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A systematic review and meta-analysis, investigating dose and time of fluvoxamine treatment efficacy for COVID-19 clinical deterioration, death, and Long-COVID complications

Prasanth et al., Scientific Reports, doi:10.1038/s41598-024-64260-9
Jun 2024  
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Mortality 78% Improvement Relative Risk Clinical deterioration 64% Fluvoxamine  Prasanth et al.  META ANALYSIS Favorsfluvoxamine Favorscontrol 0 0.5 1 1.5 2+
27th treatment shown to reduce risk in November 2021
*, now with p = 0.00014 from 21 studies, recognized in 3 countries.
No treatment is 100% effective. Protocols combine treatments. * >10% efficacy, ≥3 studies.
4,400+ studies for 79 treatments.
Systematic review and meta analysis of 14 studies showing significantly lower COVID-19 clinical deterioration and mortality with fluvoxamine treatment. Subgroup analysis indicated that higher doses (≥200mg/day) and earlier treatment (within 3 days) provided the greatest benefit in preventing clinical deterioration.
The mortality result is exaggerated due to the use of per-protocol results for Together which has clear confounding (per-protocol defined as 80% adherence)1, and the Siripongboonsitti et al. mortality result is missing, however these do not change the positive result.
8 meta analyses show significant improvements with fluvoxamine for mortality3,4, hospitalization3,5-9, progression4,9, and severity10.
Currently there are 21 fluvoxamine for COVID-19 studies, showing 44% lower mortality [15‑63%], 42% lower ventilation [-151‑86%], 10% higher ICU admission [-72‑326%], 51% lower hospitalization [8‑73%], and 27% fewer cases [18‑35%].
risk of death, 77.7% lower, OR 0.22, p < 0.001, inverted to make OR<1 favor treatment, RR approximated with OR.
clinical deterioration, 63.6% lower, OR 0.36, p = 0.02, inverted to make OR<1 favor treatment, RR approximated with OR.
Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates
Prasanth et al., 12 Jun 2024, peer-reviewed, 8 authors.
This PaperFluvoxamineAll
A systematic review and meta-analysis, investigating dose and time of fluvoxamine treatment efficacy for COVID-19 clinical deterioration, death, and Long-COVID complications
Mani Iyer Prasanth, Dhammika Leshan Wannigama, Angela Michelle Reiersen, Premrutai Thitilertdecha, Anchalee Prasansuklab, Tewin Tencomnao, Sirikalaya Brimson, James Michael Brimson
Scientific Reports, doi:10.1038/s41598-024-64260-9
There have been 774,075,242 cases of COVID-19 and 7,012,986 deaths worldwide as of January 2024. In the early stages of the pandemic, there was an urgent need to reduce the severity of the disease and prevent the need for hospitalization to avoid stress on healthcare systems worldwide. The repurposing of drugs to prevent clinical deterioration of COVID-19 patients was trialed in many studies using many different drugs. Fluvoxamine (an SSRI and sigma-1 receptor agonist) was initially identified to potentially provide beneficial effects in COVID-19-infected patients, preventing clinical deterioration and the need for hospitalization. Fourteen clinical studies have been carried out to date, with seven of those being randomized placebo-controlled studies. This systematic review and meta-analysis covers the literature from the outbreak of SARS-CoV-2 in late 2019 until January 2024. Search terms related to fluvoxamine, such as its trade names and chemical names, along with words related to COVID-19, such as SARS-CoV-2 and coronavirus, were used in literature databases including PubMed, Google Scholar, Scopus, and the database from NIH, to identify the trials used in the subsequent analysis. Clinical deterioration and death data were extracted from these studies where available and used in the meta-analysis. A total of 7153 patients were studied across 14 studies (both open-label and double-blind placebo-controlled). 681 out of 3553 (19.17%) in the standard care group and 255 out of 3600 (7.08%) in the fluvoxamine-treated group experienced clinical deterioration. The estimated average log odds ratio was 1.087 (95% CI 0.200 to 1.973), which differed significantly from zero (z = 2.402, p = 0.016). The seven placebo-controlled studies resulted in a log odds ratio of 0.359 (95% CI 0.1111 to 0.5294), which differed significantly from zero (z = 3.103, p = 0.002). The results of this study identified fluvoxamine as effective in preventing clinical deterioration, and subgrouping OPEN
Author contributions Competing interests AMR is listed as an inventor on a patent application related to methods of treating COVID-19 (including Sigma1 agonists and specifically fluvoxamine), which was filed by Washington University in St. Louis. No other author declares any potential conflict of interest or competing financial or non-financial interest in relation to the manuscript. AMR is listed on a patent application that includes the use of σ1R agonists for the treatment of COVID-19. No other authors have any conflicts to declare.
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