Mortality Risk Among Patients With COVID-19 Prescribed Selective Serotonin Reuptake Inhibitor Antidepressants

Mendelson

et al. 2021

JCM

SARS-CoV-2 continues to have devastating consequences worldwide. Though vaccinations have helped reduce spread, new strains still pose a threat. Therefore, it is imperative to identify treatments that prevent severe COVID-19 infection. Recently, acute use of SSRI antidepressants in COVID+ patients was shown to reduce symptom severity. The aim of this retrospective observational study was to determine whether COVID+ patients already on SSRIs upon hospital admission had reduced mortality compared to COVID+ patients not on chronic SSRI treatment. Electronic medical records of 9044 patients with laboratory-confirmed COVID-19 from six hospitals were queried for demographic and clinical information. Using R, a logistic regression model was run with mortality as the outcome and SSRI status as the exposure. In this sample, no patients admitted on SSRIs had them discontinued. There was no significant difference in the odds of dying between COVID+ patients on chronic SSRIs vs. those not taking SSRIs, after controlling for age category, gender, and race. This study shows the utility of large clinical databases in determining what commonly prescribed drugs might be useful in treating COVID-19. During pandemics due to novel infectious agents, it is critical to evaluate safety and efficacy of drugs that might be repurposed for treatment.

Section: Discussionmentioning

confidence: 99%

Ongoing Use of SSRIs Does Not Alter Outcome in Hospitalized COVID-19 Patients: A Retrospective Analysis

Mendelson

et al. 2021

JCM

“…From the treatment perspective, a multicenter, retrospective, observational study on hospitalized patients with COVID-19 has indicated a reduced risk of intubation or death in patients taking antidepressants, particularly fluoxetine (Hoertel et al 2021b). Similarly, a large retrospective cohort study observed reduced mortality in patients treated with fluoxetine or fluvoxamine compared to matched patients not treated with these or any other SSRIs (Oskotsky et al 2021). Two further randomized placebo-controlled trials and a prospective real-world study support the observation of a lower risk of clinical deterioration over two weeks of treatment with fluvoxamine (Lenze et al 2020;Reis et al 2022;Seftel and Boulware 2021).…”

Section: Introductionmentioning

confidence: 99%

COVID-19 and its clinical severity are associated with alterations of plasma sphingolipids and enzyme activities of sphingomyelinase and ceramidase

Mühle

Kremer

Vetter

et al. 2022

Preprint

In the current pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2; COVID-19), a better understanding of the underlying mechanisms is essential to reduce morbidity and mortality and treat post-COVID-19 disease. Here, we analyzed alterations of sphingolipids and their metabolizing enzymes in 125 men and 74 women tested positive for SARS-CoV-2 and hospitalized with mild, moderate or severe symptoms or after convalescence. The activities of acid and neutral sphingomyelinases (ASM, NSM), which hydrolyze sphingomyelin to ceramide, were significantly increased in COVID-19 patients, while the activity of neutral ceramidase (NC), which hydrolyzes ceramide to sphingosine, was reduced. These alterations could each contribute to elevated ceramide levels in patients. Accordingly, liquid chromatography tandem-mass spectrometry (LC-MS/MS) yielded increased levels of ceramides 16:0 and 18:0 with highest levels in severely affected patients and similar effects for dihydroceramides 16:0 and 18:0, whereas levels of (dihydro-)ceramides 24:0 were reduced. Furthermore, sphingomyelin 20:0; 22:0 and 24:0 as substrates of ASM and NSM as well as their dihydrosphingomyelin counterparts were reduced in patients as well as sphingosine-1-phosphate further downstream of NC activity. Effects of NSM, NC, ceramides and sphingomyelins remained significant after Bonferroni correction. SARS-CoV-2 antibody levels in convalescent patients were associated with age but none of the sphingolipid parameters. Based on our data, COVID-19 is associated with a dysregulation of sphingolipid homeostasis in a severity-dependent manner, particularly focused around a reduction of sphingomyelins and an accumulation of ceramides by increased enzyme activities leading to ceramide elevation (ASM, NSM) combined with a decreased activity of enzymes (NC) reducing ceramide levels. The potential of a combined sphingolipid/enzyme pattern as a diagnostic and prognostic marker and therapeutic target deserves further exploration.

“…The increased mortality rates among COVID 19 patients increased the demand to check for drugs that may reduce the high risk of death especially in advanced age [35, 36] . In their large multicenter retrospective observational cohort study, Oskotsky et al indicated the effectiveness of SSRIs, specifically fluoxetine and fluoxetine or fluvoxamine, in reducing the mortality rates among the groups that used this category of antidepressants compared to the control group [37] . In our review, we found that there was no significant difference in the ITT mortality rates between fluvoxamine group and placebo or SC (RR = 0.66; 95% CI: 0.36 - 1.21).…”

Section: Discussionmentioning

confidence: 99%

“…Therefore, this can give the preference to the use of fluoxetine over fluvoxamine in the reduction of mortality among COVID-19 patients. We can also infer from this the superiority of fluoxetine and fluvoxamine over the other SSRIs [37, 38] .…”

Section: Discussionmentioning

confidence: 99%

The Place of Fluvoxamine in the Treatment of Non-critically ill Patients with COVID-19: A Living Systematic Review and Meta-analysis

Kacimi

Greca

Haireche³

et al. 2021

Preprint

Background: Fluvoxamine is a selective serotonin reuptake inhibitor that is known to be used as antidepressant. Repurposing of Fluvoxamine for the treatment of COVID-19 is theorized to help in the prevention of the clinical deterioration of SARS CoV-2 patients. In our systematic review and meta-analysis, we aim to assess the safety and efficacy of the drug under study in terms of its effect on the mortality and the risk of hospitalization and mechanical ventilation in non-critically ill COVID-19 patients. Methods: We performed a systematic search of seven electronic databases. The search results were screened based on the previously determined inclusion and exclusion criteria. We determined the data related to our objectives. The mortality rates, rates of hospitalization, risk of mechanical ventilation and serious side effects were extracted from the studies that successfully met our inclusion and exclusion criteria. Then, the extracted data from the included studies was included in the meta-analysis. Results: Three studies, two randomized clinical trials and one observational cohort study, with 1762 patients, were the final outcome of our search and screening processes. Among all participants, 886 patients received Fluvoxamine while 876 were controls. Follow up periods ranged from 7 days to 28 days. There was no significant difference in the intention-to-treat mortality rates between the two groups (RR = 0.66; 95% CI: 0.36 - 1.21, p-value = 0.18; I2 = 0%). However, Fluvoxamine decreased the per-protocol mortality compared to both placebo alone or placebo/standard care (RR = 0.09; 95% CI: 0.01 - 0.64, p-value = 0.02; I2 = 0% and RR = 0.09; 95% CI: 0.01 - 0.72, respectively). As compared to placebo or standard care, the all-cause hospitalization was significantly reduced in the fluvoxamine group (RR = 0.71; 95% CI: 0.54 - 0.93, p-value = 0.01; I2 = 61%). This risk reduction was not significant when compared to placebo alone (RR = 0.76; 95% CI: 0.57 - 1.00; p-value = 0.051; I2 = 48%). Furthermore, the risk of mechanical ventilation was not improved in the fluvoxamine group as compared to placebo (RR = 0.71; 95% CI: 0.43 - 1.16, p-value = 0.17; I2 = 0%). The serious adverse effects were almost the same in the treatment group and the control (13% and 12% respectively). Conclusion: Fluvoxamine does not significantly reduce the mortality rates or the risk of mechanical ventilation in SARS CoV-2 patients. Nonetheless, it was found to have a good impact on reducing all cause hospitalization among patients with COVID-19 disease. Therefore, further clinical studies are needed to determine the effectiveness of the drug and its mechanisms of action.