title: Effects of intramuscular olanzapine vs. haloperidol and placebo on QTc intervals in acutely agitated patients.
abstract: Prolongation of the QTc interval has been reported during treatment with oral antipsychotic agents and may be more pronounced during parenteral administration. Pooled QTc interval data from acutely agitated patients across four double-blind trials were compared. Databases included: placebo-controlled [two schizophrenia, one bipolar mania trials (n=565)]; haloperidol-controlled [two schizophrenia trials (n=482)]; geriatric placebo-controlled [1 dementia trial (n=204)]. Patients received 1-3 injections of intramuscular (IM) olanzapine (2.5-10 mg/injection), IM haloperidol (7.5 mg/injection), or IM placebo. At 2 and 24 h after IM olanzapine treatment, the mean QTc interval decreased approximately 3 ms from baseline in the placebo- and haloperidol-controlled databases. When there was a statistically significant difference between IM olanzapine and IM placebo, QTc intervals decreased during treatment with IM olanzapine and increased with IM placebo. The incidences of prolonged (endpoint >/=99th percentile of healthy adults or >/=500 ms) or lengthened (increase >/=60 ms) QTc intervals during treatment with IM olanzapine (<3% placebo- and haloperidol-controlled databases, <12% geriatric placebo-controlled database) were never significantly greater than with comparators. These data suggest that IM olanzapine has a favorable QTc interval profile in acutely agitated patients with schizophrenia, bipolar mania, or dementia.
authors.affiliation: Lilly Research Laboratories, Eli Lilly and Company, Lilly Corporate Center DC 6324, 46285, Indianapolis, IN, USA. lindborg_stacy@lilly.com
authors.forename: Stacy R
authors.initials: SR
authors.lastname: Lindborg
authors.forename: Charles M
authors.initials: CM
authors.lastname: Beasley
authors.forename: Karla
authors.initials: K
authors.lastname: Alaka
authors.forename: Cindy C
authors.initials: CC
authors.lastname: Taylor
mesh_terms: D014150:Antipsychotic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D001569:Benzodiazepines / Q000008:administration & dosage / Q000627:therapeutic use*; D001714:Bipolar Disorder / Q000188:drug therapy* / Q000453:epidemiology; D003704:Dementia / Q000453:epidemiology; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004562:Electrocardiography; D006220:Haloperidol / Q000008:administration & dosage / Q000627:therapeutic use*; D006801:Humans; D007273:Injections, Intramuscular; D008133:Long QT Syndrome / Q000175:diagnosis / Q000453:epidemiology*; D000077152:Olanzapine; D011595:Psychomotor Agitation / Q000188:drug therapy* / Q000453:epidemiology; D012559:Schizophrenia / Q000188:drug therapy* / Q000453:epidemiology
chemical_list: D014150:Antipsychotic Agents; D001569:Benzodiazepines; D006220:Haloperidol; D000077152:Olanzapine