Higher-Dose Fluvoxamine Doesn’t Shorten COVID-19 Symptom Duration

Fluvoxamine, a selective serotonin reuptake inhibitor used to treat obsessive and anxiety disorders, showed promise in early studies for reducing inflammation in COVID-19. A disappointing clinical trial, however, found no evidence that the drug shortened the duration of symptoms in outpatients with mild to moderate illness. Here is more information.

CHARLOTTESVILLE, VA – In a systematic review and meta-analysis, fluvoxamine, a selective serotonin reuptake inhibitor, seemed to show promise in decreasing the host inflammatory response in COVID-19 and to prevent progression to severe illness and reduce hospitalization rates. The evidence was insufficient to recommend its use for regular treatment, however.

Now, a new randomized clinical trial has found that fluvoxamine, 100 mg twice daily, does not shorten the duration of symptoms in outpatient adults with mild to moderate COVID-19.

A University of Virginia-led study, ACTIV 6, asked whether 100 mg of fluvoxamine twice daily for 13 days, compared with placebo, shortens symptom duration among outpatient adults 30 and older with symptomatic mild to moderate COVID-19.

The trial with 1,175 U.S. participants enrolled during the time that Omicron COVID-19 subvariants were circulating determined no reportable difference in the time to sustained recovery between fluvoxamine and placebo groups (adjusted hazard ratio, 0.99 [95% credible interval, 0.89-1.09]; P for efficacy = .40). Median time to sustained recovery was 10 days (95% CI, 10-11) in both the intervention and placebo group, the researchers report. Results were reported in JAMA.

https://jamanetwork.com/journals/jama/fullarticle/2812204?resultClick=1

The ACTIV-6 platform randomized clinical trial sought to evaluate repurposed medications for mild to moderate COVID-19. Between Aug. 25, 2022, and Jan. 20, 2023, the participants were enrolled at 103 sites in the United States for evaluating fluvoxamine. Participants, who were 30 or older, all had confirmed SARS-CoV-2 infection and at least two acute COVID-19 symptoms for 7 days or less.

Patients participating in the trial had a median age of 50, with 65.8% women. About 45% identified as Hispanic/Latino and 76.8% reported receiving at least two doses of a SARS-CoV-2 vaccine.

About half of the participants were randomized to receive fluvoxamine, 50 mg twice daily on day 1 followed by 100 mg twice daily for 12 additional days, while the others received a placebo. Follow-up occurred through day 28.

Defined as the primary outcome was time to sustained recovery, i.e.at least 3 consecutive days without symptoms. Secondary outcomes included time to death; time to hospitalization or death; a composite of hospitalization, urgent care visit, emergency department visit, or death; COVID-19 clinical progression scale score; and difference in mean time unwell.

Results indicate that, among 589 participants who received fluvoxamine and 586 who received placebo included in the primary analysis, differences in time to sustained recovery were not observed (adjusted hazard ratio [HR], 0.99 [95% credible interval, 0.89-1.09]; P for efficacy = .40]).

Additionally, the unadjusted median time to sustained recovery was 10 (95% CI, 10-11) days in both the intervention and placebo groups. No deaths were reported.

The authors noted that 35 participants reported healthcare use events (a priori defined as death, hospitalization, or emergency department/urgent care visit): 14 in the fluvoxamine group compared with 21 in the placebo group (HR, 0.69 [95% credible interval, 0.27-1.21]; P for efficacy = .86) While there were 7 serious adverse events in 6 participants (2 with fluvoxamine and 4 with placebo), no deaths occurred.

“Among outpatients with mild to moderate COVID-19, treatment with fluvoxamine does not reduce duration of COVID-19 symptoms,” the researchers conclude.