Intramuscular haloperidol or lorazepam and QT intervals in schizophrenia

Anne T. Harvey, David Flockhart, J. Christopher Gorski, David J. Greenblatt, Michael Burke, Steve Werder, Sheldon H. Preskorn

Research output: Contribution to journalArticle

12 Scopus citations

Abstract

The objective of this study was to estimate the effects of intramuscular haloperidol and lorazepam on the QT interval in volunteers with schizophrenia. Intramuscular haloperidol and intramuscular lorazepam are standard treatments in the acute management of agitation and aggression. Although prolongation of the QT interval and sequelae, including torsade de pointes and death, have been reported for haloperidol (but not lorazepam), formal studies have been lacking. Volunteers with schizophrenia (n = 12) were administered a single intramuscular injection of 7.5 mg haloperidol or 4 mg lorazepam in a blinded, randomized, placebo-controlled crossover design. Serial EKGs and concurrent blood samples were obtained over 6 hours following each injection. Changes in the QT interval were evaluated, as were plasma drug and prolactin concentrations. Haloperidol injection increased the heart rate-corrected QT interval an average of 5.1 msec using Bazett's correction (QTb 90% confidence interval [CI]: 0.3, 9.8), 3.6 msec using Fridericia's correction (QTf 90% CI: 0.02, 7.2), and 4.2 msec using an empirically derived "baseline correction" (QTii 90% CI: 0.3, 8.0). Effects of lorazepam on QT were nullified by correction for the heart rate elevation (QTb 3.8 msec, 90% CI: 0.6, 7.1; QTf 0.0 msec, 90% CI:-3.2, 3.4; QTii-2.3 msec, 90% CI:-6.6, 2.0). An association between QT prolongation and occurrence of extrapyramidal symptoms was observed. On average, intramuscular haloperidol led to minimal prolongation of the QT interval. This propensity is of theoretical concern in individuals with risk factors for torsade de pointes but seems unlikely to be a problem in the vast majority of patients.

Original languageEnglish (US)
Pages (from-to)1173-1184
Number of pages12
JournalJournal of Clinical Pharmacology
Volume44
Issue number10
DOIs
StatePublished - Oct 1 2004

Keywords

  • Haloperidol
  • Intramuscular
  • Lorazepam
  • QT interval
  • Schizophrenia

ASJC Scopus subject areas

  • Pharmacology (medical)
  • Pharmacology, Toxicology and Pharmaceutics(all)

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    Harvey, A. T., Flockhart, D., Gorski, J. C., Greenblatt, D. J., Burke, M., Werder, S., & Preskorn, S. H. (2004). Intramuscular haloperidol or lorazepam and QT intervals in schizophrenia. Journal of Clinical Pharmacology, 44(10), 1173-1184. https://doi.org/10.1177/0091270004267807