Overview of the potential use of fluvoxamine for COVID-19 and long COVID

Hashimoto, Kenji

doi:10.1007/s44192-023-00036-3

Cited by 14 publications

(13 citation statements)

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“…The transcription factor XBP1 in the ER plays a role in the reactivation of EBV [ 44 ]. Given the interaction of XBP1 and sigma-1 receptor in the ER, it is likely that sigma-1 receptor agonists (i.e., fluvoxamine), which may block EBV reactivation, would be potential therapeutic drugs to limit clinical deterioration after infection and long COVID symptoms [ 51 – 53 ]. Finally, SARS-CoV-2 can enter in the GI tract and cause dysbiosis of the gut microbiota in patients with COVID-19.…”

Section: Discussionmentioning

confidence: 99%

“…Given the role of the sigma-1 receptor on the regulation of XBP-1 in the ER [ 46 , 47 ], it is proposed that the potent sigma-1 receptor agonist fluvoxamine [a selective serotonin reuptake inhibitor (SSRI)] may be a potential therapeutic drug for long COVID (Fig. 2 ) [ 48 – 53 ]. A recent population-based retrospective study reported that the use of SSRIs with sigma-1 receptor agonism at baseline (at or prior to COVID-19 infection) was associated with a reduced risk of long COVID [ 54 ].…”

Section: Underlying Mechanisms Of Long Covidmentioning

confidence: 99%

“…All other symptoms except poor concentration were less in the fluvoxamine group compared with placebo group although statistical analysis did not reach to significant differences because of low dose (100 mg daily) [ 55 ]. Therefore, it is of great interest to examine whether fluvoxamine (e.g., 100 mg twice daily for 10 days) could block the occurrence of long COVID symptoms [ 51 – 53 ]. A randomized placebo-controlled trial of fluvoxamine for long COVID (NCT05874037) is ongoing at Washington University (St. Louis, MO, USA).…”

Section: Underlying Mechanisms Of Long Covidmentioning

confidence: 99%

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Detrimental effects of COVID-19 in the brain and therapeutic options for long COVID: The role of Epstein–Barr virus and the gut–brain axis

Hashimoto

2023

Mol Psychiatry

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The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has resulted in a serious public health burden worldwide. In addition to respiratory, heart, and gastrointestinal symptoms, patients infected with SARS-CoV-2 experience a number of persistent neurological and psychiatric symptoms, known as long COVID or “brain fog”. Studies of autopsy samples from patients who died from COVID-19 detected SARS-CoV-2 in the brain. Furthermore, increasing evidence shows that Epstein–Barr virus (EBV) reactivation after SARS-CoV-2 infection might play a role in long COVID symptoms. Moreover, alterations in the microbiome after SARS-CoV-2 infection might contribute to acute and long COVID symptoms. In this article, the author reviews the detrimental effects of COVID-19 on the brain, and the biological mechanisms (e.g., EBV reactivation, and changes in the gut, nasal, oral, or lung microbiomes) underlying long COVID. In addition, the author discusses potential therapeutic approaches based on the gut–brain axis, including plant-based diet, probiotics and prebiotics, fecal microbiota transplantation, and vagus nerve stimulation, and sigma-1 receptor agonist fluvoxamine.

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Section: Discussionmentioning

confidence: 99%

Section: Underlying Mechanisms Of Long Covidmentioning

confidence: 99%

Section: Underlying Mechanisms Of Long Covidmentioning

confidence: 99%

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Detrimental effects of COVID-19 in the brain and therapeutic options for long COVID: The role of Epstein–Barr virus and the gut–brain axis

Hashimoto

2023

Mol Psychiatry

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“…15 A systematic review of studies evaluating the use of fluvoxamine for COVID-19 and Long COVID suggested that baseline use of fluvoxamine may reduce the risk of Long COVID due to the drug's sigma 1 receptor agonist activity and the role of sigma 1 receptor activity in acute COVID-19 infection. 16 Observational analyses of human electronic health record (EHR) data did not find a significant difference in the relationship between moderate to high-affinity sigma 1 receptor agonist SSRIs (fluvoxamine, fluoxetine, escitalopram, and citalopram) versus non-high affinity SSRIs (sertraline and paroxetine) in their impact on Long COVID. 13 Identifying interventions that prevent Long COVID is crucial for clinical applications as well as our understanding of underlying biological mechanisms that cause Long COVID.…”

Section: Introductionmentioning

confidence: 99%

SSRI Use During Acute COVID-19 Infection Associated with Lower Risk of Long COVID Among Patients with Depression

Butzin-Dozier,

Ji,

Deshpande

et al. 2024

Preprint

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BackgroundLong COVID, also known as post-acute sequelae of COVID-19 (PASC), is a poorly understood condition with symptoms across a range of biological domains that often have debilitating consequences. Some have recently suggested that lingering SARS-CoV-2 virus in the gut may impede serotonin production and that low serotonin may drive many Long COVID symptoms across a range of biological systems. Therefore, selective serotonin reuptake inhibitors (SSRIs), which increase synaptic serotonin availability, may prevent or treat Long COVID. SSRIs are commonly prescribed for depression, therefore restricting a study sample to only include patients with depression can reduce the concern of confounding by indication.MethodsIn an observational sample of electronic health records from patients in the National COVID Cohort Collaborative (N3C) with a COVID-19 diagnosis between September 1, 2021, and December 1, 2022, and pre-existing major depressive disorder, the leading indication for SSRI use, we evaluated the relationship between SSRI use at the time of COVID-19 infection and subsequent 12-month risk of Long COVID (defined by ICD-10 code U09.9). We defined SSRI use as a prescription for SSRI medication beginning at least 30 days before COVID-19 infection and not ending before COVID-19 infection. To minimize bias, we estimated the causal associations of interest using a nonparametric approach, targeted maximum likelihood estimation, to aggressively adjust for high-dimensional covariates.ResultsWe analyzed a sample (n= 506,903) of patients with a diagnosis of major depressive disorder before COVID-19 diagnosis, where 124,928 (25%) were using an SSRI. We found that SSRI users had a significantly lower risk of Long COVID compared to nonusers (adjusted causal relative risk 0.90, 95% CI (0.86, 0.94)).ConclusionThese findings suggest that SSRI use during COVID-19 infection may be protective against Long COVID, supporting the hypothesis that serotonin may be a key mechanistic biomarker of Long COVID.

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“…Furthermore, a recent review has emphasized the limited effectiveness of a low dose of fluvoxamine in preventing cytokine storms, as only a full dose of 200-300 mg daily can achieve this effect (Hashimoto, 2023). Other studies have highlighted conflicting results, especially for certain drugs such as tricyclic antidepressants and antipsychotics (Clelland et al, 2021;Min et al, 2022).…”

Section: Introductionmentioning

confidence: 99%

SSRIs in the course of COVID‐19 pneumonia: Evidence of effectiveness of antidepressants on acute inflammation. A retrospective study

Fei,

Bozza,

Melani

et al. 2023

Human Psychopharmacology

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IntroductionRelationships between inflammation and mood have been observed in terms of pro‐inflammatory effects induced by depressive conditions and, in parallel, by an antidepressant‐induced favorable effect on the recovery of inflammatory states. Selective serotonin reuptake inhibitor (SSRI) drugs were hypothesized to improve the prognosis of COVID‐19 pneumonia, a typical acute inflammation, in terms of decreased mortality rate and pro‐inflammatory cytokine serum levels.MethodsThe medical records of COVID‐19 pneumonia inpatients at Careggi University Hospital (Florence) were analyzed for prognosis and Interleukin 6 (IL‐6) after admission for over a period of 22 months. Medical records of patients treated at admission and not discontinued until discharge with an SSRI or with vortioxetine were identified. Two groups, one treated with antidepressants, the other not treated, were evaluated according to the mentioned parameters. Multiple linear regression and logistic regression were performed.ResultsThe entire sample composed of 1236 records (recovered patients 77.1%, deceased patients 22.9%). The treated group (n = 107) had a better prognosis than the untreated group in spite of age and comorbidity both being greater than in the untreated group. Correspondingly, IL‐6 levels in the treated group were significantly lower (p < 0.01) than the levels in the untreated group, in every comparison.ConclusionsOutcomes of this study support the hypothesis of the favorable influence of some antidepressants on the prognosis of COVID‐19, possibly mediated by IL‐6 modulation. Reduction in acute inflammation induced by the action of antidepressants was confirmed.

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Overview of the potential use of fluvoxamine for COVID-19 and long COVID

Cited by 14 publications

References 108 publications

Detrimental effects of COVID-19 in the brain and therapeutic options for long COVID: The role of Epstein–Barr virus and the gut–brain axis

Detrimental effects of COVID-19 in the brain and therapeutic options for long COVID: The role of Epstein–Barr virus and the gut–brain axis

SSRI Use During Acute COVID-19 Infection Associated with Lower Risk of Long COVID Among Patients with Depression

SSRIs in the course of COVID‐19 pneumonia: Evidence of effectiveness of antidepressants on acute inflammation. A retrospective study

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