Observational Study of Chlorpromazine in Hospitalized Patients with Covid-19

Hoertel, Nicolas; Sánchez‐Rico, Marina; Vernet, Raphaël; Jannot, Anne‐Sophie; Neuraz, Antoine; Blanco, Carlos; Lemogne, Cédric; Airagnes, Guillaume; Paris, Nicolas; Daniel, Christel; Gramfort, Alexandre; Lemaître, G; Bernaux, Mélodie; Bellamine, Ali; Beeker, Nathanaël; Limosin, Frédéric; Universities,; Initiative, Ap-Hp Covid Cdr

doi:10.1101/2020.07.15.20154310

Cited by 7 publications

(7 citation statements)

References 25 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We obtained the following data for each patient at the time of the hospitalization through electronic health records: [17][18][19] sex, age, hospital, obesity, self-reported current smoking status, any medical condition associated with increased risk of severe COVID-19 [17,[19][20][21], any medication prescribed according to compassionate use or as part of a clinical trial [22], clinical and biological markers of disease severity at admission [23,24], any current mood or anxiety disorder, any other current psychiatric disorder, and any psychotropic medication, including any antidepressant, benzodiazepine or Z-drug, mood stabilizer (i.e. lithium or antiepileptic medications with mood stabilizing effects), and antipsychotic medication [25,26]. These variables are detailed in Supplementary Text 1.…”

Section: Variables Assessedmentioning

confidence: 99%

Association between antidepressant use and reduced risk of intubation or death in hospitalized patients with COVID-19: results from an observational study

et al. 2021

Self Cite

View full text Add to dashboard Cite

A prior meta-analysis showed that antidepressant use in major depressive disorder was associated with reduced plasma levels of several pro-inflammatory mediators, which have been associated with severe COVID-19. Recent studies also suggest that several antidepressants may inhibit acid sphingomyelinase activity, which may prevent the infection of epithelial cells with SARS-CoV-2, and that the SSRI fluoxetine may exert in-vitro antiviral effects on SARS-CoV-2. We examined the potential usefulness of antidepressant use in patients hospitalized for COVID-19 in an observational multicenter retrospective cohort study conducted at AP-HP Greater Paris University hospitals. Of 7230 adults hospitalized for COVID-19, 345 patients (4.8%) received an antidepressant within 48 h of hospital admission. The primary endpoint was a composite of intubation or death. We compared this endpoint between patients who received antidepressants and those who did not in time-to-event analyses adjusted for patient characteristics, clinical and biological markers of disease severity, and other psychotropic medications. The primary analysis was a multivariable Cox model with inverse probability weighting. This analysis showed a significant association between antidepressant use and reduced risk of intubation or death (HR, 0.56; 95% CI, 0.43-0.73, p < 0.001). This association remained significant in multiple sensitivity analyses. Exploratory analyses suggest that this association was also significant for SSRI and non-SSRI antidepressants, and for fluoxetine, paroxetine, escitalopram, venlafaxine, and mirtazapine (all p < 0.05). These results suggest that antidepressant use could be associated with lower risk of death or intubation in patients hospitalized for COVID-19. Double-blind controlled randomized clinical trials of antidepressant medications for COVID-19 are needed.

show abstract

Section: Variables Assessedmentioning

confidence: 99%

Association between antidepressant use and reduced risk of intubation or death in hospitalized patients with COVID-19: results from an observational study

et al. 2021

Self Cite

View full text Add to dashboard Cite

show abstract

“…One prospective double-blind, randomized clinical trial of fluvoxamine, one FIASMA versus placebo, found that patients (community-living nonhospitalized adults with COVID-19) treated with fluvoxamine had a low likelihood of clinical deterioration over 15 days [ 22 ]. Recently, an observational multicenter retrospective study in hospitalized COVID-19 patients reported that chlorpromazine was not associated with reduced mortality [ 23 ].…”

Section: Introductionmentioning

confidence: 99%

Association between Functional Inhibitors of Acid Sphingomyelinase (FIASMAs) and Reduced Risk of Death in COVID-19 Patients: A Retrospective Cohort Study

et al. 2021

View full text Add to dashboard Cite

Given the current scarcity of curative treatment of COVID-19, the search for an effective treatment modality among all available medications has become a priority. This study aimed at investigating the role of functional inhibitors of acid sphingomyelinase (FIASMAs) on in-hospital COVID-19 mortality. In this retrospective cohort study, we included adult in-patients with laboratory-confirmed COVID-19 between 1 March 2020 and 31 August 2020 with definite outcomes (discharged hospital or deceased) from Erasme Hospital (Brussels, Belgium). We used univariate and multivariate logistic regression models to explore the risk factors associated with in-hospital mortality. We included 350 patients (205 males, 145 females) with a mean age of 63.24 years (SD = 17.4, range: 21–96 years). Seventy-two patients died in the hospital and 278 were discharged. The four most common comorbidities were hypertension (184, 52.6%), chronic cardiac disease (110, 31.4%), obesity (96, 27.8%) and diabetes (95, 27.1%). Ninety-three participants (26.6%) received a long-term prescription for FIASMAs. Among these, 60 (64.5%) received amlodipine. For FIASMAs status, multivariable regression showed increasing odds ratio (OR) for in-hospital deaths associated with older age (OR 1.05, 95% CI: 1.02–1.07; p = 0.00015), and higher prevalence of malignant neoplasm (OR 2.09, 95% CI: 1.03–4.22; p = 0.039). Nonsignificant decreasing OR (0.53, 95% CI: 0.27–1.04; p = 0.064) was reported for FIASMA status. For amlodipine status, multivariable regression revealed increasing OR of in-hospital deaths associated with older age (OR 1.04, 95% CI: 1.02–1.07; p = 0.0009), higher prevalence of hypertension (OR 2.78, 95% CI: 1.33–5.79; p = 0.0062) and higher prevalence of malignant neoplasm (OR 2.71, 95% CI: 1.23–5.97; p = 0.013), then secondarily decreasing OR of in-hospital death associated with long-term treatment with amlodipine (OR 0.24, 95% CI: 0.09–0.62; p = 0.0031). Chronic treatment with amlodipine could be significantly associated with low mortality of COVID-19 in-patients.

show abstract

“…To help account for the nonrandomized prescription of haloperidol and reduce the effects of confounding, the primary analysis used a univariate Cox regression model in a matched analytic sample for each outcome. We selected four controls for each exposed case, based on age, sex, hospital, obesity, smoking status, any medical condition, any medication prescribed according to compassionate use or as part of a clinical trial, any current diagnosis of psychiatric disorders, any prescribed antipsychotic other than haloperidol, and any other prescribed psychotropic medication [19][20][21][22]. To reduce the effects of confounding, optimal matching was used in order to obtain the PLOS ONE smallest average absolute distance across all these characteristics between each exposed patient and its corresponding non-exposed matched controls [23].…”

Section: Discussionmentioning

confidence: 99%

Observational study of haloperidol in hospitalized patients with COVID-19

et al. 2021

Self Cite

View full text Add to dashboard Cite

Background Haloperidol, a widely used antipsychotic, has been suggested as potentially useful for patients with COVID-19 on the grounds of its in-vitro antiviral effects against SARS-CoV-2, possibly through sigma-1 receptor antagonist effect. Methods We examined the associations of haloperidol use with intubation or death and time to discharge home among adult patients hospitalized for COVID-19 at Assistance Publique-Hôpitaux de Paris (AP-HP) Greater Paris University hospitals. Study baseline was defined as the date of hospital admission. The primary endpoint was a composite of intubation or death and the secondary endpoint was discharge home among survivors in time-to-event analyses. In the primary analyses, we compared these two outcomes between patients receiving and not receiving haloperidol using univariate Cox regression models in matched analytic samples based on patient characteristics and other psychotropic medications. Sensitivity analyses included propensity score analyses with inverse probability weighting and multivariable Cox regression models. Results Of 15,121 adult inpatients with a positive COVID-19 PT-PCR test, 39 patients (0.03%) received haloperidol within the first 48 hours of admission. Over a mean follow-up of 13.8 days (SD = 17.9), 2,024 patients (13.4%) had a primary end-point event and 10,179 patients (77.6%) were discharged home at the time of study end on May 1st. The primary endpoint occurred in 9 patients (23.1%) who received haloperidol and 2,015 patients (13.4%) who did not. The secondary endpoint of discharge home occurred in 16 patients (61.5%) who received haloperidol and 9,907 patients (85.8%) who did not. There were no significant associations between haloperidol use and the primary (HR, 0.80; 95% CI, 0.39 to 1.62, p = 0.531) and secondary (HR, 1.30; 95% CI, 0.74 to 2.28, p = 0.355) endpoints. Results were similar in multiple sensitivity analyses. Conclusion Findings from this multicenter observational study suggest that haloperidol use prescribed at a mean dose of 4.5 mg per day (SD = 5.2) for a mean duration of 8.4 days (SD = 7.2) may not be associated with risk of intubation or death, or with time to discharge home, among adult patients hospitalized for COVID-19.

show abstract

Observational Study of Chlorpromazine in Hospitalized Patients with Covid-19

Cited by 7 publications

References 25 publications

Association between antidepressant use and reduced risk of intubation or death in hospitalized patients with COVID-19: results from an observational study

Association between antidepressant use and reduced risk of intubation or death in hospitalized patients with COVID-19: results from an observational study

Association between Functional Inhibitors of Acid Sphingomyelinase (FIASMAs) and Reduced Risk of Death in COVID-19 Patients: A Retrospective Cohort Study

Observational study of haloperidol in hospitalized patients with COVID-19

Contact Info

Product

Resources

About