Research Article
Antipsychotic Selection for Acute Agitation and Time to
Repeat Use in a Psychiatric Emergency Department
Background: Early recognition and treatment
of agitated patients is essential to avoid vio-
lence in the psychiatric emergency depart-
ment (ED). Antipsychotics have established
efficacy in managing agitation, yet little is
known about how the choice of initial anti-
psychotic impacts time to repeat use and
length of stay (LOS) in the psychiatric ED.
Objective: To describe the impact of initial
antipsychotic selection on time to repeat use
and LOS in the psychiatric ED.
Methods: A chart review identified 388 cases in
which patients were administered an anti-
psychotic for agitation in the psychiatric ED
between July 1 and August 31, 2014. Time to
repeat use and LOS were compared for intra-
muscular (IM) haloperidol, other IM anti-
psychotics, and oral second-generation anti-
psychotics (SGAs) using the Kruskal-Wallis or
Wilcoxon-Mann-Whitney test.
Results: Of the 388 cases, 31% (n=122) required
repeat medications. Mean time to repeat use
for IM haloperidol was 20.1±18.4 hours, which
was not significantly different from mean
time to repeat use in the groups receiving
other IM antipsychotics or oral SGAs (P=0.35).
The mean LOS was 29.7±28.7 hours for IM
haloperidol, 30.3±36.9 hours for other IM anti-
psychotics, and 22.6±28.0 hours for oral
SGAs. Significant differences in LOS between
repeat and nonrepeat users of IM haloperidol
and other IM antipsychotics were observed,
but not among those who received oral
SGAs.
Conclusions: Mean time to repeat use ranged
from 14 to 20 hours with IM haloperidol, other
IM antipsychotics, and oral SGAs without
significant differences in time to repeat use in
the 3 different groups. Repeat users of IM
antipsychotics had a significantly longer LOS
in the ED compared with nonrepeat users of
IM antipsychotics. However, patients who
were initially administered oral SGAs did not
have longer LOS in the ED even if a repeat
dose was given.
450 November 2016
Copyright © 2016 Wolters Kluwer Health, Inc. All rights reserved.
SETH GOMEZ, PharmD
JULIE DOPHEIDE, PharmD, BCPP
(Journal of Psychiatric Practice 2016;22;450–
458)
KEY WORDS: acute agitation, antipsychotic, repeat
use, psychiatric emergency, emergency department,
boarding time
More than 50% of emergency department (ED)
nurses report experiencing verbal or physical vio-
lence from agitated patients that has an impact on
their personal and workplace safety.1 Agitation in
the psychiatric ED has also been noted to increase
the length of stay (LOS) and the need for additional
resources, including staff time for observation,
additional treatment (eg, medications), and con-
tainment. Each of these factors adds to the total
cost of care in both psychiatric hospitals and
emergency settings.2 Therefore, early recognition
and management of agitation is critical to avoid
harm to patients and staff, to create safer work
environments, and to reduce unnecessary stress
and costs for patients and the health care system.
Since the 1990s, several second-generation anti-
psychotics (SGAs) have been introduced in the US
market. Three SGAs—ziprasidone, olanzapine, and
aripiprazole—are available in rapid-acting inject-
able formulations and have received US Food and
Drug Administration labeling for the treatment of
agitation associated with schizophrenia.3–5 The
rapid-acting injectable formulations of olanzapine
and aripiprazole are also labeled for the treatment
of agitation associated with bipolar mania.4,5 Both
GOMEZ and DOPHEIDE: School of Pharmacy, University of
Southern California, Los Angeles, CA; DOPHEIDE: Keck
School of Medicine, University of Southern California, Los
Angeles, CA
Copyright © 2016 Wolters Kluwer Health, Inc. All rights
reserved.
Please send correspondence to: Seth Gomez, PharmD, 2000
Embarcadero Cove, Suite 400, Oakland, CA 94606 (e-mail:
sgomez@acbhcs.org).
The authors declare no conflicts of interest.
DOI: 10.1097/PRA.0000000000000186
Journal of Psychiatric Practice Vol. 22, No. 6
 ANTIPSYCHOTIC SELECTION FOR ACUTE AGITATION
intramuscular SGAs and the oral SGAs quetiapine,
olanzapine, and risperidone have shown effective-
ness comparable with the first-generation anti-
psychotic (FGA) haloperidol as measured by the
Positive and Negative Syndrome Scale–Excited
Component.6–12 Nevertheless, measurement of the
effectiveness of antipsychotics for acute agitation
beyond a 2- to 4-hour interval is uncommon. An
ideal medication should calm an agitated patient
quickly and keep the patient calm throughout a
reasonable duration of stay in the ED, but without
causing excessive sedation, which could delay the
development of an optimal treatment plan, includ-
ing discharge from the ED.
The choice of the most appropriate pharmaco-
logical agent to treat agitation in the ED depends
largely on the cause of the agitation. Possible eti-
ologies of agitation include underlying psychiatric
disorders, substance use, psychosocial stressors,
and medical conditions. In 2012, the American
Association of Emergency Psychiatry published an
expert consensus statement recommending SGAs
as first-line agents when pharmacological inter-
vention is needed for psychotic agitation.13 Similar
to other previously published algorithms, these
experts advocated prescribing orally administered
formulations to patients who are willing to take
them but also called attention to the lack of safety
data concerning the combined use of benzodiaze-
pines and SGAs.13–16
Few studies have explored antipsychotic uti-
lization in emergency settings or the time until a
repeat medication is necessary to control agitation.
A study published in 2014 by Wilson and colleagues
involving 2 large university-affiliated EDs in the US
found that, despite the expert recommendations
noted above, FGAs were administered more often
than SGAs (61.4% vs. 38.6%). This study also found
that oral formulations were utilized in 93.1% of all
antipsychotic administrations.17 However, this
study did not describe factors associated with these
prescribing practices, the mean doses of medi-
cations administered, or associations with pop-
ulations beyond patients who were acutely intoxi-
cated with alcohol. In another study involving 143
behavioral emergency code activations that occur-
red in 2006 at an Australian ED, pharmacological
agents were used in 60% (n=86) of the cases, 68% of
which required repeat medication to control agi-
tation, with nearly half needing repeat medication
Journal of Psychiatric Practice Vol. 22, No. 6
Copyright © 2016 Wolters Kluwer Health, Inc. All rights reserved.
within 1 hour.18 Benzodiazepines—diazepam and
midazolam—were most commonly administered as
the first drug, whereas antipsychotics—droperidol,
haloperidol, and quetiapine—were used in <10% of
cases for initial sedation.18 Details on the impact of
the initial drug selection and dose on time to repeat
use were not evaluated.
Given the increasing utilization of psychiatric
services, crowding in EDs, and longer ED boarding
times, the mean time to repeat use of medication for
acute agitation may have greater implications in
today’s health care environment. These factors
pressure emergency settings to function tempora-
rily more like inpatient treatment facilities for
patients with extended stays.19,20 In general,
patients with psychiatric disorders are more likely
to have an extended LOS in emergency settings
compared with patients without psychiatric
disorders.21–24 Other factors associated with
extended LOS in emergency settings include suici-
dal and homicidal ideation, holds placed late in
ED stay, lack of insurance, need for hospitalization,
medical complications, attempts to elope, depres-
sion and, recently, use of benzodiazepines
and antipsychotics.19,21,25–27 In psychiatric patients
on involuntary holds in general EDs, the use
of benzodiazepines and antipsychotics was asso-
ciated with 22.9% and 31.6% longer ED stays,
respectively, compared with those not treated
with these medications; there were no differences
based on age, sex, or ED disposition between
these groups.27 Despite this finding, it is unclear
whether the impact of benzodiazepines or anti-
psychotics on increasing LOS is a generalizable
finding in other acute care settings, including psy-
chiatric EDs.
OBJECTIVES
The primary objectives of this study were to
describe the potential impact of antipsychotic
selection on time to repeat use of agents for acute
agitation and to evaluate factors associated with
initial antipsychotic selection in a psychiatric ED.
Secondary aims were to compare LOS in the psy-
chiatric ED among groups receiving different anti-
psychotics and between patients who required a
repeat medication and those who did not require
additional medication.
November 2016 451
 ANTIPSYCHOTIC SELECTION FOR ACUTE AGITATION
METHODS
Study Site
The study site is a psychiatric ED in a large urban,
academic, level 1 trauma medical center. The ED
has nearly 100 medical beds and an onsite but
separate unit containing 20 psychiatric emergency
beds. The psychiatric emergency service evaluates,
admits, and discharges patients 24 hours/day,
7 days/week. The primary consumers of health
services at this facility are noninsured or are cov-
ered by MediCal and Medicare. This study was
approved by the University of Southern California
Institutional Review Board and, because of the
investigators’ ability to deidentify subjects,
informed consent was waived.
Study Criteria
A chart review of patients admitted into the psy-
chiatric ED between July 1, 2014 and August 31,
2014 was performed. All unique encounters were
screened for inclusion and exclusion criteria;
therefore, it was possible for a patient to be included
in the data analysis more than once. To be included,
patients had to be at least 18 years of age, to have
been acutely agitated during triage or initial eval-
uation as documented by physicians in the elec-
tronic health record, and to have been administered
an antipsychotic for acute agitation as documented
in their electronic medication administration record
(EMAR). Patients were excluded from the study for
any of the following conditions: (1) age below
18 years, (2) documentation in the health record
indicated a current pregnancy or a positive human
chorionic gonadotropin hormone test was found in
laboratory results during the encounter under
review, or (3) the initial evaluation was found to be
a consult for an agitated patient outside the psy-
chiatric ED. The electronic health record was then
used to extract demographic data and patient
characteristics including: age, sex, ethnicity,
weight, body mass index (BMI), systolic and dia-
stolic blood pressures, pulse, basic metabolic panel,
complete blood count, thyroid-stimulating hormone
concentrations, liver function tests, urinary tox-
icology results, psychiatric diagnoses, and comorbid
medical conditions.
452 November 2016
Copyright © 2016 Wolters Kluwer Health, Inc. All rights reserved.
Collection of Medication Data
The antipsychotic administered during the initial
evaluation (referred to as “the initial antipsychotic”)
was identified using the EMAR. On the basis of this
information, the patient was stratified into 1 of 3
medication groups: intramuscular (IM) haloperidol,
other IM antipsychotic, or oral antipsychotics. The
dose of the initial antipsychotic and coadministra-
tion of a benzodiazepine were also recorded when
applicable. The prevalence of SGA versus FGA
utilization and their routes of administration were
measured using descriptive statistics.
The EMAR was also used to collect information
on repeat use of medication. Repeat use of medi-
cation was defined as the administration of any
antipsychotic or benzodiazepine ordered in advance
with an indication for agitation (eg, a prn or stat
order to calm an agitated patient) at a time after
the administration of the initial antipsychotic. Only
the time when the first repeat medication was
administered was used to evaluate the time to
repeat use. The date and time when all medications
were administered are readily available in the
EMAR and this information was used to calculate
the time interval, in hours, between the admin-
istration of the initial antipsychotic that was
selected and the administration of repeat medi-
cation, if applicable. The mean time to repeat
medication was measured using descriptive sta-
tistics. The impact of the dose of the initial anti-
psychotic on the mean time to repeat use was also
evaluated.
A secondary goal of this study was to describe the
relationship between the initial antipsychotic
selected and the LOS in the psychiatric ED. LOS in
the psychiatric ED was determined by calculating
the time interval, in hours, between the date and
time the initial antipsychotic was administered and
the discharge date and time. This method was used
to analyze LOS because it was observed that, after
registration in the psychiatric ED, patients must
often wait until a psychiatric evaluation can take
place and the time of the initial antipsychotic
selection approximates the time of the psychiatric
evaluation. Mean LOS was calculated using
descriptive statistics and compared among the 3
antipsychotic groups into which the patients were
classified. Each antipsychotic group was then fur-
ther divided into 2 subgroups: patients who
Journal of Psychiatric Practice Vol. 22, No. 6
 ANTIPSYCHOTIC SELECTION FOR ACUTE AGITATION
required repeat use of medication (repeat users)
and those who did not require repeat medication
(nonrepeat users), and LOS was then compared
among these subgroups.
Statistical Analysis
Descriptive statistics were performed using Micro-
soft Excel 2011 and statistical analysis was exe-
cuted using SAS Version 9.3. Factors associated
with antipsychotic selection, demographic data, and
patient characteristics were assessed using the
Kruskal-Wallis test, χ2 test, or Fisher exact test,
when appropriate. Comparisons of mean time to
repeat use and mean LOS in each study group or
subgroup were performed using the Kruskal-Wallis
test (nonparametric ANOVA test) or Wilcoxon-
Mann-Whitney test (nonparametric t test).
RESULTS
Between July 1, 2014 and August 31, 2014, 388
admissions to the psychiatric ED involved acutely
agitated patients who were administered an anti-
psychotic medication. IM haloperidol was adminis-
tered as the initial antipsychotic in 298 cases (77%),
whereas oral SGAs were administered in 59 cases
(15%). Other IM antipsychotics—chlorpromazine,
olanzapine, and ziprasidone—were selected as the
initial antipsychotic in the other 31 cases (8%), with
chlorpromazine the most frequently used among
these agents; no IM aripiprazole was administered
(Table 1). All of the oral antipsychotics adminis-
tered in this study were SGAs; thus, for simplicity,
the oral antipsychotic group is referred to as oral
SGAs. Olanzapine was the most common oral SGA
administered. Comparing the 3 antipsychotic
groups, oral SGAs were more likely to be adminis-
tered to agitated patients diagnosed with schizo-
phrenia but least likely to be administered to agi-
tated patients diagnosed with an alcohol-induced
disorder (Table 2). The percentage of males and
average BMI for individuals who were administered
IM haloperidol as the initial antipsychotic
were significantly lower compared with the other 2
antipsychotic groups (Table 2). No variations in
antipsychotic selection were observed across other
factors (age, ethnicity, vitals, basic metabolic panel,
Journal of Psychiatric Practice Vol. 22, No. 6
Copyright © 2016 Wolters Kluwer Health, Inc. All rights reserved.
TABLE 1. Initial Antipsychotic Selection
and Dose
Dose (Mean±SD)
Antipsychotic Agents N (mg)
IM haloperidol 298 5.1±0.9
IM chlorpromazine 23 77.1±24.9
IM olanzapine 7 10±0
IM ziprasidone 1 10±0
PO olanzapine 38 10.3±3.1
PO risperidone 13 1.8±0.63
PO quetiapine 7 171.4±111.3
PO aripiprazole 1 10±0
IM indicates intramuscular; PO, oral.
complete blood count, liver panel, urinary toxicol-
ogy, and thyroid-stimulating hormone).
Coadministration of lorazepam with oral SGAs
occurred in 39% (n=34) of all oral SGAs adminis-
tered, including when oral SGAs were selected as
the initial antipsychotic and for repeat use; 4 cases
received IM lorazepam and 30 cases received oral
lorazepam. IM ziprasidone was combined with IM
lorazepam each time it was used (n=2). IM olanza-
pine was administered a total of 10 times during the
study as either the initial antipsychotic selected or
during repeat medication use. One patient received
oral lorazepam combined with IM olanzapine and
none received IM lorazepam. IM haloperidol was
administered a total of 360 times and IM chlorpro-
mazine 35 times during the study, including
administration as the initial antipsychotic and for
repeat medication use; it was more common for
these agents to be administered with IM lorazepam:
97% (n=349) and 60% (n=21), respectively. Almost
all IM haloperidol users (99.5%) were given IM
diphenhydramine (25 to 50 mg). Lorazepam was the
only benzodiazepine used for agitation in this psy-
chiatric ED. The average doses of SGAs and FGAs
used in the study are shown in Table 1. Generally
the antipsychotics that were prescribed seemed to
be used within the accepted dosing ranges. How-
ever, because the dosing of antipsychotics in this
sample showed less variation than anticipated, the
impact of dose on mean time to repeat use or
duration of ED stay could not be evaluated.
In addition to being the most prevalent anti-
psychotic used, IM haloperidol was associated with
November 2016 453
 ANTIPSYCHOTIC SELECTION FOR ACUTE AGITATION

TABLE 2. Characteristics of Acutely Agitated Patients in the Psychiatric Emergency

Department

n (%)

Initial Antipsychotic IM Haloperidol Other IM Antipsychotics Oral SGAs P

298 (76.8) 31 (8.0) 59 (15.2)

Age (mean±SD) (y) 37.4±12.6 37.8±13.4 37.5±13.4 0.98
Male 175 (58.7) 22 (71.0) 45 (76.3) 0.02*
Ethnicity† 0.73
White 26 (16.4) 3 (21.4) 4 (13.3)
Black 48 (30.2) 4 (28.6) 10 (33.3)
Hispanic 68 (42.8) 5 (35.7) 12 (40.0)
Asian 15 (9.4) 1 (7.1) 2 (6.7)
Other 2 (1.3) 1 (7.1) 2 (6.7)
BMI (mean±SD) 25.9±6.0 31.4±9.2 27.0±6.9 <0.01‡
Diagnosis§
Unspecified psychotic disorder 214 (72.3) 18 (58.1) 40 (67.8) 0.23
Unspecified mood disorder 31 (10.5) 4 (12.9) 5 (8.5) 0.80
Schizophrenia 49 (16.6) 3 (9.7) 23 (39.0) <0.01*
Schizoaffective disorder 8 (2.7) 2 (6.5) 1 (1.7) 0.33
Bipolar disorder 57 (19.3) 8 (25.8) 7 (11.9) 0.23
Major depressive disorder 0 1 (3.2) 1 (1.7) 0.05
Alcohol-induced disorder 7 (2.4) 3 (9.7) 0 0.04*
Substance-induced disorder 105 (35.5) 6 (19.4) 19 (32.2) 0.19
Comorbid conditions
Type 2 diabetes 19 (6.4) 1 (3.2) 3 (5.1) 0.93
Hypertension 16 (5.4) 4 (12.9) 7 (11.9) 0.06
Hyperlipidemia 2 (0.7) 1 (3.2) 0 0.28
Cardiovascular disease 2 (0.7) 0 1 (1.7) 0.55
Seizures 12 (4.0) 0 5 (8.5) 0.18

*The χ2 or Fisher exact test.

†Data available for 159, 14, and 30 individuals in the groups initially treated with IM haloperidol, other IM antipsychotics, and
oral SGAs, respectively.
‡Kruskal-Wallis test.
§Percentages in the IM haloperidol group are based on available data for 296 individuals.
BMI indicates body mass index; IM, intramuscular; PO, oral.

longer mean time to repeat use, 20.1±18.4 hours,
although this interval was not statistically different
from that found for the other antipsychotic groups
(P=0.35, Fig. 1). Patients who were initially treated
with oral SGAs spent less time in the ED (22.6
±28.0 h) than those who were in the groups initially
treated with IM haloperidol and other IM anti-
psychotics (29.7±28.7 h and 30.3±36.7 h, respec-
tively, P=0.038). One patient who received IM
chlorpromazine as initial antipsychotic was
excluded from analyses involving mean time to
repeat use and LOS because an ED stay of 29 days
and time to repeat medication of 28 days were
recorded, neither of which could be verified. Com-
pared with those who did not receive repeat medi-
cation, patients who required repeat medication in
general stayed in the ED longer (Fig. 2). However,
the difference in mean time spent in the ED among
repeat and nonrepeat users was 29.8, 48.6, and 3.0
hours for the 3 groups IM haloperidol, other IM
antipsychotics, and oral SGAs, respectively. These
differences reached statistical significance for the
IM haloperidol and other IM antipsychotics groups,
but not for the oral SGA group. This finding sug-
gests that, even when repeat use is necessary for
patients who were initially administered an oral

454 November 2016 Journal of Psychiatric Practice Vol. 22, No. 6

Copyright © 2016 Wolters Kluwer Health, Inc. All rights reserved.

 ANTIPSYCHOTIC SELECTION FOR ACUTE AGITATION
FIGURE 1. Mean time to repeat use for
medication to control agitation.
45
40
35
30
25
Hours
20
20.1
15
15.1 14.7
10
5
0
IM HALOPERIDOL (N=98) IM OTHER (N=10) ORAL SGAS (N=14)
The initial use of intramuscular (IM) haloperidol was
associated with a longer time to repeat use compared with
the initial use of other IM antipsychotics (IM other) and oral
second-generation antipsychotics (oral SGAs). Differences in
mean time to repeat use between these 3 groups were not
statistically significant using the Kruskal-Wallis test
(P=0.35).
SGA, the total time spent in the ED is not sig-
nificantly changed. Of note, 69% (n=266) of the 388
cases did not require repeat use of any medication
for acute agitation.
DISCUSSION
This retrospective study highlights the potential
impact of the medication selected to treat acute
agitation on time to repeat medication and the
relationship to boarding time in a psychiatric ED.
The specific goals of this study were chosen based
on clinical questions raised by the director of psy-
chiatric emergency services at the study site. The
director expressed interest in collecting data on
drug selection and time to repeat medication for
acute agitation to better inform treatment
decisions.
In our study, over a 2-month period, 31% of cases
(n=122) required a repeat medication, with mean
time to repeat use ranging from ~14 to 20 hours.
These results are comparable with those reported in
a study involving a psychiatric ED in Spain after
administration of oral olanzapine.28 In contrast,
twice the rate of repeat medication use was
Journal of Psychiatric Practice Vol. 22, No. 6
Copyright © 2016 Wolters Kluwer Health, Inc. All rights reserved.
FIGURE 2. Length of stay in the Psychiatric
Emergency Department among repeat and
nonrepeat users.
120
Repeat user
100
Non-repeat user
80
*P=<0.001
Hours
60
62.7
49.8
40
20 24.9
20 21.9
14.1
0
IM HALOPERIDOL* IM OTHER* ORAL SGAS
Patients who were initially treated with IM antipsychotics
and then required repeat medication for their agitation had
significantly longer lengths of stay than those who did not
require repeat medication, on the basis of the Wilcoxon-
Mann-Whitney test. There was no significant change in
boarding time when repeat administration was necessary for
patients who initially received oral SGAs. IM indicates
intramuscular; SGAs, second-generation antipsychotics.
reported in an Australian ED (68%) in which 48%
(n=21) of repeat users required their second
administration within 1 hour after the initial drug
was administered, which was commonly a benzo-
diazepine.18 This result differs substantially from
our findings in which only 3 cases (2.5%) required
repeat use within an hour (data not shown). The
higher rates of benzodiazepine use, higher rates of
repeat medication use, and shorter time to repeat
use in the Australian study likely reflects the more
limited sample, which included only cases involving
behavioral code activations in which patients com-
monly presented with aggression, threat to others,
or deliberate self-harm, and differences in guide-
lines on the management of acute agitation at the
time of the study. Moreover, the lack of statistical
differences in mean time to repeat use among our
antipsychotic groups adds to the growing literature
indicating that oral SGAs are comparable in effec-
tiveness to IM antipsychotics when treating acute
agitation.
Although the predominant use of the FGA IM
haloperidol along with coadministered lorazepam
November 2016 455
 ANTIPSYCHOTIC SELECTION FOR ACUTE AGITATION
and diphenhydramine is consistent with previous
research, we found an even higher rate of use of IM
FGAs and lower rates of oral SGA use in our psy-
chiatric ED than in the study in 2 large university-
affiliated EDs by Wilson et al17 described in the
introduction. This finding could be explained by the
more narrow inclusion criteria used in our study,
which examined only acutely agitated patients
admitted to a psychiatric ED where oral medi-
cations are more likely to be refused. However, even
when oral agents are not an option, expert con-
sensus statements still advocate for the use of IM
SGAs over IM FGAs when agitation is secondary to
an underlying psychiatric disorder.13 At our study
site, IM aripiprazole is not on the formulary and IM
ziprasidone is restricted as a second-line agent after
an IM haloperidol-diphenhydramine-lorazepam
cocktail. IM olanzapine is also restricted to patients
intolerant to haloperidol and at risk for QTc pro-
longation with ziprasidone. Thus, formulary
restrictions may limit the feasibility of the practice
outlined by the expert consensus statements.
The safety of combined administration of benzo-
diazepines and SGAs is understudied and warrants
attention. Combined use of a benzodiazepine with
all antipsychotic groups seems to be a common
strategy for managing acute agitation and was
found at higher frequencies in our study than in the
Wilson et al17 study in the 2 large EDs. Surpris-
ingly, 60% of patients administered IM chlorpro-
mazine (n=21) were also given IM lorazepam.
Chlorpromazine is a highly sedating low-potency
FGA with a risk of orthostatic hypotension that
increases with dose and when combined with ben-
zodiazepines. The average dose of IM chlorproma-
zine administered (77 mg) was also higher than the
usual dosing range of 25 to 50 mg.29 Although safety
outcomes of this practice were not evaluated in our
study, it is recommended that the lowest effective
dose necessary to control agitation be used and that
a combination of IM chlorpromazine and benzodia-
zepines be avoided to reduce the risk of over-
sedation and orthostatic hypotension.
The components that affect LOS in the ED are
dynamic and multifactorial. This study evaluated
differences in LOS in the psychiatric ED among the
subgroups of repeat users and nonrepeat users in
each antipsychotic group. Overall, the differences
found in LOS suggest that, when repeat admin-
istration of medication is necessary, the use of an
456 November 2016
Copyright © 2016 Wolters Kluwer Health, Inc. All rights reserved.
oral SGA does not significantly contribute to the
total time spent in the psychiatric ED. It is rea-
sonable that oral SGAs resulted in more time spent
in an arousable state allowing emergency clinicians
to perform the timely and thorough psychiatric
evaluations that are necessary for planning dis-
positions.13,14,28 However, it remains unclear
whether an IM haloperidol group alone, without
coadministered medications, would have similar
outcomes or differ from other antipsychotic groups
in metrics related to LOS. Furthermore, the lack of
any clinically significant variation in LOS within a
subgroup when stratified by BMI suggests that BMI
did not have an impact on LOS despite our obser-
vation that initial haloperidol IM users had a lower
average BMI. Also, given the observed sex differ-
ences among the antipsychotic groups, we eval-
uated what impact sex differences might have had
on LOS. Surprisingly, the females in the IM hal-
operidol group had an LOS that was 3 times longer
than the males in that group. This difference was
largely accounted for by female patients who did not
receive repeat medication; their boarding times
were 2.3 times longer than the female patients in
the group that did receive repeat medications and
5.6 times longer than the male patients in the group
that did not receive repeat medications. It is possi-
ble that the females had higher levels of anti-
psychotics compared with the males due to sex dif-
ferences in pharmacokinetics of antipsychotics
independent of organ function.30 There was not
convincing evidence of altered clearance due to
hepatic or renal dysfunction in our sample because
no trends in lab abnormalities were observed. This
pharmacokinetic difference coupled with combined
administration of IM haloperidol with lorazepam
and diphenhydramine places females at greater
risk for oversedation and extended LOS. Sex dif-
ferences in LOS in the groups that initially received
other IM antipsychotics and oral SGAs were clin-
ically insignificant. Another consideration that
might account for sex differences in ED boarding
time involves availability of female versus male
inpatient beds, although this seems an unlikely
explanation given that the sex differences in
boarding time were unique to female nonrepeat
users in the IM haloperidol group. Patients with
extended boarding times secondary to delays in
inpatient bed availability may be more likely to
receive repeat medications because of the severity
Journal of Psychiatric Practice Vol. 22, No. 6
 ANTIPSYCHOTIC SELECTION FOR ACUTE AGITATION
of their illness. Patients with lower severity of ill-
ness and/or who have greater intact psychosocial
support are better candidates for disposition back to
the community. Overall, these factors are part of
the clinicians’ decision-making process for an ED
disposition and reflect heterogenous groups. Future
research should consider these factors and explore
differences in treatment of agitation in the psychi-
atric ED and LOS by sex and disposition.
Although widely used, antipsychotics are not
recommended in every case of agitation. First, using
antipsychotics when insufficient medical informa-
tion is available is a cause for concern due to the
risk of QTc prolongation.31 The etiology or source of
the agitation should also be considered; for exam-
ple, antipsychotics are not recommended for agi-
tation due to alcohol withdrawal or stimulant
intoxication,13 and only FGAs are recommended for
agitation in the setting of alcohol intoxication due to
the less established safety of SGAs and the risk that
IM olanzapine or ziprasidone might lower these
patients’ oxygen saturation.13,32,33
LIMITATIONS
Several limitations should be considered when
interpreting these results. This study was approved
for a duration of 6 months at a single site; but
manual data extraction from the electronic health
record was feasible for only 2 months. Hence, this
sample may not be representative of the entire
population served by the study site. Because this
psychiatric ED operates 24 hours per day and
7 days per week, patients could arrive at any time
but the impact of these variables on outcomes was
not addressed. This chart review relied on doc-
umentation by providers to accurately record agi-
tation and patient histories, and standardized rat-
ing scales of agitation were not used or recorded.
The study design also creates challenges in
addressing confounding factors that might influence
initial antipsychotic selection and other study
findings such as prescriber’s preference, severity of
patients’ illness, use of scheduled medications
including antipsychotics, antihistamines, and ben-
zodiazepines, missed opportunities for a repeat use
of medication due to an early discharge or transfer,
and lack of metrics to measure the alertness of
patients throughout the patients’ stay in the psy-
chiatric ED. Overcoming these limitations in future
Journal of Psychiatric Practice Vol. 22, No. 6
Copyright © 2016 Wolters Kluwer Health, Inc. All rights reserved.
research would enhance and clarify our knowledge
about the impact of medications on variable out-
comes in the psychiatric ED.
CONCLUSIONS
In 77% of the cases examined in this study, IM
haloperidol was the initial antipsychotic selected to
treat acute agitation. Thus, IM haloperidol con-
tinues to be a highly utilized agent in the psychiatric
ED. No significant differences in mean time to
repeat use of medication to control acute agitation
were found among the groups initially treated with
IM haloperidol, other IM antipsychotics, or oral
SGAs. Longer LOS in the ED was associated with
the use of IM antipsychotics—both FGAs and SGAs
—especially when combined with lorazepam or
diphenhydramine, and when repeat use of medi-
cations was necessary. However, LOS was not sig-
nificantly increased when repeat medication was
necessary for patients who were initially treated
with oral SGAs. Our findings suggest that initial
antipsychotic selection to treat acute agitation may
contribute to patients’ LOS in the ED and provide
support for the practice of giving oral antipsychotics
to treat acute agitation when necessary in patients
who are willing to take them.
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