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VOLUME 27 , ISSUE 7 ( July, 2023 ) > List of Articles


Effect of Cyproheptadine on Ventilatory Support-free Days in Critically Ill Patients with COVID-19: An Open-label, Randomized Clinical Trial

Márcio Manozzo Boniatti, Wagner Luis Nedel, Marcos Frata Rihl, Patricia Schwarz, Edino Parolo, Miriane Melo Silveira Moretti, Thiago Costa Lisboa

Keywords : Coronavirus disease 2019, Cyproheptadine, Intensive care unit, Serotonin, Ventilatory support

Citation Information : Boniatti MM, Nedel WL, Rihl MF, Schwarz P, Parolo E, Moretti MM, Lisboa TC. Effect of Cyproheptadine on Ventilatory Support-free Days in Critically Ill Patients with COVID-19: An Open-label, Randomized Clinical Trial. Indian J Crit Care Med 2023; 27 (7):517-521.

DOI: 10.5005/jp-journals-10071-24482

License: CC BY-NC 4.0

Published Online: 30-06-2023

Copyright Statement:  Copyright © 2023; The Author(s).


Background: Serotonin is a mediator of pulmonary hypoxic vasoconstriction. Experimental studies have shown that serotonin-mediated pulmonary vasoconstriction can be inhibited by cyproheptadine. The aim of this study is to assess whether treatment with cyproheptadine compared to usual care increases ventilatory support-free days during the first 28 days in patients with coronavirus disease 2019 (COVID-19) requiring ventilatory support. Materials and methods: This randomized, single-center, open-label clinical trial included patients who were admitted to the intensive care unit (ICU) requiring ventilatory support due to COVID-19. Patients allocated to the intervention group received cyproheptadine for 10 days. The primary outcome was ventilator-free days during the first 28 days. Results: Nineteen patients were randomized to receive cyproheptadine and 21 to the control group. The number of ventilatory support-free days during the first 28 days was not different between the two groups (15.0; 95% CI, 0.0–24.0 days in the control group vs 7.0; 95% CI, 0.0–19.0 days in the intervention group; p = 0.284). Conclusion: In patients with COVID-19 and in need of ventilatory support, the use of cyproheptadine plus usual care, compared with usual care alone, did not increase the number of ventilatory support-free days in 28 days.

  1. WHO Coronavirus (COVID-19) dashboard. Available from:
  2. Carsana L, Sonzogni A, Nasr A, Rossi RS, Pellegrinelli A, Zerbi P, et al. Pulmonary post-mortem findings in a series of COVID-19 cases from northern Italy: A two-centre descriptive study. Lancet Infect Dis 2020;20(10):1135–1140. DOI: 10.1016/S1473-3099(20)30434-5.
  3. Manne BK, Denorme F, Middleton EA, Portier I, Rowley JW, Stubben C, et al. Platelet gene expression and function in patients with COVID-19. Blood 2020;136(11):1317–1329. DOI: 10.1182/blood.2020007214.
  4. Hottz ED, Azevedo-Quintanilha IG, Palhinha L, Teixeira L, Barreto EA, Pão CRR, et al. Platelet activation and platelet-monocyte aggregate formation trigger tissue factor expression in patients with severe COVID-19. Blood 2020;136(11):1330–1341. DOI: 10.1182/blood.2020007252.
  5. Zaid Y, Puhm F, Allaeys I, Naya A, Oudghiri M, Khalki L, et al. Platelets Can Associate with SARS-Cov-2 RNA and Are Hyperactivated in COVID-19. Circ Res 2020;127(11):1404–1418. DOI: 10.1161/CIRCRESAHA.120.317703.
  6. Zaid Y, Guessous F, Puhm F, Elhamdani W, Chentoufi L, Morris AC, et al. Platelet reactivity to thrombin differs between patients with COVID-19 and those with ARDS unrelated to COVID-19. Blood Adv 2021;5(3):635–639. DOI: 10.1182/bloodadvances.2020003513.
  7. Daicoff GR, Chavez FR, Anton AH, Swenson EW. Serotonin-induced pulmonary venous hypertension in pulmonary embolism. J Thorac Cardiovasc Surg 1968;56(6):810–816. PMID: 5722112.
  8. McGoon MD, Vanhoutte PM. Aggregating platelets contract isolated canine pulmonary arteries by releasing 5-hydroxytryptamine. J Clin Invest 1984;74(3):828–833. DOI: 10.1172/JCI111499.
  9. Skurikhin EG, Andreeva TV, Khmelevskaya ES, Ermolaeva LA, Pershina OV, Krupin VA, et al. Effect of antiserotonin drug on the development of lung fibrosis and blood system reactions after intratracheal administration of bleomycin. Bull Exp Biol Med 2012;152(4):519–523. DOI: 10.1007/s10517-012-1567-1.
  10. Lenze EJ, Mattar C, Zorumski CF, Stevens A, Schweiger J, Nicol GE, et al. Fluvoxamine vs placebo and clinical deterioration in outpatients with symptomatic COVID-19: A randomized clinical trial. JAMA 2020;324(22):2292–2300. DOI: 10.1001/jama.2020.22760.
  11. Reis G, Dos Santos Moreira-Silva EA, Silva DCM, Thabane L, Milagres AC, Ferreira TS, et al. Effect of early treatment with fluvoxamine on risk of emergency care and hospitalisation among patients with COVID-19: The TOGETHER randomised, platform clinical trial. Lancet Glob Health 2022;10(1):e42–e51. DOI: 10.1016/S2214-109X(21)00448-4.
  12. Facente SN, Reiersen AM, Lenze EJ, Boulware DR, Klausner JD. Fluvoxamine for the early treatment of sars-cov-2 infection: A review of current evidence. Drugs 2021;81(18):2081–2089. DOI: 10.1007/s40265-021-01636-5.
  13. Hashimoto Y, Suzuki T, Hashimoto K. Old drug fluvoxamine, new hope for COVID-19. Eur Arch Psychiatry Clin Neurosci 2022;272(1):161–163. DOI: 10.1007/s00406-021-01326-z.
  14. Menga LS, Cese LD, Bongiovanni F, Lombardi G, Michi T, Luciani F, et al. High failure rate of noninvasive oxygenation strategies in critically ill subjects with acute hypoxemic respiratory failure due to COVID-19. Respir Care 2021;66(5):705–714. DOI: 10.4187/respcare.08622.
  15. Comer SP, Cullivan S, Szklanna PB, Weiss L, Cullen S, Kelliher S, et al. COVID-19 induces a hyperactive phenotype in circulating platelets. bioRxiv medRxiv 2020. DOI:
  16. Moll M, Zon RL, Sylvester KW, Chen EC, Cheng V, Connell NT, et al. VTE in ICU Patients With COVID-19. Chest 2020;158(5):2130–2135. DOI: 10.1016/j.chest.2020.07.031.
  17. Maatman TK, Jalali F, Feizpour C, Douglas A 2nd, McGuire SP, Kinnaman G, et al. Routine venous thromboembolism prophylaxis may be inadequate in the hypercoagulable state of severe Coronavirus disease 2019. Crit Care Med 2020;48(9):e783–e790. DOI: 10.1097/CCM.0000000000004466.
  18. Ishima T, Fujita Y, Hashimoto K. Interaction of new antidepressants with sigma-1 receptor chaperones and their potentiation of neurite outgrowth in PC12 cells. Eur J Pharmacol 2014;727:167–173. DOI: 10.1016/j.ejphar.2014.01.064.
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