Antiviral efficacy of fluoxetine in early symptomatic COVID-19: an open-label, randomised, controlled, adaptive platform trial (PLATCOV)
MD Podjanee Jittamala, MBBS Simon Boyd, MBBS William Hk Schilling, James A Watson, MD Thundon Ngamprasertchai, MD Tanaya Siripoon, MD Viravarn Luvira, PhD Elizabeth M Batty, PhD Phrutsamon Wongnak, Lisia M Esper, Pedro J Almeida, MD Cintia Cruz, Fernando R Ascencao, Renato S Aguiar, PhD Najia K Ghanchi, James J Callery, MBBS Shivani Singh, PhD Varaporn Kruabkontho, MBA Thatsanun Ngernseng, Pharm.D Jaruwan Tubprasert, Wanassanan Madmanee, Kanokon Suwannasin, Amornrat Promsongsil, MD Borimas Hanboonkunupakarn, MD Kittiyod Poovorawan, MD Manus Potaporn, MD Attasit Srisubat, MD Bootsakorn Loharjun, Walter Rj Taylor, Farah Qamar, Abdul Momin Kazi, M Asim Beg, Danoy Chommanam, Sisouphanh Vidhamaly, PhD Kesinee Chotivanich, PhD Mallika Imwong, MBBS Sasithon Pukrittayakamee, Arjen M Dondorp, Nicholas Pj Day, MD Mauro M Teixeira, MD Watcharapong Piyaphanee, MD Weerapong Phumratanaprapin, Nicholas J White
doi:10.1101/2024.01.16.24301337
Background The selective serotonin reuptake inhibitors (SSRIs) fluoxetine and fluvoxamine were repurposed for the treatment of early COVID-19 based on their antiviral activity in vitro, and observational and clinical trial evidence suggesting they prevented progression to severe disease. However, these SSRIs have not been recommended in guidelines and their antiviral activity in vivo has not been characterised.
Methods PLATCOV is an open-label, multicentre, phase 2, randomised, controlled, adaptive pharmacometric platform trial running in Thailand, Brazil, Pakistan, and Laos. We recruited lowrisk adult outpatients aged 18-50 with early symptomatic COVID-19 (symptoms <4 days). Patients
Added value of the study We showed that in early COVID-19 illness the SSRI fluoxetine has weak antiviral activity in vivo. This activity is substantially less than other available antivirals such as ritonavir-boosted nirmatrelvir and molnupiravir. The pharmacometric approach described here provides a quantitative measure of in vivo antiviral effects with tractable sample sizes.
Implications of available evidence Fluoxetine has weak in vivo antiviral activity in early COVID-19. This is insufficient for treatment but, as less antiviral activity is required to prevent an infection, fluoxetine could still be beneficial in prophylaxis.
Contributors PJ-investigation, methodology, project administration, supervision, validation, and writingoriginal draft. SB-investigation, methodology, project administration, writing-original draft. PJ and SB contributed equally. WHKS-funding acquisition, investigation, methodology, project administration, supervision, validation, and writing-original draft. JAW-conceptualisation, data curation, formal analysis, funding acquisition, methodology, visualisation, and writing-original draft. TN, TS, VL-Investigation, methodology, supervision. EMB-data curation, formal analysis, visualisation. PW-data curation, formal analysis, visualisation, and writing-original draft. RA, FA, NG-formal analysis, investigation. LE, PA, CC, JJC, SS, VK, TN, JT, FQ, AMK -methodology, investigation, project administration. WM, KS, AP-investigation, methodology. BH, KP-
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