Temerty Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada.
Department of Health Research Methods, Evidence, and Impact, Faculty of Health Sciences, McMaster University, Hamilton, Ontario, Canada.
Clin Microbiol Infect. 2023 May;29(5):578-586. doi: 10.1016/j.cmi.2023.01.010. Epub 2023 Jan 16.
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.
To evaluate the efficacy and safety of SSRIs and the effect of different dosing regimens on the treatment of acute COVID-19.
Seven databases were searched from January 2020 to December 2022. Trial registries, previous reviews, and preprint servers were hand-searched.
RCTs and observational studies with no language restrictions.
COVID-19 inpatients/outpatients.
SSRIs prescribed after diagnosis were compared against a placebo or standard of care.
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.
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.
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.
Fluvoxamine remains a candidate pharmacotherapy for treating COVID-19 in outpatients. Medium-dose fluvoxamine may be preferable over low-dose fluvoxamine.
选择性 5-羟色胺再摄取抑制剂（SSRIs）在治疗急性 COVID-19 中的疗效仍在研究中，随机对照试验（RCT）的结果相互矛盾。不同的剂量方案可能导致了相互矛盾的发现。
评估 SSRIs 的疗效和安全性，以及不同剂量方案对急性 COVID-19 治疗的影响。
从 2020 年 1 月至 2022 年 12 月，检索了 7 个数据库。此外，还对试验注册处、先前的综述和预印本服务器进行了手工检索。
无语言限制的 RCT 和观察性研究。
COVID-19 门诊/住院患者。
在确诊后开具 SSRIs 与安慰剂或标准治疗进行比较。
使用修订后的 Cochrane 随机对照试验偏倚风险工具（版本 2.0）和干预措施非随机研究的偏倚风险评估工具对偏倚风险进行评估。
结局包括死亡率、住院率、住院/急诊就诊的复合结局、低氧血症、需要补充氧气、呼吸机支持和严重不良事件。RCT 数据采用随机效应荟萃分析进行汇总。观察性研究结果进行了叙述性描述。基于 SSRI 剂量进行了亚组分析，并排除了偏倚风险高的研究进行敏感性分析。采用推荐评估、制定与评价分级框架（Grading of Recommendations, Assessment, Development and Evaluations，GRADE）评估证据质量。
纳入了 6 项 RCT（N=4197）和 5 项观察性研究（N=1156）。基于中等质量的证据，荟萃分析显示氟伏沙明可降低死亡率（风险比，0.72；95%置信区间，0.63-0.82）和住院率（风险比，0.79；95%置信区间，0.64-0.99）。中剂量氟伏沙明（每天 100mg，分两次服用）与死亡率、住院率和住院/急诊就诊的复合结局降低相关，但低剂量氟伏沙明（每天 50mg，分两次服用）则不然。氟伏沙明与严重不良事件的增加无关。观察性研究支持氟伏沙明的使用，并强调氟西汀可能是治疗 COVID-19 的 SSRIs 的替代选择。
氟伏沙明仍然是治疗门诊 COVID-19 的候选药物疗法。中剂量氟伏沙明可能优于低剂量氟伏沙明。
