Psychotropic drug repurposing for COVID-19: A Systematic Review and Meta-Analysis.
Ontology highlight
ABSTRACT:
SUBMITTER: Fico G
PROVIDER: S-EPMC9581805 | biostudies-literature | 2022 Oct
REPOSITORIES: biostudies-literature
Publications
Psychotropic drug repurposing for COVID-19: A Systematic Review and Meta-Analysis.
Fico Giovanna G Isayeva Ulker U De Prisco Michele M Oliva Vincenzo V Solè Brisa B Montejo Laura L Grande Iria I Arbelo Nestor N Gomez-Ramiro Marta M Pintor Luis L Carpiniello Bernardo B Manchia Mirko M Vieta Eduard E Murru Andrea A
European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology 20221020
Several psychotropic drugs, including antidepressants (AD), mood stabilizers, and antipsychotics (AP) have been suggested to have favorable effects in the treatment of COVID-19. The aim of this systematic review and meta-analysis was to collect evidence from studies concerning the scientific evidence for the repurposing of psychotropic drugs in COVID-19 treatment. Two independent authors searched PubMed-MEDLINE, Scopus, PsycINFO, and ClinicalTrials.gov databases, and reviewed the reference lists ...[more]
Similar Datasets
Project description:Coronavirus disease 2019 (COVID-19) had caused huge health losses worldwide. Several drugs had been applied to treat patients with COVID-19, and repurposing colchicine had been proposed for its anti-inflammatory properties via several pathways. In this systematic review, we evaluated the effects of colchicine treatment. From inception to May 31, 2021, databases, including PubMed, EMbase, medRxiv, and Research Square were searched, and 11 studies were enrolled. A total of 17,205 COVID-19 patients with male predominance (62.9%) were analyzed. Patients with colchicine treatment had a significantly lower risk of mortality (odds ratio (OR): 0.57, 95% confidence interval (CI): 0.38-0.87, I2: 72%; p < 0.01) and a non-significantly lower rate of mechanical ventilation (OR: 0.67, 95%CI: 0.39-1.15). The side effects were mild and not significantly different (OR: 2.03, 95%CI: 0.51-8.09). Subgroup analysis with randomized controlled trials showed no statistically significant difference in the mortality (OR: 0.80, 95%CI: 0.44-1.46, I2: 33%; p = 0.22). In conclusion, our meta-analysis found that colchicine treatment was associated with a significantly lower risk of mortality in patients with COVID-19. However, this benefit was not observed in the subgroup analysis of randomized controlled trials. Further randomized controlled studies are required to confirm the potential benefits of colchicine treatment.
| S-EPMC8398430 | biostudies-literature
Project description:ObjectiveTo compare the effects of treatments for coronavirus disease 2019 (covid-19).DesignLiving systematic review and network meta-analysis.Data sourcesWHO covid-19 database, a comprehensive multilingual source of global covid-19 literature, up to 3 December 2021 and six additional Chinese databases up to 20 February 2021. Studies identified as of 1 December 2021 were included in the analysis.Study selectionRandomised clinical trials in which people with suspected, probable, or confirmed covid-19 were randomised to drug treatment or to standard care or placebo. Pairs of reviewers independently screened potentially eligible articles.MethodsAfter duplicate data abstraction, a bayesian network meta-analysis was conducted. Risk of bias of the included studies was assessed using a modification of the Cochrane risk of bias 2.0 tool, and the certainty of the evidence using the grading of recommendations assessment, development, and evaluation (GRADE) approach. For each outcome, interventions were classified in groups from the most to the least beneficial or harmful following GRADE guidance.Results463 trials enrolling 166 581 patients were included; 267 (57.7%) trials and 89 814 (53.9%) patients are new from the previous iteration; 265 (57.2%) trials evaluating treatments with at least 100 patients or 20 events met the threshold for inclusion in the analyses. Compared with standard care, three drugs reduced mortality in patients with mostly severe disease with at least moderate certainty: systemic corticosteroids (risk difference 23 fewer per 1000 patients, 95% credible interval 40 fewer to 7 fewer, moderate certainty), interleukin-6 receptor antagonists when given with corticosteroids (23 fewer per 1000, 36 fewer to 7 fewer, moderate certainty), and Janus kinase inhibitors (44 fewer per 1000, 64 fewer to 20 fewer, high certainty). Compared with standard care, two drugs probably reduce hospital admission in patients with non-severe disease: nirmatrelvir/ritonavir (36 fewer per 1000, 41 fewer to 26 fewer, moderate certainty) and molnupiravir (19 fewer per 1000, 29 fewer to 5 fewer, moderate certainty). Remdesivir may reduce hospital admission (29 fewer per 1000, 40 fewer to 6 fewer, low certainty). Only molnupiravir had at least moderate quality evidence of a reduction in time to symptom resolution (3.3 days fewer, 4.8 fewer to 1.6 fewer, moderate certainty); several others showed a possible benefit. Several drugs may increase the risk of adverse effects leading to drug discontinuation; hydroxychloroquine probably increases the risk of mechanical ventilation (moderate certainty).ConclusionCorticosteroids, interleukin-6 receptor antagonists, and Janus kinase inhibitors probably reduce mortality and confer other important benefits in patients with severe covid-19. Molnupiravir and nirmatrelvir/ritonavir probably reduce admission to hospital in patients with non-severe covid-19.Systematic review registrationThis review was not registered. The protocol is publicly available in the supplementary material.Readers' noteThis article is a living systematic review that will be updated to reflect emerging evidence. Updates may occur for up to two years from the date of original publication. This is the fifth version of the original article published on 30 July 2020 (BMJ 2020;370:m2980), and previous versions can be found as data supplements. When citing this paper please consider adding the version number and date of access for clarity.
| S-EPMC7390912 | biostudies-literature
Project description:BackgroundSince the beginning of the novel coronavirus (SARS-CoV-2) disease outbreak, there has been an increasing interest in finding a potential therapeutic agent for the disease. Considering the matter of time, the computational methods of drug repurposing offer the best chance of selecting one drug from a list of approved drugs for the life-threatening condition of COVID-19. The present systematic review aims to provide an overview of studies that have used computational methods for drug repurposing in COVID-19.MethodsWe undertook a systematic search in five databases and included original articles in English that applied computational methods for drug repurposing in COVID-19.ResultsTwenty-one original articles utilizing computational drug methods for COVID-19 drug repurposing were included in the systematic review. Regarding the quality of eligible studies, high-quality items including the use of two or more approved drug databases, analysis of molecular dynamic simulation, multi-target assessment, the use of crystal structure for the generation of the target sequence, and the use of AutoDock Vina combined with other docking tools occurred in about 52%, 38%, 24%, 48%, and 19% of included studies. Studies included repurposed drugs mainly against non-structural proteins of SARS-CoV2: the main 3C-like protease (Lopinavir, Ritonavir, Indinavir, Atazanavir, Nelfinavir, and Clocortolone), RNA-dependent RNA polymerase (Remdesivir and Ribavirin), and the papain-like protease (Mycophenolic acid, Telaprevir, Boceprevir, Grazoprevir, Darunavir, Chloroquine, and Formoterol). The review revealed the best-documented multi-target drugs repurposed by computational methods for COVID-19 therapy as follows: antiviral drugs commonly used to treat AIDS/HIV (Atazanavir, Efavirenz, and Dolutegravir Ritonavir, Raltegravir, and Darunavir, Lopinavir, Saquinavir, Nelfinavir, and Indinavir), HCV (Grazoprevir, Lomibuvir, Asunaprevir, Ribavirin, and Simeprevir), HBV (Entecavir), HSV (Penciclovir), CMV (Ganciclovir), and Ebola (Remdesivir), anticoagulant drug (Dabigatran), and an antifungal drug (Itraconazole).ConclusionsThe present systematic review provides a list of existing drugs that have the potential to influence SARS-CoV2 through different mechanisms of action. For the majority of these drugs, direct clinical evidence on their efficacy for the treatment of COVID-19 is lacking. Future clinical studies examining these drugs might come to conclude, which can be more useful to inhibit COVID-19 progression.
| S-EPMC7676368 | biostudies-literature
Project description:ImportanceMedication review has been proposed to achieve improved use of psychotropic drugs, but benefits have not been confirmed.ObjectiveTo synthesize evidence for focused psychotropic medication review in medication optimization.Data sourcesMedline, PsycINFO, EMBASE, and CINAHL Plus were searched from inception to February 2018 using the index terms "drug utilization review" and "psychotropic drugs" and synonyms. Additional articles were retrieved using citation tracking and reference checking.Study selectionFull-length, peer-reviewed articles that reported focused psychotropic medication review were included. Inclusion was determined against prespecified criteria and assessed independently.Data extraction and synthesisStudy quality was assessed using National Institutes for Health appraisal tools and informed a structured synthesis of results. Meta-analysis using a random effects model was conducted.Main outcomes and measuresChange in the number or dosage of psychotropic medications, change in clinical parameters, change in patient-reported outcomes, and economic data were collected.ResultsA total of 26 studies met the inclusion criteria. Four studies were randomized clinical trials (n = 712 participants), while the remainder were before-after studies (n = 7844 participants). Most studies were conducted in elderly individuals, people with dementia, and adults with intellectual disability. Focused psychotropic medication review is a complex intervention; the professional(s) involved, target drug, degree of integration with usual care, and participant involvement varied greatly among the studies. Meta-analysis included 3 studies (n = 652 participants). Psychotropic medication review was associated with a reduction in prescribing of psychotropic drugs compared with control (pooled odds ratio, 0.24; 95% CI, 0.14-0.39) in elderly participants with cognitive impairment living in nursing homes. Before-after studies consistently reported a change in psychotropic drug prescribing after medication review, regardless of the population. Studies that reported the effects of psychotropic medication review on clinical outcomes failed to demonstrate benefit. Economic implications of focused psychotropic medication review were not adequately assessed. The quality of evidence is poor and studies are at risk of bias.Conclusions and relevanceFocused psychotropic medication review was associated with a reduction in prescribing of psychotropic drugs, but has not been shown to improve clinical outcomes or to provide economic benefit. More robust evidence is needed before programs of focused psychotropic medication review can be recommended as part of routine care for any patient group.
| S-EPMC6324597 | biostudies-literature
Project description:Drug repurposing involves the identification of new applications for existing drugs at a lower cost and in a shorter time. There are different computational drug-repurposing strategies and some of these approaches have been applied to the coronavirus disease 2019 (COVID-19) pandemic. Computational drug-repositioning approaches applied to COVID-19 can be broadly categorized into (i) network-based models, (ii) structure-based approaches and (iii) artificial intelligence (AI) approaches. Network-based approaches are divided into two categories: network-based clustering approaches and network-based propagation approaches. Both of them allowed to annotate some important patterns, to identify proteins that are functionally associated with COVID-19 and to discover novel drug-disease or drug-target relationships useful for new therapies. Structure-based approaches allowed to identify small chemical compounds able to bind macromolecular targets to evaluate how a chemical compound can interact with the biological counterpart, trying to find new applications for existing drugs. AI-based networks appear, at the moment, less relevant since they need more data for their application.
| S-EPMC7665348 | biostudies-literature
Project description:BackgroundDuring the COVID-19 pandemic, the provision of quality care for behavioral and psychological symptoms in older adults with dementia may have been impeded due to physical distancing and infection control measures. Of particular concern is whether psychotropic medication use has increased despite its limited efficacy and adverse effects. This systematic review described the trajectory of psychotropic use for older adults with dementia across various settings, from community living to healthcare settings during the pandemic. Also, psychotropic use was explored in relation to patients, caregivers, and environment-related factors along with the occurrence of the pandemic.MethodsWe conducted a comprehensive search across five databases: Embase, PubMed, PsycINFO, CINAHL, and Cochrane Library. Methodological quality was assessed using Joanna Briggs Institute Critical Appraisal tools. A random-effects model was used to estimate the pooled risk ratios (RRs) of psychotropic use in older adults with dementia, comparing the pandemic period to the pre-pandemic period. Subgroup analyses based on the class of psychotropics and sensitivity analyses also were conducted. A funnel plot and Egger's regression test were used to detect potential publication bias.ResultsOf the 3,123 screened articles, 15 studies were included in this systematic review, with 10 of them being part of the meta-analysis. Our meta-analysis yielded an RR of 1.16 (95% CI = 1.05-1.26) for overall psychotropic medication use. Further subgroup analysis based on the type of psychotropic medication revealed a significantly greater prevalence in the use of antipsychotics (RR = 1.19, 95% CI = 1.08-1.30). However, no significant differences were observed in the use of anxiolytics and/or hypnotics (including benzodiazepines), antidepressants, and mood stabilizers. Among psychotropics, some studies on antipsychotic use additionally explored patients, caregivers, and environmental-related factors during the pandemic.ConclusionsThe review indicates a higher risk of psychotropic use, especially antipsychotics, during the pandemic. Nonetheless, underlying reasons for the increased psychotropic use are not fully available from the reviewed studies. Therefore, further research is needed to identify the factors driving psychotropic use during the pandemic and facilitate the development of quality improvement interventions that can be implemented to minimize inappropriate psychotropic prescribing in future pandemics.
| S-EPMC11580495 | biostudies-literature
Project description:BackgroundCoronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been declared a pandemic by the World Health Organization, and the identification of effective therapeutic strategy is a need of the hour to combat SARS-CoV-2 infection. In this scenario, the drug repurposing approach is widely used for the rapid identification of potential drugs against SARS-CoV-2, considering viral and host factors.MethodsWe adopted a host transcriptome-based drug repurposing strategy utilizing the publicly available high throughput gene expression data on SARS-CoV-2 and other respiratory infection viruses. Based on the consistency in expression status of host factors in different cell types and previous evidence reported in the literature, pro-viral factors of SARS-CoV-2 identified and subject to drug repurposing analysis based on DrugBank and Connectivity Map (CMap) using the web tool, CLUE.ResultsThe upregulated pro-viral factors such as TYMP, PTGS2, C1S, CFB, IFI44, XAF1, CXCL2, and CXCL3 were identified in early infection models of SARS-CoV-2. By further analysis of the drug-perturbed expression profiles in the connectivity map, 27 drugs that can reverse the expression of pro-viral factors were identified, and importantly, twelve of them reported to have anti-viral activity. The direct inhibition of the PTGS2 gene product can be considered as another therapeutic strategy for SARS-CoV-2 infection and could suggest six approved PTGS2 inhibitor drugs for the treatment of COVID-19. The computational study could propose candidate repurposable drugs against COVID-19, and further experimental studies are required for validation.
| S-EPMC7293190 | biostudies-literature
Project description:BackgroundRandomized trial evidence suggests that some antiviral drugs are effective in patients with COVID-19. However, the comparative effectiveness of antiviral drugs in nonsevere COVID-19 is unclear.MethodsWe searched the Epistemonikos COVID-19 L·OVE (Living Overview of Evidence) database for randomized trials comparing antiviral treatments, standard care or placebo in adult patients with nonsevere COVID-19 up to Apr. 25, 2022. Reviewers extracted data and assessed risk of bias. We performed a frequentist network meta-analysis and assessed the certainty of evidence using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach.ResultsWe identified 41 trials, which included 18 568 patients. Compared with standard care or placebo, molnupiravir and nirmatrelvir-ritonavir each reduced risk of death with moderate certainty (10.9 fewer deaths per 1000, 95% confidence interval [CI] 12.6 to 4.5 fewer for molnupiravir; 11.7 fewer deaths per 1000, 95% CI 13.1 fewer to 2.6 more). Compared with molnupiravir, nirmatrelvir-ritonavir probably reduced risk of hospital admission (27.8 fewer admissions per 1000, 95% CI 32.8 to 18.3 fewer; moderate certainty). Remdesivir probably has no effect on risk of death, but may reduce hospital admissions (39.1 fewer admissions per 1000, 95% CI 48.7 to 13.7 fewer; low certainty).InterpretationMolnupiravir and nirmatrelvir-ritonavir probably reduce risk of hospital admissions and death among patients with nonsevere COVID-19. Nirmatrelvir-ritonavir is probably more effective than molnupiravir for reducing risk of hospital admissions. Most trials were conducted with unvaccinated patients, before the emergence of the Omicron variant; the effectiveness of these drugs must thus be tested among vaccinated patients and against newer variants.
| S-EPMC9328465 | biostudies-literature
Project description:ObjectivesThe global prevalence of mental health disorders has risen significantly since the beginning of the COVID-19 pandemic. The pandemic has additionally caused disruption to mental health services, leading to a shift from in-person to remote service delivery. Given its long-term impact, it has become critical to evaluate whether changes in health delivery during the pandemic have had an effect on prescribing patterns for commonly prescribed psychotropic drugs. This study aims to assess the impact of the COVID-19 pandemic on changes in psychotropic prescribing patterns in adults, as well as differences in prescribing in different healthcare delivery approaches across various geographical contexts.Design and eligibility requirementsSystematic review of cohort, interrupted time-series and cross-sectional studies examining prescribing trends for at least one commonly prescribed psychotropic drug during and after COVID-19 in accessing care remotely or face to face between 1 January 2020 and 17 June 2022.Data sourcesMEDLINE, EMBASE, CINAHL, HMIC and PsycINFO databases were searched in addition to citation chaining of relevant reviews.Extraction and analysisStudy screening, data extraction and quality assessment were completed by two independent reviewers. The PECO strategy was used to devise the systematic review and findings were synthesised narratively.Results16 studies were eligible for inclusion. Studies documenting changes in psychotropic prescribing trends provided very conflicting findings. There were no stark differences in prescribing outcomes between different healthcare delivery methods (ie, face-to-face consultations vs remote consultations). A noteworthy finding was that the prescribing rate of benzodiazepines was higher in women than men. No particular trends were observed for the prescription rates of hypnotics, antidepressants or antipsychotics.ConclusionsFindings support mixed trends in the prescription of psychotropic medications in a range of settings, hindering conclusive statements on COVID-19's impact on prescribing. In areas where remote consultations are in use, more comprehensive research is required to assess the safety of prescribing in these settings to inform public health policy and assess if the observed trends in our systematic review persist over time (given the increased consideration of remote and telehealth care in delivering services), particularly the safe and effective deployment of these services.
| S-EPMC11425938 | biostudies-literature
Project description:ObjectiveDue to the global spread of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), guidance for the use of psychotropic drugs in this context is necessary. We aimed to review clinical evidence regarding the potential toxicity of psychiatric medications in the context of SARS-CoV-2 infection.MethodsA systematic search for all types of empirical studies and reviews in a broad set of electronic databases and trial registries was conducted up to the 15th of August 2020.ResultsWe identified 3 case series and 4 single-case reports on the occurrence of toxicity induced by various psychotropic drugs (lithium, n = 2; clozapine, n = 5; risperidone n = 2; haloperidol n = 1; duloxetine, n = 1). In addition, we provide a new case report on the possible precipitation of valproic acid-induced hyperammonemic encephalopathy. In most cases, SARS-CoV-2 infection may have precipitated drug toxicity/side effects. The management of toxicity did not diverge from the usually applied principles in the absence of infection.ConclusionsDue to the limited available evidence and the recent genomic diversity and evolution of the SARS-CoV-2, it is currently not possible to derive evidence-based recommendations for the use of psychotropic drugs in the context of SARS-CoV-2 infection. Nevertheless, we provide some guidance based on the reviewed literature. At the current state of knowledge, there is no contraindication for any psychotropic drug. Caution is warranted regarding the dosing and, in particular, the monitoring of clozapine, lithium and valproate.
| S-EPMC7890235 | biostudies-literature