The cheap, generically available anti-depressant fluvoxamine may reduce the risk of severe COVID by as much as a third in people at high risk, a Brazil study in The Lancet Global Health.showed.
A trial among about 1,500 patients in Brazil showed those who took fluvoxamine were less likely to progress to severe disease and to require hospitalisation.
CNN reports that the drug, sold under the brand name Luvox, is a selective serotonin reuptake inhibitor (SSRI) most often used to treat obsessive compulsive disorder (OCD) and depression. But it can affect inflammation, said Dr Angela Reiersen, an associate professor of psychiatry at Washington University in St Louis who worked on the study.
“Fluvoxamine may reduce the production of inflammatory molecules called cytokines, that can be triggered by SARS-CoV-2 infection,” Reiersen said. The drug might also reduce blood platelets, which could affect the clotting effects of coronavirus infection.
Reierson and colleagues gave 741 volunteers with COVID-19 100mg of fluvoxamine twice a day for 10 days while 756 volunteers got a placebo.
Among the patients who got fluvoxamine, 79, or about 11%, needed treatment in an ER or hospital room compared with nearly 16% of those given placebos. It was a 5% decrease in absolute risk and a 32% decrease in relative risk. More study is needed to see if the drug might be added to the treatments given to coronavirus patients, but it’s cheap.
“A 10-day course of fluvoxamine costs about $4 even in well-resourced settings,” the researchers wrote. It's not a cure, but if the drug can help keep patients out of the hospital, it would be useful.
“Given fluvoxamine’s safety, tolerability, ease of use, low cost, and widespread availability, these findings might influence national and international guidelines on the clinical management of COVID-19,” they concluded.
A related drug, Prozac, or fluoxetine, is also cheap and even more widely available, and the researchers said this drug should be studied to see if it might help.
“It is now crucial to establish whether a class effect exists and whether these drugs can be used interchangeably for COVID-19,” they wrote.
It wasn't a perfect study, they noted. It was done in Brazil, and the patients had a higher rate of hospitalisation than COVID-19 patients in other clinical trials.
“There is no standard of care that exists for early treatment of COVID-19 and various advocacy groups promote different interventions, including some of those evaluated in this and our previous trials. Furthermore, there is little understanding of who is at greatest risk of disease progression from this disease as some patients with numerous risk factors do recover quickly whereas some others with less established risk factors might not,” they wrote.
Study details
Effect of early treatment with fluvoxamine on risk of emergency care and hospitalisation among patients with COVID-19: the TOGETHER randomised, platform clinical trial
Gilmar Reis, Eduardo Moreira-Silva, Daniela Medeiros Silva, Prof Lehana Thabane, Aline Cruz Milagres, Thiago Ferreira, Castilho dos Santos, Vitoria de Souza Campos, Ana Maria Nogueira, Ana de Almeida, Eduardo Diniz Callegari, Adhemar Figueiredo Neto, Leonardo Savassi, Maria Simplicio, Luciene Ribeiro, Rosemary Oliveira, Jamie Forrest,
Hinda Ruton, Sheila Sprague, Paula McKay, Alla Glushchenko, Prof Eric Lenze,
Angela Reiersen, Prof Gordon Guyatt, Prof Edward Mills, for the TOGETHER investigators
Summary
Background
Recent evidence indicates a potential therapeutic role of fluvoxamine for COVID-19. In the TOGETHER trial for acutely symptomatic patients with COVID-19, we aimed to assess the efficacy of fluvoxamine versus placebo in preventing hospitalisation defined as either retention in a COVID-19 emergency setting or transfer to a tertiary hospital due to COVID-19.
Methods
This placebo-controlled, randomised, adaptive platform trial done among high-risk symptomatic Brazilian adults confirmed positive for SARS-CoV-2 included eligible patients from 11 clinical sites in Brazil with a known risk factor for progression to severe disease. Patients were randomly assigned (1:1) to either fluvoxamine (100 mg twice daily for 10 days) or placebo (or other treatment groups not reported here). The trial team, site staff, and patients were masked to treatment allocation. Our primary outcome was a composite endpoint of hospitalisation defined as either retention in a COVID-19 emergency setting or transfer to tertiary hospital due to COVID-19 up to 28 days post-random assignment on the basis of intention to treat. Modified intention to treat explored patients receiving at least 24 h of treatment before a primary outcome event and per-protocol analysis explored patients with a high level adherence (>80%). We used a Bayesian analytic framework to establish the effects along with probability of success of intervention compared with placebo. The trial is ongoing.
Findings
The study team screened 9,803 potential participants for this trial. The trial was initiated on June 2, 2020, with the current protocol reporting randomisation to fluvoxamine from Jan 20 to Aug 5, 2021, when the trial arms were stopped for superiority. 741 patients were allocated to fluvoxamine and 756 to placebo. The average age of participants was 50 years (range 18–102 years); 58% were female. The proportion of patients observed in a COVID-19 emergency setting for more than 6 h or transferred to a tertiary hospital due to COVID-19 was lower for the fluvoxamine group compared with placebo (79 [11%] of 741 vs 119 [16%] of 756); relative risk [RR] 0·68; 95% Bayesian credible interval [95% BCI]: 0·52–0·88), with a probability of superiority of 99·8% surpassing the prespecified superiority threshold of 97·6% (risk difference 5·0%). Of the composite primary outcome events, 87% were hospitalisations. Findings for the primary outcome were similar for the modified intention-to-treat analysis (RR 0·69, 95% BCI 0·53–0·90) and larger in the per-protocol analysis (RR 0·34, 95% BCI, 0·21–0·54). There were 17 deaths in the fluvoxamine group and 25 deaths in the placebo group in the primary intention-to-treat analysis (odds ratio [OR] 0·68, 95% CI: 0·36–1·27). There was one death in the fluvoxamine group and 12 in the placebo group for the per-protocol population (OR 0·09; 95% CI 0·01–0·47). We found no significant differences in number of treatment emergent adverse events among patients in the fluvoxamine and placebo groups.
Interpretation
Treatment with fluvoxamine (100 mg twice daily for 10 days) among high-risk outpatients with early diagnosed COVID-19 reduced the need for hospitalisation defined as retention in a COVID-19 emergency setting or transfer to a tertiary hospital.
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