Can selective serotonin reuptake inhibitors/serotonin and norepinephrine reuptake inhibitor antidepressants decrease the "cytokine storm" in the course of COVID-19 pneumonia?

Fei, Leonardo; Santarelli, G.; D’Anna, Giulio; Moretti, Sandra; Mirossi, Giulia; Patti, Andrea; Sanfilippo, Giuseppe; Almerigogna, Fabio; Berni, Andrea; Caldini, Eleonora; Lagi, Filippo; Para, Ombretta; Vaudo, Micol; Vultaggio, Alessandra

doi:10.23736/s0031-0808.21.04436-0

Cited by 15 publications

(42 citation statements)

References 28 publications

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“…Other selective serotonin reuptake inhibitors (SSRI), mirtazapine, venlafaxine, and trazodone were associated with reduced SARS-CoV-2 infection rates as well as reduced COVID-19 morbidity and mortality in 4 retrospective studies, 1 with psychiatric inpatients (EBM level 3) 17 and the other 3 evaluating larger general hospital samples affected by COVID-19, all EBM level 3. 7 , 9 , 19 Three further retrospective studies described no relevant influence of ADs on COVID-19 severity and mortality, 2 of them using small sample sizes (EBM level 3 20 and EBM level 4), 21 and the remaining study with a large heterogeneous COVID-19 population (EBM level 2). 4 The least specific study was cross-sectional and described that psychotropic drugs (including ADs) were associated with increased COVID-19 severity and mortality in the Danish general population (EBM level 3).…”

Section: Results/findingsmentioning

confidence: 99%

COVID-19 Outcomes: Does the Use of Psychotropic Drugs Make a Difference? Accumulating Evidence of a Beneficial Effect of Antidepressants—A Scoping Review

Bonnet

Juckel

2022

J Clin Psychopharmacol

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Purpose/BackgroundStudies for repurposed drugs in severe acute respiratory syndrome coronavirus type 2–infected and coronavirus disease 2019 (COVID-19) patients are ongoing. According to preclinical research, antidepressants (ADs) might be useful in the treatment of COVID-19.Methods/ProceduresWe conducted a scoping review including clinical studies on AD effects on SARS-CoV-2 infection and COVID-19.Finding/ResultsAs of January 2, 2022, we found 14 clinical studies, which could be included into this review. Among them, there were 2 randomized, placebo-controlled studies and 2 prospective parallel-group studies about the efficacy/effectiveness and tolerability of fluvoxamine. The remaining studies were mainly retrospective studies considering COVID-19 hospital populations predominantly exposed to fluoxetine (N = 3), other selective serotonin reuptake inhibitors (SSRI), selective norepinephrine reuptake inhibitors (SNRI), and trazodone. The vast majority were hospital studies and assessed COVID-19 severity (morbidity) and mortality as primary endpoints. The only outpatient study (fluvoxamine) investigated the COVID-19–related hospitalization rate, and 1 psychiatric hospital study (SSRI, SNRI, trazodone) focused on the SARS-CoV-2 infection rate.Implications/ConclusionsAt present, the best evidence of an “anti–COVID-19” potential of ADs exists for fluvoxamine and, to a lesser extent, for fluoxetine. Preliminary evidence had found that patients exposed to SSRI or SNRI substance classes might have a reduced mortality risk and that trazodone might reduce SARS-CoV-2 infection rates. Three studies found no relevant influence of ADs on COVID-19 morbidity and mortality, and 1 study described increased mortality. The latter study, however, did not differentiate between psychotropic medication and ADs. Tricyclics and monoamine oxidase inhibitors are still absolute “dark zones” in COVID-19 research. Further controlled studies testing the effectiveness/efficacy and tolerability/safety (as well as the treatment timing and duration) of different AD substance classes in COVID-19 and post/long-COVID patients of various populations are warranted.

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Section: Results/findingsmentioning

confidence: 99%

COVID-19 Outcomes: Does the Use of Psychotropic Drugs Make a Difference? Accumulating Evidence of a Beneficial Effect of Antidepressants—A Scoping Review

Bonnet

Juckel

2022

J Clin Psychopharmacol

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“…The selection process of articles is shown in Figure 1. Twelve articles were included and classified into the followings: six cohort studies (8,(16)(17)(18)(19)(20), three case-control studies (21)(22)(23) and three clinical trials (24)(25)(26). There were 872 cases and 879 controls in clinical trials, 15950 cases and 96638 controls in the cohort studies and 97,844 cases and 80518 controls in the case-control studies with the total population of 292701 in the whole studies (114666 cases and 178035 controls).…”

Section: Resultsmentioning

confidence: 99%

“…According to nine studies (8,(16)(17)(18)(21)(22)(23)(24)(25), the mean age of total patients was 58.1 years old with 40 and 56.5 years old in case and control groups in eight studies, respectively (8,17,18,20,21,(23)(24)(25). 49.6 percent of patients were female according to eleven studies (8,(16)(17)(18)(19)(20)(21)(23)(24)(25)(26).…”

Section: Patient Characteristicsmentioning

confidence: 99%

“…This number was 52% in case groups and 49.3% in control groups according to nine studies (17)(18)(19)(20)(21)(23)(24)(25)(26). Cases and controls were matched with age, sex, comorbidities, smoking status, BMI category and etc.…”

Section: Patient Characteristicsmentioning

confidence: 99%

“…Seven studies (18,20,21,(23)(24)(25)(26) only used or surveyed SSRIs as anti-depressant in case groups (fluvoxamine in five studies (18,20,(24)(25)(26), fluoxetine in two studies (18,23) and Escitalopram in one study (21)). In remain five studies (8,16,17,19,22) different types of SSRIs, SNRIs and TCAs were used or surveyed. Anti-depressant type, dosage, frequency and follow-up time are shown in table 6.…”

Section: Interventions and Exposures Characteristicsmentioning

confidence: 99%

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The effect of antidepressants on severity of COVID-19 in hospitalized patients: A systematic review and meta-analysis

Nakhaee

Bayati

Rahmanian

et al. 2022

Preprint

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Introduction: Clinical depression and the subsequent low immunity is a comorbidity that can act as a risk factor for severity of COVID-19 cases. Antidepressants such as SSRI and SNRI are associated with immune-modulatory effects, which dismiss inflammatory response and reduce lung tissue damage. The current systematic review and meta-analysis aims to evaluate the effect of antidepressant drugs on prognosis and severity of COVID-19 in hospitalized patients. Methods: A systematic search was carried out in PubMed/Medline, EMBASE, and Scopus up to January 16, 2022. The following keywords were used: “COVID-19”, “SARS-CoV-2”, “2019-nCoV”, “SSRI”, “SNRI”, “TCA”, “MAOI”, and “Antidepressant”. The pooled risk ratio (RR) with 95% CI was assessed using a fixed or random-effect model. We considered P < 0.05 as statistically significant for publication bias. Data were analyzed by Comprehensive Meta-Analysis software, Version 2.0 (Biostat, Englewood, NJ). Results: Twelve studies were included in our systematic review. Three of them were experimental with 1751, and nine of them were observational with 290,950 participants. Seven out of twelve articles revealed the effect of antidepressants on reducing severity of COVID-19. SSRI medications, including Fluvoxamine, Escitalopram, Fluoxetine, and Paroxetine and also among the SNRI drugs Venlafaxine are also reasonably associated with reduced risk of intubation or death. There were four studies showing no significant effect and one study showing the negative effect of antidepressants on prognosis of covid-19. The meta-analysis on clinical trials showed that fluvoxamine could significantly decrease the severity outcomes of COVID-19 (RR: 0.745; 95% CI: 0.580-0.956) Conclusions: Most of the evidence supports that the use of antidepressant medications, mainly Fluvoxamine may decrease the severity and improve the outcome in hospitalizes patients with sars-cov-2. Some studies showed contradictory findings regarding the effects of antidepressants on severity of COVID-19. Further experimental studies should be conducted to clarify the effects of antidepressants on severity of COVID-19.

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The effect of selective serotonin and norepinephrine reuptake inhibitors on clinical outcome of COVID‐19 patients: A systematic review and meta‐analysis

Firouzabadi

Kheshti

Abdollahifard

et al. 2022

Health Science Reports

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Background and Aim Due to the high social and economic burden and also mortality and morbidity caused by coronavirus disease 2019 (COVID‐19) in the past few years, researchers have aimed at finding solutions to suppressing the severity of infection. Recently, selective serotonin and serotonin‐norepinephrine reuptake inhibitors (SSRI/SNRI) have been investigated as an adjuvant treatment for COVID‐19. The aim of the current study was to investigate the impact of SSRI/SNRIs on outcomes of COVID‐19 patients. Methods In this systematic review and meta‐analysis, a comprehensive search strategy consisting of relevant words was performed by two researchers in PubMed, Scopus and EMBASE libraries. Studies reporting the effect of SSRI and/or SNRI use in COVID‐19 patients' outcome were included. Hospitalization, mortality, hospitalization event, and length of hospital stay were considered as main outcomes of this study. Analysis was carried out using Comprehensive Meta‐Analysis (CMA‐version 2) and final data were reported as odds ratio (OR) and 95% confidence interval (CI). Results Our search led to the final selection of 9 articles including 15,287 patients. The effect of fluvoxamine, fluoxetine, and the overall effect of SSRI/SNRI use on mortality of COVID‐19 patients were investigated in 3, 2, and 7 articles, respectively. The results of our analyses showed that these medications could significantly decrease mortality of COVID‐19 patients (OR and 95% [CI]: 0.595 [0.467–0.758], 0.620 [0.469–0.821], and 0.596 [0.437–0.813]). The effect of SSRI/SNRIs on hospitalization events of COVID‐19 patients was not significant (OR: 0.240% and 95% CI: 0.041–1.4). Also, length of hospital stay was longer in patients who administrated SSRIs. Conclusion According to this study's results, SSRI/SNRIs may be effective in reducing mortality of COVID‐19 patients, suggesting the superiority of fluvoxamine to fluoxetine. The safety profile and affordable cost of SSRI/SNRIs for a short‐term use may be other reasons to propose them as beneficial medications in preventing mortality in COVID‐19.

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Can selective serotonin reuptake inhibitors/serotonin and norepinephrine reuptake inhibitor antidepressants decrease the "cytokine storm" in the course of COVID-19 pneumonia?

Cited by 15 publications

References 28 publications

COVID-19 Outcomes: Does the Use of Psychotropic Drugs Make a Difference? Accumulating Evidence of a Beneficial Effect of Antidepressants—A Scoping Review

COVID-19 Outcomes: Does the Use of Psychotropic Drugs Make a Difference? Accumulating Evidence of a Beneficial Effect of Antidepressants—A Scoping Review

The effect of antidepressants on severity of COVID-19 in hospitalized patients: A systematic review and meta-analysis

The effect of selective serotonin and norepinephrine reuptake inhibitors on clinical outcome of COVID‐19 patients: A systematic review and meta‐analysis

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