COVID-19 Prognosis in Association with Antidepressant Use

Abstract

Introduction Various subtypes of severe acute respiratory syndrome coronavirus 2 and variations among immune systems in different ethnicities need to be considered to understand the outcomes of coronavirus disease 2019 (COVID-19). This study aimed to provide evidence for the association between the use of antidepressants and the severity of COVID-19.

Methods We used the National Health Information Data-COVID database. Patients with one or more prescriptions of any antidepressant were selected as the exposure group. Detailed analyses were performed to determine the type of medication associated with the prognosis.

Results The use of selective serotonin reuptake inhibitors (SSRIs) was associated with a lower risk of severe outcomes of COVID-19, whereas the use of tricyclic antidepressants (TCAs) increased the risk of poor prognosis of COVID-19. Detailed analyses showed that escitalopram was significantly associated with better clinical outcomes, and nortriptyline was linked to more severe COVID-19 outcomes.

Conclusion This study revealed an association between antidepressants and COVID-19 prognosis. SSRIs were significantly associated with a lower risk of severe outcomes, whereas TCAs were related to the poor prognosis of COVID-19.

Key words

COVID-19 - antidepressants - SSRI - TCA

Publication History

Received: 28 October 2021
Received: 27 April 2022

Accepted: 28 April 2022

Article published online:
02 June 2022

• References

• 1 WHO. (2022). WHO Coronavirus (COVID-19) Dashboard. Retrieved from https://covid19.who.int/
• 2 Korber B, Fischer WM, Gnanakaran S. et al. Tracking changes in SARS-CoV-2 spike: Evidence that D614G increases infectivity of the COVID-19 virus. Cell 2020; 182: 812-827.e19
• 3 Liu J, Li S, Liu J. et al. Longitudinal characteristics of lymphocyte responses and cytokine profiles in the peripheral blood of SARS-CoV-2 infected patients. EBioMedicine 2020; 55: 102763
• 4 Zhang W, Zhao Y, Zhang F. et al. The use of anti-inflammatory drugs in the treatment of people with severe coronavirus disease 2019 (COVID-19): The perspectives of clinical immunologists from China. Clin Immunol 2020; 214: 108393
• 5 Coates MD, Mahoney CR, Linden DR. et al. Molecular defects in mucosal serotonin content and decreased serotonin reuptake transporter in ulcerative colitis and irritable bowel syndrome. Gastroenterology 2004; 126: 1657-1664
• 6 Pacheco R, Gallart T, Lluis C. et al. Role of glutamate on T-cell mediated immunity. J Neuroimmunol 2007; 185: 9-19
• 7 Urits I, Peck J, Orhurhu MS. et al. Off-label antidepressant use for treatment and management of chronic pain: Evolving understanding and comprehensive review. Curr Pain Headache Rep 2019; 23: 66
• 8 Köhler CA, Freitas TH, Stubbs B. 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: 4195-4206
• 9 Lenze EJ, Mattar C, Zorumski CF. et al. Fluvoxamine vs placebo and clinical deterioration in outpatients with symptomatic COVID-19: A randomized clinical trial. JAMA 2020; 324: 2292-2300
• 10 Reis G, Dos Santos Moreira-Silva EA, Silva DCM. et al. Effect of early treatment with fluvoxamine on risk of emergency care and hospitalisation among patients with COVID-19: The TOGETHER randomised, platform clinical trial. Lancet Glob Health 2022; 10: e42-e51
• 11 Seftel D, Boulware DR. Prospective cohort of fluvoxamine for early treatment of coronavirus disease 19. Open Forum Infect Dis 2021; 8 ofab050
• 12 Schloer S, Brunotte L, Goretzko J. et al. Targeting the endolysosomal host-SARS-CoV-2 interface by clinically licensed functional inhibitors of acid sphingomyelinase (FIASMA) including the antidepressant fluoxetine. Emerg Microbes Infect 2020; 9: 2245-2255
• 13 Zimniak M, Kirschner L, Hilpert H. et al. The serotonin reuptake inhibitor Fluoxetine inhibits SARS-CoV-2 in human lung tissue. Sci Rep 2021; 11: 5890
• 14 Pashaei Y. Drug repurposing of selective serotonin reuptake inhibitors: Could these drugs help fight COVID-19 and save lives?. J Clin Neurosci 2021; 88: 163-172
• 15 Hoertel N, Sánchez-Rico M, Vernet R. et al. Association between antidepressant use and reduced risk of intubation or death in hospitalized patients with COVID-19: Results from an observational study [published online ahead of print, 2021 Feb 4]. Mol Psychiatry 2021;
• 16 Marrelli D, Polom K, Roviello F. Ethnicity-related differences in tumor immunity: A new possible explanation for gastric cancer prognostic variability?. Transl Gastroenterol Hepatol 2016; 1: 11
• 17 Suissa S. Immortal time bias in pharmaco-epidemiology. Am J Epidemiol 2008; 167: 492-499
• 18 Ho FK, Petermann-Rocha F, Gray SR. et al. Is older age associated with COVID-19 mortality in the absence of other risk factors? General population cohort study of 470,034 participants. PLoS One 2020; 15: e0241824
• 19 Michaud M, Balardy L, Moulis G. et al. Proinflammatory cytokines, aging, and age-related diseases. J Am Med Dir Assoc 2013; 14: 877-882
• 20 Patel SK, Velkoska E, Burrell LM. Emerging markers in cardiovascular disease: where does angiotensin-converting enzyme 2 fit in?. Clin Exp Pharmacol Physiol 2013; 40: 551-559
• 21 Cai R, Zhang J, Zhu Y. et al. Mortality in chronic kidney disease patients with COVID-19: A systematic review and meta-analysis. Int Urol Nephrol 2021; 53: 1623-1629
• 22 Sangkuhl K, Klein TE, Altman RB. Selective serotonin reuptake inhibitors pathway. Pharmacogenet Genomics 2009; 19: 907-909
• 23 Gillman PK. Tricyclic antidepressant pharmacology and therapeutic drug interactions updated. Br J Pharmacol 2007; 151: 737-748
• 24 Fallarino F, Volpi C, Fazio F. et al. Metabotropic glutamate receptor-4 modulates adaptive immunity and restrains neuroinflammation. Nat Med 2010; 16: 897-902
• 25 Talhada D, Rabenstein M, Ruscher K. The role of dopaminergic immune cell signalling in poststroke inflammation. Ther Adv Neurol Disord 2018; 11: 1756286418774225
• 26 Nataf S. An alteration of the dopamine synthetic pathway is possibly involved in the pathophysiology of COVID-19. J Med Virol 2020; 92: 1743-1744
• 27 Klempin F, Mosienko V, Matthes S. et al. Depletion of angiotensin-converting enzyme 2 reduces brain serotonin and impairs the running-induced neurogenic response. Cell Mol Life Sci 2018; 75: 3625-3634
• 28 Mathews MJ, Mathews EH, Liebenberg L. The mechanisms by which antidepressants may reduce coronary heart disease risk. BMC Cardiovasc Disord 2015; 15: 82
• 29 Herr N, Bode C, Duerschmied D. The Effects of Serotonin in immune cells. Front Cardiovasc Med 2017; 4: 48
• 30 Dionisie V, Filip GA, Manea MC. et al. The anti-inflammatory role of SSRI and SNRI in the treatment of depression: A review of human and rodent research studies. Inflammopharmacology 2021; 29: 75-90
• 31 Gałecki P, Mossakowska-Wójcik J, Talarowska M. The anti-inflammatory mechanism of antidepressants - SSRIs, SNRIs. Prog Neuropsychopharmacol Biol Psychiatry 2018; 80: 291-294
• 32 Sanchez C, Reines EH, Montgomery SA. A comparative review of escitalopram, paroxetine, and sertraline: Are they all alike?. Int Clin Psychopharmacol 2014; 29: 185-196
• 33 Murphy E, Hou L, Maher BS. et al. Race, genetic ancestry and response to antidepressant treatment for major depression. Neuropsychopharmacology 2013; 38: 2598-2606
• 34 Matsuda KT, Cho MC, Lin KM. et al. Clozapine dosage, serum levels, efficacy, and side-effect profiles: A comparison of Korean-American and Caucasian patients. Psychopharmacol Bull 1996; 32: 253-257
• 35 Fujii T, Mashimo M, Moriwaki Y. et al. Physiological functions of the cholinergic system in immune cells. J Pharmacol Sci 2017; 134: 1-21
• 36 Borovikova LV, Ivanova S, Zhang M. et al. Vagus nerve stimulation attenuates the systemic inflammatory response to endotoxin. Nature 2000; 405: 458-462