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A Naturalistic Study of Intramuscular Haloperidol Versus Intramuscular Olanzapine for the Management of Acute Agitation

MacDonald, Kai MD*; Wilson, Michael MD, PhD; Minassian, Arpi PhD*; Vilke, Gary M. MD; Becker, Olga MD*; Tallian, Kimberly PharmD; Cobb, Patrice BA*; Perez, Rachel,*; Galangue, Barbara MA, MS*; Feifel, David MD, PhD*

Journal of Clinical Psychopharmacology: June 2012 - Volume 32 - Issue 3 - p 317–322
doi: 10.1097/JCP.0b013e318253a2fe
Original Contributions

Objective Published research on agitation is limited by the difficulty in generalizing findings from trials using moderately agitated, carefully selected patients treated with single agents. More specifically, there are few comparative studies examining common intramuscular (IM) regimens (ie, haloperidol with or without benzodiazepines) with IM atypical antipsychotics. Therefore, we conducted a retrospective chart review to compare IM olanzapine and haloperidol in a “real-world” population with agitation.

Method We performed a retrospective evaluation of charts from 146 consecutive emergency department patients who received either IM haloperidol or IM olanzapine for agitation. We used a clinically oriented proxy marker of efficacy—the necessity for additional medication intervention for agitation (AMI)—as our primary outcome measure.

Results Additional medication intervention for agitation was required by 43% (13/30) patients when haloperidol was given alone and by 18% (13/72) when haloperidol was given with a benzodiazepine. In the case of olanzapine, AMI was required by 29% (6/21) of patients receiving olanzapine alone and by 18% (2/11) of patients given olanzapine plus a benzodiazepine. A significant percentage of patients had clinical characteristics (nonpsychiatric triage complaint, drug/alcohol use, severe agitation) that differ from more selective samples.

Conclusions Overall, these finding suggest that in a naturalistic emergency department setting, haloperidol monotherapy is less effective—at least in requiring AMI—than olanzapine with or without a benzodiazepine or haloperidol plus a benzodiazepine. Moreover, these later 3 regimens seemed comparable. Prospective studies examining the treatment of real-world agitation, including head-to-head comparisons of the haloperidol-benzodiazepine combination with newer IM antipsychotics, are needed.

From the Departments of *Psychiatry, †Emergency Medicine, and ‡Pharmacy, University of California, San Diego, CA.

Received January 24, 2011; accepted after revision November 29, 2011.

Reprints: Kai MacDonald, MD, Department of Psychiatry, University of California, San Diego, 9500 Gilman Dr, MC 8620, La Jolla, CA 92093-0804 (e-mail:

© 2012 Lippincott Williams & Wilkins, Inc.