Antidepressant Fluvoxamine in Reducing COVID-19 Hospitalization

By Saad Shakil¹, Sareema Eman Akhtar¹, Akhtar Ali²

 

AFFLIATIONS:

1. Ziauddin Medical University, Karachi, Pakistan.
2. Department of Pharmacology, Ziauddin Medical University, Karachi, Pakistan.

 

DOI: https://doi.org/10.36283/PJMD11-2/015

ORCID iD: 0000-0003-1622-7675

 

How to cite: Shakil S, Akhtar SE, Ali A. Antidepressant Fluvoxamine in Reducing COVID-19 Hospitalization. Pak J Med Dent. 2022;11(2): 95-96. doi: 10.36283/PJMD11-2/015

 

Dear Editor,

In this era of the 21st century, when a global pandemic has taken over the lives of millions, causing severe hospitalization and even death, the need for treatment has become an ongoing challenge despite the relative progress made by vaccination. Current data shows more than 0.57 million COVID-19 related hospitalizations being registered in the United Kingdom and more than 3.2 million in the United States^1,2.

To reduce the burden of hospitalization, different treatment modalities are being considered and tested worldwide for severely ill COVID-19 patients. Despite the availability of different medications such as corticosteroids including Dexamethasone, Prednisone, Methylprednisolone, antiviral drugs i.e., Remdesivir and IL-6 antibodies, Tocilizumab, healthcare systems still need to restrict the number of hospital admissions. Fluvoxamine [Selective Serotonin Reuptake Inhibitor (SSRI)], an antidepressant that has recently been added to the list of successful treatments for COVID-19 patients. A major clinical trial held in Brazil proved the efficacy of Fluvoxamine in reducing the risk of hospitalization in patients. According to available data, 11% of patients who were treated with fluvoxamine were shifted to tertiary care hospitals, and 16% of patients who were treated with placebo needed hospitalization which proved that early treatment with Fluvoxamine may decrease the susceptibility of hospitalization³. Fluvoxamine acts as a selective serotonin reuptake inhibitor (SSRI) and σ-1 receptor agonist. It is commonly used as an antidepressant and as a treatment for obsessive-compulsive disorder (OCD). Fluvoxamine, unlike corticosteroids used by COVID-19 patients, does not suppress the immune system’s antiviral activity, it rather acts as an immunomodulator.

It is also relatively better than other SSRIs like fluoxetine at activating the sigma-1 receptor which in turn reduces the production of cytokines (inflammatory signaling protein molecules) ⁴. It has been documented that the replication of SARS COV 2 takes place in the endoplasmic reticulum (ER) of the cells and this replication is responsible for the production of inflammatory cytokines and the development of stress in the ER. The possible mechanism behind the effectiveness of Fluvoxamine in reducing mortality is its affinity for the σ-1 receptor. Its agonistic activity at the σ-1 receptor decreases the production of inflammatory cytokines ultimately reducing the ER stress that possibly reduces the hospital stay⁵. A study by Hoertel et al. also concluded the effectiveness of Fluvoxamine; the use of the antidepressant led to reduced risk of intubation or death in hospitalized covid patients⁴. Although fluvoxamine is a widely available, inexpensive, oral drug with a relatively better safety profile, it is still reported to shows few adverse events like pneumonia, shortness of breath (SOB), headache, muscle ache, vasovagal syncope and bacterial infections⁶.

Although clinical trials favoring Fluvoxamine have shown auspicious results, it is essential to have more data from extensive, prolonged multi-centered clinical trials before prescribing it to the masses. This will enable the health workers and researchers to identify efficacy in different populations as well as other potential adverse events of the drug. Moreover, to the best of our literature search, there is still a gap of knowledge that needs to be identified in this aspect where there is a possibility of varying responses of people to this drug by those who are fully vaccinated versus those who get reinfected after inoculation. Furthermore, the effectiveness of Fluvoxamine in different COVID-19 strains including delta variant, as well as adolescent and pregnant patients still needs evaluation. We are optimistic about the use of Fluvoxamine globally especially in developing countries like Pakistan, Bangladesh, and India because of its cost-effectiveness, low adverse potential and where vaccination programs still have a long way to go.

The authors would like to acknowledge and extend our gratitude to Ziauddin Medical University, Karachi, Pakistan.

The authors declare no conflict of interest.

All authors equally contributed to this write-up.

1. Healthcare in the UK | Coronavirus in the UK [Internet]. [cited 2021 Nov 3]. Available from: https://coronavirus.data.gov.uk/details/healthcare
2. COVID Data Tracker Weekly Review | CDC [Internet]. [cited 2021 Nov 3]. Available from: https://www.cdc.gov/coronavirus/2019-ncov/covid-data/covidview/index.html
3. Reis G, dos Santos Moreira-Silva EA, Silva DC, Thabane L, Milagres AC, Ferreira TS, 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):42-51. doi: 10.1016/S2214-109X(21)00448-4
4. Hoertel N, Sánchez-Rico M, Vernet R, Beeker N, Jannot AS, Neuraz A, et al. Association between antidepressant use and reduced risk of intubation or death in hospitalized patients with COVID-19: results from an observational study. Mol Psychiatry. 2021;26(9):5199-5212. doi: 10.1038/s41380-021-01021-4
5. Hashimoto K. Repurposing of CNS drugs to treat COVID-19 infection: targeting the sigma-1 receptor. Eur Arch Psychiatry Clin Neurosci. 2021;271(2):249-258. doi: /10.1007/s00406-020-01231-x
6. Lenze EJ, Mattar C, Zorumski CF, Stevens A, Schweiger J, Nicol GE, et al. Fluvoxamine vs placebo and clinical deterioration in outpatients with symptomatic COVID-19: a randomized clinical trial. JAMA. 2020;324(22):2292-2300. doi: 10.1001/jama.2020.22760

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