Fluvoxamine vs Placebo Did not Decrease Recovery Time in Mild to Moderate COVID-19

The use of the antidepressant medication, fluvoxamine, for COVID-19 treatment in hospitalized patients has been reported to provide some benefits including decreasing the severity of the virus and improve outcomes in this patient population.

However, studies have demonstrated contradictory results. In one study, that looked at systematic review and meta-analysis of 14 studies using observational data with 290,950 participants, there was mixed findings.¹ “Eight out of fourteen articles revealed the effect of antidepressants on reducing the severity of COVID-19. Selective serotonin reuptake inhibitors drugs, including Fluvoxamine, Escitalopram, Fluoxetine, and Paroxetine, and among the Serotonin-norepinephrine inhibitors medications Venlafaxine, are reasonably associated with reduced risk of intubation or death. Five studies showed no significant effect, and only one high risk of bias article showed the negative effect of antidepressants on the prognosis of Covid-19. The meta-analysis of clinical trials showed that fluvoxamine could significantly decrease the severity outcomes of COVID-19,”¹ the investigators wrote.

In another recent study, the Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV-6) trial, looked at patients with mild or moderate COVID-19. Investigators performed a randomized trial using 50 mg of fluvoxamine taken twice daily for 10 days, compared with placebo.

People were enrolled into the fluvoxamine cohort or the placebo cohort between August 6, 2021, and May 27, 2022, at 91 sites in the United States. This was during a period when both Delta and Omicron variants were the predominant strains in the US.

“Among 1331 participants who were randomized (median age, 47 years [IQR, 38-57 years]; 57% were women; and 67% reported receiving ≥2 doses of a SARS-CoV-2 vaccine), 1288 completed the trial (674 in the fluvoxamine group and 614 in the placebo group). The median time to sustained recovery was 12 days (IQR, 11-14 days) in the fluvoxamine group and 13 days (IQR, 12-13 days) in the placebo group (hazard ratio [HR], 0.96 [95% credible interval, 0.86-1.06], posterior P = .21 for the probability of benefit [determined by an HR >1]),” the investigators wrote.

“These findings do not support the use of fluvoxamine at this dose and duration in patients with mild to moderate COVID-19,” the investigators concluded.

The study results were published in JAMA.

In accompanying commentary, the authors discussed the role of clinicians using fluvoxamine now as the pandemic has evolved.

They also credit the investigators for the continuous study of this therapy, and one of the most relevant points they made was the idea of doing follow-up studies on therapies as the pandemic evolves and new variants arise. “The repeated study of fluvoxamine over the course of the COVID-19 pandemic brings up another issue—the need for continued study of authorized antivirals as the pandemic changes,” the authors wrote. “Drugs shown to be effective earlier in immune-naive populations and against more problematic SARS-CoV-2 variants require further study to define their role in the current landscape of COVID-19.”


Reference

1. Nakhaee H, Zangiabadian M, Bayati R, Rahmanian M, Ghaffari Jolfayi A, Rakhshanderou S. The effect of antidepressants on the severity of COVID-19 in hospitalized patients: A systematic review and meta-analysis. PLoS One. 2022;17(10):e0267423. Published 2022 Oct 6. doi:10.1371/journal.pone.0267423