BACKGROUND

The efficacy of selective serotonin reuptake inhibitors (SSRIs) in the treatment of acute COVID-19 is still under investigation, with conflicting results reported from randomized controlled trials (RCTs). Different dosing regimens may have contributed to the contradictory findings.

OBJECTIVES

To evaluate the efficacy and safety of SSRIs and the effect of different dosing regimens on the treatment of acute COVID-19.

DATA SOURCES

Seven databases were searched from January 2020 to December 2022. Trial registries, previous reviews, and preprint servers were hand-searched.

STUDY ELIGIBILITY CRITERIA

RCTs and observational studies with no language restrictions.

PARTICIPANTS

COVID-19 inpatients/outpatients.

INTERVENTIONS

SSRIs prescribed after diagnosis were compared against a placebo or standard of care.

ASSESSMENT OF RISK OF BIAS

Risk of bias was rated using the revised Cochrane Risk of Bias Tool for Randomized Trials version 2.0 and Risk of Bias in Non-Randomized Studies of Interventions.

METHODS OF DATA SYNTHESIS

Outcomes were mortality, hospitalization, composite of hospitalization/emergency room visits, hypoxemia, requirement for supplemental oxygen, ventilator support, and serious adverse events. RCT data were pooled in random-effects meta-analyses. Observational findings were narratively described. Subgroup analyses were performed on the basis of SSRI dose, and sensitivity analyses were performed excluding studies with a high risk of bias. The Grading of Recommendations, Assessment, Development and Evaluations framework was used to assess the quality of evidence.

RESULTS

Six RCTs (N = 4197) and five observational studies (N = 1156) were included. Meta-analyses associated fluvoxamine with reduced mortality (risk ratio, 0.72; 95% CI, 0.63-0.82) and hospitalization (risk ratio, 0.79; 95% CI, 0.64-0.99) on the basis of moderate quality of evidence. Medium-dose fluvoxamine (100 mg twice a day) was associated with reduced mortality, hospitalization, and composite of hospitalization/emergency room visits, but low-dose fluvoxamine (50 mg twice a day) was not. Fluvoxamine was not associated with increased serious adverse events. Observational studies support the use of fluvoxamine and highlight fluoxetine as a possible alternative to SSRIs for the treatment of COVID-19.

DISCUSSION

Fluvoxamine remains a candidate pharmacotherapy for treating COVID-19 in outpatients. Medium-dose fluvoxamine may be preferable over low-dose fluvoxamine.