Proof reveals weak antiviral exercise and no enchancment in symptom outcomes.
Examine: Antiviral efficacy of fluoxetine in early symptomatic COVID-19: an open-label, randomised, managed, adaptive platform trial (PLATCOV). Picture Credit score: luchschenF/Shutterstock.com
In a current examine revealed in eClinicalMedicine, researchers characterised the antiviral exercise of a selective serotonin reuptake inhibitor (SSRI), fluoxetine, in early coronavirus illness 2019 (COVID-19).
Background
SSRIs are extensively used antidepressants which might be available and inexpensive worldwide. Observational research reported that sufferers taking fluoxetine had decrease mortality when hospitalized for COVID-19.
Later research supporting this commentary advised that SSRIs may additionally confer prophylactic advantages. SSRIs might exert antiviral motion via the purposeful inhibition of acid sphingomyelinase (FIASMA).
Whereas most research have targeted on one other SSRI (fluvoxamine), fluoxetine has essentially the most favorable pharmacokinetic properties, the best FIASMA exercise in vitro, and the very best tolerability profile.
Conducting randomized trials to evaluate the prevention of hospitalization or demise in symptomatic COVID-19 outpatients is now not possible, as was doable in the course of the pandemic.
Concerning the examine
Within the current examine, researchers assessed the antiviral efficacy of fluoxetine in early COVID-19. If that they had early symptomatic COVID-19, people aged 18–50 have been enrolled in an ongoing, part 2, randomized, managed adaptive platform trial (PLATCOV).
Pregnant people, topics taking antivirals or different medicines, and people with morbidity, continual sickness, hematological abnormalities, or contraindications to check medicine have been excluded.
The fluoxetine arm was added to the platform in April 2022 in Thailand, June 2022 in Brazil, December 2022 in Laos, and February 2023 in Pakistan and was eliminated in Might 2023. Sufferers have been randomized to one of many 11 remedy arms.
Intervention arms have been fluoxetine, molnupiravir, nitazoxanide, favipiravir, casirivimab/imdevimab, remdesivir, tixagevimab/cilgavimab, ensitrelvir, ivermectin, ritonavir-boosted nirmatrelvir, or no-study drug.
The ritonavir-boosted nirmatrelvir arm served because the positive-control group. Fluoxetine (40 mg) was given for seven days from baseline. Oropharyngeal swabs have been collected on days 0–7, 10, and 14.
Sufferers recorded their very important indicators thrice every day, in addition to signs and antagonistic results. Viral hundreds have been quantified utilizing a polymerase chain response (PCR) assay, which detects viral spike, nucleocapsid, and human RNase P genes.
The first consequence was the viral clearance fee from viral genome densities in swabs collected on days 0 to 7. Secondary outcomes have been all-cause hospitalization and the time-to-resolution of fever and signs.
The viral clearance fee was estimated beneath a hierarchical linear mannequin and fitted to log10 viral densities between days 0 and seven.
Findings
In whole, 675 sufferers have been randomized to intervention arms. Of those, 120 have been randomized to the fluoxetine arm, 151 to the no-study drug arm, and the remaining sufferers have been randomized to different interventions.
Most sufferers (90%) have been recruited in Thailand. The median interval for the reason that onset of signs was two days. The imply SARS-CoV-2 eluate density was 350,000 genomes/ml. SARS-CoV-2 Omicron BA.5, BA.2, and BA.2.75 have been the most typical infecting variants.
Fluoxetine recipients reported greater somnolence than the no-study drug group. Two sufferers didn’t full the fluoxetine course. No critical antagonistic occasions, hospitalizations, or deaths occurred. Furthermore, the time to symptom or fever decision was not considerably completely different between the fluoxetine and no-study drug arms.
Fluoxetine recipients had a 15% sooner viral clearance, on common, than the no-study drug arm. The median viral clearance half-life was 14 hours within the fluoxetine arm and 14.9 hours within the no-study drug group.
A submit hoc sensitivity evaluation estimating fluoxetine’s remedy impact utilizing knowledge from the primary 5 days post-randomization confirmed a considerably bigger remedy impact (at 26%).
As well as, a meta-analysis of all medicine and antibodies was carried out utilizing particular person affected person knowledge. This revealed that fluoxetine elevated clearance by 16% relative to the no-study drug arm. It additionally had a better clearance fee relative to favipiravir and ivermectin.
Nonetheless, fluoxetine’s remedy impact was decrease than that of remdesivir, ritonavir-boosted nirmatrelvir, casirivimab/imdevimab, and molnupiravir.
Conclusions
In sum, the findings illustrate fluoxetine’s weak antiviral exercise in adults with early symptomatic COVID-19. There have been no vital variations within the time to symptom or fever decision between fluoxetine and no examine drug arms.
The acceleration in viral clearance with fluoxetine was considerably decrease than contemporaneous antivirals. As such, fluoxetine is unlikely for use in COVID-19 remedy, provided that different more practical antivirals can be found.