelial cells. Cell Reports Med. 2020;1:100142.
doi: 10.1016/j.xcrm.2020.100142
Zimniak M, Kirschner L, Hilpert H, Seibel J, Bodem J. The serotonin reuptake inhibitor Fluoxetine inhibits SARS-CoV-2. BioRxiv. 2020. https://www.biorxiv.org/content/10.1101/2020.06.14.150490v2 .
Lenze EJ, Mattar C, Zorumski CF, Stevens A, Schweiger J, Nicol GE, et al. Fluvoxamine vs placebo and clinical deterioration in outpatients with symptomatic COVID-19: a randomized clinical trial. JAMA. 2020;324:2292–2300.
doi: 10.1001/jama.2020.22760
Cipriani A, Furukawa TA, Salanti G, Chaimani A, Atkinson LZ, Ogawa Y, et al. Comparative efficacy and acceptability of 21 antidepressant drugs for the acute treatment of adults with major depressive disorder: a systematic review and network meta-analysis. Focus. 2018;16:420–9.
doi: 10.1176/appi.focus.16407
Tham A, Jonsson U, Andersson G, Söderlund A, Allard P, Bertilsson G. Efficacy and tolerability of antidepressants in people aged 65 years or older with major depressive disorder–a systematic review and a meta-analysis. J Affect Disord. 2016;205:1–12.
doi: 10.1016/j.jad.2016.06.013
Krause M, Gutsmiedl K, Bighelli I, Schneider-Thoma J, Chaimani A, Leucht S. Efficacy and tolerability of pharmacological and non-pharmacological interventions in older patients with major depressive disorder: A systematic review, pairwise and network meta-analysis. Eur Neuropsychopharmacol. 2019;29:1003–22.
doi: 10.1016/j.euroneuro.2019.07.130
Williamson E, Walker AJ, Bhaskaran KJ, Bacon S, Bates C, Morton CE, et al. OpenSAFELY: factors associated with COVID-19-related hospital death in the linked electronic health records of 17 million adult NHS patients. MedRxiv. 2020. https://doi.org/10.1101/2020.05.06.20092999 .
Devlin J, Chang M-W, Lee K, Toutanova K. Bert: Pre-training of deep bidirectional transformers for language understanding. ArXiv. 2018. https://arxiv.org/abs/1810.04805 .
Zhou F, Yu T, Du R, Fan G, Liu Y, Liu Z, et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet. 2020;395:1054–62.
doi: 10.1016/S0140-6736(20)30566-3
Ruan Q, Yang K, Wang W, Jiang L, Song J. Clinical predictors of mortality due to COVID-19 based on an analysis of data of 150 patients from Wuhan, China. Intensive Care Med. 2020;46:846–8.
doi: 10.1007/s00134-020-05991-x
Hur K, Price CP, Gray EL, Gulati RK, Maksimoski M, Racette SD, et al. Factors associated with intubation and prolonged intubation in hospitalized patients with COVID-19. Otolaryngol Head Neck Surg. 2020;163:170–8.
doi: 10.1177/0194599820929640
Hoertel N, Sánchez-Rico M, Vernet R, Beeker N, Neuraz A, Alvarado JM, et al. Dexamethasone use and Mortality in Hospitalized Patients with Coronavirus Disease 2019: a Multicenter Retrospective Observational Study. MedRxiv. 2020. https://doi.org/10.1101/2020.10.23.20218172 .
Haut Conseil de la Santé Publique. Statement on the management at home or in a care facility of suspected or confirmed Covid-19 patients. April 8, 2020. Statement on the management at home or in a care facility of suspected or confirmed Covid-19 patients. https://www.hcsp.fr\textgreater.
Lagunas‐Rangel FA. Neutrophil‐to‐lymphocyte ratio and lymphocyte‐to‐C‐reactive protein ratio in patients with severe coronavirus disease 2019 (COVID‐19): a meta‐analysis. J Med Virol. 2020;92:1733–4.
doi: 10.1002/jmv.25819
Hoertel N, Sánchez-Rico M, Vernet R, Jannot A-S, Neuraz A, Blanco C, et al. Observational study of chlorpromazine in hospitalized patients with Covid-19. MedRxiv. 2020. 2020. https://doi.org/10.1101/2020.07.15.20154310 .
Hoertel N, Sánchez-Rico M, Vernet R, Jannot A-S, Neuraz A, Blanco C, et al. Observational study of haloperidol in hospitalized patients with Covid-19. MedRxiv. 2020. https://doi.org/10.1101/2020.07.15.20150490 .
Robins JM, Hernán MÁ, Brumback B. Marginal structural models and causal inference in epidemiology. Epidemiology. 2000;11:550–60.
doi: 10.1097/00001648-200009000-00011
Geleris J, Sun Y, Platt J, Zucker J, Baldwin M, Hripcsak G, et al. Observational study of hydroxychloroquine in hospitalized patients with Covid-19. N. Engl J Med. 2020;382:2411–8.
doi: 10.1056/NEJMoa2012410
Kaplan EL, Meier P. Nonparametric estimation from incomplete observations. J Am Stat Assoc. 1958;53:457–81.
doi: 10.1080/01621459.1958.10501452
Efron B. Nonparametric standard errors and confidence intervals. Can J Stat. 1981;9:139–58.
doi: 10.2307/3314608
Hayasaka Y, Purgato M, Magni LR, Ogawa Y, Takeshima N, Cipriani A, et al. Dose equivalents of antidepressants: evidence-based recommendations from randomized controlled trials. J Affect Disord. 2015;180:179–84.
doi: 10.1016/j.jad.2015.03.021
Von Elm E, Altman DG, Egger M, Pocock SJ, Gøtzsche PC, Vandenbroucke JP. The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies. Ann Intern Med. 2007;147:573–7.
doi: 10.7326/0003-4819-147-8-200710160-00010
Wang QQ, Kaelber DC, Xu R, Volkow ND. COVID-19 risk and outcomes in patients with substance use disorders: analyses from electronic health records in the United States. Mol Psychiatry. 2021;26:30–9.
doi: 10.1038/s41380-020-00880-7
Li L, Li F, Fortunati F, Krystal JH. Association of a prior psychiatric diagnosis with mortality among hospitalized patients with coronavirus disease 2019 (COVID-19) Infection. JAMA Netw Open. 2020;3:e2023282–e2023282.
doi: 10.1001/jamanetworkopen.2020.23282
Le Strat Y, Hoertel N. Correlation is no causation: gymnasium proliferation and the risk of obesity. Addiction. 2011;106:1871–2.
doi: 10.1111/j.1360-0443.2011.03547.x