Observational study of haloperidol in hospitalized patients with COVID-19

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

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.

Publication types

  • Clinical Trial
  • Multicenter Study
  • Observational Study

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Antipsychotic Agents / administration & dosage*
  • Antiviral Agents / administration & dosage*
  • COVID-19 / mortality*
  • COVID-19 / therapy*
  • Disease-Free Survival
  • Female
  • Haloperidol / administration & dosage*
  • Hospitalization*
  • Humans
  • Male
  • Middle Aged
  • Receptors, sigma / antagonists & inhibitors
  • SARS-CoV-2*
  • Survival Rate

Substances

  • Antipsychotic Agents
  • Antiviral Agents
  • Receptors, sigma
  • sigma-1 receptor
  • Haloperidol

Grant support

The authors received no specific funding for this work.