Summary of COVID-19 cyproheptadine studies
1. Boniatti et al., Effect of Cyproheptadine on Ventilatory Support-free Days in Critically Ill Patients with COVID-19: An Open-label, Randomized Clinical Trial
40 patient cyproheptadine late treatment RCT: 11% higher mortality (p=1) and 49% longer hospitalization (p=0.09).RCT 40 critically ill COVID-19 patients showing no significant difference in outcomes with cyproheptadine. Cyproheptadine is a serotonin (5-HT) receptor antagonist, particularly at 5-HT2 receptors. Its effects may depend heavily on disease stage. In early disease it may reduce platelet hyperactivation: excessive platelet activation, platelet reactivity, and platelet-leukocyte aggregates are recognized as a pathogenic feature of COVID-19. Among the mediators released from activated platelet granules, serotonin is unique in that its clearance relies heavily on a healthy pulmonary endothelium, which is known to be injured in COVID-19. Cyproheptadine may also prevents serotonin accumulation: early blockade prevents the cycle of platelet activation → serotonin release → endothelial injury → more inflammation. Additionally, cyproheptadine has anti-inflammatory effects. However in late stage disease, anticholinergic adverse events may cause significant harm. Cyproheptadine may also cause..
Jun 2023, Indian J. Critical Care Medicine, https://www.ijccm.org/doi/10.5005/jp-journals-10071-24482, https://c19p.org/boniatti
2. Auld et al., The Effects of Cyproheptadine on Severe COVID-19 From the ISPY-COVID Adaptive Platform Trial
96 patient cyproheptadine late treatment RCT: 51% higher mortality (p=0.32), 206% higher combined mortality/intubation (p=0.002), and 122% worse recovery (p=0.004).RCT 96 critically ill COVID-19 patients in the USA showing higher mortality/ventilation and worse recovery with cyproheptadine. Anticholinergic adverse events (delirium, urinary retention, bronchial obstruction/atelectasis, ileus) were higher in the cyproheptadine arm. Cyproheptadine is a serotonin (5-HT) receptor antagonist, particularly at 5-HT2 receptors. Its effects may depend heavily on disease stage. In early disease it may reduce platelet hyperactivation: excessive platelet activation, platelet reactivity, and platelet-leukocyte aggregates are recognized as a pathogenic feature of COVID-19. Among the mediators released from activated platelet granules, serotonin is unique in that its clearance relies heavily on a healthy pulmonary endothelium, which is known to be injured in COVID-19. Cyproheptadine may also prevents serotonin accumulation: early blockade prevents the cycle of platelet activation → serotonin release → endothelial injury → more inflammation. Additionally,..
Jan 2023, CHEST Critical Care, https://www.sciencedirect.com/science/article/pii/S2949788425000747, https://c19p.org/auld2