J Clin Pharmacol
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ADVERSE EFFECTS

Intramuscular Haloperidol or Lorazepam and QT Intervals in Schizophrenia

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

From the Psychiatric Research Institute, Wichita, Kansas (Dr. Harvey, Dr. Werder, Dr. Preskorn); Department of Psychiatry, University of Kansas School of Medicine, Wichita, Kansas (Dr. Harvey, Dr. Burke, Dr. Werder, Dr. Preskorn); Division of Clinical Pharmacology, Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana (Dr. Flockhart, Dr. Gorski); Department of Pharmacology and Experimental Therapeutics, Tufts University School of Medicine, Boston, Massachusetts (Dr. Greenblatt).

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.

Key Words: Haloperidol • lorazepam • QT interval • schizophrenia • intramuscular

Address for reprints: Anne T. Harvey, PhD, Via Christi Research, Inc., 1100 N. St. Francis, Suite 200, Wichita, KS 67214-2878.






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