Background Coronavirus disease 2019 (COVID-19) continues to pose a significant threat to public health worldwide. The purpose of this study was to review current evidence obtained from randomized clinical trials on the efficacy of antivirals for COVID-19 treatment. Methods A systematic literature search was performed using PubMed to identify randomized controlled trials published up to September 4, 2021 that examined the efficacy of antivirals for COVID-19 treatment. Studies that were not randomized controlled trials or that did not include treatment of COVID-19 with approved antivirals were excluded. Risk of bias was assessed using the Scottish Intercollegiate Guidelines Network (SIGN) method. Due to study heterogeneity, inferential statistics were not performed and data were expressed as descriptive statistics. Results Of the 2,284 articles retrieved, 31 (12,440 patients) articles were included. Overall, antivirals were more effective when administered early in the disease course. No antiviral treatment demonstrated efficacy at reducing COVID-19 mortality. Sofosbuvir/daclatasvir results suggested clinical improvement, although statistical power was low. Remdesivir exhibited efficacy in reducing time to recovery, but results were inconsistent across trials. Conclusions Although select antivirals have exhibited efficacy to improve clinical outcomes in COVID-19 patients, none demonstrated efficacy in reducing mortality. Larger RCTs are needed to conclusively establish efficacy.

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BACKGROUND Psilocybin is a naturally occurring psychedelic that induces feelings of euphoria and spiritual awakening when administered in doses of approximately 20-30 mg/70 kg. In the last decade, there has been renewed interest in using psilocybin for major depressive disorder (MDD). OBJECTIVE This individual patient data meta-analysis will investigate the efficacy and safety of psilocybin for MDD. METHODS This study will be performed as a living systematic review housed in the Nested Knowledge online platform, allowing for data extraction, analysis, and synthesis to occur on an ongoing basis as new evidence emerges. The study is registered with PROSPERO (ID: CRD42021290905) and will be compliant with Preferred Reporting Items for Systematic Review and Meta-Analysis of Individual Participant Data (PRISMA-IPD). Major databases (PubMed, Embase, SCOPUS, PyschINFO) and international clinical trials registries will be systematically searched for relevant trials. Randomized and non-randomized trials of psilocybin for the treatment of MDD will be included; authors will be contacted if individual patient data is not readily available. The three populations of interest are patients with MDD, patients with treatment-resistant MDD, and patients with MDD and life-threatening illness. The primary outcome is depression as measured by validated clinical scales (e.g., GRID-Hamilton Depression Rating Scale [GRID-HAMD], Beck Depression Inventory [BDI], Hospital Anxiety and Depression Scale - Depression Subscale [HADS-D]). Heterogeneous scale results will be transformed to z-scores and aggregated to create a composite depression outcome. Secondary outcomes include anxiety, demoralization/hopelessness, quality of life, and death acceptance. We will analyze outcome data using hierarchical mixed-effects regression models. In order to consider clustering effects from study to study, a three-level hierarchical structure will be used: the participants within each trial are considered level one, the study is level two, and the treatment group is level three. Hierarchical regressions are also conducted to examine various effect moderators of treatment outcomes, including patient age, patient sex, baseline score for a given clinical outcome, history of psilocybin use, and psilocybin dose (including the interaction of dose volume and dose schedule). All analyses will be performed on a modified intention-to-treat basis. Repeat literature searches, screening, and subsequent updates to the review will be conducted on an ongoing basis. RESULTS The initial review and subsequent updates will be published in a peer-reviewed journal and made available online via the Nested Knowledge platform. CONCLUSIONS Despite growing interest in psilocybin as a therapy for chronic, severe, or intractable MDD, there are gaps in the literature. A rapidly expanding evidence base requires a living systematic review to adequately inform clinical practice and policymaking around psychedelics for psychological and mood disorders. This meta-analysis seeks to meet that need by providing a transparent, up-to-date, and accessible living review of psilocybin for MDD.