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The acutely agitated patient
Brian Levine, MD
Program Director
Emergency Medicine Residency
Christiana Care Health System
Department of Emergency Medicine
Associate Professor of Emergency Medicine
Jefferson Medical College
Objectives
To
update healthcare providers regarding current
issues in the acute psychiatric setting, including
Historical use of pharmacotherapy in the acute psychiatric
setting
 Predictors of involuntary return to acute psychiatric services and
increasing frequency of acute psychiatric events
 Importance of initial assessment for development of a treatment
plan
 Treatment guidelines and considerations in acute psychiatric
settings and ongoing care
 Benefits of early intervention

Overview
Definition
of an acute psychiatric event
Historical
use of pharmacotherapy and restraint in
the acute psychiatric setting
Predictors
and frequency of presentation to acute
psychiatric settings


Medication nonadherence
Diagnoses associated with acute psychiatric events
Initial
assessment during an acute psychiatric event
Treatment guidelines and considerations during
acute agitation
Definition and Historical Use of
Interventions During an Acute
Psychiatric Event
Defining an Acute Psychiatric
Event
An
acute disturbance of thought, mood, behavior, or
social relationship that requires an immediate
intervention as defined by the patient, family, or
community
A set of circumstances in which the
Behavior or condition of an individual is perceived by someone,
often not the identified individual, as having the potential to
rapidly eventuate in a catastrophic outcome
 Resources available to understand and deal with the situation are
not available at the time and place of the occurrence

APA. Report and Recommendations Regarding Psychiatric Emergency and Crisis Services. Arlington, VA: APA;
2002.
Historical Use of Pharmacotherapy
Sedative use was widespread
and nonspecific aimed at
controlling disturbed behavior
whatever the cause1,2
Introduction of
antipsychotics to treat
psychosis and acute
mental disorders3
Sedation is increasingly
considered an adverse effect that
should be avoided especially
when treating disorders such as
anxiety or depression4
Antiquity
1800
Ethanol,
opium tinctures,
and herbals2
1850
1900
Bromide2
Barbiturates2
1950
2000
Benzodiazapines2
Chlorpromazine3
1. Lader M. Introduction to Psychopharmacology. London, UK: SCOPE; 1983:56; 2. Adapted from Charney DS,
Mihic SJ, Harris RA. Hypnotics and Sedatives. In: Eds. Hardman JG, Limbird LE. Goodman & Gilman’s: The
Pharmacologic Basis of Therapeutics. New York, NY: McGraw-Hill; 2001:400; 3. López-Muñoz F et al. Ann Clin
Psychiatry. 2005;17:113-135; 4. Bourin M, Briley M. Hum Psychopharmacol Clin Exp. 2004;19:135-139.
Historical Use of Restraint During
an Acute Psychiatric Event
Management
policies in psychiatry began minimizing
the use of restraint by the 1940s1
In 1998, estimates of 50 to 150 deaths per year by
restraint or seclusion in the US2
Use of restraint is an extraordinary practice and should
only be considered as a last resort when2,3
All less restrictive measures have failed3
 Severely aggressive or destructive behavior places the patient or
others in immediate danger3

1. Lader M. Introduction to Psychopharmacology. London, UK: SCOPE; 1983:8.
2. Currier GW, Allen MH. Psychiatr Serv. 2000;51:717-719.
3. Allen MH et al. Postgrad Med. May 2001;(Spec No):1-88.
Predictors, Frequency, and
Diagnoses Associated With
Acute Psychiatric Events
Estimated Annual
Hospitalization Rates (%)
Medication Nonadherence Is Associated
With Higher Hospitalization Rates in
Patients With Schizophrenia
40
Psychiatric
Medical
35
30
†
25
20
*
15
10
*
5
0
‡
Nonadherent
Partially
Adherent
Adherent
Excess Filler
N=2801 patient years among Medicaid beneficiaries with schizophrenia.
*P<.001 vs nonadherent and excess filler groups.
†P<.001 vs adherent group.
‡Excess filling of medications may occur due to actual overuse or loss/theft of medications.
Adapted from Gilmer TP et al. Am J Psychiatry. 2004;161:692-699.
Patients Reporting
Barrier (%)
Barriers to Medication Adherence in
Patients With Schizophrenia
50
45
40
35
30
25
20
15
10
5
0
Modified from Hudson TJ et al. J Clin Psychiatry. 2004;65:211-216.
Involuntary Return to the Acute
Psychiatric Setting
29%
of patients treated in the acute psychiatric setting
returned within 12 months
Primary predictors of an involuntary return to the
acute psychiatric setting included patients who were
Psychotic (increased likelihood of return by 241%)
 Deemed more dangerous
 Deemed less treatable

Involuntary
returnees and nonreturnees did not differ
in age, gender, racial composition, or their substance
abuse involvement
N=417 patients admitted due to an acute psychiatric event; 66% of patients presented with a psychotic
diagnosis (56% of those had a schizophrenic condition, 22% had an affective disorder, 22% had another
psychotic condition), and 33% had a condition complicated by substance abuse.
Segal SP et al. Soc Work Health Care. 2002;1/2:591-603.
Increased Frequency of Emergency
Department Visits Due to Psychosis
Emergency Department
Visits Due To Psychosis
Acute psychiatric events represent 5.4% (~4.3 million)
of total ED visits, which has increased by 15%*
2000 Values
1992 Values
0
10
20
Percent
*National probability sample of adults comparing rates in 1992 vs 2000.
26% patients seen for neuroses in the ED.
ED=emergency department.
Hazlett SB et al. Acad Emerg Medicine. 2004;11:193-195.
30
Incidence (%)
Diagnoses of Schizophrenia and Psychosis
Account for Majority of Involuntary Admissions to
a Psychiatric Unit
50
45
40
35
30
25
20
15
10
5
0
48
N=1755*
16.8
8.4
8.9
6.5
4.4
3
3.2
d
S
O
ic
er
ia
on
D/ O
man
mixe
ty D/
essi
s NO
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hren
i
i
i
r
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p
s
O
O
d
p
a
/
/
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D
D
e
a
h
i
o
D
t
c
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h
s
e
e
n
y
r
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n
S
ta
Ps
Pe
me
cti v
cti v
subs
an i c
r af fe
r af fe
e
g
a
a
l
l
r
v
i
o
o
t
O
Bip
Bip
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0.9
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Ot he
*Study included 2200 consecutive admissions to an intensive psychiatric treatment unit of a university
hospital over an 18-month period; 34.5% admissions represented multiple admissions to the unit.
D/O=disorder; NOS=not otherwise specified.
Adapted from Sanguineti VR et al. Am J Psychiatry. 1996;153:392-396.
Who is agitated?






Anyone who waits a while to get seen in the ED!
Hx of psychiatric problems: BPD, personality
disorders, psychotics, mania
drugs/alcohol/intoxication/withdrawal
medical (sepsis, hypoxia, med rxn)
fighting with the law
Well known that sudden cardiac death can occur
in healthy patient who are struggling and never
received tranquilization
Altered MS (to the EP)

Infection
meningitis/encephalitis
 sepsis
 UTI/pneumonia


Toxic
drugs (including ETOH and withdrawal)
 Environmental exposure (CO)

Altered MS

Metabolic
electrolyte (Na, Ca)
 endocrine (glycemia, adrenal, thyroid)
 hepatic encephalopathy
 uremia
 environmental (hypothermia)


Hypoxia

CHF, PE, COPD
Altered MS

Cerebrovascular
trauma (SDH)
 CVA
 CNS vasculitis
 HTN encephalopathy


CNS - other trauma
space occupying lesions
 seizures and postictal states

Altered MS

Psychiatric

Severe depression

Functional psychosis

schizophrenia
Assessment Is Key to Appropriate
Intervention
Effective
and appropriate treatments are based on
accurate, relevant diagnostic and clinical assessments1
Initial
assessment clearly plays a key role in selecting
the most appropriate intervention during an acute
psychiatric event2
During
an acute psychiatric event, reductions in
symptoms without sedation allow the patient to
participate in further assessment and treatment3
1. APA. Practice Guideline for the Treatment of Patients With Schizophrenia. 2nd ed. Arlington, VA: APA; 2004.
2. Allen MH et al. Postgrad Med. May 2001;(Spec No):1-88.
3. Allen MH et al. J Psychiatr Pract. 2005;11(suppl 1):5-108.
Calming Versus Sedating
During an Acute Psychiatric Event
 Time-limited
sedation may be preferred in situations where
there is no pharmacologic treatment for the underlying disorder1
 Calming
the patient rather than sedating them may be the
appropriate end point of interventions for acute psychiatric
events1
 These
recommendations from the Treatment of Behavioral
Emergencies Expert Consensus Guideline (2005) are consistent
with the Clinical Guideline on Schizophrenia from the National
Institute for Clinical Excellence (NICE) in the United
Kingdom2
1. Allen MH et al. J Psychiatr Pract. 2005;11(suppl 1):5-108.
2. National Institute for Health and Clinical Excellence (NICE). Clinical Guideline 1: Schizophrenia: Core
interventions in the treatment and management of schizophrenia in primary and secondary care. London:
National Institute for Clinical Excellence; December 2002.
APA Treatment Guidelines for Patients
With Schizophrenia and Bipolar Disorder
Schizophrenia1
 Prevent harm
 Control disturbed behavior
 Reduce the severity of psychosis and
associated symptoms
 Formulate short- and long-term
treatment plans
 Develop an alliance with the patient and
family
 Effect a rapid return to the best level of
functioning
 Connect the patient with appropriate
aftercare in the community
Bipolar Disorder2
 Rapid control of agitation,
aggression, and impulsivity
 Ensure the safety of patients and
those around them
 Stabilization of the acute episode
 Achieve remission

Defined as a complete return to
baseline level of functioning and a
virtual lack of symptoms
Strategies with a narrow focus that determine short-term outcomes may do
so at the cost of relationship issues that influence long-term outcomes3
1. APA. Practice Guideline for the Treatment of Patients With Schizophrenia. 2nd ed. Arlington, VA: APA; 2004.
2. APA. Am J Psychiatry. 2002;159(suppl 4):1-50.
3. Allen MH et al. Postgrad Med. May 2001;(Spec No):1-88.
Our role



Protect the patient from harm
Protect the staff from the patient
Select the appropriate mechanism for restraint
talk them down (occasionally works)
 physical
 chemical


Determine the etiology (“medically clear”)
Chemical Restraints

The EP must think carefully about every
medicine we order and give:
indications
 side-effects
 toxicities
 medical hx of pt
 drug interactions

Considerations When Choosing
an Antipsychotic Following Diagnosis
Patient’s
Prior Treatment
Response
Adverse
Effects of
Medications
General
Medical
Problems
Patient
Preferences
Optimal
Clinical
Management
Short-term
Goals
Favorable
Long-term
Outcomes
Modified from Allen MH et al. Postgrad Med. May 2001;(Spec No):1-88; APA. Practice Guideline for the
Treatment of Patients With Schizophrenia. 2nd ed. Arlington, VA: APA; 2004.
Considerations When Choosing an
Antipsychotic
Some important factors to consider1
Speed
of onset
Reliability
Patient
of delivery
preference
Interactions
with other medications
Overarching treatment plans should serve
the patient's short- and long-term needs2
1. Allen MH et al. J Psychiatr Pract. 2005;11(suppl 1):5-108.
2. APA. Practice Guideline for the Treatment of Patients With Schizophrenia. 2nd ed. Arlington, VA: APA; 2004.
Benzodiazepines

Ativan (lorezepam), Valium (diazepam) and
Versed (midazalam) are the only three we
basically use
fast onset (minutes)
 effective sedation
 few side-effects (can get hypotension/resp
depression)
 can be titrated/combined/IM/IV

Haloperidol





Butyrophenone (like poor old Droperidol)
titratable (2mg or 5mg increments)
often combined with Ativan for synergism (911)
works in 15-30min, can last an hour or two
dopamine blocker - leading to side effects

extrapyramidal (dystonia, akisthisia, anticholinergic
effects, Parkinsonism, cardiovascular- Tordsades,
hypotension)
Thus the search….





For a quality antipsychotic agent with sedating
qualities for use in the ED
need easy route of administration for the acutely
agitated/psychotic agent (IM or IV)
few side effects
few interactions
predictable
Atypical antipsychotics


Fewer adverse effects than haloperidol
comparable QTc at max concentrations




no significant cardiac toxicity
Effects seen within 25 min (8-12); lasts 4 hours
minimal drug interactions
For ED use: olanzapine (Zyprexa), ziprazadone
(Geodon), aripiprazole (Abilify), asenapine
(Saphris)
Study 050:
ABILIFY Injection Rapidly Controls
Agitation in Schizophrenia
Time After First Intramuscular (IM) Injection (min)
0
15
30
45
60
75
90
105
120
PANSS™-EC
*P.05 vs placebo
-1
Improvement
Mean Change
in PANSS™-EC Score
0
-2
-3
-4
-5
*
-6
-7
-8
*
*
*
*
*
*
*
Significant reduction of agitation at
primary endpoint (2 hours) vs placebo
Placebo (n=62)
ABILIFY 5.25 mg (n=63)
*
*
*
*
*
ABILIFY 9.75 mg (n=57)
*
*
*

Uncooperativeness

Poor impulse control

Hostility

Excitement

Tension
**
Haloperidol 7.5 mg (n=60)
ABILIFY 15 mg (n=58)
Baseline scores ranged between 18.84 and 19.45.
LOCF=last observation carried forward.
PANSS™-EC=Positive and Negative Syndrome Scale–Excited Component.
Daniel D et al. Presented at: 157th Annual Meeting of the American Psychiatric Association;
May 1-6, 2004; New York, NY.
Please see IMPORTANT SAFETY INFORMATION, including Boxed WARNING,
and INDICATIONS for ABILIFY (aripiprazole) on slides 25-31.
Long-Term Stabilization Begins With Acute
Management of Psychiatric Events
Acute Episode
Symptoms
Increasing Stability
Prolonged Stability
Time
Adapted from APA. Practice Guideline for the Treatment of Patients With Schizophrenia. 2nd ed. Arlington, VA:
APA; 2004.
Your ED, 0330





A disheveled, combative patient is thrown
onto the stretcher in CT-2 by PD and the
constables.
He’s fighting the police, screaming, kicking;
he has a cut on his lip and is spitting blood at
anyone who gets near.
He bit a chunk out of the arm of a constable
at triage.
He’s singing Creed’s “With Arms Wide
Open” and screaming that he’s Jesus Christ.
What do you do? What do you order?
Does your order change if:






He’s a known PCP user?
He’s a known schizophrenic?
He’s a known alcoholic?
He’s a 75 year-old man?
He’s a 14 year-old?
Did you ever wonder if there was
any method to your madness?

me neither
Agitated/Combative Patients in
the ER



What medications are best
for safe, effective, quick
sedation?
Are there different
populations where different
drugs should be used?
What evidence (if any)
exists in the literature?

Yes, we’re talking about
psych literature.


Archives of General Psychiatry, May 2002
Study objective:



To determine if Olanzapine (Zyprexa) will demonstrate a dose
dependant decrease in agitation
To compare efficacy to haloperidol (Haldol) and placebo
Patient population:


Hospitalized patients 18 and older, clinically diagnosed with
schizophrenia, schizophreniform disorder, or schizoaffective
disorder.
Acutely agitated, but “not so agitated that they were unable to
provide written consent or cooperate with the requirements of the
study.”
Methods

270 patients randomized
to:






IM olanzapine 2.5mg IM
IM olanzapine 5.0mg IM
IM olanzapine 7.5mg IM
IM olanzapine 10mg IM
IM haloperidol 7.5mg IM
IM placebo

Conducted at:

4 sites in Croatia


1 site in Italy


3 patients
3 sites in Romania


69 patients
82 patients
6 sites in South Africa

116 patients
Results


There was a statistically significant
dose-dependant improvement in
agitation when compared with placebo.
There was no significant difference
when compared with haloperidol.



Most common side effect encountered
was hypotension in each group.
Zero cases of dystonia in olanzapine
group



Higher doses of olanzapine trended
towards better agitation control.
2/40 haloperidol patients
No incidence of QTc prolongation
greater than 500 milliseconds in any
group
Conclusion:

Olanzapine has a dose-dependant
sedative effect, is safe to use, and may
be safer than haloperidol.
Limitations

Sponsored by Eli Lilly



Multi-center, multi-country
study
Additional benzodiazepine
administration allowed in all
groups



Olanzapine IM was not yet
FDA approved in US
Noted in article that there
was no difference of use in
any group except placebo,
data not reported
Low numbers in all groups
Patients had to be calm
enough to sign consent


Journal of Clinical Psychopharmacology, February 2004
Study Objective:


To examine the effect on QTc of six commonly used antipsychotic
agents
Patient population:



Patients aged 18-59 years who required chronic treatment of a
psychotic disorder
Patients had not had an exacerbation of psychosis in the past 3
months
Multiple exclusion criteria:

BMI limits, resting heart rate, substance abuse, use of other medications within the
past 3 months, congenital long QT, pregnant, smoking more than 40 cigarettes per
day, unable to give written informed consent
Methods/Results


Prospective, randomized,
parallel-group study
Drugs studied:


Haloperidol, Ziprasadone,
Quetiapine, Olanzapine,
Risperidone, Thioridazine
300 patients screened


183 randomized
164 completed the study



7 discontinued due to adverse
drug events (not QTc related)
12 for “other reasons”
Conclusion:

No clinically significant
prolongation of QTc in any
group

Heart rate increased in all
groups
Limitations






Lead author works for Pfizer
(Geodon)
Not powered to determine
differences between agents
Small numbers per group
Not blinded
About 10% of patients
dropped out of the study,
some for unknown reasons
For our purposes, not exactly
what we want


Psychopharmacology, June 2001
Study objective:


To compare ziprasidone IM 2mg and 20mg in the acute
control and short-term management of agitated psychotic
patients
Patient population:


Admitted patients over the age of 18 who had acute agitation
in association with either schizophrenia, schioaffective
disorder, bipolar disorder with psychotic features or “another
psychotic disorder”
Excluded if ETOH or substance positive (except marijuana or
benzodiazepines), suicidal, unable to give written consent,
pregnant, EKG abnormalities
Methods/Results


Prospective, randomized, doubleblinded study
99 patients screened



Fewer patients in the 20mg cohort
required more than two doses
Statistically significant decrease in
agitation in both groups




79 patients randomized to 2mg IM or
20mg IM
20mg cohort significantly better than
2mg
Only ADE was a priapism that
resolved spontaneously (2mg)
No significant QTc change
Conclusion:

Ziprasadone is an effective, safe agent
for sedation of an agitated patient with
psychosis.
Limitations




No comparisons to other
treatment modalities
Only studied the calm,
cooperative psychotic
patient
Sponsored by Pfizer
Small numbers
But what about the kids?


Journal of American Academic Child and Adolescent Psychiatry,
February 2008
Study Objective:



To review the current literature and develop guidelines for emergency medicine
use
Review article focused on medication use and dosage
(No official guidelines exist for this population)

2006 ACEP recommendations:


No Level A recommendations
Level B:





Use a benzodiazepine (lorazepam or midazolam) or a conventional antipsychotic
(haloperidol or droperidol) as effective monotherapy in the acutely agitated
undifferentiated patient in the ED.
If rapid sedation required, use droperidol instead of haloperidol.
Use an antipsychotic (typical or atypical) as effective monotherapy for both
management of agitation and initial drug therapy for the patient with known
psychiatric illness.
Use a combination of oral benzodiazepine and an oral antipsychotic for agitated but
cooperative patients.
Level C:

The combination of a parenteral benzodiazepine and haloperidol may produce more
rapid sedation than monotherapy in the acutely agitated psychiatric patient in the
ED.
What about Droperidol?


Droperidol is a butyrophenone antipsychotic;
antiemetic effect is a result of blockade of
dopamine stimulation of the chemoreceptor
trigger zone
Other effects include alpha-adrenergic blockade,
peripheral vascular dilation, and reduction of the
pressor effect of epinephrine resulting in
hypotension and decreased peripheral vascular
resistance; may also reduce pulmonary artery
pressure
What about Droperidol?






Dose
1.25-2.5 mg IV/IM
Uses
Antiemetic, agitation, migraine/headache
Administration
Rate no faster than 2.5 mg /min
What about Droperidol?

Monitor

Blood pressure, respiration and EKG
Adverse Reactions











Cardiovascular: cardiac arrest, hypertension, hypotension (especially orthostatic), QTc prolongation (dose dependent), tachycardia, torsade de pointes,
ventricular tachycardia
Central nervous system: Anxiety, chills, depression (postoperative, transient), dizziness, drowsiness (postoperative) increased, dysphoria, extrapyramidal
symptoms (akathisia, dystonia, oculogyric crisis), hallucinations (postoperative), hyperactivity, neuroleptic malignant syndrome (NMS) (rare),
restlessness
Respiratory: Bronchospasm, laryngospasm
Miscellaneous: Anaphylaxis, shivering
Precautions
[U.S. Boxed Warning]: Cases of QT prolongation and torsade de pointes, including some fatal cases, have been reported. Use extreme caution in
patients with bradycardia (<50 bpm), cardiac disease, concurrent MAO inhibitor therapy, Class I and Class III antiarrhythmics or other drugs known to
prolong QT interval, and electrolyte disturbances (hypokalemia or hypomagnesemia), including concomitant drugs which may alter electrolytes (diuretics).
May cause anticholinergic effects (constipation, xerostomia, blurred vision, urinary retention)
May cause extrapyramidal symptoms (pseudoparkinsonism, acute dystonic reactions, akathisia, tardive dyskinesia). Risk of dystonia (and possibly other
EPS) may be greater with increased doses
Neuroleptic malignant syndrome
Orthostatic hypotension
Sedation
What about Droperidol?

Pharmacodynamics/kinetics
Onset: 3-10 mins (peak effect ~30 min)
 Duration 2-4 hours


Patients require continuous EKG
monitoring for at least three hours after the
drug is administered
What about Ketamine?

The Combative Multi-Trauma Patient: A
Protocol for Prehospital Management




Melamed E, et al, Euro J Emerg Med 2007;14(5):265
Israel, 11 patients – access to Ketamine and
benzos, retrospective
Traumatic injuries – mean time almost 2 hours
Successful in all attempts
Ketamine






“the safest anesthetic in the world”
“the lights are on and nobody’s home”
dissociates cortical activity from the brainstem
rather than depressing CNS function:
sedative/analgesic
VS maintained, airway reflexes intact
increase BP, pulse
weak bronchodilator
Ketamine (con’t)

IM: 4-5mg/kg


IV: 1-2mg/kg



onset 5 minutes, lasts 30-45 min (can take over 1 hour for
recovery)
onset 1 minute, lasts 20-30 minutes
can titrate with an additional dose
Most studies show same effects on discharge,
satisfaction. AVOID IV?
Ketamine: adverse effects
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Increased oral/bronchial secretions
emergence effect = nightmares, greatest under the age
of 5 – 22% vs 12%
N, V (5-10%-most at home), ↑ICP
laryngospasm: rare, may need a minute of bagging
(<1%)
Bronchorrhea: atropine recommended for under 5yo
Abnormal gait up to 1/3
Roving eyes, The Exorcist
Ketamine for adults
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Some literature support
people fear emergence reactions
adjunctive sedation controls/prevents
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versed
Most studies show for children, versed adds
NOTHING, except added sedation
Contraindications to Ketamine
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<3 months
pulmonary/tracheal disease
significant CAD
Glaucoma/globe injury (↑IOP)
psychiatric illness?
recently ate?
Summary
 Acute
psychiatric events include disturbances of thought,
mood, behavior, or social relationship that require an immediate
intervention
 Treatment nonadherence and psychotic symptoms are
predictors of future psychiatric hospitalizations
 Calming the patient rather than sedating them may be the
appropriate end point of interventions for acute psychiatric
events
 Acute treatment should attempt to return the patient to the best
level of functioning while considering the long-term treatment
goals of the patient and caregiver
 Choice of therapy is complex and involves numerous factors
 Clinical judgment, early intervention, and maintenance
treatment may help prevent relapse
References
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Breier A. et al. A double-blind, placebo-controlled dose-response comparison of intramuscular olanzapine
and haloperidol in the treatment of acute agitation in schizophrenia. Archives of General Psychiatry.
59(5):441-8, 2002 May.
Harrigan EP. et al. A randomized evaluation of the effects of six antipsychotic agents on QTc, in the
absence and presence of metabolic inhibition. Journal of Clinical Psychopharmacology. 24(1):62-9, 2004
Feb.
Nobay F. et al. A prospective, double-blind, randomized trial of midazolam versus haloperidol versus
lorazepam in the chemical restraint of violent and severely agitated patients. Academic Emergency
Medicine. 11(7):744-9, 2004 Jul.
MacDonald K. et al. A retrospective analysis of intramuscular haloperidol and intramuscular olanzapine in
the treatment of agitation in drug- and alcohol-using patients. General Hospital Psychiatry. 32(4):443-5,
2010 Jul-Aug.
Daniel DG. et al. Intramuscular (IM) ziprasidone 20 mg is effective in reducing acute agitation associated
with psychosis: a double-blind, randomized trial. Psychopharmacology. 155(2):128-34, 2001 May.
Wilson, MP. et al. A Comparison of the Safety of Olanzapine and Haloperidol in Combination with
Benzodiazepines in Emergency Department Patients with Acute Agitation. The Journal of Emergency
Medicine. 5(1): 1-8, 2011 Jan.
Baldacara, L. et al. Rapid Tranquilization for Agitated Patients in Emergency Psychiatric Rooms: A
Randomized Trial of Olanzapine, Ziprasadone, Haloperidol plus Promethazine, Haloperidol plus
Midazolam and Haloperidol Alone. Brazilian Review of Psychiatry. 33(1): 30-9. 2011 Mar.
Hilt, RJ, Woodward, TA. Agitation Treatment for Pediatric Emergency Patients. The Journal of American
Academic Child Adolescent Psychiatry. 47(2): 132-8. 2008 Feb.
Lukens, TW. et al. Clinical Policy: Critical Issues in the Diagnosis and Management of the Adult Psychiatric
Patient in the Emergency Department. Annals of Emergency Medicine. 47(1): 79-99. 2006 Jan.
Questions?