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

  1. Salah Eddine Oussama Kacimi
  2. Elona Greca
  3. Mohamed Amine Haireche
  4. Ahmed Sallam ElHawary
  5. Mounir Ould Setti
  6. Rebecca Caruana
  7. Sahar Rizwan
  8. Hidayet Benyettou
  9. Mohammad Yasir Essar
  10. Jaffer Shah
  11. Sherief Ghozy

Reviewed by

Read the full article See related articles

Discuss this preprint

Start a discussion What are Sciety discussions?

Listed in

Log in to save this article

Abstract

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; I 2 = 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; I 2 = 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; I 2 = 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; I 2 = 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; I 2 = 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.

Article activity feed

  1. ScreenIT

    SciScore for 10.1101/2021.12.19.21268044: (What is this?)

    Please note, not all rigor criteria are appropriate for all manuscripts.

    Table 1: Rigor

    Ethicsnot detected.
    Sex as a biological variablenot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    One investigator systematically searched Medline, Google Scholar, Scopus, Opengrey, Clinicaltiral.gov, Cochrane, and MedRxiv from database inception till November 1st, 2021 to retrieve studies in humans of the efficacy and safety of Fluvoxamine in the treatment of non-critically ill patients with confirmed COVID-19 diagnosis.
    Medline
    suggested: (MEDLINE, RRID:SCR_002185)
    Google Scholar
    suggested: (Google Scholar, RRID:SCR_008878)
    Cochrane
    suggested: (Cochrane Library, RRID:SCR_013000)

    Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).

    Results from LimitationRecognizer: An explicit section about the limitations of the techniques employed in this study was not found. We encourage authors to address study limitations.

    Results from TrialIdentifier: No clinical trial numbers were referenced.

    Results from Barzooka: We did not find any issues relating to the usage of bar graphs.

    Results from JetFighter: We did not find any issues relating to colormaps.

    Results from rtransparent:
    • Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
    • Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
    • No protocol registration statement was detected.

    Results from scite Reference Check: We found no unreliable references.

    About SciScore

    SciScore is an automated tool that is designed to assist expert reviewers by finding and presenting formulaic information scattered throughout a paper in a standard, easy to digest format. SciScore checks for the presence and correctness of RRIDs (research resource identifiers), and for rigor criteria such as sex and investigator blinding. For details on the theoretical underpinning of rigor criteria and the tools shown here, including references cited, please follow this link.

  2. Version published to 10.1101/2021.12.19.21268044 on medRxiv