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Review 2: "SSRIs and SNRIs and Risk of Death or Intubation in COVID-19: Results from an Observational Study"

Paper claims that antidepressants lower the risk of death or intubation in patients with COVID-19. The findings suggest antidepressants may contribute to the treatment of COVID-19, but it would require extensive research to validate the claims.

Published onAug 11, 2020
Review 2: "SSRIs and SNRIs and Risk of Death or Intubation in COVID-19: Results from an Observational Study"
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key-enterThis Pub is a Review of
SSRIs and SNRIs and Risk of Death or Intubation in COVID-19: Results from an Observational Study

Importance: On the grounds of their anti-inflammatory and potential antiviral effects, we hypothesized that SSRIs and SNRIs might be effective treatments for Covid-19. Methods: We examined the association of antidepressant use with intubation or death in hospitalized patients with COVID-19. The primary endpoint was a composite of intubation or death in time-to-event analyses adjusted for numerous potential confounders. We compared this endpoint between patients who received antidepressants and those who did not. The primary analyses were multivariable Cox models with inverse probability weighting. Results: Of the 9,509 inpatients with positive Covid-19 RT-PCR test, 2,164 patients (22.8%) were excluded because of missing data or exclusion criterion (i.e. less than 18 years old of age). Of the remaining 7,345 adult inpatients, 460 patients (6.3%) received an antidepressant during the hospitalization. The primary endpoint occurred respectively in 143 patients exposed to antidepressants (31.1%) and 1,188 patients who were not (17.3%). After adjusting for the older age [74.8 (SD=15.5) versus 56.8 (SD=19.3); Welch9s t-test=23.7; p<0.001] and the greater medical severity of patients receiving antidepressants, the primary analyses showed a significant negative association of the composite endpoint with exposure to any antidepressant (HR, 0.64; p<0.001), SSRIs (HR, 0.56; p<0.001), and SNRIs (HR, 0.57; p=0.034), but not with other antidepressant classes. Exposure to escitalopram, fluoxetine, and venlafaxine was significantly associated with lower risk of intubation or death (all p<0.05). Results were similar in multiple sensitivity analyses. Conclusions: SSRIs and SNRIs may be associated with lower risk of death or intubation in patients with COVID-19.

RR:C19 Evidence Scale rating by reviewer:

  • Potentially informative. The main claims made are not strongly justified by the methods and data, but may yield some insight. The results and conclusions of the study may resemble those from the hypothetical ideal study, but there is substantial room for doubt. Decision-makers should consider this evidence only with a thorough understanding of its weaknesses, alongside other evidence and theory. Decision-makers should not consider this actionable, unless the weaknesses are clearly understood and there is other theory and evidence to further support it.



This observational study has tried to assess the use of SSRIs and SNRIs and risk of death or intubation in COVID-19 patients.

In the abstract section, some background information would be helpful in addition to the importance provided. The other part of the abstract seems fine.

The introduction provided is fine. It provides the background information on COVID-19. It focuses on the absence of a vaccine or curative treatment and the need of effective treatment for COVID-19. Evidences on the use of antidepressants to lower the plasma levels of cytokines involved in pathogenesis of COVID-19 has been explained. Based on the evidences, the study has hypothesized that use of antidepressants would be associated with reduced risk of intubation or death.

In the methods part, the settings of the study is well described. The data sources is fine and the variables assessed is sufficiently presented. In the section 2.4 exposure to antidepressants, it would be better to describe the number of persons exposed to antidepressants and the rationale for it. The schedule of provision of antidepressants or its different types are not clear. The section of statistical analysis is fine.

The results have been presented in different subheadings. The characteristics of the cohort and the study endpoints have been well described. Necessary tables and figures have been presented. However, I am not quite sure about the e-tables and e-figures as there was no access to them.

The discussion seems fine.

The references are valid and sufficient.

In the present context of COVID-19, the findings can be considered novel. The use of antidepressant may be associated with lower risk of intubation and death. However, this association has not been established. This provides the insights that further studies and clinical trials are required. Also, the findings can be considered interesting as the preliminary findings from this study indicated that use of antidepressants can lower the risk of intubation and deaths from COVID-19. So more evidences are required to prove this. This call for more research and clinical trials to see the association between use of antidepressants and low risk of intubation and death. The societal impact is that the use of antidepressants could save lives of people from COVID-19.

The study design and analysis requires more descriptions in terms of provision of antidepressants. The schedule/interval, doses, follow up etc needs to be explained.

The conclusions drawn are supported by the results.

The article cites the current literature. The article has discussed about its limitations as well.

The structure of the paper can be improved. The article seems a little long, hence it should focus on only the major parts to be covered in the article. Other parts of the paper is fine.

The etables and efigures mentioned in the article are not accessible. The data and code used are also not accessible.

Regarding ethical concerns, the authors mentions about getting approval from IRB and that the study has adhered to all ethical standards but not adequately described.

Based on the review, the article can be considered for publications with minor revisions as mentioned above.

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