Visos Varela, IreneZapata Cachafeiro, MaruxaPiñeiro Lamas, MaríaCarracedo Martínez, EduardoSaez, MarcHerdeiro, Maria Teresa FerreiraFigueiras Guzmán, AdolfoSalgado Barreira, Ángel2023-05-312023-05-312023European Neuropsychopharmacology 71 (2023) 96–108http://hdl.handle.net/10347/30629The World Health Organization has proposed that a search be made for alternatives to vaccines for the prevention and treatment of COVID-19, with one such alternative being selective serotonin reuptake inhibitors (SSRIs). This study thus sought to assess: the impact of previous treatment with SSRI antidepressants on the severity of COVID-19 (risk of hospitalisation, admission to an intensive care unit [ICU], and mortality), its influence on susceptibility to SARS-CoV-2 and progression to severe COVID-19. We conducted a population-based multiple case-control study in a region in the north-west of Spain. Data were sourced from electronic health records. Adjusted odds ratios (aORs) and 95%CIs were calculated using multilevel logistic regression. We collected data from a total of 86,602 subjects: 3060 cases PCR+, 26,757 non-hospitalised cases PCR+ and 56,785 controls (without PCR+). Citalopram displayed a statistically significant decrease in the risk of hospitalisation (aOR=0.70; 95% CI 0.49–0.99, p = 0.049) and progression to severe COVID-19 (aOR=0.64; 95% CI 0.43–0.96, p = 0.032). Paroxetine was associated with a statistically significant decrease in risk of mortality (aOR=0.34; 95% CI 0.12 – 0.94, p = 0.039). No class effect was observed for SSRIs overall, nor was any other effect found for the remaining SSRIs. The results of this large-scale, real-world data study indicate that, citalopram, could be a candidate drug for being repurposed as preventive treatment aimed at reducing COVID-19 patients’ risk of progressing to severe stages of the disease.eng© 2023 The Author(s). Published by Elsevier B.V. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/)http://creativecommons.org/licenses/by/4.0/Serotonin and noradrenaline reuptake inhibitorsCitalopramAntidepressantsCOVID-19HospitalisationDrug repositioningjournal article10.1016/j.euroneuro.2023.03.0110924-977Xopen access