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Progress in Neuro-Psychopharmacology & Biological Psychiatry 30 (2006) 586 – 598
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Review article
Managing the aggressive and violent patient in the psychiatric emergency
Paola Rocca a,⁎, Vincenzo Villari b , Filippo Bogetto a
a
b
Department of Neuroscience, Unit of Psychiatry, University of Turin, via Cherasco 11, 10126 Turin, Italy
Emergency Department, Psychiatric Emergency Service, S. Giovanni Hospital, Corso Bramante 88, 10 126 Turin, Italy
Accepted 30 January 2006
Available online 6 March 2006
Abstract
Throughout history most societies have assumed a link between mental disorders and violence. Although the majority of users of mental health
services are not violent, it is clear that a small yet significant minority are violent in inpatient settings and in the community. The assessment of a
violent patient may be very difficult due to the lack of a full medical and psychiatric history and the non-cooperativeness of the patient. Thus a full
assessment is important for the early decisions that the clinician has to take in a very quick and effective way. The primary task and the short term
outcome in a behavioral emergency is to act as soon as possible to stop the violence from escalating and to find the quickest way to keep the
patient's agitation and violence under control with the maximum of safety for everybody and using the less severe effective intervention. The
pharmacological treatment of acute, persisting and repetitive aggression is a serious problem for other patients and staff members. Currently, there
is no medication approved by the Food and Drug Administration (FDA) for the treatment of aggression. Based on rather limited evidence, a wide
variety of medications for the pharmacological treatment of acute aggression has been recommended: typical and atypical antipsychotics and
benzodiazepines.
© 2006 Elsevier Inc. All rights reserved.
Keywords: Aggression; Antipsychotics; Benzodiazepines; Psychiatric emergency; Violence
Contents
1.
2.
3.
4.
Introduction . . . . . . . . . . . . . . . . .
Assessment . . . . . . . . . . . . . . . . .
2.1. Diagnostic assessment . . . . . . . .
2.2. Violence risk assessment . . . . . . .
Clinical management . . . . . . . . . . . .
3.1. Non-coercive interventions . . . . . .
3.2. Patient–therapist relationship . . . . .
3.3. Coercive interventions . . . . . . . .
3.4. Show of force . . . . . . . . . . . .
3.5. Involuntary medications and chemical
3.6. Physical restraint and seclusion . . .
Treatment of acute aggression and violence .
4.1. Rapid tranquillisation. . . . . . . . .
4.2. Typical antipsychotics . . . . . . . .
4.3. Atypical antipsychotics . . . . . . . .
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Abbreviations: BPSD, Behavioral and psychological symptoms of dementia; ECA, Epidemiological Catchement Area; FDA, Food and Drug Administration;
GABA, γ-Aminobutyric acid; MOAS, Modified overt aggression scale; OAS, Overt aggression scale; PET, Positron Emission Tomography; PTSD, Posttraumatic
stress disorder; PANSS, Positive and Negative Syndrome Scale; PANSS-EC, Positive and Negative Syndrome Scale Excited component; SCL-90, Self-report
symptom inventory.
⁎ Corresponding author. Tel.: +39 011 6634848; fax: +39 011 673473.
E-mail address: [email protected] (P. Rocca).
0278-5846/$ - see front matter © 2006 Elsevier Inc. All rights reserved.
doi:10.1016/j.pnpbp.2006.01.015
P. Rocca et al. / Progress in Neuro-Psychopharmacology & Biological Psychiatry 30 (2006) 586–598
4.4. Benzodiazepines . .
5. Management of aggressive
6. Conclusion . . . . . . . .
References . . . . . . . . . . .
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1. Introduction
Aggression and violence have various meanings. Aggression
may be defined as an intentional act that inflicts physical or
mental harm on somebody. Some studies have referred to
violence as an aggressive act that causes physical injury; for
others it has to be associated to both verbal and physical
aggression (Barratt et al., 1997; Filley et al., 2001; Moeller et
al., 2001). In this paper, we adopted the Webster Dictionary
(1993) definitions. Violence is “the exertion of any physical
force so as to injure or abuse; an instance of violent treatment or
procedure; injury in the form of revoking, repudation,
distortion, infringement or irreverence to a thing, notion or
quality filthy valued or observed” (Webster Dictionary, 1993).
The focus is mainly on acts and on interactions between two or
more people, thus we use the expressions violence, violent and
aggressive behavior as synonymous. Violence is not always
physically acted, because also a mental attitude, an interpersonal relationship or an institution can be violent (ethically,
morally, etc.).
Aggression has a broader meaning that goes from “an
offensive action or procedure” to “a form of psychobiological
energy either innate or arising in response to or intensified by
frustration” (Webster Dictionary, 1993). Often this drive does
not produce an open form of violence but can be transformed by
high mental processes, such as introjection and sublimation, and
become something useful for the individual and socially
accepted like compete for career or playing sports. In a recent
review on qualitatively distinct subtypes of human aggression
the dichotomy between impulsive–reactive–hostile–affective
subtype and a controlled–proactive–instrumental–predatory
subtype has emerged as the most promising construct (Vitiello
and Stoff, 1997).
In a traditional categorical approach aggression and violence
are not a diagnostic entity although they are present as
symptoms in many mental disorders. That is way they have a
transnosographical meaning. On the other hand in many studies
and meta-analysis (Lindenmayer et al., 2004; Akiskal et al.,
2003) the factor analysis of data allows to describe the
dimension aggression–violence. This is very useful in the
research field to address new studies and in clinic to target the
management and the pharmacological treatment of patients.
Although clinicians prefer to assess the patients through the
unstructured clinical observation (Allen et al., 2001) the use of
rating scales can be helpful to better measure and document the
aggression and the violent behavior. There are many specific
tools ideated for this purpose. The most used in research are
self-assessment scales, like the Buss Durkee Hostility-Inventory
(Buss and Durkee, 1957) and the Self-report symptom
inventory 90 (SCL 90) Anger–Hostility Subscale (Derogatis
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et al., 1970), good to assess aggression in fully cooperative
people. Of course with violent and uncooperative real patients
observer rating scales are needed. They can be specially tailored
for this purpose or sub-scales derived by component of general
scales. The most used are: Overt Aggression Scale (OAS)
(Yudofsky et al., 1986), Modified Overt Aggression Scale
(MOAS) (Kay et al., 1988), PANSS Excited Component Score
(PANSS-EC) (Kay et al., 1987; Lindenmayer et al., 2004).
Aggressive and violent symptoms vary from threatening
behavior and agitation to assault and can be seen in patients with
the following diagnoses: organic psychoses, such as after head
injures, cerebral infections, metabolic diseases, drug intoxication, etc.; personality disorders such as borderline and antisocial
personality disorders; developmental disabilities; dementia;
bipolar affective disorders and schizophrenia, most often during
acute psychosis. Violence is one of the most detrimental factors
in the continued stigmatisation of mental illness.
Several recent large-scale studies have determined that there
is a relationship between mental disorders and violence.
Although the majority of users of mental health services are
not violent, it is clear that a small yet significant minority are
violent in inpatient settings and dangerous for the community
(Swanson et al., 1990; Hiday, 1997).
The rates of violence differ across diagnostic categories,
suggesting that it is essential to examine the diagnostic
condition separately in relationship to the risk of violent
behavior (Swanson et al., 1990; Steadman et al., 1998). An
important study used a sample of 10059 adult residents from
Epidemiologic Catchment Area (ECA) study sites and examined the relationship between violence and psychiatric disorders
(Swanson et al., 1990). Eight percent of those with schizophrenia alone were violent, compared to 2% of those without mental
illness. Comorbidity with substance abuse increased this
percentage to 30%. Another community-based study of
follow-up at 1-year (Steadman et al., 1998) showed that only
17.9% of mentally ill patients without a substance use diagnosis
were violent, which was equal to the rate of violence among
non-mentally ill persons who did not abuse of substances. Rate
rose to 73% in people with mental illness and substance use and
up to 240% if the substance was used by patients with
personality disorders.
A review (Nestor, 2002) examines the relationship of a
greater risk of violence among persons with certain mental
disorders in terms of four fundamental personality dimensions.
Low impulse control and affective regulation was found to
increase the risk of violence across various disorders, especially
for primary and comorbid substance abuse disorders, while
paranoid cognitive personality style and narcissistic injury was
found to increase the risk of violence respectively in
schizophrenia spectrum disorders and personality disorders.
588
P. Rocca et al. / Progress in Neuro-Psychopharmacology & Biological Psychiatry 30 (2006) 586–598
Risk assessment is an inexact science. Ultimately the
decision of risk is based on clinical judgment which should
be made by a multidisciplinary team with all the clinicians
involved in the care, treatment and management of the
individual being assessed. Clinical factors associated to risk
of violence may be identified as targets of potential treatment
and prevention, especially important considering that many, if
not all, mentally disordered violent subjects are seen in
mainstream mental health settings, often a long time before
becoming violent (Taylor et al., 1998).
Aggression and violence are likely to result from a complex
interaction of biologic, psychologic and social variables.
Impulsive, affective aggression may be the product of a failure
of emotion regulation, with a low threshold for activating
negative affect, which includes anger, distress, and agitation,
and with a tendency to act without regard to the consequences of
these actions. Two major functional systems, the limbic system
and the frontal lobes, are thought to be implicated in various
aspects of aggressive and violent behavior. Aggressive behavior
has been thought to arise from the operations of the limbic
system under certain circumstances, and the amygdala is the
structure most often implicated.
Studies of regional glucose metabolism assessed with
Positrin Emission Tomography (PET) reveal that hypoactivation in prefrontal territories as well as hyperactivation in the
amygdala in individuals prone to impulsive aggression and
lesion in orbitofrontal and adjacent prefrontal cortex regions
produce syndromes characterized by impulsivity and aggression
(Davidson et al., 2000; Raine et al., 2000; Filley et al., 2001;
Blair, 2003).
Neurotransmitters, including serotonin, norephinephrin,
dopamine, and γ-aminobutyric acid (GABA), have been
considered in order to explain the origin of aggression and
impulsivity and may be relevant to treatment. Aggression and
impulsivity result from a failure of the balance between
dopamine, with a strong role in activation and the initiation of
behavior, and serotonin with its inhibitory control. Changes in
noradrenergic activity associated with stress or overstimulation
may result in increased impulsivity. The balance between
excitatory (glutamate) and inhibitory (GABA) amino acid
function has an important role in the level of arousal (Davidson
et al., 2000; Lesch and Merschdorf, 2000; Krakowski, 2003;
Swann, 2003).
Pharmachological treatments favouring inhibitory transmission (GABA), enhancing serotonergic activity and reducing
dopamine function, targeting the D2 receptor family, may
influence aggressive behavior. Interventions that combine
pharmacological and psychosocial strategies, which will likely
both operate on the neural circuitry of emotion regulation, may
be optimal in reducing aggressive and violent behavior.
2. Assessment
The assessment of a violent patient could be very difficult
due to the lack of a full medical and psychiatric history and to
the non-cooperativeness of the patient. Thus a full assessment is
important for the early decisions that the clinician has to take in
a very quick and effective way. We can distingue two different steps: the diagnostic assessment and the violence risk
assessment.
2.1. Diagnostic assessment
Violent people are not a homogeneous group and not all
people that have a violent behavior, or even just a violent
ideation, have a mental disorder. We can roughly divide the
violence into cognitive and emotional: the former is usually
more related to a criminal attitude than to mental disorders,
the opposite is for the latter (Petit, 2004). The first aim of a
clinician is to distinguish between these two situations, although the boundary is not always certain. If there is a
reasonable possibility that the behavioral problem is related to
a pathological situation it is needed to perform an initial
diagnostic evaluation, even though some authors found that
the early decisions of clinicians in managing a violent patient
are strongly influenced by symptoms, their severity and speed
of onset, and less by diagnosis (Gerson and Bassuk, 1980). A
well performed medical clearance, too often neglect with this
kind of patients and with all people roughly thought to be
affected by mental disorders, is a key step to select the most
appropriate and etiologically oriented interventions. Otherwise the only possibility is to act a non-specific intervention
in order to control the behavior, as the specific approach and
the most genuine medical contribution to the problem solution
is missing. An important early step is to determine whether
the clinical situation is due to a Substance Related Disorders
or to a General Medical Condition Related Disorders. If
possible, it would be advisable to check the vital signs and
perform a physical examination or at least a visual
examination of patient. Toxicological screening and blood
exams can be useful for the diagnosis of possible general
medical condition underlying the behavioral problem. A
pregnancy test is recommended in order to select the
potentially dangerous treatment.
• Substance Related Disorders (included delirium). It is crucial
to distinguish between drug intoxication and withdrawal. In
the first case alcohol and psychostimulants are the
substances more frequently involved, in the second alcohol
and benzodiazepines are important. This distinction is
essential to target the pharmacological treatment and the
choice of an agonist or antagonist agent.
• General Medical Conditions Related Disorders (included
delirium, dementia and neurological syndromes such as
complex partial seizures and brain temporal, frontal or limbic
lesions). It is important to determine the specific medical
condition related to the behavioral problem in order to target
the therapeutic approach. Very often patients with psychiatric
presentation do not undergo a complete triage and medical
clearance and so it is very common a high prevalence of
unrecognized medical illness causative of the psychiatric
symptoms or even just concomitant. A full assessment of
those medical problems is very important for an effective and
target oriented therapeutic approach.
P. Rocca et al. / Progress in Neuro-Psychopharmacology & Biological Psychiatry 30 (2006) 586–598
• A violent behavior could be due to a mental illness even in
comorbidity with the above listed causes. The potential risk
of harm to others is aspecific and transnosografic and so not
closely linked to the underling diagnosis. Almost any kind of
mental disorder can undergo a life-time episode of violent or
agitated behavior, but some of them are more frequently
involved in such problems and are: first episode psychosis,
chronic schizophrenia with exacerbation, mood disorders,
cluster B personality disorders, panic disorders and other
acute anxiety disorders including Posttraumatic stress
disorder (PTSD).
2.2. Violence risk assessment
The violence risk assessment is important for a clinician
when a final decision has to be made: the risk factors have to be
carefully considered, checked and recorded and the ones that are
likely to be modifiable should be targeted by specific individual
or environmental interventions. Many kind of different
presentations are possible: the overt aggression at the moment
of the visit, the presence of signs of imminent acting, the
declaration of specific will (“I want to kill my neighbour”), the
presence of a peculiar state of mind and feelings (“I feel very
angry, as I wanted to hurt somebody”).
Although violent patients are not a homogeneous group, the
factors associated to violence risk share many common aspects.
A past history of violence is widely considered the best predictor of future risk (Gerson and Bassuk, 1980; Parks, 1990;
Lindenmayer et al., 2002; Buckley et al., 2003; Petit, 2004)
(Table 1).
It is important to make the assessment as soon as possible in
order to stop the behaviors escalate with early interventions. It is
also important not to forget that the interview itself and the first
clinical approach needed to assess the patient could be also the
first step of containment of aggressiveness. Special attention
should be paid to triggers and targets of violence.
A peculiar problem is what to do in order to protect the
potential victims. People affected by mental illness often hurt
family members or other acquaintances. The clinician has to
protect and warn the intended victims and, if an imminent
Table 1
Violence risk assessment
Risk of violence among psychiatric patients has been associated with the
following factors
•Demographic—male, young (15–24 years old), poor, uneducated, unemployed,
minority, no supportive social network
•Past history—early victimization, past violence, substance abuse, early onset,
poor parental model
•Diagnostic—organic brain syndrome (including intoxications), personality
disorder, psychosis, comorbidity with substance abuse
•Clinical features—command auditory hallucinations, paranoid delusions and
suspiciousness, poor impulse control, poor insight and low adherence to
treatment, low IQ score, low GAF score
•Psychological—low tolerance for frustration, criticism and interpersonal
closeness, low self-esteem, tendency toward projection and externalization,
anger, irritability, patient's previous methods of coping with similar stressors,
motivation and capacity to participate in the treatment process
589
violent acting is planned, the police and anyone else that can be
helpful have to be alerted. This is something that can overcome
the patient's confidentiality and is regulated by laws that vary
by different jurisdictions.
3. Clinical management
The primary task and the short term outcome in a behavioral emergency is to act as soon as possible in order to stop
the violence from escalating and to find the quickest way to
keep the patient's agitation and violence under control with
the maximum of safety for everybody and using the less
severe effective intervention. A good start is the first step of
containment, which is itself a part of talk down interventions:
it is important not to forget that an imminent violence can be
triggered very easily even with a therapeutic approach, so first
of all it is necessary to operate cautiously and choose the less
traumatic way to reach the final goal. To this end, there are
multiple steps of talk down interventions and non-coercive
behavioral and environmental treatments. If this kind of
approach is not effective more coercive treatments are needed.
Anyway it must be kept clear in mind that the best intervention is the less coercive and aggressive possible. The
Expert Consensus Guidelines on Treatment of Behavioral
Emergencies consider the following options as appropriate
interventions for an imminently violent patient (in order of
preference among the experts as treatment of choice) (Allen
et al., 2001): Verbal intervention (76%); Voluntary medication
(65%); Show of force (51%); Emergency medication (without
consent) (45%); Offer of food, beverage, or other assistance
(39%); Physical restraints (27%); Locked seclusion (23%);
Unlocked seclusion (quiet room) (21%); Leave the area (4%).
On the other hand the quality of intervention and the
physician–patient relationship is the most important long
term goal and has relevant implications on the treatment plan
and on the course of the illness.
Whatever the chosen interventions are the patient do not
have to be left alone.
3.1. Non-coercive interventions
First verbal approach, clinical interview, talk down interventions, non-coercive behavioral and environmental interventions are all de-escalation techniques (Gerson and Bassuk,
1980; Parks, 1990; Lindenmayer et al., 2002; Rosenberg and
Sulkowicz, 2002) used to stop the violent behavior escalate that
generally comes before a violent acting out.
Non-coercive treatments are based on talk down early
interventions oriented to split the emotional and the motor
aspects of the patient's condition acting as a buffer between
them. Through an “as empathic as possible approach” the
clinician tries to establish a good enough relationship with the
patient aimed to an alliance that makes him feeling to be
understood in emotions and negative feelings and so she or he
can shift and stop the motor component of his violent behavior.
This is a difficult goal that requests trained physicians and
acceptable milieu conditions.
590
P. Rocca et al. / Progress in Neuro-Psychopharmacology & Biological Psychiatry 30 (2006) 586–598
Safety comes first and you have to protect yourself and the
staff, so at the very beginning of the approach it has to be carefully
checked if the patient has any kind of potentially dangerous
objects, including hot beverages and glasses, with whom he can
hurt others: in that case nothing has to be done until he surrenders
these objects, even with the intervention of hospital security guard
or police. You must never interview an armed patient. It can be
helpful to tell him that the hospital is a safe place and no arms are
needed to be protected: it is important to remember that the one
who needs to carry an arm can feel in a state of deep discomfort or
even vulnerable without it.
The setting and the environmental situation influence the
patient's presentation and also the clinician's behavior and
judgement. The emergency room is a busy place and it is not easy
to provide a quiet and safe room in which the patient can be
isolated and evaluated. Any effort should be made to obtain the
most acceptable environmental situation to perform such a
difficult and dangerous task: do not forget that the first approach
can trigger a violent escalation or even an acting out that
represents an immediate risk for all the people involved in the
situation. Generally a violent behavior follows a preliminary
period in which early signs can predict the imminent danger, so
pay attention to: change in speed, tone and contents of speech;
restlessness; signs of tense posture and motor tension such as
clenched fist or jaw; answer to questions with increasing irritable
tone; open envy toward the interviewer. If you think that the
patient is close to loose the control tell him that, if necessary, any
needed intervention will be done to assure his and everybody's
safety. While doing that, be very careful and remain nonconfrontational.
A complete physical examination has to be possibly done
because it is needed for a complete medical and psychiatric
assessment and sometimes can help to reassure and calm the
patient showing him that he is a normal person and has to
undertake the normal medical procedure like everyone else.
If possible the interview has to be long enough to perform a
careful mental state examination and a full violence risk
Table 2
Behavioral and environmental interventions
•Use a room or an area big and calm enough, not isolated to allow others to
come quickly if help is needed.
•You and the patient should be in such a position to allow the both of you to
reach easily the door that must be open.
•Choose an as calm as possible environment without intense stimulations or
triggers.
•The environment must be safe, without objects that can be potentially
dangerous.
•If a suitable room is not available choose an open space.
•Keep distance, do not be too close: the violent patient needs more room than
others. Never approach the patient from behind and in a rough manner.
•Never turn your back to the patient.
•Do not be confrontational, do not look the patient in the eyes, try to assume a
neutral facial expression and voice tone, and a relaxed body posture, better
avoid positions as crossed arms or hands behind the back.
•The patient don't have to be left alone.
•If others represent a trigger for patient's violence ask them to leave the area.
•Give information and support to relatives and significant others.
•Perform a debriefing with the staff and if possible also with the patient.
Table 3
Verbal approach
•Introduce yourself and explain what are you going to do
•Use easy words, short and clear sentences, calm manner
•Use a confidential but formal tone. Pay attention to be tuned
•Help the patient to understand what is happening and reassure him about the
diagnostic and therapeutic procedure he will undertake
•Help the patient to restore the orientation
•Prefer, at least at the beginning, alliance oriented questions and wait for more
delicate issues
•When possible try to talk about the real motivations of the violence
•Set limits of acceptable behavior and tell the patient that violations will not be
allowed
•Encourage the verbal expression of feelings, states of mind, fantasies, also if
violent
•Discourage acting out, make it clear that he or she will be held responsible for
his or her actions
•When you have to communicate your decision do it in a clear and simple way
assessment. Recommendations on Behavioral and Environmental Interventions and on Verbal Approach are listed in Tables 2
and 3.
3.2. Patient–therapist relationship
The relationship with a violent patient is a stressful
experience for the clinician that have to manage the
dangerous behavior of the patient and his own negative
feelings and countertransference aspects (Gerson and Bassuk,
1980; Parks, 1990). No one can face such a difficult situation
without an emotional involvement: the main difference is
related to the clinician's level of experience and awareness of
those emotional reactions and how she or he copes with. A
well-trained and experienced clinician can manage the
situation even if he is disturbed by countertransference feelings such as anger, hostility, hate, fear, etc. He also knows
when to ask for help without embarrassment. Another bias
can derive from the social distance normally existent between
a middle- or upper-class therapist and a lower-class patient. It
is important to keep those aspects under control to avoid that
they would affect the quality of relationship, the reliability of
assessment and the kind of dispositions. It is possible that
therapists would swing between helplessness and omnipotent
positions. The former could lead to the prevalence of strong
negative feelings and emotional coldness with a nihilistic
approach to the problem solution. The latter could lead to
ingenuous ideas about global caring of very difficult
situations and real risk of dangerous violations of therapeutics
boundaries. For these reasons a constant supervision is
requested as well as a clinical discussion, with the direct
involvement of expert clinicians in order to develop a good
enough therapeutic approach, that is realistic and problem
solving oriented. Educational programs are needed especially
with less experienced or less formally trained members of the
staff.
Table 4 presents a list of recommendations useful to check
and manage the emotional quality of the patient–therapist
relationship.
P. Rocca et al. / Progress in Neuro-Psychopharmacology & Biological Psychiatry 30 (2006) 586–598
Table 4
Patient–therapist relationship variables
•Try to make procedures as flexible as possible
•If possible prioritize patient's requests
•Show empathy and talk about the negative aspects of present situation
(“I understand that this is not a good period for you, it seems to me that you
feel bad, you look afraid of something”)
•Engage a therapeutic alliance (“in such a difficult situation you need help,
allow me to help you”)
•Don't lie nor betray the patient's trust
•Do not challenge the patient, do not be confrontational, do not look the patient
in the eyes
•Offer your help to discuss therapeutic aspects of mental disorder
•Give help for problem solving, specially with low copers, give alternatives to
violent behavior
•Evaluate the presence of acute and chronic stressors, specially if active as
violence triggers and related to past violence and victimization
•Give reassurance for present or past paranoid features
•Be careful with gender issues
•If needed give an opportunity for a time out, offer food and beverage, if
possible allow the patient to smoke a cigarette or to make a phone call
3.3. Coercive interventions
In case the non-coercive interventions are ineffective in
stopping the violent behavior from escalating and the patient
becomes combative it is important to act fast and decisively. The
sooner you act, the safer the situation will evolve for everyone.
When a patient has crossed the boundary of allowed behaviors
and there is a real and imminent danger, it is time to act coercive
interventions that are: show of force, involuntary medications
and chemical restrain, physical restraint, seclusion (Allen et al.,
2001).
It is important that the patient really goes over a reasonable
threshold. As said before, it is better try to make procedures as
flexible as possible giving priority to patient's requests: a refuse
to cooperate with routine procedures is not enough to act
coercive interventions that should never be used as punishment
or for the convenience of the staff, but just to limit the patient's
dangerousness.
In order to have the best possible results in terms of safety
and quality of interventions in a way that is respectful of the
rights of patients–keeping an eye to the abuse of medical and
psychiatric social control and police-like power–it is very
important to develop policies and procedures of cooperation
with police and hospital security guards. It is also crucial to have
well experienced and trained staff, set procedures, briefing,
debriefing and stress coping strategies.
3.4. Show of force
It is a sort of last chance to stop the violence from escalating
before acting involuntary interventions. It is important to
perform this last step of de-escalation techniques with a nonchallenging and a non-confrontational approach. Through the
show of force the patient has to realize emotionally that the staff
is still there to help him and is fully able to contain his
destructiveness and to protect all the others. On the other hand
the presence of adequate security forces gives also more
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confidence to the clinician that is responsible of the situation
and has to take the last decision.
3.5. Involuntary medications and chemical restrain
This is an argument that can be seen by different points of
view leading to quite different conclusions. We will discuss two
problems: 1) what is the limit between voluntary and
involuntary treatments? 2) what is the limit between treatment
and chemical restraint?
The Expert Consensus Guidelines on Treatment of Behavioral Emergencies (Allen et al., 2001) consider voluntary “any
dose of oral medication to which a patient assents in an
emergency situation” and “rejected the idea that the situation is
so coercive that any medication must be involuntary even if the
patient appears to accept it”. It can be reasonable to say that in
such a difficult situation as is the one determined by an
imminent violent patient we do not need a fully informed
consent and the assent can be considered sufficient. A more
radical approach could be impossible to apply and dangerous
for anyone involved in the emergency.
Also with regards to chemical restrain there are different
points of view. The Health Care Financing Administration
(Rosenberg and Sulkowicz, 2002) establishes: “A drug used as
a restraint is a medication used to control behavior or to restrict
the patient's freedom of movement and is not a standard
treatment for the patient's medical or psychiatric condition”.
Differently the Joint Commission on Accreditation of Healthcare Organizations (2002) does not accept the idea of chemical
restraint and considers a medication used to calm an agitated or
violent patient as a treatment. The Expert Consensus Guidelines
on Treatment of Behavioral Emergencies (Allen et al., 2001) is
more in agreement with the latter position. A possible mediation
between those two different approaches is offered by the Health
Care Financing Administration (2000): “... it is the process of
prescribing rather than the agent prescribed that distinguishes
treatment from restraint. If a medication is prescribed as part of
an assessment and rational plan of care, whether on a scheduled
or on as-needed basis, it is a treatment. If prescribed simply as a
reaction to the patient's behavior, it is a restraint. Hence the
same medication administered to the same patient might be a
treatment in some circumstances and a restraint in others”.
3.6. Physical restraint and seclusion
The current definitions and limitations given by Joint
Commission on Accreditation of Healthcare Organizations
(2002) are: “Restraint: direct application of physical force to a
patient, with or without the patient's permission, to restrict his o
her freedom of movement. The physical force may be human,
mechanical devices, or a combination thereof. Seclusion:
involuntary confinement of a person alone in a locked room.
The behavioral health care reasons for the use of restraint and
seclusion are primarily to protect the patient against injury to
self or others because of an emotional or behavioral disorder.” If
all above listed less restrictive interventions have been
ineffective, it could be necessary to use the most coercive
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approach as final response to a belligerent person not otherwise
manageable. This comports the actuation of risky procedures
that have to be done properly by well trained and experienced
staff to avoid physical and psychological traumas or even death
(Fisher, 1994; Currier and Allen, 2000). It is crucial to have
enough people to do the last attempt of show of force and to act
the intervention in the safest and quickest way. It is suggested a
minimum of 5 staff members. At the beginning the decision has
to be made by the staff leader that will perform a short briefing
to define details and roles of staff members. At this point
generally it is late for any negotiation with the patient, however
he should be informed on what is going to happen to him (“we
are going to touch you and to put you on the bed with stretcher
to each limb”) and asked to cooperate, as the show of force and
the imminent application of physical force can act as a form of
persuasion. It is also important the formal authorization and a
complete documentation inclusive of the reasons of less
restrictive methods ineffectiveness and of the correct actuation
of the procedures for restraint and seclusion. In the case that the
intervention is initiated by a nurse staff it is needed that within 1
h a physician licensed to order seclusion and restraint confirms
the decision after a direct physical and psychiatric examination
and assessment. The initial order cannot last more than 4 h (2 for
under 18 years old patients) after which another medical
examination and evaluation has to be performed. If the
seclusion or restraint has to continue a new order has to be
written. During the entire period of seclusion or restraint, the
patient has to be visited by a physician as often as possible and
checked by nurses every 15 min in order to assess the vital
signs, injuries, correct position of restraint, psychic state, the
response to the treatment and the possibility to switch it to a less
restrictive level. When this is possible, the alternative treatment
has to be acted as soon as possible, giving a full documentation
of the state of patient at the end of seclusion or restrain. A
debriefing with staff, and if possible also with patient, is needed
to check physical and psychological traumas.
During the entire duration of seclusion and restraint any
effort must be done and documented to ensure the respect of
patient's rights, dignity and privacy.
and selective serotonin reuptake inhibitors. Randomized
controlled trials were sought that specifically addressed the
acute situation, rather than ongoing management of chronic
conditions.
4.1. Rapid tranquillisation
Acute behavioral disturbance in psychiatric patients may
require urgent treatment. If non-pharmacological methods have
failed to resolve the situation and oral medication is not an
option, then rapid tranquillisation with intramuscular or
intravenous antipsychotics, benzodiazepines or other sedative
drugs may be indicated. The immediate goal in the acute
management of the violent and psychotic patient is behavioral
control, not sedation. Clearly in situation of acute behavioral
disturbance, sedation may also be an appropriate goal.
Pilowsky et al. (1992) studied incidents of rapid tranquillisation over a 5-month period involving 102 incidents and where
all alternative measures (psychological, seclusion and physical
restrain) were utilised. The most prescribed medications were
diazepam (range 10–80 mg) and haloperidol (range 10–60 mg),
followed by droperidol (range 10–20 mg) and chlorpromazine
(range 50–400 mg). The most common route for administration
of diazepam was intravenous. This study showed that intravenous sedation with diazepam alone or in combination with
haloperidol appeared to be more predictable and rapidly
effective than other drugs given intramuscularly. Similar
findings were made in another survey which discovered that
90% of clinicians would use an antipsychotic drugs: 49% would
use haloperidol, 34% chlorpromazine and 15% droperidol. This
would be used by 24% of the total sample in combination with a
benzodiazepine, diazepam or lorazepam (Simpson and Anderson, 1996).
There has been little research into the effectiveness of rapid
tranquillisation treatments. However, the effectiveness of
antipsychotics and benzodiazepines alone and especially in
combination has been confirmed. This led to the development
of a number of guidelines, which recommended nonpharmacological and oral therapy before embarking on parenteral
treatment (McAllister-Williams and Ferrier, 2001).
4. Treatment of acute aggression and violence
4.2. Typical antipsychotics
Treatment of aggressive and violent behavior includes acute
treatment of a medical or situational problem, treatment of an
onset of a psychiatric disorder or an exacerbation of a chronic
illness and long-term management of persistent aggression and
is a serious problem in a mental health facility. Based on
mechanisms described above, treatment for aggression and
violence should enhance an inhibitory system, such as serotonin
and inhibit an activating system, such as dopamine. Moreover it
should stabilize fluctuations in inhibitory and/or exicitatory
systems and protect against overstimulation.
Currently, there is no medication approved by the FDA for
the treatment of aggression. Based on rather limited evidence, a
wide variety of medications for the pharmacological treatment
of aggression has been recommended: typical and atypical
antipsychotics, benzodiazepines, mood stabilizers, beta-blokers
High-potency antipsychotics, such as haloperidol, have been
the most commonly used and prescribed medication for
treatment of aggression in the context of active psychoses
until a few years ago. These agents have been preferred because
of their efficacy; ease of use and titration; and, particularly, their
availability in tablet, liquid, and intramuscular forms. The
immediate antiaggressive effect is not specific or selective, but
seems to be a side effect of the sedation. However their use is
limited by a plethora of side-effects, including hypotension,
anticholinergic effects, lowering of the seizure threshold, and
most notably extrapyramidal symptoms, including acute dystonia. High-dose application has been shown to be able to
aggravate aggression, probably by worsening akatisia
(Volawka, 1995). A small double-blind study, comparing the
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efficacy of i.m. chlorpromazine (50 mg) and i.m. haloperidol
(5 mg) shows that both drugs were effective in treating
symptoms of severe agitation, assaultiveness, hostility and
mania in an average time of 2.5 h (Man and Chen, 1973). A
review of randomised controlled trials reports convincing evidence that chlorpromazine reduces relapses and brings improvement in symptomatology of schizophrenia (Thornley et al.,
2002).
Haloperidol has the best evidence among conventional
antipsychotics for the treatment of aggression, as shown by a
recent review of 20 double-blind studies (Allen, 2000). A review
of several studies examining haloperidol dosing for acute psychosis found little to none additional benefit after 10 to 15 mg i.m. had
been administered (Baldessarini et al., 1988).
Droperidol had become a standard treatment for the rapid
control of severely agitated or violent patients in both psychiatric
and medical emergency departments. Droperidol has been found
to produce a more rapid and greater degree of sedation than
lorazepam over a period of 60 min in a prospective, randomised,
non-blinded study of 202 acutely agitated emergency patients
(Richards et al., 1998). Droperidol resulted in a more rapid control
of agitated patients than haloperidol (Thomas et al., 1992; Chambers and Druss, 1999). However, following several reports of
deaths associated with QTc prolongation and torsades de pointes,
FDA dictates a black box warning. A recent review of the
literature regarding droperidol and dysrhythmia for the years
1960–2002 concludes that, in clinical practice, droperidol is an
effective and safe method for treating acutely agitated or violent
patients. Droperidol may have the same QT interval prolongation
risk of thioridazine, but there is no pattern of sudden deaths
analogous to those provoked the FDA warning about thioridazine
(Shale et al., 2003).
In a Cochrane review of all relevant randomised clinical
trials, zuclopentixol acetate has not been found more effective
than standard treatment in controlling symptoms of aggression,
behavioral disorganisation, acute psychotic symptoms, or
preventing side effects (Fenton et al., 2002). It could be useful
in non-cooperative patients because the effect of a single i.m.
dose could last up to 72 h.
4.3. Atypical antipsychotics
Second generation antipsychotics appear to have a broader
spectrum of action than older agents and lower rates of motor
side effects. In addition, the use of new formulations of second
generation antipsychotics is convenient in the crisis situation.
The Expert Consensus Guidelines for the Treatment of
Behavioral Emergency (Allen et al., 2001) recommended for
acute schizophrenia and bipolar disorders equally oral typical or
atypical antipsychotic in combination with benzodiazepines,
while other guidelines prefer atypical over typical antipsychotics
(Expert Consensus Guideline, 1999; APA, 2002; Lehman et al.,
2004).
Oral risperidone with oral lorazepam worked as well as
intramuscolar haloperidol and intramuscolar lorazepam. Currier
and Simpson (2001) carried out a prospective, non-randomized,
rate-blinded, double-arm study comparing risperidone liquid
593
with intramuscular haloperidol, both in combination with
lorazepam, on a sample of psychotic patients. A significant
decline in agitation scales was observed in both treatment groups
at 30 and 60 min, without between drug-differences. These
treatments were compared again in a recently reported
randomized multicenter clinical trial involving 162 patients
and using blinded raters. Oral risperidone was as effective as
intramuscular haloperidol in controlling acute psychotic behavioral disorders in an acute setting, without the oversedation that
was sometimes observed with haloperidol (Currier et al., 2004).
A multicenter trial compared risperidone and aripripazole in
the treatment of acute exacerbation of schizophrenia and
schizoaffective disorder. Both drugs were significantly better
than placebo on all efficacy measures and separation from placebo
occurred at week 1 for PANSS total and positive score with
aripripazole and risperidone and for PANSS negative score for
aripripazole (Potkin et al., 2003).
A European, multicenter, open-label, active-controlled trial
compared oral risperidone plus lorazepam to standard care with
intramuscular conventional neuroleptics with or without lorazepam in the emergency treatment of acutely psychotic patients.
Oral risperidone/oral lorazepam was more successful at 2 h and
significantly not inferior to standard care (Lejeune et al., 2004).
In a recent study comparing oral risperidone (2–6 mg/day)
and oral zuclopentixol (20–50 mg/day), associated with
lorazepam as needed, in the treatment of acute psychosis,
aggression has been shown to decrease steadily and similarly in
both groups, but the mean decrease in hostility at study endpoint was statistically significant in the risperidone treated
group, and not in the zuclopentixol group (Hovens et al., 2005).
Oral olanzapine has also been used in the treatment of
agitation. In a double-blind multicenter study, patients with
schizophrenia, schizoaffective, schizophreniform disorder, or
bipolar I disorder were randomised to receive either a minimum
of olanzapine 20 mg/day (up to 40 mg on days 1 and 2, and up to
30 mg on days 3 and 4) or 10 mg/day (with lorazepam as needed)
(n = 148). Improvement was observed in both groups, but at the
24-h rating higher olanzapine dosing was significantly more
effective (Baker et al., 2003).
The development of intramuscular formulations of olanzapine and ziprasidone offers new treatment options for patients
experiencing acute psychotic episodes. For many years,
intramuscular treatment with benzodiazepines or typical antipsychotics has been the mainstay treatment for acute psychosis
but the poor tolerability of neuroleptics compromises their
usefulness.
A double-blind, randomised comparison of the efficacy
and safety of intramuscular injection of olanzapine (10 mg,
first two injections; 5 mg, third injection), lorazepam (2 mg;
first two injections; 1 mg, third injection) or placebo
(placebo, first two injections; olanzapine, 10 mg, third injection) in treating acutely agitated patients with bipolar
mania showed 2 h after the first injection a significant greater
improvement in the olanzapine treatment group than in the
placebo and lorazepam treatment groups. The olanzapine
treated patients appeared to respond significantly earlier than
the lorazepam and placebo treatment groups from 30 min and
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continuing through 2 h after the first injection. No significant
difference among the three treatment groups were observed in
safety measures (Meehan et al., 2001). In a double-blind,
multicenter, intramuscular placebo-controlled clinical trial
intramuscular olanzapine was compared to intramuscular
haloperidol in the treatment of acute agitation in 311
hospitalised patients with schizophrenia. After 24 h patients
then entered a 4-day oral phase. The improvement from
baseline was statistically significant with olanzapine and
haloperidol, being shown to be superior to placebo but with
no significant difference between them (Jones et al., 2001). In
a multicenter, randomised, double-blind, placebo-controlled
parallel study comparing intramuscular olanzapine (2.5 or
5 mg) and intramuscular lorazepam (1 mg) in acutely agitated
patients with dementia, a significant improvement of
agitation was observed in both treatment groups, with no
differences between treatment groups in adverse effects.
However, the highest dose of olanzapine had the fastest onset
of effect, and both doses of olanzapine were longer lasting
than lorazepam (Meehan et al., 2002).
A review of prospective randomized, controlled trials that
evaluated efficacy and safety endpoints of intramuscular
olanzapine in the management of acute agitation suggests that
olanzapine is comparable to haloperidol or lorazepam monotherapy in managing acute agitation associated with schizophrenia and dementia and superior to lorazepam monotherapy
in the management of agitation associated with bipolar disorder
(Tulloch and Zed, 2004).
In a recent multicenter, double-blind, placebo-controlled
study, both i.m. olanzapine and i.m. haloperidol showed
superior efficacy than placebo in the treatment of acute
exacerbation of patients with a diagnosis of schizophrenia
spectrum disorder. For the olanzapine group, the effect was
evident after 2 h and a change in psychosis was evident within
the first 24 h for both drugs (Kapur et al., 2005).
A 24-h, double-blind, fixed dosed clinical trial comparing
fixed doses of ziprasidone (2 mg and 10 mg) has shown a
reduction of acute agitation with ziprasidone 10 mg i.m. within
15 min. The 2 mg dose of 10 mg was significantly less effective
(Lesem et al., 2001). The analysis of data from three studies in
which patients received sequential i.m. and oral ziprasidone
(n = 725) or i.m./oral haloperidol (n = 280) has shown that sequential i.m./oral ziprasidone therapy was efficacious in
decreasing agitation and reducing psychotic symptoms and
that improvement was maintained on oral therapy. Sustained
clinical improvement was similar in both ziprasidone and
haloperidol treated groups (Daniel et al., 2002). The efficacy and
tolerability of ziprasidone in the management of acute psychotic
agitation has been confirmed in another report, considering two
24-h studies, two 7-day studies and a 6-week trial (Mendelowitz,
2004).
4.4. Benzodiazepines
Benzodiazepines are often used in monotherapy regimen
or in combination with antipsychotics in treating acute
agitation. Benzodiazepines have a relatively benign side
effect profile. Short-term disadvantages include excessive
sedation, memory impairment and respiratory depression.
The advantage of benzodiazepines is their large variety of
substances with very different pharmacokinetic characteristics and their variety of preparations.
In a review of 24 studies comparing different medications
for the acute management of agitation, lorazepam alone was
superior to haloperidol alone on measures of aggressive
behavior and clinical global improvement and in two doubleblind studies the combination of haloperidol and lorazepam
was superior to lorazepam alone (Allen, 2000).
The Expert Consensus Guidelines for the Treatment of
Behavioral Emergency (Allen et al., 2001) recommended
benzodiazepines, alone or in combination with antipsychotics, conventional or atypical, for agitation suspected to be
due to a primary psychiatric disturbance. Benzodiazepines
alone were the preferred choice when there are no data to
base a provisional diagnosis and also for agitation suspected
to be due to posttraumatic stress disorder. Benzodiazepines
were high second-line recommendation for personality
disorder and were also indicated in psychotic depression in
combination with typical or atypical antipsychotics. In
schizophrenia and mania, benzodiazepines in combination
with typical or atypical antipsychotic are considered high
first-line option. Benzodiazepines alone were the most
popular medication of choice for oral or parenteral treatment
of agitation presumed to be secondary to a general medical
condition or most substance intoxication. Lorazepam has
been found to be superior to haloperidol when added to ongoing neuroleptic treatment in the immediate control (after
2 h) of psychotic disruptive and aggressive inpatients, with
the advantage of being associated with fewer acute EPS
(Salzman et al., 1991). Another more recent double-blind
study compared lorazepam (2 mg) and haloperidol (5 mg),
either i.m. or oral, for the management of highly agitated
patients exhibiting psychotic symptoms presented at a
psychiatric emergency department. Medication was administered every 30 min for 4 h until the patient was sedated or
until their behavior was judged no longer dangerous. Both
lorazepam and haloperidol were equally effective over the
time of the study, but patients treated with lorazepam showed
better improvement, as judged by the Clinical Global
Impression, than individuals receiving haloperidol at hours
1, 2 and 3, but not at hour 4 (Foster et al., 1997). There is also
evidence that lorazepam is effective in the treatment of
aggressive behavior in patients with a bipolar disorder. A
double-blind study of lorazepam vs. haloperidol in patients
with a DSM III-R diagnosis of bipolar disorder, concomitantly treated with lithium, showed a mean reduction of manic
symptoms by about 60% within 1 week in both treatment
groups (Lenox et al., 1992). In a double-blind study,
lorazepam appeared superior to clonazepam in acute mania
(Bradwejn et al., 1990).
A large pragmatic randomised trial comparing intramuscular combination of haloperidol plus promethazine vs.
intramuscular lorazepam for controlling agitation and violence in people with serious psychiatric disorders has shown
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that both interventions are effective for controlling violent and
agitated behavior. If speed of sedation is required, the
haloperidol–promethazine combination has advantages over
lorazepam (Alexander et al., 2004).
Clonazepam has been shown to be more effective than
placebo in manic patients in reducing their manic but not
psychotic symptoms (Edwards et al., 1991). In a small
double-blind trial in acutely agitated psychotic patients with
manic or manic-like symptoms, intramuscular clonazepam
produced a degree of tranquillisation similar to the one
obtained with haloperidol (Chouinard et al., 1994). A single
dose of 4–5 mg of intramuscular clonazepam achieved
tranquillisation in 8 of 12 acute agitated patients within 1 h
(Benazzi et al., 1993).
Midazolam has been found to be effective in reducing
agitation in psychiatric patients (Mendoza et al., 1987; Wyant
et al., 1990; Ramoska et al., 1991). A large pragmatic
randomised study comparing intramuscular midazolam vs.
intramuscular haloperidol plus promethazine for emergency
tranquillisation of violent mentally ill people reported that
both treatments were effective. Midazolam was more rapidly
sedating than haloperidol–promethazine, reducing the time
people are exposed to aggression (TREC Collaborative
Group, 2003). A recent prospective, double-blind, randomised trial of midazolam vs. haloperidol vs. lorazepam in the
management of violent and severely agitated patients in the
emergency department has shown that midazolam has a
significant shorter time to onset of sedation and a more rapid
time to arousal than lorazepam or haloperidol. The efficacies
of all these drugs appear to be similar (Nobay et al., 2004).
A randomised double-blind study comparing intramuscular flunitrazepam vs. intramuscular haloperidol for the
immediate control of agitated or aggressive behavior in
acutely psychotic patients treated with neuroleptics showed
that the maximum antiaggressive effect of flunitrazepam was
achieved more rapidly, as early as after 30 min. Both agents,
used as an adjunct to the existing neuroleptic treatment, were
found to be significantly effective in controlling agitated and
aggressive behavior in acute psychosis (Dorevitch et al.,
1999).
Several authors found a synergy between lorazepam and
haloperidol: their combination has been suggested to be
superior to the use of lorazepam alone in controlling
aggressive and violent behavior (Battaglia et al., 1997;
Garza-Trevino et al., 1989; Bieniek et al., 1998).
A recent review of published studies comparing typical
antipsychotic, benzodiazepines, and/or combination of both
in controlling agitation and aggressive behavior in psychiatric
emergency has identified 11 trials, eight with a double-blind
design. Combination treatment has been suggested to be
superior to the either agent alone with higher improvement
rates and lower incidence of extrapyramidal side effects. The
same review analyzed the available data on the use of atypical
antipsychotics as acute antiagitation compounds. Five studies
were identified, three with a double-blind design. Atypical
antipsychotics have been found to be as effective as the
typical ones. It has been suggested that their use with or
595
without benzodiazepine should be considered first in the
treatment of acute agitation (Yildiz et al., 2003).
5. Management of aggressive behavior in the elderly
In the elderly, aggression occurs in a variety of psychiatric
disorders such as schizophrenia and psychotic depression,
delirium and dementia.
Antipsychotics are widely used for the treatment of
psychiatric disorders in elderly patients. There are few
controlled trials to guide clinical decision-making in the use
of antipsychotics in this population. Most data derived from
studies in dementia. The Expert Consensus Guideline for Using
Antipsychotic Agents in Older Patients recommended the use of
antipsychotics for disorders with psychotic symptoms, like
schizophrenia, mania with psychosis, agitated dementia with
delusions, psychotic major depression, and delusional disorder
(Alexopoulos et al., 2004).
In the elderly physiological changes in the absorption,
distribution, metabolism, and excretion of medications may
results in prolonged drug effects and greater sensitivity to
medications, both in terms of therapeutic response and side
effects. Aging is also characterized by a different pharmacodynamic profile that may further influence drug response.
Recommended starting doses are one-quarter to one-half of
the usual adult starting dose (Kane et al., 2003; Alexopoulos et
al., 2004). Moreover, in elderly patients the risk of adverse
effects and drug–drug interactions is higher as they are more
likely to have comorbid medical conditions and to be taking
multiple medications. For patients with diabetes, dyslipidemia,
or obesity, clozapine, olanzapine, and conventional antipsychotics (especially low- and mid-potency) should be avoided.
Quetiapine is first line for a patient with Parkinson's disease.
The expert would avoid clozapine, ziprasidone, and conventional antipsychotics (especially low- and mid-potency) in
patients with QTc prolongation or congestive hearth failure. For
patients with cognitive impairment, constipation, diabetes,
diabetic neuropathy, dyslipidemia, xeriphthalmia, and xerostomiathe risperidone is considered high first-line option and
quetiapine high second line (Alexopoulos et al., 2004).
Several evidences show that both typical and atypical
antipsychotics are efficacious in treating aggressive behavior
in demented patients, although atypical antipsychotics have
better side effects profiles in the elderly (Brodaty and Low,
2003; Lawlor, 2004). Conventional antipsychotics, such as
haloperidol, have shown modest benefit over placebo in the
treatment of psychosis and agitation in patients with dementia
with one meta-analysis concluding that only 18% of dementia
patients benefited from neuroleptic treatment beyond that of
placebo (Schneider et al., 1990).
A recent review (Tariot et al., 2004) on the efficacy of
atypical antipsychotics in elderly patients with dementia has
analyzed data on risperidone (3 published placebo-controlled
studies), olanzapine (1 abstract regarding a placebo-controlled
trial and a published placebo-controlled trial), quetiapine (1
published open-label trial and an abstract regarding a placebocontrolled trial), and aripripazole (1 abstract regarding a
596
P. Rocca et al. / Progress in Neuro-Psychopharmacology & Biological Psychiatry 30 (2006) 586–598
placebo-controlled trial). Some evidence of efficacy have been
reported for each atypical antipsychotic. These drugs seem to be
efficacious for the treatment of agitation in dementia, with less
clear impact on psychosis. They show important differences in
safety and tolerability.
Warnings of a possible risk between risperidone and
olanzapine use and cerebrovascular adverse events have led to
controversy among clinicians (US FDA, 2004; Health Canada,
2004; Duff, 2004). To date, these warnings only extend to older
adults receiving atypical antipsychotics for Behavioral and
Psychological Symptoms in Dementia and not to patients
receiving these drugs for schizophrenia or other indications. A
recent population based retrospective cohort study shows that
older adults with dementia who take atypical antipsychotics have
a similar risk of ischemic stroke to those taking typical
antipsychotics (Gill et al., 2005).
In conclusion, atypical antipsychotics seem to be efficacious
and safe in treating aggressive behavior in the elderly. Their use
should be reserved for treatment of clinically significant
aggression.
6. Conclusion
Aggressive outbursts that result in harm and injury present
a major problem in psychiatry care, both from categorical and
dimensional approaches, and there are no adequate treatment
options. The traditional categorical approach to psychiatry
delegates aggression to secondary status as a symptom.
Violent and threatening behavior is a frequent reason for
admission, and may continue after admission. Behavioral,
psychological, and pharmacological interventions are used
simultaneously for the treatment of violence. Clinical
judgement, risk assessment and provisional diagnosis might
indicate that monotherapy will be sufficient in the first line
strategy. In addition, a combination of an antipsychotic and
benzodiazepine may be an effective treatment in patients for
whom monotherapy will be insufficient (Brieden et al., 2003;
Hughes and Kleespies, 2003; Humble and Berk, 2003;
Citrome, 2004).
Nonetheless, it appears timely and useful to examine novel
pharmacological and molecular tools that target the neural
mechanisms for different kinds of aggressive behavior more
selectively than previously possible, and to outline potential
pharmachotherapeutic opportunities. The field awaits more
research, including double-blind randomized head-to-head
clinical trials, to determine which medications and which
behavioral approaches alone or in combination with medications are most effective in the treatment of violent patients.
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