Hydroxyzine Use and Mortality in Patients Hospitalized for COVID-19: A Multicenter Observational Study

Abstract

(1) Background: Based on its antiviral activity, anti-inflammatory properties, and functional inhibition effects on the acid sphingomyelinase/ceramide system (FIASMA), we sought to examine the potential usefulness of the H1 antihistamine hydroxyzine in patients hospitalized for COVID-19. (2) Methods: In a multicenter observational study, we included 15,103 adults hospitalized for COVID-19, of which 164 (1.1%) received hydroxyzine within the first 48 h of hospitalization, administered orally at a median daily dose of 25.0 mg (SD = 29.5). We compared mortality rates between patients who received hydroxyzine at hospital admission and those who did not, using a multivariable logistic regression model adjusting for patients’ characteristics, medical conditions, and use of other medications. (3) Results: This analysis showed a significant association between hydroxyzine use and reduced mortality (AOR, 0.51; 95%CI, 0.29–0.88, p = 0.016). This association was similar in multiple sensitivity analyses. (4) Conclusions: In this retrospective observational multicenter study, the use of the FIASMA hydroxyzine was associated with reduced mortality in patients hospitalized for COVID-19. Double-blind placebo-controlled randomized clinical trials of hydroxyzine for COVID-19 are needed to confirm these results, as are studies to examine the potential usefulness of this medication for outpatients and as post-exposure prophylaxis for individuals at high risk for severe COVID-19.

Association between FIASMA psychotropic medications and reduced risk of intubation or death in individuals with psychiatric disorders hospitalized for severe COVID-19: an observational multicenter study

“…We found that FIASMA psychotropic medication use was significantly and substantially associated with reduced risk of intubation or death among patients with psychiatric disorders hospitalized for severe COVID-19, and that this association was not specific to one FIASMA psychotropic class or medication in this population. These findings are in line with prior preclinical [8,12,[51][52][53][54], observational [21][22][23][24][55][56][57], and clinical [27][28][29][30] evidence that FIASMA antidepressant medications may substantially prevent cells from being infected with SARS-CoV-2 in vitro [8,12], and that FIASMA antidepressants and potentially the FIASMA anti-histamine hydroxyzine at their usual respective antidepressant and antihistaminic doses, may reduce mortality among patients with COVID-19.…”

“…A retrospective observational study also established a similar association between chronic administration of a FIASMA medication and diminished mortality in patients hospitalized with COVID-19, that was significant for the FIASMA amlodipine [22]. Furthermore, data from the AP-HP Health Data Warehouse [23][24][25] showed that use of antidepressants, many of them being FIASMA, and the FIASMA hydroxyzine, were significantly associated with reduced mortality in patients hospitalized for COVID-19. Finally, results from a large US retrospective cohort study found that selective serotonin reuptake inhibitor (SSRI) antidepressants, and more specifically fluoxetine and fluoxetine or fluvoxamine, which are FIASMA, were significantly associated with reduced mortality [26].…”

“…To our knowledge, no clinical study to date has examined the potential usefulness of FIASMA psychotropic medications in patients with psychiatric disorders hospitalized for COVID-19. Observational studies of patients with COVID-19 taking medications for other indications can help decide which treatment should be prioritized for randomized clinical trials and reduce the risk for patients of being exposed to potentially harmful and ineffective treatments [23,24,[34][35][36]. Observational studies examining the potential usefulness of FIASMA psychotropic medications in COVID-19 are also important because in vitro FIASMA effects may not translate to clinical FIASMA effects in humans for all individual FIASMA psychotropic medications, which depends on the dose used and pharmacokinetics of each molecule.…”

Association between benzodiazepine receptor agonist use and mortality in patients hospitalised for COVID-19: a multicentre observational study

“…A multicentre observational retrospective cohort study was conducted at 36 Assistance publique-Hôpitaux de Paris (AP-HP) hospitals (Hoertel et al, 2021c(Hoertel et al, , 2021dSánchez-Rico et al, 2021). We included all adults aged 18 years or over who have been admitted to these medical centres from the beginning of the epidemic in France, i.e.…”

“…COVID-19 was ascertained by a positive reversetranscriptase-polymerase chain reaction (RT-PCR) test from analysis of nasopharyngeal or oropharyngeal swab specimens. This observational study using routinely collected data received approval from the Institutional Review Board of the AP-HP clinical data warehouse (decision CSE-20-20_COVID19, IRB00011591, 8 April 2020) and is part of a broader project aiming at examining the potential associations between psychotropic medications and COVID-19-related mortality, deposited in French at the 'Entrepôt de Données de Santé' (EDS) website (https://eds.aphp.fr/recherches-en-cours), which has led to several publications (Hoertel et al, 2021c(Hoertel et al, , 2021dSánchez-Rico et al, 2021). AP-HP clinical Data Warehouse initiatives ensure patient information and informed consent regarding the different approved studies through a transparency portal in accordance with European Regulation on data protection and authorisation no.…”