Rapid effect of suvorexant and high-dose melatonin on COVID-19 associated delirium.
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ABSTRACT:
SUBMITTER: Nazeer S
PROVIDER: S-EPMC9851718 | biostudies-literature | 2023 Jan
REPOSITORIES: biostudies-literature
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Rapid effect of suvorexant and high-dose melatonin on COVID-19 associated delirium.
Nazeer Sahana S Preud'homme Xavier X Rivelli Sarah S Hankey Maria Stack MS Kablinger Anita A
General hospital psychiatry 20230120
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| S-EPMC7255123 | biostudies-literature
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| S-EPMC7255217 | biostudies-literature
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| S-EPMC7162748 | biostudies-literature
Project description:BackgroundThe pandemic of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has emerged as one of the biggest health threats of our generation. A significant portion of patients are presenting with delirium and neuropsychiatric sequelae of the disease. Unique examination findings and responses to treatment have been identified.ObjectiveIn this article, we seek to provide pharmacologic and treatment recommendations specific to delirium in patients with COVID-19.MethodsWe performed a literature search reviewing the neuropsychiatric complications and treatments in prior coronavirus epidemics including Middle Eastern respiratory syndrome and severe acute respiratory syndrome coronaviruses, as well as the emerging literature regarding COVID-19. We also convened a work group of consultation-liaison psychiatrists actively managing patients with COVID-19 in our hospital. Finally, we synthesized these findings to provide preliminary pharmacologic recommendations for treating delirium in these patients.ResultsDelirium is frequently found in patients who test positive for COVID-19, even in the absence of respiratory symptoms. There appears to be a higher rate of agitation, myoclonus, abulia, and alogia. No data are currently available on the treatment of delirium in patients with COVID-19. Extrapolating from general delirium treatment, Middle Eastern respiratory syndrome/severe acute respiratory syndrome case reports, and our experience, preliminary recommendations for pharmacologic management have been assembled.ConclusionsCOVID-19 is associated with neuropsychiatric symptoms. Low-potency neuroleptics and alpha-2 adrenergic agents may be especially useful in this setting. Further research into the pathophysiology of COVID-19 will be key in developing more targeted treatment guidelines.
| S-EPMC7240270 | biostudies-literature
Project description:The association of age with a higher vulnerability to COVID-19 infection is a subject of major importance. Several factors, including higher stress due to social isolation, diminished melatonin levels with age, and higher exposure of individuals to light at the evening, which reduces melatonin levels and disrupts circadian rhythmicity are relevant for maintaining the circadian health in aged individuals. Properly administered, chronotherapy restores the optimal circadian pattern of the sleep–wake cycle in the elderly. It involves adequate sleep hygiene, timed light exposure, and the use of a chronobiotic medication like melatonin, which affects the output phase of circadian rhythms thus controlling the biological clock. Besides, the therapeutic potential of melatonin as an agent to counteract the consequences of COVID-19 infections has been advocated due to its wide-ranging effects as an antioxidant, anti-inflammatory, and as an immunomodulatory agent, as well as to a possible antiviral action. This article discusses how chronotherapy may reverse the detrimental circadian condition of the elderly in the COVID-19 pandemic.
| S-EPMC7519696 | biostudies-literature
Project description:Background COVID-19 causes significant morbidity and mortality. Despite the high prevalence of delirium and delirium-related symptoms in COVID-19 patients, data and evidence-based recommendations on the pathophysiology and management of delirium are limited. Objective We conducted a rapid review of COVID-19-related delirium literature to provide a synthesis of literature on the prevalence, pathoetiology, and management of delirium in these patients. Methods Systematic searches of Medline, Embase, PsycInfo, LitCovid, WHO-COVID-19, and Web of Science electronic databases were conducted. Grey literature was also reviewed, including preprint servers, archives, and websites of relevant organizations. Search results were limited to the English language. We included literature focused on adults with COVID-19 and delirium. Papers were excluded if they did not mention signs or symptoms of delirium. Results 229 studies described prevalence, pathoetiology, and/or management of delirium in adults with COVID-19. Delirium was rarely assessed with validated tools. Delirium affected >50% of all patients with COVID-19 admitted to the ICU. The etiology of COVID-19 delirium is likely multifactorial, with some evidence of direct brain effect. Prevention remains the cornerstone of management in these patients. To date, there is no evidence to suggest specific pharmacological strategies. Discussion Delirium is common in COVID-19 and may manifest from both indirect and direct effects on the central nervous system. Further research is required to investigate contributing mechanisms. As there is limited empirical literature on delirium management in COVID-19, management with non-pharmacological measures and judicious use of pharmacotherapy is suggested.
| S-EPMC7762623 | biostudies-literature
Project description:BackgroundThere is no effective therapy for the severe acute respiratory syndrome by coronavirus 2 (SARS-CoV2) responsible for the Coronavirus disease 2019 (Covid-19). To date, dexamethasone has shown a decrease in mortality in patients who require oxygen, especially those with invasive mechanical ventilation. However, it is unknown if another corticosteroid can be used, the optimal dose and its duration, to achieve a better clinical outcome. The objective of the study was to compare the differences in clinical outcome and laboratory results in hospitalized patients with severe SARS-CoV2 Pneumonia treated with dexamethasone at 6 mg doses versus patients treated with high-dose methylprednisolone.Materials and methodsAmbispective cohort study with survival analysis of 216 patients diagnosed with severe Covid-19 pneumonia confirmed by polymerase chain reaction for SARS-CoV2 by Berlin protocol, who were hospitalized in a high-complexity clinic in Medellín, Colombia. The patients should also have supplementary oxygen and radiological confirmation of Pneumonia by chest tomography. Sample size was not calculated since the total population that met the inclusion criteria was evaluated. 111 patients were treated with the institutional protocol with intravenous dexamethasone 6 mg QD for seven to 10 days if they required oxygen. Since September 15, 2020, the hospitalization protocol of the clinic was modified by the Infectious Diseases and Pulmonology service, recommending a high dose of methylprednisolone of 250 to 500 mg every day for three days with a subsequent change to oral prednisone 50 mg every day for 14 days. The protocol was not applied in the intensive care unit, where dexamethasone continued to be administered. The clinical outcome and differences in laboratory results of the patients who received dexamethasone vs. the prospective cohort that received methylprednisolone from September 15 to October 31, 2020, were evaluated. Follow-up was carried out by outpatient consultation one month after discharge or by telephone, inquiring about readmission or living-dead status.Results216 patients had Covid-19 pneumonia documented by ground-glass imaging and alveolar pressure / inspired oxygen fraction (PaFi) less than 300. 111 patients received dexamethasone (DXM) and 105 received methylprednisolone (MTP). Patients in the DXM group evolved to severe ARDS in a higher proportion (26.1% vs 17.1% than the MTP group). Upon completion 4 days of treatment with parenteral corticosteroid, laboratory markers of severity decreased significantly in the group that received MTP, CRP 2.85 (2.3-3.8) vs 7.2 (5.4-9.8), (p-value < 0.0001), D-dimer 691 (612-847) vs 1083 (740-1565) (p-value = 0.04) and DHL 273 (244-289) vs 355 (270.6-422) (p-value = 0.01). After starting the corticosteroid, transfer to the intensive care unit (4.8% vs. 14.4%) and mortality (9,5% vs. 17.1%) was lower in the group that received MTP. Recovery time was shorter in patients treated with MTP, three days (3-4) vs. DXM 6 days (5-8) (p-value < 0.0001). At 30-day follow-up, 88 (92.6%) were alive in MTP vs 58 (63.1%) of those who received dexamethasone.ConclusionsIn this study, the treatment of severe Covid-19 Pneumonia with high-dose methylprednisolone for three days followed by oral prednisone for 14 days, compared with 6 mg dexamethasone for 7 to 10 days, statistically significantly decreased the recovery time, the need for transfer to intensive care and the severity markers C-reactive protein (CRP), D-dimer and LDH. Randomized controlled studies with methylprednisolone are required to corroborate its effect, and studies in a population hospitalized in intensive care wards.
| S-EPMC8148307 | biostudies-literature
Project description:BackgroundThis study investigated the relationship between coronavirus disease 2019 (COVID-19), delirium, and 1-year mortality. Factors associated with delirium in COVID-19 patients were identified, along with the influence of psychotropic medications on delirium.MethodsThe study used the South Korean National Health Insurance Service database. Adult COVID-19 patients diagnosed between October 2020 and December 2021 were included, with a propensity score-matched control group. Time-dependent Cox regression assessed associations among COVID-19, delirium, and mortality. Logistic regression analyzed the impact of psychotropic medications on delirium incidence.ResultsThe study included 832,602 individuals, with 416,301 COVID-19 patients. COVID-19 (hazard ratio [HR], 3.03; 95% confidence interval [CI], 2.92-3.13) and delirium (HR, 2.33; 95% CI, 2.06-2.63) were independent risk factors for 1-year mortality. Comorbidities, insurance type, and residence were also related to mortality. Among COVID-19 patients, antipsychotic use was associated with lower delirium incidence (odds ratio [OR], 0.38; 95% CI, 0.30-0.47), while mood stabilizers (OR, 1.77; 95% CI, 1.40-2.21) and benzodiazepines (OR, 8.62; 95% CI, 7.46-9.97) were linked to higher delirium incidence.ConclusionCOVID-19 and delirium are risk factors for 1-year mortality. Some factors associated with delirium in COVID-19 patients are modifiable and can be targeted in preventive and therapeutic interventions.
| S-EPMC11333801 | biostudies-literature
Project description:The clinical outcome of the disease provoked by the SARS-CoV-2 infection, COVID-19, is largely due to the development of interstitial pneumonia accompanied by an Acute Respiratory Distress Syndrome (ARDS), often requiring ventilatory support therapy in Intensive Care Units (ICUs). Current epidemiologic evidence is demonstrating that the COVID-19 prognosis is significantly influenced by its acute complications. Among these, delirium figures as one of the most frequent and severe, especially in the emergency setting, where it shows a significantly negative prognostic impact. In this regard, the aim of our study is to identify clinical severity factors of delirium complicating COVID-19 related-ARDS. We performed a comparative and correlation analysis using demographics, comorbidities, multisystemic and delirium severity scores and anti-delirium therapy in two cohorts of ARDS patients with delirium, respectively, due to COVID-19 (n = 40) or other medical conditions (n = 39). Our results indicate that delirium in COVID-19-related ARDS is more severe since its onset despite a relatively less severe systemic condition at the point of ICU admission and required higher dosages of antipsychotic and non-benzodiazepinic sedative therapy respect to non-COVID patients. Finally, the correlation analysis showed a direct association between the male gender and maximum dosage of anti-delirium medications needed within the COVID-19 group, which was taken as a surrogate of delirium severity. Overall, our results seem to indicate that pathogenetic factors specifically associated to severe COVID-19 are responsible for the high severity of delirium, paving the way for future research focused on the mechanisms of the cognitive alterations associated with COVID-19.
| S-EPMC8987982 | biostudies-literature
Project description:BackgroundThere are limited antiviral options for the treatment of patients with COVID-19. Ivermectin (IVM), a macrocyclic lactone with a wide anti-parasitary spectrum, has shown potent activity against SARS-CoV-2 in vitro. This study aimed at assessing the antiviral effect of IVM on viral load of respiratory secretions and its relationship with drug concentrations in plasma.MethodsProof-of-concept, pilot, randomized, controlled, outcome-assessor blinded trial to evaluate antiviral activity of high-dose IVM in 45 COVID-19 hospitalized patients randomized in a 2:1 ratio to standard of care plus oral IVM at 0·6 mg/kg/day for 5 days versus standard of care in 4 hospitals in Argentina. Eligible patients were adults with RT-PCR confirmed SARS-CoV-2 infection within 5 days of symptoms onset. The primary endpoint was the difference in viral load in respiratory secretions between baseline and day-5, by quantitative RT-PCR. Concentrations of IVM in plasma were measured. Study registered at ClinicalTrials.gov: NCT04381884.Findings45 participants were recruited (30 to IVM and 15 controls) between May 18 and September 9, 2020. There was no difference in viral load reduction between groups but a significant difference was found in patients with higher median plasma IVM levels (72% IQR 59-77) versus untreated controls (42% IQR 31-73) (p = 0·004). Mean ivermectin plasma concentration levels correlated with viral decay rate (r: 0·47, p = 0·02). Adverse events were similar between groups. No differences in clinical evolution at day-7 and day-30 between groups were observed.InterpretationA concentration dependent antiviral activity of oral high-dose IVM was identified at a dosing regimen that was well tolerated. Large trials with clinical endpoints are necessary to determine the clinical utility of IVM in COVID-19.FundingThis work was supported by grant IP-COVID-19-625, Agencia Nacional de Promoción de la Investigación, el Desarrollo Tecnológico y la Innovación, Argentina and Laboratorio ELEA/Phoenix, Argentina.
| S-EPMC8225706 | biostudies-literature