Dear Editor,
We appreciated the thoughtful letter by Dr. Mazza positing that the antidepressant effect of fluvoxamine could make it a useful treatment for patients experiencing depression in the wake of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2; coronavirus disease 2019 [COVID-19]) infection [1]. This highlights two important points: (1) the critical need to find effective treatments for the neuropsychiatric sequelae of COVID-19 and (2) the potential to repurpose selective serotonin reuptake inhibitors (SSRIs) and other psychotropics towards this goal.
Neuropsychiatric problems are common after COVID-19, including mood and anxiety disorders, cognitive impairment, psychosis, and stroke. A large electronic health record database study found that one in three COVID-19 survivors experienced neuropsychiatric illness after 6 months, including 17% with new-onset anxiety disorder and 14% with new-onset depression [2]. Etiologies include central inflammation, delirium, post-intensive care unit syndrome, cerebrovascular accidents, and psychosocial stress.
Dr. Mazza recently showed that “COVID depression” may be particularly responsive to SSRIs, suggesting that these drugs may have a role in reducing the substantial morbidity of post-COVID neuropsychiatric syndromes [3]. Serotonin reuptake inhibitors (SRIs) have manifold effects on human physiology, including anti-inflammatory and neurorestorative effects in some studies [4]. Some SRIs have secondary molecular targets, such as the sigma-1 receptor, which motivated our repurposing of fluvoxamine (a strong activator of this receptor) for acute COVID-19.
More studies are needed to confirm and extend the findings of Mazza et al. [1] in COVID-depression and other neuropsychiatric manifestations of this disease.
Eric J Lenze MD
Angela M Reiersen MD
Declarations
Conflict of interest
Dr. Reiersen and Dr. Lenze are listed on a patent application related to methods of treating COVID-19 that was filed by Washington University in St. Louis. Dr Facente has no conflicts of interest that are directly relevant to the content of this letter.
Funding
The original article this letter relates to was supported in part by a gift to the Keck School of Medicine of the University of Southern California by the W.M. Keck Foundation.
Author contributions
AMR and EJL prepared the reply. All authors read and approved the reply.
Ethics approval
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References
- 1.Mazza MG, Vai B, De Picker L, Benedetti F, Zanardi R. Comment on: “Fluvoxamine for the early treatment of SARS-CoV-2 infection: a review of current evidence”. Drugs. 2022 doi: 10.1007/s40265-022-01682-7. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 2.Taquet M, Luciano S, Geddes JR, Harrison PJ. Bidirectional associations between COVID-19 and psychiatric disorder: retrospective cohort studies of 62 354 COVID-19 cases in the USA. Lancet Psychiatry. 2021;8(2):130–140. doi: 10.1016/S2215-0366(20)30462-4. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 3.Mazza MG, Zanardi R, Palladini M, Rovere-Querini P, Benedetti F. Rapid response to selective serotonin reuptake inhibitors in post-COVID depression. Eur Neuropsychopharmacol. 2022;54:1–6. doi: 10.1016/j.euroneuro.2021.09.009. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 4.Nykamp MJ, Zorumski CF, Reiersen AM, Nicol GE, Cirrito J, Lenze EJ. Opportunities for drug repurposing of serotonin reuptake inhibitors: potential uses in inflammation, infection, cancer, neuroprotection, and Alzheimer's disease prevention. Pharmacopsychiatry. 2022;55(1):24–29. doi: 10.1055/a-1686-9620. [DOI] [PubMed] [Google Scholar]