Nicolas Hoertel1,2,3, Marina Sánchez-Rico1,4, Raphaël Vernet5, Anne-Sophie Jannot3,5,6, Antoine Neuraz6,7, Carlos Blanco8, Cédric Lemogne1,2,3, Guillaume Airagnes1,2,3, Nicolas Paris9,10, Christel Daniel9,11, Alexandre Gramfort12, Guillaume Lemaitre12, Mélodie Bernaux13, Ali Bellamine14, Nathanaël Beeker14, Frédéric Limosin1,2,3. 1. Département de Psychiatrie, Hôpital Corentin-Celton, Centre Université de Paris, AP-HP, Issy-les-Moulineaux, France. 2. INSERM, Institut de Psychiatrie et Neurosciences de Paris, Paris, France. 3. Faculté de Santé, UFR de Médecine, Université de Paris, Paris, France. 4. Faculty of Psychology, Department of Psychobiology & Behavioural Sciences Methods, Universidad Complutense de Madrid, Madrid, Spain. 5. Biostatistics and Public Health Department, Hôpital Européen Georges Pompidou, Medical Informatics, AP-HP, Centre-Université de Paris, Paris, France. 6. INSERM, UMR_S 1138, Cordeliers Research Center, Université de Paris, Paris, France. 7. Department of Medical Informatics, Necker-Enfants Malades Hospital, AP-HP, Centre-Université de Paris, Paris, France. 8. National Institute on Drug Abuse, Bethesda, MD, United States of America. 9. AP-HP, DSI-WIND, Paris, France. 10. LIMSI, CNRS, Université Paris-Sud, Université Paris-Saclay, Orsay, France. 11. Sorbonne University, University Paris 13, Sorbonne Paris Cité, INSERM UMR_S 1142, Paris, France. 12. Université Paris-Saclay, Inria, CEA, Palaiseau, France. 13. Direction de la stratégie et de la transformation, AP-HP, Paris, France. 14. Unité de Recherche clinique, Hôpital Cochin, AP-HP, Centre-Université de Paris, Paris, France.
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.
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.
Authors: Nicolas Hoertel; Marina Sánchez-Rico; Erich Gulbins; Johannes Kornhuber; Alexander Carpinteiro; Eric J Lenze; Angela M Reiersen; Miriam Abellán; Pedro de la Muela; Raphaël Vernet; Carlos Blanco; Céline Cougoule; Nathanaël Beeker; Antoine Neuraz; Philip Gorwood; Jesús M Alvarado; Pierre Meneton; Frédéric Limosin Journal: Clin Pharmacol Ther Date: 2021-07-02 Impact factor: 6.903
Authors: Nicolas Hoertel; Marina Sánchez-Rico; Pedro de la Muela; Miriam Abellán; Carlos Blanco; Marion Leboyer; Céline Cougoule; Erich Gulbins; Johannes Kornhuber; Alexander Carpinteiro; Katrin Anne Becker; Raphaël Vernet; Nathanaël Beeker; Antoine Neuraz; Jesús M Alvarado; Juan José Herrera-Morueco; Guillaume Airagnes; Cédric Lemogne; Frédéric Limosin Journal: Biol Psychiatry Glob Open Sci Date: 2022-01-04
Authors: Marc De Hert; Victor Mazereel; Marc Stroobants; Livia De Picker; Kristof Van Assche; Johan Detraux Journal: Front Psychiatry Date: 2022-01-13 Impact factor: 4.157