Managing The Aggressive And Violent Patient In The Psychiatric Emergency

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Progress in Neuro-Psychopharmacology & Biological Psychiatry xx (2006) xxx – xxx www.elsevier.com/locate/pnpbp

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

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

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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 restrain 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 PNP-06353; No of Pages 13

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4.4. Benzodiazepines . . . . . . . . 5. Management of aggressive behavior in 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.

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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

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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.

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• 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

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.

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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.

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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.

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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

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.

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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

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

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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

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

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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. References Akiskal HS, Azorin JM, Hantouche EG. Proposed multidimensional structure of mania: beyond the euphoric–dysphoric dichotomy. J Affect Disord 2003;73:7-18. Alexander J, Tharyan P, Adams C, John T, Mol C, Philip J. Rapid tranquillisation of agitated patients in a psychiatric emergency setting. Pragmatic randomized trial of intramuscular lorazepam versus haloperidol plus promethazine. Brit J Psychiatry 2004;185:63–9.

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Alexopoulos GS, Streim J, Carpenter D, Docherty JP. The expert consensus guideline series. Using antipsychotics agents in older patients. J Clin Psychiatry 2004;65(Suppl2). Allen MH. Managing the agitated psychotic patient: a reappraisal of the evidence. J Clin Psychiatry 2000;61(Suppl. 14):S1-S20. Allen MH, Currier GW, Hughes DH, Reyes-Harde M, Docherty JP. Consensus panel for behavioral emergencies. The expert consensus guideline series. Treatment of behavioral emergencies. Postgrad Med May (Spec. No.) 2001;1–88:89–90 (quiz). American Psychiatric Association. Practice guideline for the treatment of patients with bipolar disorder [revision]. Am J Psychiatry 2002;159(Suppl. 4):Sl-S50. Baker RW, Kinon BJ, Maguire GA, Liu H, Hill AL. Effectiveness of rapid initial dose escalation of up to 40 mg per day of oral olanzapine in acute agitation. J Clin Psychopharmacol 2003;23(Suppl. 4):S342–8. Baldessarini RJ, Cohen MB, Teicher MH. Significance of neuroleptics dose and plasma level in the pharmacological treatment of psychosis. Arch Gen Psychiatry 1988;45:79–91. Barratt ES, Stanford MS, Kent TA, Felthous A. Neuropsychological and cognitive psychophysiological substrates of impulsive aggression. Biol Psychiatry 1997;41:1045–61. Battaglia J, Moss S, Rush J, Kang J, Mendoza R, Leedom L, et al. Haloperidol, lorazepam, or both for psychotic agitation? A multicenter, prospective, doubleblind, emergency department study. Am J Emerg Med 1997;15(4):335–40. Benazzi F, Mazzoli M, Rossi E. A study of intramuscolar clonazepam for psychotic agitation (letter). Can J Psychiatry 1993;38:70–1. Bieniek SA, Ownby RL, Penalver A, Dominguez RA. A double-blind study of lorazepam versus the combination of haloperidol and lorazepam in managing agitation. Pharmacotherapy 1998;Jan-18(l):57–62. Blair RJR. A neurocognitive model of the psychopathic individual. Disorders of Brain and Mind, vol. 2. Cambridge; 2003. p. 400–17. Bradwejn J, Shriqui C, Koszycki D, Meterissian G. Double-blind comparison of the effects of clonazepam and lorazepam in acute mania. J Clin Psychopharmacology 1990;10:403–8. Brieden T, Ujeyl M, Naber D. Psychopharmacological treatment of aggression in schizophrenic patients. Pharmachopsychiatry 2003;35:83–9. Brodaty H, Low LF. Aggression in the elderly. J Clin Psychiatry 2003;64 (Suppl. 4):36–43. Buckley PF, Noffsinger G, Smith DA, Hrouda DR, Knoll JL. Treatment of the psychotic patient who is violent. Psychiatr Clin North Am 2003;26:23l–72. Buss AH, Durkee A. An inventory for assessing different kinds of hostility. J Consult Psychol 1957;21:343–9. Chambers RA, Druss BG. Droperidol: efficacy and side effects in psychiatric emergencies. J Clin Psychiatry 1999;60:664–7. Chouinard G, Safadi G, Beauclair L. A double blind controlled study of intramuscular zuclopenthixol acetate and liquid oral haloperidol in the treatment of schizophrenic patients with acute exacerbation. J Clin Psychopharmacol 1994;14:377–84. Citrome L. New treatments for agitation. Psychiatr Q 2004;75(3):197–213. Currier GW, Allen MH. Physical and chemical restraint in the psychiatric emergency service. Psychiatr Serv 2000;51:717–9. Currier GW, Simpson GM. Risperidone liquid concentrate and oral lorazepam versus intramuscular haloperidol and intramuscular lorazepam for treatment of psychotic agitation. J Clin Psychiatry 2001;62:153–7. Currier GW, Chou JC-Y, Feifel D, Bossie CA, Turkoz I, Mahmoud RA, et al. Acute treatment of psychotic agitation: a randomized comparison of oral treatment with risperidone and lorazepam versus intramuscular treatment with haloperidol and lorazepam. J Clin Psychiatry 2004;65:386–94. Daniel D, Brook S, Benattia I. Transition from IM to oral ziprasidone: clinical efficacy and safety data. Presented at the XXIIIrd Congress of the Collegium Internationale Neuro-Psychopharmacologicum (CINP), Montreal, Canada, June; 2002. p. 23–7. Davidson RJ, Putnam KM, Larson CL. Dysfunction in the neural circuitry of emotion regulation—a possible prelude to violence. Science 2000;289:591–4. Derogatis LR, Covi L, Lipman RS, Rickels K. Dimensions of outpatient neurotic pathology: comparison of a clinical vs. empirical assessment. J Consult Clin Psychol 1970;34:164–71.

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