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Clinical Trial
. 2021 Feb 19;16(2):e0247122.
doi: 10.1371/journal.pone.0247122. eCollection 2021.

Observational study of haloperidol in hospitalized patients with COVID-19

Nicolas Hoertel  1   2   3 , Marina Sánchez-Rico  1   4 , Raphaël Vernet  5 , Anne-Sophie Jannot  3   5   6 , Antoine Neuraz  6   7 , Carlos Blanco  8 , Cédric Lemogne  1   2   3 , Guillaume Airagnes  1   2   3 , Nicolas Paris  9   10 , Christel Daniel  9   11 , Alexandre Gramfort  12 , Guillaume Lemaitre  12 , Mélodie Bernaux  13 , Ali Bellamine  14 , Nathanaël Beeker  14 , Frédéric Limosin  1   2   3 ; AP-HP/Universities/INSERM Covid-19 research collaboration and AP-HP Covid CDR Initiative
Affiliations
Clinical Trial

Observational study of haloperidol in hospitalized patients with COVID-19

Nicolas Hoertel et al. PLoS One. .

Abstract

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.

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Conflict of interest statement

I have read the journal’s policy and the authors of this manuscript have the following competing interests: NH has received personal fees and non-financial support from Lundbeck, outside the submitted work. FL has received speaker and consulting fees from Janssen-Cilag, Euthérapie-Servier, and Lundbeck, outside the submitted work. CL reports personal fees and non-financial support from Janssen-Cilag, Lundbeck, Otsuka Pharmaceutical, and Boehringer Ingelheim, outside the submitted work. GA reports personal fees from Pfizer, Pierre Fabre and Lundbeck, outside the submitted work. Other authors declare no competing interests. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Figures

Fig 1
Fig 1
Kaplan-Meier curves for intubation or death in the full sample crude analysis (N = 15,121) (A), in the full sample analysis with inverse probability weighting (N = 15,121) (B) and in the matched analytic sample using a 1:4 ratio (N = 195) (C) of patients who had been hospitalized for COVID-19, according to haloperidol use. The shaded areas represent pointwise 95% confidence intervals.
Fig 2
Fig 2
Kaplan-Meier curves for discharge home among survivors in the full sample crude analysis (N = 11,572) (A), in the full sample analysis with inverse probability weighting (N = 11,572) (B) and in the matched analytic sample using a 1:4 ratio (N = 130) (C) of patients who had been hospitalized for COVID-19, according to haloperidol use. The shaded areas represent pointwise 95% confidence intervals.
See this image and copyright information in PMC

References

    1. Hoertel N, Blachier M, Blanco C, Olfson M, Massetti M, Sanchez-Rico M, et al. A stochastic agent-based model of the SARS-CoV-2 epidemic in France. Nature Medicine. 2020. pp. 1417–1421. 10.1038/s41591-020-1001-6 - DOI - PubMed
    1. Hoertel N, Blachier M, Blanco C, Olfson M, Massetti M, Limosin F, et al. Facing the COVID-19 epidemic in NYC: a stochastic agent-based model of various intervention strategies. medRxiv. 2020. 10.1101/2020.04.23.20076885 - DOI - PMC - PubMed
    1. Anderson RM, Heesterbeek H, Klinkenberg D, Hollingsworth TD. How will country-based mitigation measures influence the course of the COVID-19 epidemic? Lancet. 2020;395: 931–934. 10.1016/S0140-6736(20)30567-5 - DOI - PMC - PubMed
    1. Gordon DE, Jang GM, Bouhaddou M, Xu J, Obernier K, White KM, et al. A SARS-CoV-2 protein interaction map reveals targets for drug repurposing. Nature. 2020;583: 459–468. 10.1038/s41586-020-2286-9 - DOI - PMC - PubMed
    1. Chevance A, Gourion D, Hoertel N, Llorca P-M, Thomas P, Bocher R, et al. Ensuring mental health care during the SARS-CoV-2 epidemic in France: A narrative review. L’Encephale. 2020;46: 193–201. 10.1016/j.encep.2020.04.005 - DOI - PMC - PubMed