Fluvoxamine COVID-19 studies. Treatment recommendations are available from Ontario.
Recent:Deng Glebov Marcec Sidky Trkulja Lu McCarthy.
Fluvoxamine has been officially adopted
for early treatment in all or part of 3 countries (5 including non-government medical organizations).
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Feb 5 |
(Preprint) (meta analysis) | Fluvoxamine for COVID-19: real-time meta analysis of 13 studies |
| Statistically significant improvement is seen for cases. 8 studies from 8 independent teams in 4 different countries show statistically significant improvements in isolation (4 for the most serious outcome). • Meta analysis using the mo.. | ||
Jan 14 |
et al., Clinical Microbiology and Infection, doi:10.1016/j.cmi.2023.01.010 | Efficacy and safety of selective serotonin reuptake inhibitors in COVID-19 management: A systematic review and meta-analysis |
| 28% lower mortality [p<0.0001] and 21% lower hospitalization [p=0.03]. 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 inc.. | ||
Dec 20 |
et al., medRxiv, doi:10.1101/2022.12.15.22283507 (Preprint) | Antidepressant drug prescription and incidence of COVID-19: a retrospective cohort study |
| 43% fewer cases [p=0.04]. Retrospective 5,664 mental health patients in the UK, showing lower risk of COVID-19 cases with recent antidepressant prescriptions overall, and for the subset of patients receiving SSRIs. | ||
Nov 17 |
et al., Journal of Infection, doi:10.1016/j.jinf.2022.11.011 | A meta-analysis regarding fluvoxamine and hospitalization risk of COVID-19 patients: TOGETHER making a difference |
| 43% lower hospitalization [p=0.03]. Meta analysis of 7 fluvoxamine outpatient studies showing significantly lower hospitalization with treatment. | ||
Nov 10 |
et al., medRxiv, doi:10.1101/2022.11.09.22282142 (Preprint) | Assessing the Effect of Selective Serotonin Reuptake Inhibitors in the Prevention of Post-Acute Sequelae of COVID-19 |
| N3C retrospective 17,933 COVID-19 patients in the USA, showing lower risk of PASC for SSRIs with or without S1R agonist activity. | ||
Nov 7 |
et al., Research Square, doi:10.21203/rs.3.rs-2239187/v1 (Preprint) | Outpatients prescribed with fluvoxamine around the time of COVID-19 diagnosis are not at a reduced risk of subsequent hospitalization and death compared to their non-prescribed peers: population-based matched cohort study |
| 27% lower mortality [p=0.41] and 37% higher hospitalization [p=0.5]. Retrospective COVID+ patients in Croatia, showing no significant difference in outcomes with fluvoxamine prophylaxis. | ||
Oct 18 |
et al., JAMA, doi:10.1001/jama.2022.24100 (date from earlier preprint) | Effect of Fluvoxamine vs Placebo on Time to Sustained Recovery in Outpatients With Mild to Moderate COVID-19 |
| 4% worse recovery [p=0.45]. RCT low-risk outpatients with very late treatment (median 5 days, 20% ≥8 days) in the USA, showing no significant differences with low-dose fluvoxamine treatment. Many of the issues noted for the ivermectin arm [ Naggie ] also apply to th.. | ||
Oct 13 |
et al., Journal of Infection and Public Health, doi:10.1016/j.jiph.2022.10.010 | Effect of fluvoxamine on outcomes of nonhospitalized patients with COVID-19: A systematic review and meta-analysis |
| 31% lower hospitalization [p=0.02] and 41% fewer combined hospitalization/ER visits [p=0.0004]. Systematic review and meta analysis of 4 fluvoxamine outpatient trials, showing lower hospitalization with treatment. | ||
Oct 6 |
et al., The Primary Care Companion For CNS Disorders, doi:10.4088/PCC.22br03337 | Protective Effect of Fluvoxamine for COVID-19 in Obsessive-Compulsive Disorder |
| 28% fewer cases [p<0.0001]. TriNetX PSM retrospective 82,069 OCD patients, showing lower risk of COVID-19 with fluvoxamine use. | ||
Oct 4 |
et al., medRxiv, doi:10.1101/2022.09.27.22280428 (Preprint) | Impact of Fluvoxamine on outpatient treatment of COVID-19 in Honduras |
| 96% lower mortality [p=0.005], 77% lower need for oxygen therapy [p=0.0004], and 54% lower hospitalization [p=0.04]. Prospective study of 657 COVID+ outpatients in Honduras, 594 accepting fluvoxamine treatment, showing significantly lower mortality and hospitalization with treatment. | ||
Aug 22 |
et al., Translational Psychiatry, doi:10.1038/s41398-022-02109-3 | Association between antidepressant use and ED or hospital visits in outpatients with SARS-CoV-2 |
| Retrospective 25,034 COVID+ outpatients showing significantly lower ER/hospitalization with antidepressants and FIASMA antidepressants, and a dose-dependent response. | ||
Aug 18 |
et al., NEJM, doi:10.1056/NEJMoa2201662 | Randomized Trial of Metformin, Ivermectin, and Fluvoxamine for Covid-19 |
| 11% higher combined mortality/hospitalization [p=0.88], 16% higher progression [p=0.68], and 2% lower hospitalization [p=1]. COVID-OUT remotely operated RCT, showing no significant difference in outcomes. Results for other treatments are listed separately - metformin , ivermectin . The "control" group includes patients receiving metformin, which is known to be .. | ||
May 20 |
et al., Epidemiology International Journal, doi:10.23880/eij-16000234 | Repurposing Drugs for Covid-19 by a Developing Country |
| Review of a multiphasic multidrug early treatment protocol for COVID-19 in Honduras, showing one death from 415 patients, which was for a patient not receiving early treatment (presenting on the 5th day in need of hospitalization and supp.. | ||
May 6 |
et al., JAMA Network Open, doi:10.1001/jamanetworkopen.2022.10743 | Association Between the Use of Psychotropic Medications and the Risk of COVID-19 Infection Among Long-term Inpatients With Serious Mental Illness in a New York State–wide Psychiatric Hospital System |
| 30% more cases [p=0.16]. Retrospective 1,958 consecutive psychiatric patients in the USA, showing higher cases and lower mortality with fluvoxamine, without statistical significance. There was only 25 fluvoxamine patients. | ||
Apr 16 |
et al., PLOS ONE, doi:10.1371/journal.pone.0267423 (date from earlier preprint) | The effect of antidepressants on the severity of COVID-19 in hospitalized patients: A systematic review and meta-analysis |
| Meta analysis of 12 studies concluding that evidence supports the use of antidepressants, mainly fluvoxamine, for COVID-19. Fluvoxamine significantly reduced severity, RR 0.76 [0.60-0.97]. | ||
Mar 29 |
et al., Open Forum Infectious Diseases, doi:10.1093/ofid/ofac156 | Screening Large Population Health Databases for Potential COVID-19 Therapeutics: A Pharmacopeia-Wide Association Study (PWAS) of Commonly Prescribed Medications |
| 14% fewer cases [p=0.02]. Retrospective 26,121 cases and 2,369,020 controls ≥65yo in Canada, showing lower cases with chronic use of fluoxetine. | ||
Mar 3 |
et al., Infection & Chemotherapy, doi:10.3947/ic.2021.0142 | Fluvoxamine Treatment of Patients with Symptomatic COVID-19 in a Community Treatment Center: A Preliminary Result of Randomized Controlled Trial |
| Early terminated RCT with 52 COVID+ patients in South Korea, showing no significant difference in progression with fluvoxamine treatment. There were only 2 events in each arm, and only one event for fluvoxamine in PP analysis. The trial w.. | ||
Feb 24 |
et al., Journal of Clinical Medicine Research, doi:10.14740/jocmr4658 (Review) | “MATH+” Multi-Modal Hospital Treatment Protocol for COVID-19 Infection: Clinical and Scientific Rationale |
| Review of the data supporting the MATH+ hospital treatment protocol for COVID-19. | ||
Jan 7 |
et al., Molecular Psychiatry, doi:10.1038/s41380-021-01432-3 (Review) | Mechanisms of action of fluvoxamine for COVID-19: a historical review |
| Review of the potential mechanisms of action of fluvoxamine for COVID-19. | ||
Dec 21 2021 |
et al., JAMA Network Open, doi:10.1001/jamanetworkopen.2022.6269 (date from earlier preprint) (meta analysis) | Fluvoxamine for Outpatient Management of COVID-19 to Prevent Hospitalization: A Systematic Review and Meta-analysis |
| Systematic review and meta analysis of outpatient RCTs, showing hospitalization RR 0.75 [0.57-0.97]. For discussion see [twitter.com]. | ||
Nov 15 2021 |
et al., JAMA Network Open, doi:10.1001/jamanetworkopen.2021.33090 | Mortality Risk Among Patients With COVID-19 Prescribed Selective Serotonin Reuptake Inhibitor Antidepressants |
| Retrospective database analysis of 83,584 patients in the USA, showing lower mortality with existing fluoxetine use in PSM analysis. There were 11 fluvoxamine patients, showing non-statistically significant higher mortality. | ||
Nov 1 2021 |
et al., British Journal of Clinical Pharmacology, doi:10.1111/bcp.15126 | Safety and efficacy of fluvoxamine in COVID-19 ICU patients: an open label, prospective cohort trial with matched controls |
| 42% lower mortality [p=0.03]. Prospective PSM study of 51 COVID-19 ICU patients in Croatia and 51 matched controls, showing significantly lower mortality with treatment. | ||
Oct 26 2021 |
et al., medRxiv, doi:10.1101/2021.10.25.21265218 (Preprint) | Ongoing use of SSRIs and the hospital course of COVID-19 patients: a retrospective outcome analysis |
| 2% lower mortality [p=0.83]. Retrospective 9,043 COVID-19+ patients in the USA, 832 with existing SSRI use, showing no significant difference in mortality. None of the patients were on fluvoxamine. Authors note that specific SSRIs such as fluvoxamine may be effective.. | ||
Sep 2 2021 |
et al., European Archives of Psychiatry and Clinical Neuroscience, doi:10.1007/s00406-021-01326-z (Review) | Old drug fluvoxamine, new hope for COVID-19 |
| Review of research supporting the use of fluvoxamine for COVID-19. Authors note the favorable safety profiles, widespread availability, very low cost, and oral administration. | ||
Aug 23 2021 |
et al., The Lancet Global Health, doi:10.1016/S2214-109X(21)00448-4 (date from earlier preprint) | Effect of early treatment with fluvoxamine on risk of emergency care and hospitalisation among patients with COVID-19: the TOGETHER randomised, platform clinical trial |
| 30% lower mortality [p=0.24], 22% lower ventilation [p=0.33], 22% lower hospitalization [p=0.1], and 32% fewer combined hospitalization/ER visits [p=0.004]. Together Trial showing significantly lower hospitalization/extended ER visits with fluvoxamine treatment. Adherence was only 73.2%. Symptom onset was unspecified or >= 4 days for 57% of patients. The schedule of study activities specifies.. | ||
Aug 20 2021 |
, E. (News) | Fluvoxamine for Early Treatment of COVID-19: The STOP COVID Clinical Trials |
| 7% lower hospitalization [p=1]. Presentation noting that STOP COVID 2 was terminated early for futility with only 30/551 cases of detioration and no significant treatment effect. The main results are not available yet, however partial results presented suggest that earl.. | ||
Aug 12 2021 |
et al., Ideggyógyászati szeml, doi:10.18071/ISZ.74.0389 (date from earlier preprint) | Fluoxetine use is associated with improved survival of patients with COVID-19 pneumonia: A retrospective case-control study |
| 58% lower mortality [p=0.002]. Retrospective 269 hospitalized patients in Hungary, 110 treated with fluoxetine, showing lower mortality with treatment. | ||
Aug 12 2021 |
et al., Molecular Psychiatry, doi:10.1038/s41380-021-01254-3 (Review) | Repurposing antidepressants inhibiting the sphingomyelinase acid/ceramide system against COVID-19: current evidence and potential mechanisms |
| Review of the mechanisms of action and clinical studies for the treatment of COVID-19 with FIASMA antidepressants such as fluoxetine, fluvoxamine, paroxetine, escitalopram, or amitriptyline. | ||
Jun 29 2021 |
et al., Psychiatry, Psychotherapy and Clinical Psychology, doi:10.34883/PI.2021.12.2.007 | Fluvoxamine in the Treatment of Patients with COVID-19 |
| Report on the use of fluvoxamine for COVID-19 noting that "patients with COVID-19 taking fluvoxamine did not report clinical complications of coronavirus infection". Only the abstract is currently available. | ||
May 29 2021 |
et al., Clinical Pharmacology & Therapeutics, doi:10.1002/cpt.2317 | Association Between FIASMAs and Reduced Risk of Intubation or Death in Individuals Hospitalized for Severe COVID-19: An Observational Multicenter Study |
| 42% lower combined mortality/intubation [p<0.0001]. Retrospective 2,846 severe COVID-19 patients in France, 277 taking a FIASMA medication, showing lower risk of intubation of death with FIASMA use. | ||
Apr 20 2021 |
et al., Front. Pharmacol., doi:10.3389/fphar.2021.652688 (Review) | Fluvoxamine: A Review of Its Mechanism of Action and Its Role in COVID-19 |
| Review of mechanisms of action of fluvoxamine and other SSRIs that could be beneficial for COVID-19 treatment, including lower platelet aggregation, decreased mast cell degranulation, interference with endolysosomal viral trafficking, reg.. | ||
Mar 7 2021 |
et al., Pharmaceuticals, doi:10.3390/ph14030226 | Association between Functional Inhibitors of Acid Sphingomyelinase (FIASMAs) and Reduced Risk of Death in COVID-19 Patients: A Retrospective Cohort Study |
| 41% lower mortality [p=0.06]. Retrospective 350 COVID-19 hospitalized patients in Belgium, showing lower mortality with existing long-term FIASMA treatment, not quite reaching statistical significance for all FIASMA medications, but reaching statistical significance f.. | ||
Mar 6 2021 |
, S. (Review) (Preprint) | COVID FAQ |
| COVID FAQ from the founder of the COVID-19 Early Treatment Fund [treatearly.org], including an extensive analysis of the fluvoxamine trials and other supporting evidence. | ||
Feb 1 2021 |
et al., Open Forum Infectious Diseases, doi:10.1093/ofid/ofab050 | Prospective cohort of fluvoxamine for early treatment of COVID-19 |
| 84% lower combined mortality/ICU admission [p=0.15], 94% lower hospitalization [p=0.003], and 99% improved recovery [p<0.0001]. Prospective quasi-randomized (patient choice) study with 125 outpatients, 77 treated with fluvoxamine, showing lower death/ICU admission (0 of 77 vs. 2 of 48), lower hospitalization (0 of 77 vs. 6 of 48), and faster recovery with treatmen.. | ||
Nov 12 2020 |
et al., JAMA, doi:10.1001/jama.2020.22760 | Fluvoxamine vs Placebo and Clinical Deterioration in Outpatients With Symptomatic COVID-19: A Randomized Clinical Trial |
| 93% lower progression [p=0.009] and 82% lower hospitalization [p=0.009]. RCT 152 outpatients, 80 treated with fluvoxamine showing lower progression with treatment (0 of 80 versus 6 of 72 control). STOP COVID trial. NCT04342663. | ||
Aug 17 2020 |
et al., Molecular Psychiatry, doi:10.1038/s41380-021-01021-4 | Association between antidepressant use and reduced risk of intubation or death in hospitalized patients with COVID-19: results from an observational study |
| 44% lower combined mortality/intubation [p<0.0001]. Retrospective 7,230 hospitalized COVID-19 patients in France, 345 receiving an antidepressant medication within 48 hours of admission. There was a significant association between antidepressant use and reduced risk of intubation or death... | ||
Jun 4 2020 |
, P., Cell Stress and Chaperones, doi:10.1007/s12192-020-01126-9 (Theory) | COVID-19 and heme oxygenase: novel insight into the disease and potential therapies |
| Proposal that COVID-19 risk is related to low intracellular heme oxygenase (HO-1), and that therapies that raise HO-1 may be beneficial, which includes fluvoxamine, certain anesthetics (sevoflurane or isoflurane), hemin, estrogen, statins.. | ||
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