ABSTRACT
Preliminary meta-analyses suggested that fluvoxamine was effective in treating COVID-19 infection. However, the reliability of this evidence has not yet been examined. MEDLINE, CENTRAL, EMBASE, PsycINFO, and ClinicalTrials.gov were searched to identify any randomized controlled trials (RCTs) from the inception of the databases to 5 February 2023. We used trial sequential analysis (TSA) to examine the reliability of the current existing evidence on the benefits of fluvoxamine on COVID-19 infection. The primary outcome was clinical deterioration, as defined in the original study (reported as odds ratio (OR), with 95% confidence intervals), and the secondary outcome was hospitalization. In the TSA, we used the relative risk reduction thresholds of 10, 20, and 30%. The updated meta-analysis of the five RCTs showed that fluvoxamine was not associated with lower odds of clinical deterioration when compared with a placebo (OR: 0.81;0.59–1.11). The effect of fluvoxamine lay within the futility boundary (i.e., lack of effect) when using a 30% relative risk reduction threshold. The effect estimates lay between the superiority and futility boundary using the 10% and 20% threshold, and the required size of information was not reached for these two thresholds. The effect of fluvoxamine on the odds of hospitalization was not statistically significant (0.76;0.56–1.03). In conclusion, there is no reliable evidence that fluvoxamine, when compared to a placebo, reduces the relative risk of clinical deterioration among adult patients with COVID-19 infection by 30%, and a relative risk reduction of 20% or 10% is still uncertain. The role of fluvoxamine as a COVID-19 treatment cannot be justified.
ABSTRACT
Preliminary meta-analyses suggested that fluvoxamine was effective in treating COVID-19 infection. However, the reliability of this evidence has not yet been examined. MEDLINE, CENTRAL, EMBASE, PsycINFO, and ClinicalTrials.gov were searched to identify any randomized controlled trials (RCTs) from the inception of the databases to 5 February 2023. We used trial sequential analysis (TSA) to examine the reliability of the current existing evidence on the benefits of fluvoxamine on COVID-19 infection. The primary outcome was clinical deterioration, as defined in the original study (reported as odds ratio (OR), with 95% confidence intervals), and the secondary outcome was hospitalization. In the TSA, we used the relative risk reduction thresholds of 10, 20, and 30%. The updated meta-analysis of the five RCTs showed that fluvoxamine was not associated with lower odds of clinical deterioration when compared with a placebo (OR: 0.81; 0.59-1.11). The effect of fluvoxamine lay within the futility boundary (i.e., lack of effect) when using a 30% relative risk reduction threshold. The effect estimates lay between the superiority and futility boundary using the 10% and 20% threshold, and the required size of information was not reached for these two thresholds. The effect of fluvoxamine on the odds of hospitalization was not statistically significant (0.76; 0.56-1.03). In conclusion, there is no reliable evidence that fluvoxamine, when compared to a placebo, reduces the relative risk of clinical deterioration among adult patients with COVID-19 infection by 30%, and a relative risk reduction of 20% or 10% is still uncertain. The role of fluvoxamine as a COVID-19 treatment cannot be justified.
Subject(s)
COVID-19 , Clinical Deterioration , Humans , Adult , Fluvoxamine/adverse effects , COVID-19 Drug Treatment , PatientsABSTRACT
The severe acute respiratory syndrome coronavirus 2 disease (SARS-CoV-2) is the most severe manifestation of the coronavirus disease 2019 (COVID-19) pandemic. Accruing evidence indicates that the COVID-19 pandemic may have profound deleterious neurological, psychiatric, and psychological outcomes. The number of systematic reviews (SRs) and meta-analyses (MAs) on this topic has grown exponentially. This protocol aims to synthesize all evidence from SRs and MAs on the associations between the COVID-19 pandemic and neuropsychiatric outcomes. The following electronic databases will be systematically searched from inception up to 15 January 2022: PubMed, Embase, APA PsycINFO, and Cochrane Reviews. An umbrella review (UR) of SRs and MAs of observational studies will be conducted. SRs and/or MAs of observational studies examining any direct or indirect association of COVID-19 with the neuropsychiatric outcomes will be deemed eligible for potential inclusion in this UR. The direct associations include the impact on the (1) prognosis of COVID-19 and (2) neuropsychiatric sequelae after COVID-19 infection. The indirect associations include the influence of the COVID-19 pandemic on the (1) treatments and (2) outcomes of neurological and psychiatric conditions associated with the COVID-19 pandemic.