Efficacy and safety of selective serotonin reuptake inhibitors in COVID-19 management: A systematic review and meta-analysis

Abstract

Background

The efficacy of selective serotonin reuptake inhibitors (SSRIs) in acute COVID-19 treatment remains 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 impact of different dosing regimens in acute COVID-19 treatment.

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 compared against placebo or standard of care.

Assessment of risk of bias

Risk of bias was rated with RoB2 and ROBINS-I.

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 (SAEs). RCT data was pooled in random-effects meta-analyses. Observational findings were narratively described. Subgroup analyses were conducted based on SSRI dose, and sensitivity analyses were conducted excluding high risk of bias studies. GRADE was used to assess quality of evidence (QoE).

Results

Six RCTs (N=4,197) and 5 observational studies (N=1,156) were included. Meta-analyses associated fluvoxamine with reduced mortality (risk ratio [RR] 0.72, 95% confidence interval [CI] 0.63-0.82) and hospitalization (RR 0.79, 95% CI 0.64-0.99) based on moderate QoE. Medium-dose fluvoxamine (100 mg b.i.d.) was associated with reduced mortality, hospitalization, and composite of hospitalization/emergency room visits but not low-dose fluvoxamine (50 mg b.i.d.). Fluvoxamine was not associated with increased SAEs. Observational studies support fluvoxamine use and highlighted fluoxetine as a possible alternative SSRI for COVID-19 treatment.

Conclusions

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