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Efficacy and safety of selective serotonin reuptake inhibitors in COVID-19 management: A systematic review and meta-analysis

Deng et al., Clinical Microbiology and Infection, doi:10.1016/j.cmi.2023.01.010
Jan 2023  
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Mortality 28% Improvement Relative Risk Mortality, 100mg 29% Hospitalization 21% Hospitalization, 100mg 20% Hospitalization, 50mg 2% Fluvoxamine for COVID-19  Deng et al.  META ANALYSIS Favorsfluvoxamine Favorscontrol 0 0.5 1 1.5 2+
26th 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.
4,300+ studies for 75 treatments.
Meta analysis of 6 fluvoxamine RCTs showing fluvoxamine associated with lower mortality and hospitalization. 100mg bid showed lower mortality and hospitalization, but 50mg bid did not.
Authors use the Hartung-Knapp adjustment and they include trials reporting zero events in both arms - 5 of 6 trials for mortality. This narrows the confidence interval from the Together Trial so that it becomes significant, but this is not logical - zero mortality in both arms does not provide information on the mortality benefit of fluvoxamine.
Bias evaluation is not accurate. For example, authors rate the Together Trial as low risk of bias except for some concerns for deviations from the intended interventions. However, this trial not only shows a very high theoretical risk of bias, but also has very high actual bias, randomization failure, blinding failure, and reports conflicting data that is impossible to be correct1.
8 meta analyses show significant improvements with fluvoxamine for mortality2,3, hospitalization2,4-8, progression3,8, and severity9.
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, 28.0% lower, RR 0.72, p < 0.001.
risk of death, 29.0% lower, RR 0.71, p = 0.004, 100mg bid.
risk of hospitalization, 21.0% lower, RR 0.79, p = 0.03.
risk of hospitalization, 20.0% lower, RR 0.80, p = 0.007, 100mg bid.
risk of hospitalization, 2.0% lower, RR 0.98, p = 0.99, 50mg bid.
Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates
Deng et al., 14 Jan 2023, peer-reviewed, 10 authors.
This PaperFluvoxamineAll
Efficacy and safety of selective serotonin reuptake inhibitors in COVID-19 management: A systematic review and meta-analysis
Jiawen Deng, Daniel Rayner, Harikrishnaa Ba Ramaraju, Umaima Abbas, Cristian Garcia, Kiyan Heybati, Fangwen Zhou, Emma Huang, Ye-Jean Park, Myron Moskalyk
Clinical Microbiology and Infection, doi:10.1016/j.cmi.2023.01.010
This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
Lastly, we found that fluvoxamine was not associated with reduced hospitalization once we excluded one study with a high risk of bias rating. This was likely due to loss of precision from a reduced sample size given the small number of studies and patients included in this review. The incorporation of larger, betterdesigned RCTs in future meta-analyses can help confirm our findings relating to hospitalization. CONCLUSION This systematic review and meta-analysis of 6 RCTs and 5 observational studies found that fluvoxamine may reduce mortality and hospitalization based on moderate quality of evidence. Medium J o u r n a l P r e -p r o o f CONFLICT OF INTEREST The authors declare no conflicts of interest. J o u r n a l P r e -p r o o f GRADE Working Group quality of evidence rating [28] High quality: We are very confident that the true effect lies close to that of the estimate of the effect Moderate quality: We are moderately confident in the effect estimate; the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different Low quality: Our confidence in the effect estimate is limited; the true effect may be substantially different from the estimate of the effect Very low quality: We have very little confidence in the effect estimate; the true effect is likely to be substantially different from the estimate of effect a The risk in the intervention group (and its 95% CI) is based on the assumed risk in..
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