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Last Updated: December 20, 2023

Fluvoxamine is a selective serotonin reuptake inhibitor (SSRI) that is approved by the Food and Drug Administration (FDA) for the treatment of obsessive-compulsive disorder and is used for other conditions, including depression. Fluvoxamine is not approved by the FDA for the treatment of any infection.

In a murine sepsis model, fluvoxamine was found to bind to the sigma-1 receptor on immune cells, resulting in reduced production of inflammatory cytokines.1 In an in vitro study of human endothelial cells and macrophages, fluvoxamine reduced the expression of inflammatory genes.2


  • The COVID-19 Treatment Guidelines Panel (the Panel) recommends against the use of fluvoxamine for the treatment of COVID-19 in nonhospitalized patients (AIIa).
  • There is insufficient evidence for the Panel to recommend either for or against the use of the combination of inhaled budesonide plus fluvoxamine for the treatment of COVID-19 in nonhospitalized patients.
  • Patients with COVID-19 who are receiving fluvoxamine for an underlying condition should continue this therapy as directed by their health care provider (AIII).


Six randomized trials have studied the use of fluvoxamine for the treatment of nonhospitalized patients with COVID-19.3-8 The TOGETHER and STOP COVID 2 trials enrolled unvaccinated patients with COVID-19 who had at least 1 risk factor for disease progression.3,5 These studies did not identify a consistent benefit of using fluvoxamine in these patients, although STOP COVID 2 was stopped early due to low primary outcome rates. Other outpatient therapies (i.e., ritonavir-boosted nirmatrelvir [Paxlovid], remdesivir) have been shown to be effective in preventing hospitalization or death in unvaccinated patients who are at high risk of disease progression. In subsequent trials where the majority of enrolled patients were vaccinated against COVID-19, fluvoxamine did not significantly reduce the risk of hospitalization or death, the time to recovery, or health care utilization.6-8 In several of these studies, fluvoxamine was associated with decreased adherence and/or an increase in the occurrence of nonserious adverse effects, primarily gastrointestinal symptoms.3,5,6

The TOGETHER trial was a large, double-blind, placebo-controlled, adaptive randomized trial in Brazil that evaluated the use of inhaled budesonide plus oral fluvoxamine in patients with COVID-19.9 Over 90% of the patients had received at least 2 doses of a COVID-19 vaccine. Treatment with this combination significantly reduced the incidence of the primary outcome, which was a composite of hospitalization or retention in an emergency setting for >6 hours. The proportion of patients who were hospitalized was the same in the treatment and placebo arms (0.9% vs. 1.1%), and the treatment did not significantly impact secondary outcomes such as health care attendance or the need for an emergency setting visit. It is unclear how the >6-hour emergency setting outcome translates to other settings. In addition, treatment with budesonide plus fluvoxamine was associated with significantly more adverse events.

Summaries of the studies that informed the Panel’s recommendations can be found in Table 7a.

Monitoring, Adverse Effects, and Drug-Drug Interactions

When fluvoxamine is used to treat psychiatric conditions, the most common adverse effect is nausea, but adverse effects can include other gastrointestinal effects (e.g., diarrhea, indigestion), neurologic effects (e.g., asthenia, insomnia, somnolence, anxiety, headache), and, rarely, suicidal ideation.

Fluvoxamine is a cytochrome P450 (CYP) 2D6 substrate, a potent inhibitor of CYP1A2 and CYP2C19, and a moderate inhibitor of CYP2C9, CYP2D6, and CYP3A4.10 Fluvoxamine can enhance the serotonergic effects of other SSRIs or monoamine oxidase inhibitors, resulting in serotonin syndrome; therefore, it should not be used within 2 weeks of receiving other SSRIs or monoamine oxidase inhibitors. Fluvoxamine may enhance the anticoagulant effects of antiplatelets and anticoagulants. Patients who are receiving these drugs should be closely monitored.

Considerations in Pregnant People

Fluvoxamine is not thought to increase the risk of congenital abnormalities; however, the data on its use in pregnant individuals are limited.11,12 An association between SSRI use in the late third trimester and a small increase in the risk of primary persistent pulmonary hypertension in newborns has not been excluded, although the absolute risk is likely low.13

Considerations in Children

Fluvoxamine is approved by the FDA for the treatment of obsessive-compulsive disorder in children aged ≥8 years.14 The adverse effects of SSRI use seen in children are similar to those seen in adults, although children and adolescents appear to have higher rates of activation and vomiting than adults.15 There are no data on the use of fluvoxamine for the prevention or treatment of COVID-19 in children.


  1. Rosen DA, Seki SM, Fernández-Castañeda A, et al. Modulation of the sigma-1 receptor-IRE1 pathway is beneficial in preclinical models of inflammation and sepsis. Sci Transl Med. 2019;11(478):eaau5266. Available at:
  2. Rafiee L, Hajhashemi V, Javanmard SH. Fluvoxamine inhibits some inflammatory genes expression in LPS/stimulated human endothelial cells, U937 macrophages, and carrageenan-induced paw edema in rat. Iran J Basic Med Sci. 2016;19(9):977-984. Available at:
  3. Reis G, Dos Santos Moreira-Silva EA, Medeiros Silva DC, et al. Effect of early treatment with fluvoxamine on risk of emergency care and hospitalisation among patients with COVID-19: the TOGETHER randomised, platform clinical trial. Lancet Glob Health. 2022;10(1):e42-e51. Available at:
  4. Lenze EJ, Mattar C, Zorumski CF, et al. Fluvoxamine vs placebo and clinical deterioration in outpatients with symptomatic COVID-19: a randomized clinical trial. JAMA. 2020;324(22):2292-2300. Available at:
  5. Reiersen AM, Mattar C, Bender Ignacio RA, et al. The STOP COVID 2 study: fluvoxamine vs placebo for outpatients with symptomatic COVID-19, a fully remote randomized controlled trial. Open Forum Infect Dis. 2023;10(8):ofad419. Available at:
  6. Stewart TG, Rebolledo PA, Mourad A, et al. Higher-dose fluvoxamine and time to sustained recovery in outpatients with COVID-19: the ACTIV-6 randomized clinical trial. JAMA. 2023;Published online ahead of print. Available at:
  7. McCarthy MW, Naggie S, Boulware DR, et al. Effect of fluvoxamine vs placebo on time to sustained recovery in outpatients with mild to moderate COVID-19: a randomized clinical trial. JAMA. 2023;329(4):296-305. Available at:
  8. Bramante CT, Huling JD, Tignanelli CJ, et al. Randomized trial of metformin, ivermectin, and fluvoxamine for COVID-19. N Engl J Med. 2022;387(7):599-610. Available at:
  9. Reis G, Dos Santos Moreira Silva EA, Medeiros Silva DC, et al. Oral fluvoxamine with inhaled budesonide for treatment of early-onset COVID-19: a randomized platform trial. Ann Intern Med. 2023;176(5):667-675. Available at:
  10. Hemeryck A, Belpaire FM. Selective serotonin reuptake inhibitors and cytochrome P-450 mediated drug-drug interactions: an update. Curr Drug Metab. 2002;3(1):13-37. Available at:
  11. Einarson A, Choi J, Einarson TR, Koren G. Incidence of major malformations in infants following antidepressant exposure in pregnancy: results of a large prospective cohort study. Can J Psychiatry. 2009;54(4):242-246. Available at:
  12. Furu K, Kieler H, Haglund B, et al. Selective serotonin reuptake inhibitors and venlafaxine in early pregnancy and risk of birth defects: population based cohort study and sibling design. BMJ. 2015;350:h1798. Available at:
  13. Huybrechts KF, Bateman BT, Palmsten K, et al. Antidepressant use late in pregnancy and risk of persistent pulmonary hypertension of the newborn. JAMA. 2015;313(21):2142-2151. Available at:
  14. Fluvoxamine maleate tablets [package insert]. Food and Drug Administration. 2019. Available at:
  15. Safer DJ, Zito JM. Treatment-emergent adverse events from selective serotonin reuptake inhibitors by age group: children versus adolescents. J Child Adolesc Psychopharmacol. 2006;16(1-2):159-169. Available at: