Journal of the Formosan Medical Association (2015) 114, 438e445

Available online at www.sciencedirect.com

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journal homepage: www.jfma-online.com

ORIGINAL ARTICLE

Intramuscular olanzapine versus

intramuscular haloperidol plus lorazepam
for the treatment of acute schizophrenia
with agitation: An open-label, randomized
controlled trial
Charles Lung-Cheng Huang a,b,g, Tzung-Jeng Hwang c,*,g,
Yi-Hsing Chen d, Guan-Hua Huang e, Ming H. Hsieh c,
Hsiu-Hsi Chen f, Hai-Gwo Hwu c
a

Department of Psychiatry, Chi-Mei Medical Center, Tainan, Taiwan

Department of Social Worker, Chia Nan University of Pharmacy and Science, Tainan, Taiwan
c
Department of Psychiatry, National Taiwan University Hospital and Collage of Medicine,
National Taiwan University, Taipei, Taiwan
d
Department of Psychiatry, Chang Bing Show Chwan Memorial Hospital, Changhua County, Taiwan
e
Institute of Statistics, National Chiao Tung University, Hsinchu, Taiwan
f
Division of Biostatistics, Graduate Institute of Epidemiology and Preventive Medicine,
College of Public Health, National Taiwan University, Taipei, Taiwan
b

Received 7 October 2014; received in revised form 24 January 2015; accepted 29 January 2015

KEYWORDS
agitation;
haloperidol;
injection;
lorazepam;
olanzapine;
schizophrenia

Background/Purpose: To compare the efficacy and safety profile between intramuscular (IM)
olanzapine and IM haloperidol plus IM lorazepam in acute schizophrenic patients with moderate to severe agitation.
Methods: This was a prospective, randomized, open-label study. Acutely agitated patients
with schizophrenia or schizoaffective disorder (n Z 67) were randomized to receive 10 mg
IM olanzapine (n Z 37) or 5 mg IM haloperidol plus 2 mg IM lorazepam (n Z 30). Agitation
was measured with Positive and Negative Syndrome Scale Excited Component (PANSS-EC)
and AgitationeCalmness Evaluation Scale (ACES) during the first 2 hours and at 24 hours after
the first injection. Safety was assessed using the SimpsoneAngus Scale and Barnes Akathisia

Conflicts of interest: Dr. Tzung-Jeng Hwang has received honoraria for continuous medical education from Pfizer, AstraZeneca, and
Otsuka Taiwan, and served on an advisory board for dementia research from Eli Lilly and Company. The other authors declare no financial
relationships relevant to the subject of this article.
* Corresponding author. Department of Psychiatry, National Taiwan University Hospital, Number 7 Chung-Shan South Road, Taipei 10002,
Taiwan.
E-mail address: tjhwang@ntu.edu.tw (T.-J. Hwang).
g
These authors contributed equally as first authors to this work.
http://dx.doi.org/10.1016/j.jfma.2015.01.018
0929-6646/Copyright 2015, Elsevier Taiwan LLC & Formosan Medical Association. All rights reserved.

Intramuscular olanzapine for acute schizophrenia

439

Rating Scale and by recording adverse events at 24 hours following the first injection. The Clinical Global Impression-Severity scale was also rated.
Results: The PANSS-EC scores decreased significantly at 2 hours after the first injection in both
groups (olanzapine:
10.2, p < 0.001; haloperidol lorazepam:
9.9, p < 0.001). Haloperidol
plus lorazepam was not inferior to olanzapine in reducing agitation at 2 hours. There were no
significant differences in PANSS-EC or ACES scores between the two groups within 2 hours
following the first injection. The frequencies of adverse events and changes in Clinical Global
Impression-Severity, SimpsoneAngus Scale, and Barnes Akathisia Rating Scale scores from
baseline to 24 hours showed no significant differences between the groups.
Conclusion: The findings suggest that IM haloperidol (5 mg) plus lorazepam (2 mg) is not inferior to IM olanzapine (10 mg) in the treatment of acute schizophrenic patients with moderate
to severe agitation (ClinialTrials.gov identifier number NCT00797277).
Copyright 2015, Elsevier Taiwan LLC & Formosan Medical Association. All rights reserved.

Introduction
Schizophrenia is a disorder with a complex course.1 Acute
agitation is common in the course of schizophrenia and may
be accompanied by destructive and/or violent behaviors.2,3
Rapid tranquilization with preferred intramuscular (IM)
formulations of psychotropic medications is usually warranted under such circumstances.4e7 Traditionally, the
most common approach of rapid tranquilization is
concomitant
administration
of
haloperidol
and
lorazepam.8e10 However, there have been concerns over
the potential adverse effects of acute dystonia and extrapyramidal symptoms with antipsychotics, and sedation,
confusion, and respiratory depression with benzodiazepines.4,11 A combination approach was initially proposed to
minimize the likelihood of producing extrapyramidal effects and minimizing the need for additional doses of
haloperidol.12,13 However, it increases the risks of the side
effects of two agents compared with one.4 As a result of the
reported improved tolerability profiles of atypical antipsychotics, it has been suggested that a parenteral atypical
antipsychotic formulation would represent a significant
advance in the treatment of acute agitation.11,14
More recently, data from randomized clinical trials have
shown that IM olanzapine is safe and effective in reducing
acute agitation in patients with schizophrenia,15e18 bipolar
mania,19 and dementia.20 In the management of agitation,
IM olanzapine has been reported to be comparable to IM
haloperidol monotherapy in schizophrenia,15,17,18 superior
to IM lorazepam monotherapy in bipolar mania,19 and
comparable to IM lorazepam monotherapy in dementia.20
Preliminary evidence has demonstrated that IM olanzapine is associated with fewer adverse movement disorders
than monotherapy with IM haloperidol.15,17,18 Based on
currently available data with regard to parenteral therapy
in acute agitation, an expert consensus panel has endorsed
second-generation antipsychotic monotherapy (e.g., olanzapine) or the combination of a benzodiazepine and a firstgeneration antipsychotic (e.g., haloperidol) for the treatment of behavioral emergencies in patients with
schizophrenia.21
However, most of the previous randomized controlled
studies of IM olanzapine in schizophrenia were sponsored by a

pharmaceutical company, and only compared IM olanzapine

with IM haloperidol, although such patients are frequently
treated with a combination of IM haloperidol and lorazepam
injection in clinical practice.15,17,18,22 Moreover, the
schizophrenia patients in previous randomized studies15,17,18
were usually mildly to moderately agitated as demonstrated
by the baseline Positive and Negative Syndrome Scale Excited
Component (PANSS-EC) scores. To determine the most
appropriate use of this expensive agent, additional studies
comparing IM olanzapine and combination therapy with an
antipsychotic plus benzodiazepine injection in more severely
agitated patients are needed.18,23 The aim of this study,
therefore, was to compare the efficacy and safety profile
between IM olanzapine and IM haloperidol plus IM lorazepam
in acute schizophrenic patients with moderate to severe
agitation. We hypothesized that IM haloperidol plus lorazepam would be noninferior to IM olanzapine in terms of the
PANSS-EC change at 2 hours.

Methods
This study was a prospective, randomized, parallel trial
comparing IM olanzapine and IM haloperidol plus IM lorazepam in three acute psychiatric inpatient units [National
Taiwan University Hospital (NTUH) and its Yun-Lin branch
hospital, Yu-Li Psychiatric Hospital] in a 24-hour treatment
period. It was conducted from September 2006 to February
2009, and was performed in accordance with the principles
of the Declaration of Helsinki and Good Clinical Practice.
The study protocol was approved by the institutional review
board of each participating center, and all participants
provided informed consent. There was no commercial
funding for this study; however, Eli Lilly and Company
(Taipei, Taiwan) supplied the injectable olanzapine medication. The study is registered at ClinialTrials.gov identifier
number NCT00797277.

Patients
Recently hospitalized patients who were 18e65 years old
and who had been clinically diagnosed by the study investigators as having schizophrenia or schizoaffective

440
disorder (according to the Diagnostic and Statistical Manual
of Mental Disorders, 4th Edition)24 were recruited. In order
to enroll patients with different degrees of agitation, the
patients signed informed consent forms for this trial and for
admission on the day of admission after the study procedure had been fully explained to them. However, they were
only enrolled into the study when their clinical condition
fulfilled the enrollment criteria as specified below.
The inclusion criteria included: (1) having a total score
of  14 (of a maximum of 35) on the PANSS-EC, which
comprises five items: tension, uncooperativeness, hostility,
poor impulse control, and excitement; (2) having a score of
 4 (of a maximum of 7) on at least one of these five items;
and (3) being acutely agitated to the extent that parenteral
antipsychotic therapy was indicated.
The exclusion criteria included: (1) women who were
pregnant or lactating; (2) patients with severe medical illnesses; (3) patients who had received injectable depot
antipsychotics within 1 month; (4) patients who had used
psychostimulants or reserpine within 1 week; (5) patients
who had received newly added oral or IM benzodiazepines
within 4 hours; (6) patients who had received newly added
oral or rapid-acting IM antipsychotics within 2 hours; and (7)
patients with a history of allergic reaction or intolerance to
the study medication(s).

C.L.-C. Huang et al.

Anticholinergic medication was permitted for newly emergent extrapyramidal symptoms, but not for prophylactic
use.
Experienced clinical staff were trained to handle and
administer injections according to the randomization code.
To ensure adequate reliability among raters, joint evaluations of six agitated patients (2 with mild agitation and 4
moderate to severe agitation) between the principal
investigator (T.-J.H.) and other raters were conducted
before the study commenced. The ratings were compared
and discrepancies discussed until a consensus was reached.
After a series of six patients, > 80% of agreement among
raters was achieved. In terms of efficacy and safety
assessment, ratings were completed by one psychiatrist in
two centers, and by two attending psychiatrists in the third
center. All raters were not blinded to the medications. To
further minimize bias in rating, each unblinded psychiatrist
completed the ratings together with the respective
attending nurse who observed the patients condition most
closely.

Efficacy assessments

Treatment assignments were based on a computergenerated random number list created by the central office prior to the start of the study. The central office prepared consecutively numbered, sealed, identical opaque
envelopes with a randomization code inside according to
the random number list. The envelope and relevant questionnaires and rating scales for each participant were
placed together in a folder. These folders were then sent to
the three study sites where the clinical staff performed the
study according to the order found inside the sealed envelopes. By concealment of allocation, selection bias could
be avoided. The random number list and randomization
codes were kept from the clinical staff until the end of the
data analysis of the study.

Patients were assessed by the study investigators at the

screening visit and at 15 minutes, 30 minutes, 60 minutes,
and 120 minutes after the first injection. The primary efficacy measure was PANSS-EC, which was derived from the
PANSS by its originators using a principal-components factor
analysis, and includes the items of tension, uncooperativeness, hostility, poor impulse control, and excitement.25,26 The score of each item ranges from 1 (normal) to
7 (most severe), with a total sum score ranging from 5 to
35. Agitation was further assessed by the AgitationeCalmness Evaluation Scale (ACES) (Copyright 1998), a single-item
scale developed by Eli Lilly and Company, where
1 Z marked agitation; 2 Z moderate agitation; 3 Z mild
agitation; 4 Z normal; 5 Z mild calmness; 6 Z moderate
calmness; 7 Z marked calmness; 8 Z deep sleep; and
9 Z unable to be aroused. The Clinical Global ImpressionSeverity27 (CGI-S) scale was used to assess the general
psychiatric condition. For each patient, the same rater
conducted the assessment throughout the study.

Procedures

Safety assessments

This study consisted of a screening phase and a 24-hour

treatment phase. Following screening, the patients who
fulfilled the inclusion and exclusion criteria were randomly
allocated to treatment with IM olanzapine or IM haloperidol
plus lorazepam. The dose of haloperidol plus lorazepam
was based on the prevailing clinical practice,8e10 whereas
the dose of olanzapine was determined according to the
published literature.15e18 The patients could receive a
maximum of three injections within the 24-hour period.
Second and third injections were prescribed at the discretion of the clinical investigators. A second injection was
allowed after 2 hours had elapsed since the first injection.
A third injection was allowed after 4 hours had passed since
the second injection. Prohibited medications included antiarrhythmics, antipsychotics, antidepressants, anticonvulsants, antiemetics, and other psychotropic drugs.

During the 24-hour treatment period, safety was assessed

by clinical examination, recording spontaneously reported
adverse events, and completing the SimpsoneAngus Scale28
(SAS) and Barnes Akathisia Rating Scale.29

Randomization and allocation concealment

Statistical analysis
The efficacy analyses were based on the intent to treat
population defined as all of the randomized patients. The
last observation carried forward dataset was used to estimate the missing data. Demographic characteristics and
clinical parameters at baseline were compared by the
treatment group using the t test for continuous variables
and Chi-square test for categorical variables. The primary
endpoint was the change in PANSS-EC score 2 hours after
the first injection, and the secondary endpoints included

Intramuscular olanzapine for acute schizophrenia

441

change in ACES score 2 hours after the first injection, and

change in PANSS-EC, ACES, and CGI-S scores 24 hours after
the first injection. For the primary endpoint, the lower limit
of noninferiority was defined a priori as 40% of the observed
mean change from baseline to 2 hours following the first
olanzapine injection. A lower boundary of the one-sided
97.5% confidence interval of zero or less but greater than
the lower limit indicated no between-treatment difference
and noninferiority, i.e., haloperidol plus lorazepam was not
inferior to olanzapine. Within-group comparison was performed using paired t test. Responder was defined as those
with at least 40% reduction from baseline on the PANSS-EC
at 2 hours. To compare the number of differences in
adverse events and response rate between the two treatment groups, Fishers exact test was used. Data were
analyzed using the statistical program R Language version
2.8.0 (http://www.r-project.org/).

NTUH Yun-Lin branch, 21; Yu-Li Psychiatric Hospital, 40)

were entered into the randomization phase. The patient
flow is shown in Fig. 1. The main reasons for exclusion were
did not sign informed consent and having received
recent depot injections or newly added benzodiazepines or
antipsychotics. Another 180 patients did not enter the
randomization phase because of inadequate severity of
agitation as judged by the raters. The 67 patients, including
58 individuals with schizophrenia and nine with schizoaffective disorder, were randomized to the two treatment
groups (37 in the olanzapine group, 30 in the haloperidol
plus lorazepam group), and they all completed the trial.
Overall, the patients were moderately to severely agitated
(mean PANSS-EC score: 21.4  4.2). There were no significant between-group differences in sex, age, age of onset,
length of current psychotic episode, or baseline PANSS-EC
score (Table 1).

Results

Efficacy

Demographic characteristics and clinical

parameters at baseline

In terms of primary endpoint, the PANSS-EC scores decreased

significantly at 2 hours following the first injection in both
groups (olanzapine: e10.2  6.5, t Z 9.750, p < 0.001;
haloperidol lorazepam: e9.9  5.6, t Z 9.900, p < 0.001).
The difference between haloperidol plus lorazepam and

A total of 294 patients received an initial assessment after

acute admission. After exclusion, 67 patients (NTUH, 6;

Figure 1

Summary of participant flow.

442

C.L.-C. Huang et al.

Table 1

Demographic characteristics and clinical parameters at baseline.

Characteristic

Olanzapine 10 mg
(n Z 37)

Haloperidol 5 mg lorazepam
2 mg (n Z 30)

Male/female
Mean age (y)
Age of onset (y)
Length of current psychotic episode (d)
PANSS-EC scorea

22/15
37.1  10.8
22.3  9.1
20.4  28.1
21.1  4.4
(range 14e32)
2.0  0.6
(range 1e3)

19/11
41.3  11.3
19.3  3.8
49.0  13.4
20.9  3.6
(range 15e29)
2.1  0.7
(range 1e4)

0.750
0.127
0.075
0.274
0.783

ACES scoreb
a
b

0.327

Positive and Negative Syndrome Scale-Excited Component; five-term scale, with a maximum total score of 35.
AgitationeCalmness Evaluation Scale; one-item scale, with a range of 1e9.

olanzapine was 0.3 units favoring olanzapine (with one-sided

lower 97.5% confidence limit Z
3); therefore noninferiority (
3 vs.
10.2  0.4 Z
4.1) could be concluded.
Regarding sedative effect, the ACES scores increased
significantly at 2 hours in both groups (olanzapine: 2.1  1.7,
t Z 7.225, p < 0.001; haloperidol lorazepam: 2.2  1.7,
p < 0.001). There were no significant differences in PANSSEC or ACES scores between the two groups at 15 minutes,
30 minutes, 60 minutes, and 120 minutes following the first
injection (Figs. 2 and 3), although the olanzapine group
tended to have faster action in the 1st hour after the first
injection. The percentage of responder (defined as at least
40% reduction from baseline on the PANSS-EC at 2 hours)
was not significantly different between the two groups
[19 (51%) in the olanzapine group vs. 11 (37%) in the

haloperidol lorazepam group; Fishers exact test,

p Z 0.323]. The percentage of participants with ACES of 8 or
9 was also not significantly different between the two groups
[3 (8%) in the olanzapine group vs. 4 (13%) in the
haloperidol lorazepam group; Fishers exact test,
p Z 0.692]. The changes in CGI-S and PANSS-EC from baseline to 24 hours after the first injection showed no significant
difference between the two groups (Table 2). Five patients
(13.5%) received a second injection, and two patients (5.4%)
received a third injection in the olanzapine group, whereas
in the haloperidol plus lorazepam group, five (16.7%) patients received a second injection, and no participant
received a third injection. However, the injection frequencies between the two groups were not significantly
different.

Figure 2 Changes in Positive and Negative Syndrome Scale

Excited Component (PANSS-EC) score within 2 hours after the
first injection. There were no significant differences in PANSSEC scores between the two groups at 15 minutes, 30 minutes,
60 minutes, and 120 minutes following the first injection.

Figure 3 Change in AgitationeCalmness Evaluation Scale

(ACES) score within 2 hours after the first injection. There were
no significant differences in ACES scores between the two
groups at 15 minutes, 30 minutes, 60 minutes, and 120 minutes
following the first injection.

Intramuscular olanzapine for acute schizophrenia

443

Table 2 Comparisons of mean changes in PANSS-EC, ACES, CGI, SAS, and BARS from baseline to 24 hours after the first
injection.
Haloperidol 5 mg lorazepam 2 mg

Olanzapine
Score at baseline
PANSS-EC
ACES
CGI-S
SAS
BARS

21.1
2.0
5.0
13.4
2.4







4.4
0.6
0.8
4.3
2.7

Score at 24 h
12.0
3.2
4.2
13.0
1.6







4.9
0.9
0.8
3.8
2.3

Paired difference

Score at baseline

9.2  5.4
1.2  0.9

0.8  0.6

0.4  1.3

0.8  1.7

20.9
2.1
5.2
13.9
2.1







3.6
0.7
0.7
5.5
2.5

Score at 24 h
12.7
3.5
4.4
13.2
1.6







4.0
0.9
0.9
3.8
2.3

pa

Paired difference

8.1  3.1
1.3  1.0

0.8  0.7

0.6  2.8

0.6  2.1

0.450
0.393
0.896
0.765
0.551

ACES Z Agitation Calmness Evaluation Scale; BARS Z Barnes Akathisia Rating Scale; CGI-S Z Clinical Global ImpressionsdSeverity of
Illness; PANSS-EC Z Positive and Negative Syndrome Scale-Excited Component; SAS Z SimpsoneAngus Scale.
a
p value for comparing paired differences between two treatment groups, adjusting for centers.

Adverse effects
The changes in SAS and Barnes Akathisia Rating Scale scores
from baseline to 24 hours after the first injection showed no
significant differences between the two groups (Table 2).
The incidences of adverse reactions were also not significantly different between the two groups (Table 3). However, acute dystonia only occurred in the haloperidol plus
lorazepam group.

Discussion
To the best of our knowledge, this study is the first randomized controlled trial in a Chinese population comparing
IM olanzapine with a frequently used combination of IM
haloperidol plus IM lorazepam in the treatment of acute
schizophrenia with moderate to severe agitation. The results showed that 5 mg IM haloperidol plus 2 mg IM lorazepam were not inferior to 10 mg IM olanzapine for the
treatment of acute agitation, as revealed by the changes in
the PANSS-EC scores within and at 2 hours after the first
injection. Furthermore, the treatment regimens demonstrated similar efficacy as measured by injection frequency
and the changes in CGI-S score from baseline to 24 hours
after the first injection.
In previous studies comparing with 7.5 mg IM haloperidol
in the treatment of acute agitation of schizophrenia, 10 mg
IM olanzapine repeatedly showed a more rapid reduction in

Table 3

the PANSS-EC score within the 1st hour after the initial injection, but the difference became smaller at 2
hours.15,17,22,30 Similar phenomena were observed in the
treatment of agitated patients with dementia or mania
when IM olanzapine was compared with IM lorazepam.19,20
Thus, one interesting clinical question would be how efficacious and fast-acting it would be when 10 mg IM olanzapine is compared with 5 mg IM haloperidol plus 2 mg
lorazepam. Our data showed that there was still a trend of
a slightly faster action of IM olanzapine treatment as
observed by the changes in the PANSS-EC scores within 1
hour after the first injection. However, the differences did
not reach statistical significance and became nearly zero at
2 hours after the first injection, suggesting that IM olanzapine may have faster action, but IM haloperidol plus lorazepam are not inferior at 2 hours following the first
injection (Fig. 2). A study comparing 10 mg IM olanzapine
with 5 mg IM haloperidol plus 15 mg midazolam in the
treatment of agitated psychiatric patients also showed that
olanzapine had a more rapid action in the first 2 hours after
the initial intervention.31 However, the effect may be
related to the dosage chosen. If a lower dose of olanzapine
is chosen for comparison, the difference between the two
groups may be less.17
In terms of calming effect (as measured by the ACES),
although our study did not show significant between-group
differences during the first 2 hours or at the end of 24
hours, IM olanzapine seemed to have slightly faster action
in the 1st hour; however, IM haloperidol plus lorazepam

Incidence of treatment emergent adverse events.

Primary term

Olanzapine 10 mg
(n Z 37)

Haloperidol 5 mg lorazepam
2 mg (n Z 30)

All adverse events

Dizziness
Drowsiness
Malaise
Nausea
Palpitation
Anxiety
Headache
Acute dystonia
Restlessness

9
1
3
1
1
1
1
0
0
1

10
2
5
0
0
0
0
1
1
1

>
>
>
>

>

0.430
0.583
0.451
0.99
0.99
0.99
0.99
0.448
0.448
0.99

444
caught up 2 hours after the initial injection (Fig. 3). The
findings were compatible with those of recent studies
comparing 10 mg IM olanzapine with 2.5e5 mg IM haloperidol plus 7.5e15 mg midazolam.31,32 Furthermore, our
study showed these two treatments both demonstrated an
acceptable calming effect without too much sedation in the
first 2 hours after injection.
Although our study found no significant differences in
adverse events between the two groups at the end of 24
hours (Table 3), their profiles were slightly different. For
example, acute dystonia only occurred in the haloperidol
plus lorazepam group (1 of 30 patients, 3.3%), and the
figure was lower than 4.0e7.1% reported in association with
IM 7.5 mg haloperidol in previous studies.15,17,22 Moreover,
there seemed to be a higher incidence of dizziness/
drowsiness in the haloperidol plus lorazepam group. By
contrast, only one patient in the olanzapine group reported
palpitations. Previous studies have demonstrated that,
compared with IM haloperidol, olanzapine causes a lower
degree of dystonia and parkinsonism, but a greater degree
of hypotension.15,17,18 Compared with IM lorazepam, olanzapine has been reported to cause a similar incidence of
somnolence and dizziness.19,20 When haloperidol is combined with lorazepam, the additional effects of benzodiazepines may allow for a lower incidence of acute dystonia;
however, the potential risk of synergistic sedative effects
may be raised.12,13
There are several limitations to this study. First, this is
an open-label trial, so some bias may have been introduced
into the evaluation process. We tried to avoid this by rater
training and joint evaluation by the attending physician and
nursing specialist. Furthermore, the rating of the primary
outcome was behavior-based rather than interview-based,
thus minimizing subjective bias. Second, there was no
placebo group, although the efficacy of these drugs has
already been proven, which cannot be explained by a placebo effect. Third, our sample size may not be large
enough to have adequate power to detect differences between the two treatment regimens. Fourth, the severity of
agitation of the 180 excluded patients was based on the
raters clinical judgment rather than formal rating using the
PANSS-EC scale; thus, some of them might have been
qualified for enrollment if they had received formal ratings.
However, this would not significantly bias the results
because we adopted a randomization procedure in this
study. Further research needs to be undertaken with welldesigned, double-blind, placebo-controlled studies with a
larger sample size to provide more evidence for the efficacy
and safety of these treatment regimens.

Acknowledgments
The study was supported by a grant from Mr Ya-Jen Chengs
Foundation, Taipei, Taiwan. The preparation of this
manuscript was supported by a grant from National Science
Council (97-2314-B-002-129-MY3). We are grateful to Dr YiFang Chuang and Ms Shuang-Sui Chen for their help in the
data collection of this study, Eli Lilly and Company for
supplying short-acting injectable olanzapine, and Dr Susan
Shur-Fen Gau for her comments on this paper. The authors
also acknowledge statistical assistance provided by the

C.L.-C. Huang et al.

Taiwan Clinical Trial Bioinformatics and Statistical Center,
Training Center, and Pharmacogenomics Laboratory (which
was founded by the National Research Program for Biopharmaceuticals at the Ministry of Science and Technology
of Taiwan; MOST 103-2325-B-002-033).

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