Intramuscular haloperidol or lorazepam and QT intervals in schizophrenia.
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" (QT(ii) 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.
Harvey
Anne T
AT
Psychiatric Research, Institute, Wichita, KS 67214-2878.
Flockhart
David
D
Gorski
J Christopher
JC
Greenblatt
David J
DJ
Burke
Michael
M
Werder
Steve
S
Preskorn
Sheldon H
SH
D000328:Adult; D016001:Confidence Intervals; D018592:Cross-Over Studies; D004562:Electrocardiography / Q000379:methods; D005260:Female; D006220:Haloperidol / Q000008:administration & dosage* / Q000009:adverse effects* / Q000097:blood; D006801:Humans; D007273:Injections, Intramuscular; D008133:Long QT Syndrome / Q000097:blood / Q000139:chemically induced* / Q000503:physiopathology; D008140:Lorazepam / Q000008:administration & dosage* / Q000009:adverse effects* / Q000097:blood; D008297:Male; D008875:Middle Aged; D012559:Schizophrenia / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology
D006220:Haloperidol; D008140:Lorazepam