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Progress in Neuro-Psychopharmacology & Biological Psychiatry xx (2006) xxx – xxx

Review article
Managing the aggressive and violent patient in the psychiatric emergency
Paola Rocca a,⁎, Vincenzo Villari b , Filippo Bogetto a
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


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
© 2006 Elsevier Inc. All rights reserved.

Keywords: Aggression; Antipsychotics; Benzodiazepines; Psychiatric emergency; Violence


1. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0
2. Assessment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0
2.1. Diagnostic assessment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0
2.2. Violence risk assessment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0
3. Clinical management . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0
3.1. Non-coercive interventions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0
3.2. Patient–therapist relationship . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0
3.3. Coercive interventions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0
3.4. Show of force . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0
3.5. Involuntary medications and chemical restrain . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0
3.6. Physical restraint and seclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0
4. Treatment of acute aggression and violence . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0
4.1. Rapid tranquillisation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0
4.2. Typical antipsychotics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0
4.3. Atypical antipsychotics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0

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: (P. Rocca).

0278-5846/$ - see front matter © 2006 Elsevier Inc. All rights reserved.

PNP-06353; No of Pages 13
2 P. Rocca et al. / Progress in Neuro-Psychopharmacology & Biological Psychiatry xx (2006) xxx–xxx

4.4. Benzodiazepines . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0
5. Management of aggressive behavior in the elderly . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0
6. Conclusion. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0

1. Introduction et al., 1970), good to assess aggression in fully cooperative

people. Of course with violent and uncooperative real patients
Aggression and violence have various meanings. Aggression observer rating scales are needed. They can be specially tailored
may be defined as an intentional act that inflicts physical or for this purpose or sub-scales derived by component of general
mental harm on somebody. Some studies have referred to scales. The most used are: Overt Aggression Scale (OAS)
violence as an aggressive act that causes physical injury; for (Yudofsky et al., 1986), Modified Overt Aggression Scale
others it has to be associated to both verbal and physical (MOAS) (Kay et al., 1988), PANSS Excited Component Score
aggression (Barratt et al., 1997; Filley et al., 2001; Moeller et (PANSS-EC) (Kay et al., 1987; Lindenmayer et al., 2004).
al., 2001). In this paper, we adopted the Webster Dictionary Aggressive and violent symptoms vary from threatening
(1993) definitions. Violence is “the exertion of any physical behavior and agitation to assault and can be seen in patients with
force so as to injure or abuse; an instance of violent treatment or the following diagnoses: organic psychoses, such as after head
procedure; injury in the form of revoking, repudation, injures, cerebral infections, metabolic diseases, drug intoxica-
distortion, infringement or irreverence to a thing, notion or tion, etc.; personality disorders such as borderline and antisocial
quality filthy valued or observed” (Webster Dictionary, 1993). personality disorders; developmental disabilities; dementia;
The focus is mainly on acts and on interactions between two or bipolar affective disorders and schizophrenia, most often during
more people, thus we use the expressions violence, violent and acute psychosis. Violence is one of the most detrimental factors
aggressive behavior as synonymous. Violence is not always in the continued stigmatisation of mental illness.
physically acted, because also a mental attitude, an interper- Several recent large-scale studies have determined that there
sonal relationship or an institution can be violent (ethically, is a relationship between mental disorders and violence.
morally, etc.). Although the majority of users of mental health services are
Aggression has a broader meaning that goes from “an not violent, it is clear that a small yet significant minority are
offensive action or procedure” to “a form of psychobiological violent in inpatient settings and dangerous for the community
energy either innate or arising in response to or intensified by (Swanson et al., 1990; Hiday, 1997).
frustration” (Webster Dictionary, 1993). Often this drive does The rates of violence differ across diagnostic categories,
not produce an open form of violence but can be transformed by suggesting that it is essential to examine the diagnostic
high mental processes, such as introjection and sublimation, and condition separately in relationship to the risk of violent
become something useful for the individual and socially behavior (Swanson et al., 1990; Steadman et al., 1998). An
accepted like compete for career or playing sports. In a recent important study used a sample of 10059 adult residents from
review on qualitatively distinct subtypes of human aggression Epidemiologic Catchment Area (ECA) study sites and exam-
the dichotomy between impulsive–reactive–hostile–affective ined the relationship between violence and psychiatric disorders
subtype and a controlled–proactive–instrumental–predatory (Swanson et al., 1990). Eight percent of those with schizophre-
subtype has emerged as the most promising construct (Vitiello nia alone were violent, compared to 2% of those without mental
and Stoff, 1997). illness. Comorbidity with substance abuse increased this
In a traditional categorical approach aggression and violence percentage to 30%. Another community-based study of
are not a diagnostic entity although they are present as follow-up at 1-year (Steadman et al., 1998) showed that only
symptoms in many mental disorders. That is way they have a 17.9% of mentally ill patients without a substance use diagnosis
transnosographical meaning. On the other hand in many studies were violent, which was equal to the rate of violence among
and meta-analysis (Lindenmayer et al., 2004; Akiskal et al., non-mentally ill persons who did not abuse of substances. Rate
2003) the factor analysis of data allows to describe the rose to 73% in people with mental illness and substance use and
dimension aggression–violence. This is very useful in the up to 240% if the substance was used by patients with
research field to address new studies and in clinic to target the personality disorders.
management and the pharmacological treatment of patients. A review (Nestor, 2002) examines the relationship of a
Although clinicians prefer to assess the patients through the greater risk of violence among persons with certain mental
unstructured clinical observation (Allen et al., 2001) the use of disorders in terms of four fundamental personality dimensions.
rating scales can be helpful to better measure and document the Low impulse control and affective regulation was found to
aggression and the violent behavior. There are many specific increase the risk of violence across various disorders, especially
tools ideated for this purpose. The most used in research are for primary and comorbid substance abuse disorders, while
self-assessment scales, like the Buss Durkee Hostility-Inventory paranoid cognitive personality style and narcissistic injury was
(Buss and Durkee, 1957) and the Self-report symptom found to increase the risk of violence respectively in
inventory 90 (SCL 90) Anger–Hostility Subscale (Derogatis schizophrenia spectrum disorders and personality disorders.
P. Rocca et al. / Progress in Neuro-Psychopharmacology & Biological Psychiatry xx (2006) xxx–xxx 3

Risk assessment is an inexact science. Ultimately the a very quick and effective way. We can distingue two dif-
decision of risk is based on clinical judgment which should ferent steps: the diagnostic assessment and the violence risk
be made by a multidisciplinary team with all the clinicians assessment.
involved in the care, treatment and management of the
individual being assessed. Clinical factors associated to risk 2.1. Diagnostic assessment
of violence may be identified as targets of potential treatment
and prevention, especially important considering that many, if Violent people are not a homogeneous group and not all
not all, mentally disordered violent subjects are seen in people that have a violent behavior, or even just a violent
mainstream mental health settings, often a long time before ideation, have a mental disorder. We can roughly divide the
becoming violent (Taylor et al., 1998). violence into cognitive and emotional: the former is usually
Aggression and violence are likely to result from a complex more related to a criminal attitude than to mental disorders,
interaction of biologic, psychologic and social variables. the opposite is for the latter (Petit, 2004). The first aim of a
Impulsive, affective aggression may be the product of a failure clinician is to distinguish between these two situations, al-
of emotion regulation, with a low threshold for activating though the boundary is not always certain. If there is a
negative affect, which includes anger, distress, and agitation, reasonable possibility that the behavioral problem is related to
and with a tendency to act without regard to the consequences of a pathological situation it is needed to perform an initial
these actions. Two major functional systems, the limbic system diagnostic evaluation, even though some authors found that
and the frontal lobes, are thought to be implicated in various the early decisions of clinicians in managing a violent patient
aspects of aggressive and violent behavior. Aggressive behavior are strongly influenced by symptoms, their severity and speed
has been thought to arise from the operations of the limbic of onset, and less by diagnosis (Gerson and Bassuk, 1980). A
system under certain circumstances, and the amygdala is the well performed medical clearance, too often neglect with this
structure most often implicated. kind of patients and with all people roughly thought to be
Studies of regional glucose metabolism assessed with affected by mental disorders, is a key step to select the most
Positrin Emission Tomography (PET) reveal that hypoactiva- appropriate and etiologically oriented interventions. Other-
tion in prefrontal territories as well as hyperactivation in the wise the only possibility is to act a non-specific intervention
amygdala in individuals prone to impulsive aggression and in order to control the behavior, as the specific approach and
lesion in orbitofrontal and adjacent prefrontal cortex regions the most genuine medical contribution to the problem solution
produce syndromes characterized by impulsivity and aggression is missing. An important early step is to determine whether
(Davidson et al., 2000; Raine et al., 2000; Filley et al., 2001; the clinical situation is due to a Substance Related Disorders
Blair, 2003). or to a General Medical Condition Related Disorders. If
Neurotransmitters, including serotonin, norephinephrin, possible, it would be advisable to check the vital signs and
dopamine, and γ-aminobutyric acid (GABA), have been perform a physical examination or at least a visual
considered in order to explain the origin of aggression and examination of patient. Toxicological screening and blood
impulsivity and may be relevant to treatment. Aggression and exams can be useful for the diagnosis of possible general
impulsivity result from a failure of the balance between medical condition underlying the behavioral problem. A
dopamine, with a strong role in activation and the initiation of pregnancy test is recommended in order to select the
behavior, and serotonin with its inhibitory control. Changes in potentially dangerous treatment.
noradrenergic activity associated with stress or overstimulation
may result in increased impulsivity. The balance between • Substance Related Disorders (included delirium). It is crucial
excitatory (glutamate) and inhibitory (GABA) amino acid to distinguish between drug intoxication and withdrawal. In
function has an important role in the level of arousal (Davidson the first case alcohol and psychostimulants are the
et al., 2000; Lesch and Merschdorf, 2000; Krakowski, 2003; substances more frequently involved, in the second alcohol
Swann, 2003). and benzodiazepines are important. This distinction is
Pharmachological treatments favouring inhibitory transmis- essential to target the pharmacological treatment and the
sion (GABA), enhancing serotonergic activity and reducing choice of an agonist or antagonist agent.
dopamine function, targeting the D2 receptor family, may • General Medical Conditions Related Disorders (included
influence aggressive behavior. Interventions that combine delirium, dementia and neurological syndromes such as
pharmacological and psychosocial strategies, which will likely complex partial seizures and brain temporal, frontal or limbic
both operate on the neural circuitry of emotion regulation, may lesions). It is important to determine the specific medical
be optimal in reducing aggressive and violent behavior. condition related to the behavioral problem in order to target
the therapeutic approach. Very often patients with psychiatric
2. Assessment presentation do not undergo a complete triage and medical
clearance and so it is very common a high prevalence of
The assessment of a violent patient could be very difficult unrecognized medical illness causative of the psychiatric
due to the lack of a full medical and psychiatric history and to symptoms or even just concomitant. A full assessment of
the non-cooperativeness of the patient. Thus a full assessment is those medical problems is very important for an effective and
important for the early decisions that the clinician has to take in target oriented therapeutic approach.
4 P. Rocca et al. / Progress in Neuro-Psychopharmacology & Biological Psychiatry xx (2006) xxx–xxx

• A violent behavior could be due to a mental illness even in violent acting is planned, the police and anyone else that can be
comorbidity with the above listed causes. The potential risk helpful have to be alerted. This is something that can overcome
of harm to others is aspecific and transnosografic and so not the patient's confidentiality and is regulated by laws that vary
closely linked to the underling diagnosis. Almost any kind of by different jurisdictions.
mental disorder can undergo a life-time episode of violent or
agitated behavior, but some of them are more frequently 3. Clinical management
involved in such problems and are: first episode psychosis,
chronic schizophrenia with exacerbation, mood disorders, The primary task and the short term outcome in a beha-
cluster B personality disorders, panic disorders and other vioral emergency is to act as soon as possible in order to stop
acute anxiety disorders including Posttraumatic stress the violence from escalating and to find the quickest way to
disorder (PTSD). keep the patient's agitation and violence under control with
the maximum of safety for everybody and using the less
2.2. Violence risk assessment severe effective intervention. A good start is the first step of
containment, which is itself a part of talk down interventions:
The violence risk assessment is important for a clinician it is important not to forget that an imminent violence can be
when a final decision has to be made: the risk factors have to be triggered very easily even with a therapeutic approach, so first
carefully considered, checked and recorded and the ones that are of all it is necessary to operate cautiously and choose the less
likely to be modifiable should be targeted by specific individual traumatic way to reach the final goal. To this end, there are
or environmental interventions. Many kind of different multiple steps of talk down interventions and non-coercive
presentations are possible: the overt aggression at the moment behavioral and environmental treatments. If this kind of
of the visit, the presence of signs of imminent acting, the approach is not effective more coercive treatments are needed.
declaration of specific will (“I want to kill my neighbour”), the Anyway it must be kept clear in mind that the best inter-
presence of a peculiar state of mind and feelings (“I feel very vention is the less coercive and aggressive possible. The
angry, as I wanted to hurt somebody”). Expert Consensus Guidelines on Treatment of Behavioral
Although violent patients are not a homogeneous group, the Emergencies consider the following options as appropriate
factors associated to violence risk share many common aspects. interventions for an imminently violent patient (in order of
A past history of violence is widely considered the best pre- preference among the experts as treatment of choice) (Allen
dictor of future risk (Gerson and Bassuk, 1980; Parks, 1990; et al., 2001): Verbal intervention (76%); Voluntary medication
Lindenmayer et al., 2002; Buckley et al., 2003; Petit, 2004) (65%); Show of force (51%); Emergency medication (without
(Table 1). consent) (45%); Offer of food, beverage, or other assistance
It is important to make the assessment as soon as possible in (39%); Physical restraints (27%); Locked seclusion (23%);
order to stop the behaviors escalate with early interventions. It is Unlocked seclusion (quiet room) (21%); Leave the area (4%).
also important not to forget that the interview itself and the first On the other hand the quality of intervention and the
clinical approach needed to assess the patient could be also the physician–patient relationship is the most important long
first step of containment of aggressiveness. Special attention term goal and has relevant implications on the treatment plan
should be paid to triggers and targets of violence. and on the course of the illness.
A peculiar problem is what to do in order to protect the Whatever the chosen interventions are the patient do not
potential victims. People affected by mental illness often hurt have to be left alone.
family members or other acquaintances. The clinician has to
protect and warn the intended victims and, if an imminent 3.1. Non-coercive interventions

First verbal approach, clinical interview, talk down inter-

Table 1
Violence risk assessment
ventions, non-coercive behavioral and environmental interven-
tions are all de-escalation techniques (Gerson and Bassuk,
Risk of violence among psychiatric patients has been associated with the
1980; Parks, 1990; Lindenmayer et al., 2002; Rosenberg and
following factors
Sulkowicz, 2002) used to stop the violent behavior escalate that
•Demographic—male, young (15–24 years old), poor, uneducated, unemployed,
generally comes before a violent acting out.
minority, no supportive social network
•Past history—early victimization, past violence, substance abuse, early onset, Non-coercive treatments are based on talk down early
poor parental model interventions oriented to split the emotional and the motor
•Diagnostic—organic brain syndrome (including intoxications), personality aspects of the patient's condition acting as a buffer between
disorder, psychosis, comorbidity with substance abuse them. Through an “as empathic as possible approach” the
•Clinical features—command auditory hallucinations, paranoid delusions and
clinician tries to establish a good enough relationship with the
suspiciousness, poor impulse control, poor insight and low adherence to
treatment, low IQ score, low GAF score patient aimed to an alliance that makes him feeling to be
•Psychological—low tolerance for frustration, criticism and interpersonal understood in emotions and negative feelings and so she or he
closeness, low self-esteem, tendency toward projection and externalization, can shift and stop the motor component of his violent behavior.
anger, irritability, patient's previous methods of coping with similar stressors, This is a difficult goal that requests trained physicians and
motivation and capacity to participate in the treatment process
acceptable milieu conditions.
P. Rocca et al. / Progress in Neuro-Psychopharmacology & Biological Psychiatry xx (2006) xxx–xxx 5

Safety comes first and you have to protect yourself and the Table 3
staff, so at the very beginning of the approach it has to be carefully Verbal approach
checked if the patient has any kind of potentially dangerous •Introduce yourself and explain what are you going to do
objects, including hot beverages and glasses, with whom he can •Use easy words, short and clear sentences, calm manner
•Use a confidential but formal tone. Pay attention to be tuned
hurt others: in that case nothing has to be done until he surrenders •Help the patient to understand what is happening and reassure him about the
these objects, even with the intervention of hospital security guard diagnostic and therapeutic procedure he will undertake
or police. You must never interview an armed patient. It can be •Help the patient to restore the orientation
helpful to tell him that the hospital is a safe place and no arms are •Prefer, at least at the beginning, alliance oriented questions and wait for more
needed to be protected: it is important to remember that the one delicate issues
•When possible try to talk about the real motivations of the violence
who needs to carry an arm can feel in a state of deep discomfort or •Set limits of acceptable behavior and tell the patient that violations will not be
even vulnerable without it. allowed
The setting and the environmental situation influence the •Encourage the verbal expression of feelings, states of mind, fantasies, also if
patient's presentation and also the clinician's behavior and violent
judgement. The emergency room is a busy place and it is not easy •Discourage acting out, make it clear that he or she will be held responsible for
his or her actions
to provide a quiet and safe room in which the patient can be •When you have to communicate your decision do it in a clear and simple way
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 assessment. Recommendations on Behavioral and Environmen-
represents an immediate risk for all the people involved in the tal Interventions and on Verbal Approach are listed in Tables 2
situation. Generally a violent behavior follows a preliminary and 3.
period in which early signs can predict the imminent danger, so
pay attention to: change in speed, tone and contents of speech; 3.2. Patient–therapist relationship
restlessness; signs of tense posture and motor tension such as
clenched fist or jaw; answer to questions with increasing irritable The relationship with a violent patient is a stressful
tone; open envy toward the interviewer. If you think that the experience for the clinician that have to manage the
patient is close to loose the control tell him that, if necessary, any dangerous behavior of the patient and his own negative
needed intervention will be done to assure his and everybody's feelings and countertransference aspects (Gerson and Bassuk,
safety. While doing that, be very careful and remain non- 1980; Parks, 1990). No one can face such a difficult situation
confrontational. without an emotional involvement: the main difference is
A complete physical examination has to be possibly done related to the clinician's level of experience and awareness of
because it is needed for a complete medical and psychiatric those emotional reactions and how she or he copes with. A
assessment and sometimes can help to reassure and calm the well-trained and experienced clinician can manage the
patient showing him that he is a normal person and has to situation even if he is disturbed by countertransference fee-
undertake the normal medical procedure like everyone else. lings such as anger, hostility, hate, fear, etc. He also knows
If possible the interview has to be long enough to perform a when to ask for help without embarrassment. Another bias
careful mental state examination and a full violence risk 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
Table 2
they would affect the quality of relationship, the reliability of
Behavioral and environmental interventions
assessment and the kind of dispositions. It is possible that
•Use a room or an area big and calm enough, not isolated to allow others to
therapists would swing between helplessness and omnipotent
come quickly if help is needed.
•You and the patient should be in such a position to allow the both of you to positions. The former could lead to the prevalence of strong
reach easily the door that must be open. negative feelings and emotional coldness with a nihilistic
•Choose an as calm as possible environment without intense stimulations or approach to the problem solution. The latter could lead to
triggers. ingenuous ideas about global caring of very difficult
•The environment must be safe, without objects that can be potentially
situations and real risk of dangerous violations of therapeutics
•If a suitable room is not available choose an open space. boundaries. For these reasons a constant supervision is
•Keep distance, do not be too close: the violent patient needs more room than requested as well as a clinical discussion, with the direct
others. Never approach the patient from behind and in a rough manner. involvement of expert clinicians in order to develop a good
•Never turn your back to the patient. enough therapeutic approach, that is realistic and problem
•Do not be confrontational, do not look the patient in the eyes, try to assume a
solving oriented. Educational programs are needed especially
neutral facial expression and voice tone, and a relaxed body posture, better
avoid positions as crossed arms or hands behind the back. with less experienced or less formally trained members of the
•The patient don't have to be left alone. staff.
•If others represent a trigger for patient's violence ask them to leave the area. Table 4 presents a list of recommendations useful to check
•Give information and support to relatives and significant others. and manage the emotional quality of the patient–therapist
•Perform a debriefing with the staff and if possible also with the patient.
6 P. Rocca et al. / Progress in Neuro-Psychopharmacology & Biological Psychiatry xx (2006) xxx–xxx

Table 4 confidence to the clinician that is responsible of the situation

Patient–therapist relationship variables and has to take the last decision.
•Try to make procedures as flexible as possible
•If possible prioritize patient's requests 3.5. Involuntary medications and chemical restrain
•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”) This is an argument that can be seen by different points of
•Engage a therapeutic alliance (“in such a difficult situation you need help, view leading to quite different conclusions. We will discuss two
allow me to help you”) problems: 1) what is the limit between voluntary and
•Don't lie nor betray the patient's trust involuntary treatments? 2) what is the limit between treatment
•Do not challenge the patient, do not be confrontational, do not look the patient
in the eyes
and chemical restraint?
•Offer your help to discuss therapeutic aspects of mental disorder The Expert Consensus Guidelines on Treatment of Behav-
•Give help for problem solving, specially with low copers, give alternatives to ioral Emergencies (Allen et al., 2001) consider voluntary “any
violent behavior dose of oral medication to which a patient assents in an
•Evaluate the presence of acute and chronic stressors, specially if active as emergency situation” and “rejected the idea that the situation is
violence triggers and related to past violence and victimization
•Give reassurance for present or past paranoid features
so coercive that any medication must be involuntary even if the
•Be careful with gender issues patient appears to accept it”. It can be reasonable to say that in
•If needed give an opportunity for a time out, offer food and beverage, if such a difficult situation as is the one determined by an
possible allow the patient to smoke a cigarette or to make a phone call 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
3.3. Coercive interventions for anyone involved in the emergency.
Also with regards to chemical restrain there are different
In case the non-coercive interventions are ineffective in points of view. The Health Care Financing Administration
stopping the violent behavior from escalating and the patient (Rosenberg and Sulkowicz, 2002) establishes: “A drug used as
becomes combative it is important to act fast and decisively. The a restraint is a medication used to control behavior or to restrict
sooner you act, the safer the situation will evolve for everyone. the patient's freedom of movement and is not a standard
When a patient has crossed the boundary of allowed behaviors treatment for the patient's medical or psychiatric condition”.
and there is a real and imminent danger, it is time to act coercive Differently the Joint Commission on Accreditation of Health-
interventions that are: show of force, involuntary medications care Organizations (2002) does not accept the idea of chemical
and chemical restrain, physical restraint, seclusion (Allen et al., restraint and considers a medication used to calm an agitated or
2001). violent patient as a treatment. The Expert Consensus Guidelines
It is important that the patient really goes over a reasonable on Treatment of Behavioral Emergencies (Allen et al., 2001) is
threshold. As said before, it is better try to make procedures as more in agreement with the latter position. A possible mediation
flexible as possible giving priority to patient's requests: a refuse between those two different approaches is offered by the Health
to cooperate with routine procedures is not enough to act Care Financing Administration (2000): “... it is the process of
coercive interventions that should never be used as punishment prescribing rather than the agent prescribed that distinguishes
or for the convenience of the staff, but just to limit the patient's treatment from restraint. If a medication is prescribed as part of
dangerousness. an assessment and rational plan of care, whether on a scheduled
In order to have the best possible results in terms of safety or on as-needed basis, it is a treatment. If prescribed simply as a
and quality of interventions in a way that is respectful of the reaction to the patient's behavior, it is a restraint. Hence the
rights of patients–keeping an eye to the abuse of medical and same medication administered to the same patient might be a
psychiatric social control and police-like power–it is very treatment in some circumstances and a restraint in others”.
important to develop policies and procedures of cooperation
with police and hospital security guards. It is also crucial to have 3.6. Physical restraint and seclusion
well experienced and trained staff, set procedures, briefing,
debriefing and stress coping strategies. The current definitions and limitations given by Joint
Commission on Accreditation of Healthcare Organizations
3.4. Show of force (2002) are: “Restraint: direct application of physical force to a
patient, with or without the patient's permission, to restrict his o
It is a sort of last chance to stop the violence from escalating her freedom of movement. The physical force may be human,
before acting involuntary interventions. It is important to mechanical devices, or a combination thereof. Seclusion:
perform this last step of de-escalation techniques with a non- involuntary confinement of a person alone in a locked room.
challenging and a non-confrontational approach. Through the The behavioral health care reasons for the use of restraint and
show of force the patient has to realize emotionally that the staff seclusion are primarily to protect the patient against injury to
is still there to help him and is fully able to contain his self or others because of an emotional or behavioral disorder.” If
destructiveness and to protect all the others. On the other hand all above listed less restrictive interventions have been
the presence of adequate security forces gives also more ineffective, it could be necessary to use the most coercive
P. Rocca et al. / Progress in Neuro-Psychopharmacology & Biological Psychiatry xx (2006) xxx–xxx 7

approach as final response to a belligerent person not otherwise and selective serotonin reuptake inhibitors. Randomized
manageable. This comports the actuation of risky procedures controlled trials were sought that specifically addressed the
that have to be done properly by well trained and experienced acute situation, rather than ongoing management of chronic
staff to avoid physical and psychological traumas or even death conditions.
(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 4.1. Rapid tranquillisation
the intervention in the safest and quickest way. It is suggested a
minimum of 5 staff members. At the beginning the decision has Acute behavioral disturbance in psychiatric patients may
to be made by the staff leader that will perform a short briefing require urgent treatment. If non-pharmacological methods have
to define details and roles of staff members. At this point failed to resolve the situation and oral medication is not an
generally it is late for any negotiation with the patient, however option, then rapid tranquillisation with intramuscular or
he should be informed on what is going to happen to him (“we intravenous antipsychotics, benzodiazepines or other sedative
are going to touch you and to put you on the bed with stretcher drugs may be indicated. The immediate goal in the acute
to each limb”) and asked to cooperate, as the show of force and management of the violent and psychotic patient is behavioral
the imminent application of physical force can act as a form of control, not sedation. Clearly in situation of acute behavioral
persuasion. It is also important the formal authorization and a disturbance, sedation may also be an appropriate goal.
complete documentation inclusive of the reasons of less Pilowsky et al. (1992) studied incidents of rapid tranquillisa-
restrictive methods ineffectiveness and of the correct actuation tion over a 5-month period involving 102 incidents and where
of the procedures for restraint and seclusion. In the case that the all alternative measures (psychological, seclusion and physical
intervention is initiated by a nurse staff it is needed that within 1 restrain) were utilised. The most prescribed medications were
h a physician licensed to order seclusion and restraint confirms diazepam (range 10–80 mg) and haloperidol (range 10–60 mg),
the decision after a direct physical and psychiatric examination followed by droperidol (range 10–20 mg) and chlorpromazine
and assessment. The initial order cannot last more than 4 h (2 for (range 50–400 mg). The most common route for administration
under 18 years old patients) after which another medical of diazepam was intravenous. This study showed that intra-
examination and evaluation has to be performed. If the venous sedation with diazepam alone or in combination with
seclusion or restraint has to continue a new order has to be haloperidol appeared to be more predictable and rapidly
written. During the entire period of seclusion or restraint, the effective than other drugs given intramuscularly. Similar
patient has to be visited by a physician as often as possible and findings were made in another survey which discovered that
checked by nurses every 15 min in order to assess the vital 90% of clinicians would use an antipsychotic drugs: 49% would
signs, injuries, correct position of restraint, psychic state, the use haloperidol, 34% chlorpromazine and 15% droperidol. This
response to the treatment and the possibility to switch it to a less would be used by 24% of the total sample in combination with a
restrictive level. When this is possible, the alternative treatment benzodiazepine, diazepam or lorazepam (Simpson and Ander-
has to be acted as soon as possible, giving a full documentation son, 1996).
of the state of patient at the end of seclusion or restrain. A There has been little research into the effectiveness of rapid
debriefing with staff, and if possible also with patient, is needed tranquillisation treatments. However, the effectiveness of
to check physical and psychological traumas. antipsychotics and benzodiazepines alone and especially in
During the entire duration of seclusion and restraint any combination has been confirmed. This led to the development
effort must be done and documented to ensure the respect of of a number of guidelines, which recommended nonpharmaco-
patient's rights, dignity and privacy. logical 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 High-potency antipsychotics, such as haloperidol, have been
onset of a psychiatric disorder or an exacerbation of a chronic the most commonly used and prescribed medication for
illness and long-term management of persistent aggression and treatment of aggression in the context of active psychoses
is a serious problem in a mental health facility. Based on until a few years ago. These agents have been preferred because
mechanisms described above, treatment for aggression and of their efficacy; ease of use and titration; and, particularly, their
violence should enhance an inhibitory system, such as serotonin availability in tablet, liquid, and intramuscular forms. The
and inhibit an activating system, such as dopamine. Moreover it immediate antiaggressive effect is not specific or selective, but
should stabilize fluctuations in inhibitory and/or exicitatory seems to be a side effect of the sedation. However their use is
systems and protect against overstimulation. limited by a plethora of side-effects, including hypotension,
Currently, there is no medication approved by the FDA for anticholinergic effects, lowering of the seizure threshold, and
the treatment of aggression. Based on rather limited evidence, a most notably extrapyramidal symptoms, including acute dys-
wide variety of medications for the pharmacological treatment tonia. High-dose application has been shown to be able to
of aggression has been recommended: typical and atypical aggravate aggression, probably by worsening akatisia
antipsychotics, benzodiazepines, mood stabilizers, beta-blokers (Volawka, 1995). A small double-blind study, comparing the
8 P. Rocca et al. / Progress in Neuro-Psychopharmacology & Biological Psychiatry xx (2006) xxx–xxx

efficacy of i.m. chlorpromazine (50 mg) and i.m. haloperidol with intramuscular haloperidol, both in combination with
(5 mg) shows that both drugs were effective in treating lorazepam, on a sample of psychotic patients. A significant
symptoms of severe agitation, assaultiveness, hostility and decline in agitation scales was observed in both treatment groups
mania in an average time of 2.5 h (Man and Chen, 1973). A at 30 and 60 min, without between drug-differences. These
review of randomised controlled trials reports convincing evi- treatments were compared again in a recently reported
dence that chlorpromazine reduces relapses and brings impro- randomized multicenter clinical trial involving 162 patients
vement in symptomatology of schizophrenia (Thornley et al., and using blinded raters. Oral risperidone was as effective as
2002). intramuscular haloperidol in controlling acute psychotic behav-
Haloperidol has the best evidence among conventional ioral disorders in an acute setting, without the oversedation that
antipsychotics for the treatment of aggression, as shown by a was sometimes observed with haloperidol (Currier et al., 2004).
recent review of 20 double-blind studies (Allen, 2000). A review A multicenter trial compared risperidone and aripripazole in
of several studies examining haloperidol dosing for acute psycho- the treatment of acute exacerbation of schizophrenia and
sis found little to none additional benefit after 10 to 15 mg i.m. had schizoaffective disorder. Both drugs were significantly better
been administered (Baldessarini et al., 1988). than placebo on all efficacy measures and separation from placebo
Droperidol had become a standard treatment for the rapid occurred at week 1 for PANSS total and positive score with
control of severely agitated or violent patients in both psychiatric aripripazole and risperidone and for PANSS negative score for
and medical emergency departments. Droperidol has been found aripripazole (Potkin et al., 2003).
to produce a more rapid and greater degree of sedation than A European, multicenter, open-label, active-controlled trial
lorazepam over a period of 60 min in a prospective, randomised, compared oral risperidone plus lorazepam to standard care with
non-blinded study of 202 acutely agitated emergency patients intramuscular conventional neuroleptics with or without loraze-
(Richards et al., 1998). Droperidol resulted in a more rapid control pam in the emergency treatment of acutely psychotic patients.
of agitated patients than haloperidol (Thomas et al., 1992; Cham- Oral risperidone/oral lorazepam was more successful at 2 h and
bers and Druss, 1999). However, following several reports of significantly not inferior to standard care (Lejeune et al., 2004).
deaths associated with QTc prolongation and torsades de pointes, In a recent study comparing oral risperidone (2–6 mg/day)
FDA dictates a black box warning. A recent review of the and oral zuclopentixol (20–50 mg/day), associated with
literature regarding droperidol and dysrhythmia for the years lorazepam as needed, in the treatment of acute psychosis,
1960–2002 concludes that, in clinical practice, droperidol is an aggression has been shown to decrease steadily and similarly in
effective and safe method for treating acutely agitated or violent both groups, but the mean decrease in hostility at study end-
patients. Droperidol may have the same QT interval prolongation point was statistically significant in the risperidone treated
risk of thioridazine, but there is no pattern of sudden deaths group, and not in the zuclopentixol group (Hovens et al., 2005).
analogous to those provoked the FDA warning about thioridazine Oral olanzapine has also been used in the treatment of
(Shale et al., 2003). agitation. In a double-blind multicenter study, patients with
In a Cochrane review of all relevant randomised clinical schizophrenia, schizoaffective, schizophreniform disorder, or
trials, zuclopentixol acetate has not been found more effective bipolar I disorder were randomised to receive either a minimum
than standard treatment in controlling symptoms of aggression, of olanzapine 20 mg/day (up to 40 mg on days 1 and 2, and up to
behavioral disorganisation, acute psychotic symptoms, or 30 mg on days 3 and 4) or 10 mg/day (with lorazepam as needed)
preventing side effects (Fenton et al., 2002). It could be useful (n = 148). Improvement was observed in both groups, but at the
in non-cooperative patients because the effect of a single i.m. 24-h rating higher olanzapine dosing was significantly more
dose could last up to 72 h. effective (Baker et al., 2003).
The development of intramuscular formulations of olanza-
4.3. Atypical antipsychotics pine and ziprasidone offers new treatment options for patients
experiencing acute psychotic episodes. For many years,
Second generation antipsychotics appear to have a broader intramuscular treatment with benzodiazepines or typical anti-
spectrum of action than older agents and lower rates of motor psychotics has been the mainstay treatment for acute psychosis
side effects. In addition, the use of new formulations of second but the poor tolerability of neuroleptics compromises their
generation antipsychotics is convenient in the crisis situation. usefulness.
The Expert Consensus Guidelines for the Treatment of A double-blind, randomised comparison of the efficacy
Behavioral Emergency (Allen et al., 2001) recommended for and safety of intramuscular injection of olanzapine (10 mg,
acute schizophrenia and bipolar disorders equally oral typical or first two injections; 5 mg, third injection), lorazepam (2 mg;
atypical antipsychotic in combination with benzodiazepines, first two injections; 1 mg, third injection) or placebo
while other guidelines prefer atypical over typical antipsychotics (placebo, first two injections; olanzapine, 10 mg, third in-
(Expert Consensus Guideline, 1999; APA, 2002; Lehman et al., jection) in treating acutely agitated patients with bipolar
2004). mania showed 2 h after the first injection a significant greater
Oral risperidone with oral lorazepam worked as well as improvement in the olanzapine treatment group than in the
intramuscolar haloperidol and intramuscolar lorazepam. Currier placebo and lorazepam treatment groups. The olanzapine
and Simpson (2001) carried out a prospective, non-randomized, treated patients appeared to respond significantly earlier than
rate-blinded, double-arm study comparing risperidone liquid the lorazepam and placebo treatment groups from 30 min and
P. Rocca et al. / Progress in Neuro-Psychopharmacology & Biological Psychiatry xx (2006) xxx–xxx 9

continuing through 2 h after the first injection. No significant effect profile. Short-term disadvantages include excessive
difference among the three treatment groups were observed in sedation, memory impairment and respiratory depression.
safety measures (Meehan et al., 2001). In a double-blind, The advantage of benzodiazepines is their large variety of
multicenter, intramuscular placebo-controlled clinical trial substances with very different pharmacokinetic characteris-
intramuscular olanzapine was compared to intramuscular tics and their variety of preparations.
haloperidol in the treatment of acute agitation in 311 In a review of 24 studies comparing different medications
hospitalised patients with schizophrenia. After 24 h patients for the acute management of agitation, lorazepam alone was
then entered a 4-day oral phase. The improvement from superior to haloperidol alone on measures of aggressive
baseline was statistically significant with olanzapine and behavior and clinical global improvement and in two double-
haloperidol, being shown to be superior to placebo but with blind studies the combination of haloperidol and lorazepam
no significant difference between them (Jones et al., 2001). In was superior to lorazepam alone (Allen, 2000).
a multicenter, randomised, double-blind, placebo-controlled The Expert Consensus Guidelines for the Treatment of
parallel study comparing intramuscular olanzapine (2.5 or Behavioral Emergency (Allen et al., 2001) recommended
5 mg) and intramuscular lorazepam (1 mg) in acutely agitated benzodiazepines, alone or in combination with antipsycho-
patients with dementia, a significant improvement of tics, conventional or atypical, for agitation suspected to be
agitation was observed in both treatment groups, with no due to a primary psychiatric disturbance. Benzodiazepines
differences between treatment groups in adverse effects. alone were the preferred choice when there are no data to
However, the highest dose of olanzapine had the fastest onset base a provisional diagnosis and also for agitation suspected
of effect, and both doses of olanzapine were longer lasting to be due to posttraumatic stress disorder. Benzodiazepines
than lorazepam (Meehan et al., 2002). were high second-line recommendation for personality
A review of prospective randomized, controlled trials that disorder and were also indicated in psychotic depression in
evaluated efficacy and safety endpoints of intramuscular combination with typical or atypical antipsychotics. In
olanzapine in the management of acute agitation suggests that schizophrenia and mania, benzodiazepines in combination
olanzapine is comparable to haloperidol or lorazepam mono- with typical or atypical antipsychotic are considered high
therapy in managing acute agitation associated with schizo- first-line option. Benzodiazepines alone were the most
phrenia and dementia and superior to lorazepam monotherapy popular medication of choice for oral or parenteral treatment
in the management of agitation associated with bipolar disorder of agitation presumed to be secondary to a general medical
(Tulloch and Zed, 2004). condition or most substance intoxication. Lorazepam has
In a recent multicenter, double-blind, placebo-controlled been found to be superior to haloperidol when added to on-
study, both i.m. olanzapine and i.m. haloperidol showed going neuroleptic treatment in the immediate control (after
superior efficacy than placebo in the treatment of acute 2 h) of psychotic disruptive and aggressive inpatients, with
exacerbation of patients with a diagnosis of schizophrenia the advantage of being associated with fewer acute EPS
spectrum disorder. For the olanzapine group, the effect was (Salzman et al., 1991). Another more recent double-blind
evident after 2 h and a change in psychosis was evident within study compared lorazepam (2 mg) and haloperidol (5 mg),
the first 24 h for both drugs (Kapur et al., 2005). either i.m. or oral, for the management of highly agitated
A 24-h, double-blind, fixed dosed clinical trial comparing patients exhibiting psychotic symptoms presented at a
fixed doses of ziprasidone (2 mg and 10 mg) has shown a psychiatric emergency department. Medication was adminis-
reduction of acute agitation with ziprasidone 10 mg i.m. within tered every 30 min for 4 h until the patient was sedated or
15 min. The 2 mg dose of 10 mg was significantly less effective until their behavior was judged no longer dangerous. Both
(Lesem et al., 2001). The analysis of data from three studies in lorazepam and haloperidol were equally effective over the
which patients received sequential i.m. and oral ziprasidone time of the study, but patients treated with lorazepam showed
(n = 725) or i.m./oral haloperidol (n = 280) has shown that se- better improvement, as judged by the Clinical Global
quential i.m./oral ziprasidone therapy was efficacious in Impression, than individuals receiving haloperidol at hours
decreasing agitation and reducing psychotic symptoms and 1, 2 and 3, but not at hour 4 (Foster et al., 1997). There is also
that improvement was maintained on oral therapy. Sustained evidence that lorazepam is effective in the treatment of
clinical improvement was similar in both ziprasidone and aggressive behavior in patients with a bipolar disorder. A
haloperidol treated groups (Daniel et al., 2002). The efficacy and double-blind study of lorazepam vs. haloperidol in patients
tolerability of ziprasidone in the management of acute psychotic with a DSM III-R diagnosis of bipolar disorder, concomi-
agitation has been confirmed in another report, considering two tantly treated with lithium, showed a mean reduction of manic
24-h studies, two 7-day studies and a 6-week trial (Mendelowitz, symptoms by about 60% within 1 week in both treatment
2004). groups (Lenox et al., 1992). In a double-blind study,
lorazepam appeared superior to clonazepam in acute mania
4.4. Benzodiazepines (Bradwejn et al., 1990).
A large pragmatic randomised trial comparing intramus-
Benzodiazepines are often used in monotherapy regimen cular combination of haloperidol plus promethazine vs.
or in combination with antipsychotics in treating acute intramuscular lorazepam for controlling agitation and vio-
agitation. Benzodiazepines have a relatively benign side lence in people with serious psychiatric disorders has shown
10 P. Rocca et al. / Progress in Neuro-Psychopharmacology & Biological Psychiatry xx (2006) xxx–xxx

that both interventions are effective for controlling violent and without benzodiazepine should be considered first in the
agitated behavior. If speed of sedation is required, the treatment of acute agitation (Yildiz et al., 2003).
haloperidol–promethazine combination has advantages over
lorazepam (Alexander et al., 2004). 5. Management of aggressive behavior in the elderly
Clonazepam has been shown to be more effective than
placebo in manic patients in reducing their manic but not In the elderly, aggression occurs in a variety of psychiatric
psychotic symptoms (Edwards et al., 1991). In a small disorders such as schizophrenia and psychotic depression,
double-blind trial in acutely agitated psychotic patients with delirium and dementia.
manic or manic-like symptoms, intramuscular clonazepam Antipsychotics are widely used for the treatment of
produced a degree of tranquillisation similar to the one psychiatric disorders in elderly patients. There are few
obtained with haloperidol (Chouinard et al., 1994). A single controlled trials to guide clinical decision-making in the use
dose of 4–5 mg of intramuscular clonazepam achieved of antipsychotics in this population. Most data derived from
tranquillisation in 8 of 12 acute agitated patients within 1 h studies in dementia. The Expert Consensus Guideline for Using
(Benazzi et al., 1993). Antipsychotic Agents in Older Patients recommended the use of
Midazolam has been found to be effective in reducing antipsychotics for disorders with psychotic symptoms, like
agitation in psychiatric patients (Mendoza et al., 1987; Wyant schizophrenia, mania with psychosis, agitated dementia with
et al., 1990; Ramoska et al., 1991). A large pragmatic delusions, psychotic major depression, and delusional disorder
randomised study comparing intramuscular midazolam vs. (Alexopoulos et al., 2004).
intramuscular haloperidol plus promethazine for emergency In the elderly physiological changes in the absorption,
tranquillisation of violent mentally ill people reported that distribution, metabolism, and excretion of medications may
both treatments were effective. Midazolam was more rapidly results in prolonged drug effects and greater sensitivity to
sedating than haloperidol–promethazine, reducing the time medications, both in terms of therapeutic response and side
people are exposed to aggression (TREC Collaborative effects. Aging is also characterized by a different pharmacody-
Group, 2003). A recent prospective, double-blind, rando- namic profile that may further influence drug response.
mised trial of midazolam vs. haloperidol vs. lorazepam in the Recommended starting doses are one-quarter to one-half of
management of violent and severely agitated patients in the the usual adult starting dose (Kane et al., 2003; Alexopoulos et
emergency department has shown that midazolam has a al., 2004). Moreover, in elderly patients the risk of adverse
significant shorter time to onset of sedation and a more rapid effects and drug–drug interactions is higher as they are more
time to arousal than lorazepam or haloperidol. The efficacies likely to have comorbid medical conditions and to be taking
of all these drugs appear to be similar (Nobay et al., 2004). multiple medications. For patients with diabetes, dyslipidemia,
A randomised double-blind study comparing intramuscu- or obesity, clozapine, olanzapine, and conventional antipsycho-
lar flunitrazepam vs. intramuscular haloperidol for the tics (especially low- and mid-potency) should be avoided.
immediate control of agitated or aggressive behavior in Quetiapine is first line for a patient with Parkinson's disease.
acutely psychotic patients treated with neuroleptics showed The expert would avoid clozapine, ziprasidone, and conven-
that the maximum antiaggressive effect of flunitrazepam was tional antipsychotics (especially low- and mid-potency) in
achieved more rapidly, as early as after 30 min. Both agents, patients with QTc prolongation or congestive hearth failure. For
used as an adjunct to the existing neuroleptic treatment, were patients with cognitive impairment, constipation, diabetes,
found to be significantly effective in controlling agitated and diabetic neuropathy, dyslipidemia, xeriphthalmia, and xerosto-
aggressive behavior in acute psychosis (Dorevitch et al., miathe risperidone is considered high first-line option and
1999). quetiapine high second line (Alexopoulos et al., 2004).
Several authors found a synergy between lorazepam and Several evidences show that both typical and atypical
haloperidol: their combination has been suggested to be antipsychotics are efficacious in treating aggressive behavior
superior to the use of lorazepam alone in controlling in demented patients, although atypical antipsychotics have
aggressive and violent behavior (Battaglia et al., 1997; better side effects profiles in the elderly (Brodaty and Low,
Garza-Trevino et al., 1989; Bieniek et al., 1998). 2003; Lawlor, 2004). Conventional antipsychotics, such as
A recent review of published studies comparing typical haloperidol, have shown modest benefit over placebo in the
antipsychotic, benzodiazepines, and/or combination of both treatment of psychosis and agitation in patients with dementia
in controlling agitation and aggressive behavior in psychiatric with one meta-analysis concluding that only 18% of dementia
emergency has identified 11 trials, eight with a double-blind patients benefited from neuroleptic treatment beyond that of
design. Combination treatment has been suggested to be placebo (Schneider et al., 1990).
superior to the either agent alone with higher improvement A recent review (Tariot et al., 2004) on the efficacy of
rates and lower incidence of extrapyramidal side effects. The atypical antipsychotics in elderly patients with dementia has
same review analyzed the available data on the use of atypical analyzed data on risperidone (3 published placebo-controlled
antipsychotics as acute antiagitation compounds. Five studies studies), olanzapine (1 abstract regarding a placebo-controlled
were identified, three with a double-blind design. Atypical trial and a published placebo-controlled trial), quetiapine (1
antipsychotics have been found to be as effective as the published open-label trial and an abstract regarding a placebo-
typical ones. It has been suggested that their use with or controlled trial), and aripripazole (1 abstract regarding a
P. Rocca et al. / Progress in Neuro-Psychopharmacology & Biological Psychiatry xx (2006) xxx–xxx 11

placebo-controlled trial). Some evidence of efficacy have been Alexopoulos GS, Streim J, Carpenter D, Docherty JP. The expert consensus
reported for each atypical antipsychotic. These drugs seem to be guideline series. Using antipsychotics agents in older patients. J Clin
Psychiatry 2004;65(Suppl2).
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2001;1–88:89–90 (quiz).
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