Antiviral efficacy of fluoxetine in early symptomatic COVID-19: an open-label, randomised, controlled, adaptive platform trial (PLATCOV)

medRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Янв. 18, 2024

Abstract Background The selective serotonin reuptake inhibitors (SSRIs) fluoxetine and fluvoxamine were repurposed for the treatment of early COVID-19 based on their antiviral activity in vitro , observational clinical trial evidence suggesting they prevented progression to severe disease. However, these SSRIs have not been recommended guidelines vivo has characterised. Methods PLATCOV is an open-label, multicentre, phase 2, randomised, controlled, adaptive pharmacometric platform running Thailand, Brazil, Pakistan, Laos. We recruited low-risk adult outpatients aged 18-50 with symptomatic (symptoms <4 days). Patients assigned using block randomisation one eleven arms including oral (40mg/day 7 days), or no study drug. Uniform ratios applied across active groups while drug group comprised ≥20% patients at all times. primary endpoint was rate oropharyngeal viral clearance assessed a modified intention-to-treat population (>2 days follow-up). estimated under Bayesian hierarchical linear model fitted log10 densities standardised duplicate swab eluates taken daily over week (18 measurements per patient). This ongoing registered ClinicalTrials.gov ( NCT05041907 ). Findings Between 5 April 2022 8 May 2023 271 concurrently randomised either (n=120) (n=151). Fluoxetine well tolerated accelerated relative arm by 15% (95% credible interval (CrI): 2% 34%). In pooled meta-analysis unblinded substantially less than ritonavir-boosted nirmatrelvir-85% increase CrI: 61 112%); remdesivir 35% (14 59%), molnupiravir 37% 60%), casirivimab/imdevimab 29% (10 48%). Interpretation against SARS-CoV-2. Although level efficacy other currently available drugs, might still be useful prophylaxis where effect required. Funding Wellcome Trust Grant ref: 223195/Z/21/Z through Therapeutics Accelerator. Evidence before this proposed as therapeutics initially observational, evidence. reports suggested that taking had reduced probability developing dying. searched PubMed EMBASE studies English up until 30 th November search terms “fluoxetine”, “fluvoxamine” “COVID-19” restricted controlled trials (RCTs). Eight outpatient RCTs identified. There outpatients. A compatible moderate reduction hospitalisation death risk ratio 0.80 CI: 0.62,1.01). Added value showed illness SSRI weak . antivirals such nirmatrelvir molnupiravir. approach described here provides quantitative measure effects tractable sample sizes. Implications COVID-19. insufficient but, required prevent infection, could beneficial prophylaxis.

Язык: Английский

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Antidepressant Drugs and COVID-19: A Review of Basic and Clinical Evidence

Journal of Clinical Medicine, Год журнала: 2022, Номер 11(14), С. 4038 - 4038

Опубликована: Июль 12, 2022

The COVID-19 pandemic has encouraged the repurposing of existing drugs as a shorter development strategy in order to support clinicians with this difficult therapeutic dilemma. There is evidence theory that some antidepressants can reduce concentrations different cytokines humans and animals and, recently, antiviral activity against SARS-CoV-2 been reported. aims narrative review are evaluate possible role treatment infection benefits risks patients taking for mental disorders infection. A was performed analyse current literature identify antidepressant medication patients. electronic search completed MEDLINE MedRxiv/BioRxiv published ClinicalTrials.gov ongoing clinical trials. results show from preclinical data observational studies about efficacy specific treating In addition, two phase II testing fluvoxamine showed positive deterioration hospitalization rate versus placebo. Seven trials fluvoxamine, fluoxetine, tramadol (as per its anti-inflammatory effect) still early phases. Although available limited, sum several provide basis evaluating use humans. Further investigations will be needed application.

Язык: Английский

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Antiviral efficacy of fluoxetine in early symptomatic COVID-19: an open-label, randomised, controlled, adaptive platform trial (PLATCOV)

EClinicalMedicine, Год журнала: 2025, Номер 80, С. 103036 - 103036

Опубликована: Янв. 18, 2025

Язык: Английский

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Could antidepressants increase mood and immunity at the same time?

Frontiers in Psychiatry, Год журнала: 2025, Номер 16

Опубликована: Март 12, 2025

A review of scientific literature suggests that the use antidepressants can be broadly extended to address various forms stress and inflammation as an adjunctive therapy enhances host resistance. While effects on mood are well-documented in terms their emotional, cognitive, behavioral impacts, these aspects do not fully explain cellular mechanisms action. At level, exert trophic promote neurogenesis synaptic connectivity. Studies demonstrate improve cell survival, enhance stem proliferation, reduce danger perception (mood effects) depressed patients animal models depression. These properties highlight a deeper biological mechanism beyond mood-related benefits. The acid sphingomyelinase (ASM) theory offers more compelling explanation compared monoamine hypothesis. Antidepressants functionally inhibit ASM enzyme, thereby reducing production ceramide, which directs cells toward increased cytoprotection, reproduction, well improved mood. This also highlights research demonstrating resistance infections, immunological challenges, stress, findings support potential bolster resilience scenarios involving vaccinations, aggression, depression, even aging.

Язык: Английский

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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

Health Science Reports, Год журнала: 2022, Номер 5(6)

Опубликована: Окт. 17, 2022

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

Язык: Английский

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Medications Modulating the Acid Sphingomyelinase/Ceramide System and 28-Day Mortality among Patients with SARS-CoV-2: An Observational Study

Pharmaceuticals, Год журнала: 2023, Номер 16(8), С. 1107 - 1107

Опубликована: Авг. 4, 2023

Prior evidence indicates the potential central role of acid sphingomyelinase (ASM)/ceramide system in infection cells with SARS-CoV-2. We conducted a multicenter retrospective observational study including 72,105 adult patients laboratory-confirmed SARS-CoV-2 who were admitted to 36 AP-HP (Assistance Publique-Hôpitaux de Paris) hospitals from 2 May 2020 31 August 2022. examined association between ongoing use medications functionally inhibiting (FIASMA), which reduces vitro, upon hospital admission 28-day all-cause mortality 1:1 ratio matched analytic sample based on clinical characteristics, disease severity and other (N = 9714). The univariate Cox regression model showed that FIASMA medication at was associated significantly lower risks (HR 0.80; 95% CI 0.72-0.88; p < 0.001). In this study, substantially reduced among hospitalized COVID-19. These findings support continuation these during treatment infections. Randomized trials (RCTs) are needed confirm results, starting molecules greatest effect size e.g., fluoxetine, escitalopram, amlodipine.

Язык: Английский

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

Journal of Clinical Medicine, Год журнала: 2021, Номер 11(1), С. 70 - 70

Опубликована: Дек. 24, 2021

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

Язык: Английский

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Acid sphingomyelinase (ASM) and COVID‐19: A review of the potential use of ASM inhibitors against SARS‐CoV‐2

Cell Biochemistry and Function, Год журнала: 2023, Номер 41(3), С. 284 - 295

Опубликована: Март 17, 2023

Abstract In the last 2 years, different pharmacological agents have been indicated as potential inhibitors of SARS‐CoV‐2 in vitro. Specifically, drugs termed functional acid sphingomyelinase (FIASMAs) proved to inhibit replication using types cells. Those therapeutic share several chemical structure characteristics and some well‐known representatives are fluoxetine, escitalopram, fluvoxamine, others. Most FIASMAs primarily used effective treat pathologies, therefore, they natural drug candidates for repositioning strategy. this review, we summarize two main proposed mechanisms mediating (ASM) inhibition how can explain by FIASMAs. The first mechanism implies a disruption lysosomal pH fall endosome–lysosome moves toward interior cell. fact, changes cholesterol levels membranes, which associated with ASM is thought be mediated proton pump (ATP‐ase) inactivation. second involves formation an extracellular ceramide‐rich domain, blocked domains believed facilitate entrance into host

Язык: Английский

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Psychiatric polygenic risk as a predictor of COVID-19 risk and severity: insight into the genetic overlap between schizophrenia and COVID-19

Translational Psychiatry, Год журнала: 2023, Номер 13(1)

Опубликована: Июнь 6, 2023

Despite the high contagion and mortality rates that have accompanied coronavirus disease-19 (COVID-19) pandemic, clinical presentation of syndrome varies greatly from one individual to another. Potential host factors accompany greater risk COVID-19 been sought schizophrenia (SCZ) patients seem present more severe than control counterparts, with certain gene expression similarities between psychiatric reported. We used summary statistics last SCZ, bipolar disorder (BD), depression (DEP) meta-analyses available on Psychiatric Genomics Consortium webpage calculate polygenic scores (PRSs) for a target sample 11,977 cases 5943 subjects unknown status. Linkage disequilibrium score (LDSC) regression analysis was performed when positive associations were obtained PRS analysis. The SCZ significant predictor in case/control, symptomatic/asymptomatic, hospitalization/no hospitalization analyses total female samples; symptomatic/asymptomatic status men. No found BD or DEP LDSC SNP-based genetic but not DEP, may be associated higher SARS-CoV-2 infection severity, especially among women; however, predictive accuracy barely exceeded chance level. believe inclusion sexual loci rare variations genomic overlap will help elucidate commonalities these conditions.

Язык: Английский

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Repurposing fluvoxamine, and other psychiatric medications, for COVID‐19 and other conditions

World Psychiatry, Год журнала: 2022, Номер 21(2), С. 314 - 315

Опубликована: Май 7, 2022

Early in the COVID-19 pandemic, repurposing some already-approved drugs was proposed for reducing morbidity and mortality risk of those who were infected. For example, UK RECOVERY trial demonstrated benefits dexamethasone severe respiratory illness, leading to its widespread adoption by mid-2020. Many psychiatric have antiviral immune modulatory effects, are candidates other non-psychiatric conditions. Fluvoxamine is a potent activator sigma-1 receptor (S1R), dampening cellular stress responses anti-inflammatory effects1. In 2020, we conducted randomized placebo-controlled which that fluvoxamine prevented clinical deterioration from COVID-192. These findings replicated larger study, TOGETHER trial, 1,497 patients 100 mg twice daily or placebo 10 days. The found 32% reduction disease progression with fluvoxamine. Among compliant their treatment regimen, taking at least 80% pills, there 66% hospitalization fluvoxamine, only one death group compared 12 group3. has now been recommended use several organizations, including Ontario province Canada. Two ongoing trials testing lower dose 50 daily: ACTIV-6 COVID OUT trial. Based on this growing scientific evidence, as well safety profile availability, believe should be used outpatients high complications infection. 10-15 days, can adjusted based tolerability. No laboratory monitoring needed, but co-prescribed evaluated potential interactions, because fluvoxamine's inhibition cytochromes P450 (CYP) 1A2 2C19. Patients theophylline, clozapine, olanzapine tizanidine, CYP1A2 substrates, not administered most cases. Caffeine, CYP­1A2 substrate, eliminated greatly reduced during treatment. Also, already serotonin reuptake inhibitor (SSRI) serotonin-norepinephrine (SNRI), would discourage adding switching it Other mechanisms suggested effects SSRIs, beyond alone, hypercoagulable states excess release platelets, functional acid sphingomyelinase, entry propagation SARS-CoV-2 into cells1. study adults hospitalized medication sphingomyelinase (including all SSRIs) less likely intubated die4. A inpatients New York state first wave pandemic 2020 SSRIs SNRIs, specifically fluoxetine, showed protective effect against infection5. 83,584 particular fluoxetine had mortality6. Given time costs conducting large con­trolled trials, tempting data these observational studies sufficient evidence drug repurposing. Yet, known suffer biases, confounding indication. Although techniques exist reduce remains controversial assert drug's benefit new indication purely data. class might appear COVID-19, yet proxy patient characteristic behavior (e.g., social isolation depression). Thus, promising will still require corroboration accomplishments such show rapid innovations possi­ble. antidepressants also help long­er-term neuropsychiatric manifestations COVID-19. "Neuro­psychiatric long COVID" refers fact cognitive psy­chiatric symptoms proportion constellation post-acute either chronic intermittent, bothersome, painful disabling. Patient-Led Research Collaborative assessed prevalence 3,762 persons over 7 months post-COVID7. They preponderance symptoms, particularly memory dysfunction, experienced 85% respondents, negative impacts functioning. common insomnia, anxiety, depression, occasionally hallucinations (olfactory other). etiological factors involved may include persistent infection prolonged hyper-inflammatory state, compounded psychosocial stress. Unfortunately, little research to-date COVID. One recent report post-COVID depressive illness8 55/60 (92%) response after 4 weeks SSRI This strong antidepressant seen irrespective gender, previous history, type. authors speculated could due direct action neuroinflammation, addition typical (which remain unclear). single-site, open-label more needed regarding efficacy various treatments. But shows an important role psychiatrists managing, supervising, long-term With continuing evolve, critical keep answering key questions about acute illness. What best timing how effective combination treatments (such monoclonal antibodies)? Is S1R affinity shown promise preclinical studies, treatment, considering widely available easier use? And what COVID, patients? many psychotropics appreciated molecular, physiological in­cluding anti-inflammatory, neuroprotective cardioprotective, antiproliferative, expect lessons learned medications efforts, ranging infectious inflammatory diseases, neurodegenerative diseases Alzheimer's disease, cancer9.

Язык: Английский

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