Psychomotor agitation and aggression: psychiatric emergencies. A narrative review of the literature

Psychomotor agitation represents an emergency situation that psychiatrists deal with on a daily basis. It requires rapid and timely intervention procedures, which include risk assessment and careful management in the various diagnostic-therapeutic phases.

Psychomotor agitation has multifactorial genesis, and is not always determined by a psychiatric pathology, for this reason an accurate differential diagnosis is necessary.

This clinical dimension is often associated with episodes of hetero- and self-directed aggression.

The complexity of the patient with acute behavioural disorder would require a multidisciplinary approach which, unfortunately, is not always well codified; these situations can therefore generate not only ineffective management of the patient, but can also simultaneously expose the patient to the risk of possible injuries and the staff to episodes of aggression.

The aim of the study is to provide a narrative review of the main testimonies described in the literature on the topic of aggression and agitation. The intent is to raise awareness on the topic in order to lead to the creation of effective protocols for the management of psychiatric emergencies in first aid settings, as well as in psychiatry departments.

INTRODUCTION

Psychomotor agitation is a clinical condition characterized by excessive activity which manifests itself with emotional, ideational, motor and behavioural alterations, sometimes aimless in relation to the state of consciousness. States of psychomotor agitation can also occur independently of psychiatric pathology.

The genesis is multifactorial, recognizing biological, psychological, family and environmental influences. In general, the probability of behavioural and violent alterations increases with the number of risk factors. The course of the behavioural disorder is generally unstable over time and can result in verbal and/or physical aggression ¹.

Psychomotor agitation therefore represents an emergency in a clinical setting whose management requires intervention procedures that imply the estimation of the patient’s and the environment’s resources, a timely risk assessment, a careful balance between the risks and benefits of therapeutic choices, in the more general context of overall management in the various diagnostic-therapeutic phases. In the absence of appropriate management, escalation is easily determined which can quickly lead to an exacerbation with a high risk of both self- and hetero-aggressive agitation.

Psychomotor agitation and aggression can be considered as psychopathological dimensions rather than as symptoms or disorders, since they fall on a continuum that goes from normal and physiological functions to psychopathological conditions; they are not an expression of specific disorders, but are rather transdiagnostic and also share underlying neurobiological patterns. Although both literature and clinical experience support this distinction, the boundaries between activation and aggression, and even more so between their clinical expression, are not always clear but often overlap. This is also supported by the classification of subtypes of agitation which identifies four distinct components: aggressive physical component; aggressive verbal component; non-aggressive physical component; and non-aggressive verbal component ². Furthermore, in some clinical conditions, for example, acute anxiety conditions, patients may show agitation, but are unlikely to be aggressive, anxiety being a protective factor for the risk of aggression. Aggression does not necessarily fall within the scope of psychopathology as it represents instinctive behaviour with adaptive properties, but on the other hand aggression can be defined as “behaviour directed by an individual against another individual, an object or themselves, with the aim of causing harm” ³.

Aggression has always been a debated conceptual issue, and this is confirmed by the speculations that have crossed the ideologies of various philosophers over time.

In ancient Greek thought, for example, aggression was considered a positive value, as it obeyed rationality, becoming synonymous with courage in battle. For Latin thought, specifically in Seneca’s theorizations, aggression was considered an equivalent of madness.

Nowadays this different vision can be translated into the distinction between impulsive aggression and instrumental aggression. Impulsive aggression is aimed at removing the obstacle to the goal that leads to frustration. Instrumental aggression, also known as predatory, is premeditated, aimed at a goal. It does not imply high levels of affect, but is rather associated with insensitivity, whether it manifests suddenly as a response to a perceived threat or provocation and involves affective arousal with anger, rage, or hostility ^4,5. Although one form of aggression may be predominant, both types of aggression can be observed in the same person, as occurs for example in antisocial personality disorder. Compared to predatory aggression, the impulsivity subtype is more commonly observed in psychiatric and medical settings, is frequently associated with a number of clinical conditions, and can be treated with pharmacological and non-pharmacological interventions ^4,5.

AIM OF THE STUDY

METHODS

In compiling the present review, we preferred to distinguish three macro-themes, namely: psychomotor agitation, violent behaviour towards healthcare workers, acts of self-harming. This distinction was used in the search for studies. We used the following key-words: “psychomotor agitation”; “violent behaviour”; “self-harming”; “harming behaviour”; “health-care violence”. We used the most common website for medical search, namely: PUBMED; EMBASE; MEDLINE; CINHAL. Papers published between 1990 and 2024 have been included.

Through screening, studies with a title not relevant to the review issue were excluded. The full text of studies considered relevant was obtained and evaluated to detect pertinent studies.

PSYCHOMOTOR AGITATION AND OTHER-HARMING BEHAVIOURS

to data published by the Ministry of Health, the number of accesses to Italian emergency rooms for psychiatric pathologies in 2022 (data is including acute behavioural disorders, too) represented 3.2% of the total ⁶. Data coming from available literature reported that approximately 10% of psychiatric evaluations in emergency services regarded agitation or frankly violent behaviours at the time of the first examination ⁷.

Agitation is very common in schizophrenia (prevalence of 64.2%), in manic episodes and in mixed states of bipolar disorder with a variation between 19.5% and 87.9%), in dementia (with a variation Between 10% and 90%) ⁸. Aggression, as previously mentioned, is a transversal phenomenon that can be observed both in patients with a purely psychiatric diagnosis (psychotic and mood disorders), and in patients with alcohol and/or substance abuse. Furthermore, patients with both problems are even more prone to violent and aggressive behaviours than the general population. Scientific literature reports a prevalence of aggression between 4.4% 15% in hospitalized psychiatric patients 9-11. Restraint can be adopted as a last intervention with openly aggressive patients. Such intervention can be considered as an indirect index of aggression in psychiatric wards, showing accordingly a prevalence between 7% and 12% ¹². Schizophrenia is commonly associated with aggression: and hospitalized patients affected by schizophrenia show a prevalence of aggression between 14% and 53.2%. Such prevalence increases significantly up to 30% in subjects with comorbidity of substance abuse ¹¹. Aggressive behaviours are also frequent among first-episode patients of psychosis (40% of patients presenting to services), bipolar disorder (15% of patients) and dementia (22% of patients) ^13-15. As transdiagnostic dimensions, it should be underlined that agitation and aggression can be observed in a wide spectrum of psychopathological conditions, but can be secondary to medical and neurological pathologies, to conditions of abstinence or intoxication from alcohol and/or substances (Tabs. I, II) ^16-18.

Aggression and agitation can also be observed in conditions do not strictly relate to psychopathology and do not necessarily occur at the same time. Primary emotions such as anger, fear, and even happiness can induce varying degrees of activation; anger generates aggressive behaviour as well as fear, activating the fight or flight response. Aggression and agitation can therefore be observed in non-clinical contexts as a consequence of an intense emotional response to acute or prolonged stressors.

Agitation can also manifest itself in the absence of aggressive behaviour. For example, acute conditions of anxiety or depression generate activation and agitation can lead to self-directed aggressive acts, but are usually unlikely to translate into hetero-aggressive behaviour.

Anxiety and depression are internalizing dimensions with an internal focus and can actually be considered protective factors against hetero-aggression but not self-aggression.

Other disorders include aggression among their typical symptoms, besides not necessarily associated with agitation or with agitation playing only a marginal role. Such disorders include all conditions in which patients are more likely to demonstrate a form of cold aggression, instrumental aggression, which is typically planned and premeditated with a predatory purpose. This can be observed, for example, in paraphilic disorders such as paedophilia and sexual sadism disorder ¹⁹. Individuals with antisocial personality disorder also frequently display cold aggression, although they may also display impulsive aggression reactive to an emotional response. Psychopathy traits are indeed a risk factor for premeditated aggression among patients with antisocial personality disorder ²⁰. Finally, intermittent explosive disorder as well as other disruptive, impulse control, and conduct disorders include aggression among their hallmarks. The DSM-5 ²¹ recognizes for these psychopathological pictures a significant emotional and behavioural dysregulation, with greater prevalence of one or the other depending on the specific disorder. Indeed, according to the diagnostic criteria for intermittent explosive disorder the aggression must be related to impulsive behaviour and/or anger and not premeditated and goal-oriented. On the contrary, this is not a criterion for conduct disorders where it is possible to specify whether psychopathic traits are present, admitting both the presence of impulsiveness and cold aggression. Globally, although activation and agitation can occur together with aggression, they are not a typical manifestation of such disorders, the hallmark of which is aggression.

VIOLENCE AGAINST HEALTHCARE WORKERS

Within the topic of psychomotor agitation, hetero-aggressive agitation and the management of these behaviours in emergency situations, it is necessary to dedicate space to a highly relevant phenomenon: episodes of aggression towards healthcare workers.

2,243 cases of violence, aggression and threats against healthcare personnel have been ascertained by INAIL (National Institute for Assurance against Workplace Injury) in Italy in 2022, representing an increase of 14% compared to the previous year. These are mainly episodes of violence carried out by people outside the company (reactions from patients or their families) ²⁵. In the three-year period 2020-2022, there were around six thousand cases of violence in healthcare and social assistance, with an incidence of 41% compared to all those recorded in the same period among industry and service workers. About 70% involved women. Health technicians is the category most involved in violence and aggression (41% of the total), followed by qualified professions in health and social services (27%) and that of personal and similar services (13%). The category of doctors apart, regarding only 3.5% of cases of aggression in healthcare, which does not include general practitioners and freelancers in the INAIL insurance obligation. Almost one attack in out of three occurred in the North-West (17% in Lombardy and 8% in Piedmont), 28% in the North-East (14% in Emilia Romagna and 9% in Veneto), 22% in the South (7% in Sicily and 5% in Puglia) and 19% in the Center (9% in Tuscany and 6% in Lazio) ²⁵.

These data are consistent with those observed internationally: US Bureau of Labor Statistics and National Crime Victimization Survey show that healthcare workers experience a 20% higher rate of workplace violence compared to other employees ²⁶. WHO reports that around a quarter of health workers experience physical violence during their careers. Many others are threatened, exposed to verbal attacks and social stigma. Workplace violence could result in serious physical and psychological injury with long-term consequences for the affected healthcare workers such as sleep disorders, stress, increased turnover intention, and burnout ²⁷.

The most affected professions are nurses and professional educators in service with minors, drug addicts, alcoholics, prisoners, the disabled, psychiatric patients and the elderly ²⁸.

During the Covid-19 pandemic, staff shortages and growing social tensions have increased the level of violence against healthcare workers and attacks on emergency facilities and vehicles. The mainly involved scenarios are emergency rooms, wards, outpatient departments, psychiatric wards, intensive care units, 118 ambulances, nursing homes and prisons. Concerning the type of violence: 60% are threats, 20% beatings, 10% armed violence and the remaining 10% vandalism. The perpetrators of the crime are 49% patients, 30% family members, 11% relatives and 8% users in general. Nurses are the most affected followed by doctors and social-health workers, while t emergency rooms and inpatient areas are the places at highest risk ^29-31.

As regards the training of health workers, which represents one of the prevention measures, over the last few years training activities have been organized according to the minimum standards identified by Onseps (National Observatory on the safety of health and socio-health professionals) in collaboration with the National Agency for Regional Health Services (AGENAS). Another critical element is represented by the lack of human resources, identified as the first cause to be removed to hinder the phenomenon of attacks against healthcare personnel. This measure must be associated with other organizational interventions that allow operators not to work alone, especially in higher risk situations. Communication difficulties are recognized by 33% of the sample as the most frequent problem in dealing with risk situations. A survey shows that all operators complain of about negative psychological and emotional effects as a consequence of the violence suffered: anger and frustration are the most experienced feelings. According to 90% of the professionals interviewed, the experience of violence worsens the quality of the victim’s subsequent healthcare services ^32,33.

SELF-HARMING BEHAVIOURS

Agitation can occur even in the absence of aggressive behaviour. Some acute psychiatric conditions generate activation and agitation, do not result in hetero-aggressive behaviour, but can instead lead to self-directed aggression.

Agitation can also be a major indicator of imminent, impulsive suicidal behaviour.

The World Health Organization (WHO) highlights that every year almost one million people die from suicide worldwide, with a “global” mortality rate of 16 cases per 100,000 people, making suicide a global health concern ³⁴.

Although research has identified several risk factors for suicidal thoughts and behaviours, suicide attempts and completion rates have not seen significant reductions. Therefore researchers have asked what are the factors that determine the transition to acting out ³⁵.

Several studies have demonstrated how an intense state of psychomotor agitation and subsequent impulse dyscontrol is an acute risk factor for suicidal behaviour ^36,37. Agitation is characterized by increased motor function (e.g., restlessness, physical tension) and concomitant painful mental arousal (emotional turmoil, distress). A large prospective study identified psychomotor agitation as a significant predictor of suicide over a 1-year follow-up ³⁸.

Literature shows how the highest suicidal risk is found in mood disorders (monopolar and bipolar depression), substance abuse disorders and conduct disorders, while cognitive impairment prevails in the elderly.

In particular, the diagnosis most associated with suicidal risk is bipolar disorder. The suicide rate in patients suffering from this pathology is twenty times higher than in the general population and even fifty times higher for adolescents ³⁹.

Depressive states mixed with psychomotor agitation, or “agitated unipolar depression”, which is characterized by mental and motor agitation, intense emotional tension, and/or crowded thoughts, have been strongly associated with suicidal behaviour, measured both prospectively and posthumously through medical record review ^40-42.

Substance abuse is often comorbid with depressive spectrum disorders, a relationship that increases the risk of committing suicide; it is estimated that 25-33% of those who commit suicide have a history of substance abuse ⁴³.

As regards conduct disorders, Megan and colleagues (2016) highlighted that 70% of subjects who died by suicide had exhibited antisocial behaviour during their lifetime; it is no coincidence that prison inmates have a higher suicide risk than the general population. Conduct disorders, depression and substance abuse disorders often co-occur, increasing the frequency and lethality of suicide attempts ⁴³.

Another type of pathology that frequently correlates with the risk of suicide is borderline personality disorder, often diagnosed even among those who engage in parasuicidal behaviour, which manifests itself with affective imbalances, intense anger and impulsive behaviour. Impulsivity not only leads to angry behaviour, but also supports low frustration tolerance and an absence of planning.

However, emerging clinical conditions that deserve to be mentioned nowadays are diagnosis of autism spectrum disorder, eating disorders and all those conditions related to gender dysphoria or gender-modification surgery. With regard to autism spectrum disorders, the risk of suicide appears greater especially in case of comorbidity with behavioural anomalies, psychotic or low-functioning symptoms and history of abuse ⁴⁴. Eating disorders have seen an increase in suicide risk, especially in the second part of the pandemic period and in general when associated with depressive and anxiety symptoms ^45,46. Finally, regarding gender dysphoria, the risk of suicide would be greater than that in autism spectrum pathologies, with a greater incidence in female-to-male transitions ⁴⁷. In particular, the risk of suicide is greater in those who have already undergone sex change surgery ⁴⁸, although there are no indications of a contribution of hormone therapy in the increase of suicidal risk in this category of patients.

The comorbidity of cognitive impairment and geriatric pathology are more frequent in women, especially over 75 years of age ⁴⁹.

MANAGEMENT OF PSYCHOMOTOR AGITATION

Psychomotor agitation is a health emergency, requires immediate professional care and seriously compromises the safety of the patient. In addition, in some circumstances, it can also put the safety of the operator at risk. The treatment and management of patients suffering from psychomotor agitation presents considerable difficulties; motor impairment, lability, disinhibition, lack of cooperation and the possibility of aggressive behaviour make it difficult to assist, treat and take care of the patient. Agitation may also be a major indicator of imminent and impulsive suicidal behaviour. These characteristics cause the patient to require immediate attention, as well as quality professional care, but the patient’s lack of cooperation during episodes often delays obtaining an adequate psychiatric history and initiating treatment. The assessment of psychomotor agitation represents a challenge for healthcare professionals, since adequate assessment is fundamental to effectively manage the patient. Psychomotor agitation requires early recognition and appropriate assessment and management to minimize consequences and risks to the patient, professionals and the surrounding environment ^24,29.

Over the years, an incorrect clinical practice has spread according to which the management of psychomotor agitation and aggression is the prerogative of the psychiatrist.

The emergency room environment is often chaotic and highly emotional, therefore the first contact with the patient is not always immediate and effective, the operators often do not have adequate training: these are factors that can exacerbate the state of agitation. The psychiatrist is often called upon to carry out an immediate evaluation, which is rather complex as discriminating between a “functional” disorder or a state of agitation supported by an organic pathology often requires diagnostic tests and a longitudinal evaluation. The psychiatrist in turn has a defined field of expertise and at the same time is forced to evaluate clinical pictures that require complex anamnestic connections ^28,50.

A survey conducted by AcEMC (Academy of Emergency Medicine and Care) in 2016 among ED doctors and nurses highlighted a serious difficulty in knowing how to recognize a patient suffering from acute mental disorders and even more in knowing how to identify a patient at risk of harmful behaviour ⁵¹. In other cases, the presence of a psychiatric pathology in the anamnesis creates a tendency to underestimate organic comorbidities which may constitute the true emergency or which may be the cause of psychomotor agitation. In fact, the data shows that in 50% of cases a clinical evaluation is not routinely carried out to exclude an organic cause. Furthermore, the lack of adequate training of emergency room staff generates incorrect use of routes, spaces and resources.

The complexity of the patient with acute behavioural disorder in the ED often requires a multidisciplinary approach (emergency medicine doctors, mental health center doctors and general practitioners) which, unfortunately, is not always well codified to date ⁵¹.

These situations can therefore generate not only ineffective patient management, but can also simultaneously expose the patient to possible injuries and the staff to episodes of aggression.

As regards the Italian reality, a review of the national and international guidelines and recommendations of scientific societies was carried out in 2022 ^22,52-54, and a document was drawn up involving a network of Italian scientific societies (AcEMC, Academy of Medicine and Emergency Care, CNI-SPDC Italian National Coordination of Diagnosis and Psychiatric Care, SIP-Lo Lombardy Region Section of the Italian Society of Psychiatry, SITOX Italian Society of Toxicology) with the aim of standardizing the organisation, evaluation and management of the adult patient with acute behavioural disorder in ER ²⁸.

The document focuses on aspects such as the timeliness of the assessment, the multidisciplinary approach, team management, assistance in clinical and environmental safety.

Unfortunately, this standardization is not always feasible in the hospital context, as it is unfortunately hindered by critical issues such as the inadequacy of the environments, the lack of staff and lack of training of the operators.

PHARMACOLOGICAL AND NON-PHARMACOLOGICAL TREATMENT

Management of psychomotor agitation in emergency settings depends on the severity of the patient’s symptoms and the nature of the care setting. Figure 1 shows algorithm for the initial identification and first steps in the management of the patient with psychomotor agitation ⁵⁵.

The first approach should be non-pharmacological management ⁵⁶.

Therefore, the approach to an agitated patient should begin with environmental modification and verbal de-escalation in order to promote physical comfort and minimize external stimuli. Environmental issues and professional attitudes play a key role in the management of an agitated patient in an emergency room setting ⁵⁷. Environmental and/or organizational measures that can reduce the risk of violence include the implementation of general safety protocols, the assignment of a reserved room, a rapid and effective communication system to alert staff of the admission of a patient with a history of violent behavior, the availability of security personnel, easy access to an emergency exit, the removal of objects that could be used as weapons, the minimization of external stimuli, and continuous observation by staff to remove disruptive individuals when necessary. Professional attitudes are also important for the management of the agitated patient. A calm, positive, empathetic and respectful approach by trained staff can limit or alleviate agitation ^{58, 59}.

Descalation is an interactive and complex technique, a dynamic process in which the patient is led to a state of calm while the therapeutic relationship is established. Verbal de-escalation has been shown to reduce psychomotor agitation and the risk of symptom escalation, as well as the need for coercive measures. The goals of verbal de-escalation are: to re-establish the patient’s self-control; to introduce clear behavioural limits; to ensure the safety of the patient, staff and other users of the healthcare system; to achieve a therapeutic alliance with the patient that allows for an appropriate diagnostic assessment; to ensure the patient’s involvement in his or her therapeutic decision-making; and to reduce hostility and aggression, preventing possible episodes of violence ^{60, 61}.

Effective management requires that healthcare professionals act in a coordinated and timely manner, but it is recommended that only one person interact directly with the patient when verbal de-escalation is attempted. This interaction should be calm and concise using simple language, active listening, and repetition to establish trust and identify the patient’s feelings and needs ^60-62.

Pharmacological intervention becomes necessary when verbal and behavioral methods are ineffective.

Before administering any medication, clinicians should always attempt to diagnose the cause of agitation in order to discriminate the most appropriate pharmacological treatment ⁶³.

The ideal treatment for the acute management of psychomotor agitation in an emergency department setting should: be easy to administer and non-traumatic; rapidly calm the patient without excessive sedation; have rapid efficacy with low pharmacokinetic variability, as well as a low risk of adverse events and drug interactions ^{60, 64, 65}. Parenteral routes of administration (intramuscular, intravenous) ensure rapid action, but are nevertheless invasive and considered potentially traumatic for a patient in distress. Accordingly, oral administration should be the first-line route of administration for the pharmacological treatment of psychomotor agitation in order to create a therapeutic alliance, while parenteral routes are reserved for cases of severe agitation.

Furthermore, when possible, the drug should be administered as monotherapy.

Both verbal de-escalation and environmental modification techniques should be maintained throughout the process.

Figure 2 provides an algorithm for the selection of appropriate pharmacological agents, guided by the underlying cause and severity of agitation ⁵⁵.

Pharmacological management of agitation has traditionally employed three classes of drugs: first-generation antipsychotics (FGAs), benzodiazepines (BZDs), and second-generation antipsychotics (SGAs). Pharmacological treatment options for psychomotor agitation are summarized in Table III ⁶⁶. In this review, we focused on available parenteral and inhaled medications.

If agitation is due to psychotic symptoms the preferred pharmacological treatment option is antipsychotic agents, although benzodiazepines may also be considered when agitation is due to non-psychotic agitation. In cases where a rapid onset of antipsychotic medication is needed and the patient is cooperative, consider a medication with an inhaled route of administration (loxapine; or an oral/sublingual formulation (olanzapine, risperidone, asenapine, aripiprazole, quetiapine, ziprasidone, or haloperidol). Intramuscular (IM) antipsychotic agents (haloperidol, olanzapine, ziprasidone, aripiprazole, and levomepromazine) may be considered for patients who refuse to cooperate with an inhaled or oral medication. Although antipsychotics have been widely used in the treatment of psychomotor agitation, it should be noted that some are not specifically indicated for psychomotor agitation, but for the possible underlying psychiatric condition (oral formulations for olanzapine, risperidone, asenapine, aripiprazole, quetiapine, ziprasidone, and haloperidol; and oral formulations for olanzapine, risperidone, asenapine, aripiprazole, quetiapine, ziprasidone, and haloperidol). IM formulations of haloperidol and levomepromazine) ^{55, 66, 67}.

Caution should be exercised when the diagnostic etiology is not sufficiently clear (undifferentiated agitation) and the patient presents an altered state of consciousness, in this situation a medical condition should be considered for psychomotor agitation until proven otherwise. In this regard, both psychomotor agitation due to a medical condition and undifferentiated agitation should be initially treated with antipsychotic agents ^{64, 67}.

Furthermore, when the probable cause of psychomotor agitation is related to alcohol and/or benzodiazepine intoxication, caution should be exercised with the use of sedatives due to the risk of respiratory depression. Antipsychotics should be considered to avoid the risk of arterial hypertension and respiratory depression. In cases of alcohol and/or benzodiazepine withdrawal, a benzodiazepine should be considered to reduce the risk of seizures and delirium tremens. In addition, the addition of vitamin B treatment in these patients may also prevent serious complications in alcohol-using patients ⁶⁷.. In cases of cocaine and synthetic drug intoxication, initial sedation with benzodiazepines should be considered instead of antipsychotics to reduce the potential risk of seizures ⁶⁴.

In special circumstances and as a last resort to control the patient, uncooperative patients with severe psychomotor agitation may require the use of isolation and physical restraint to ensure the safety of the patient, caregivers, and staff, and to ensure pharmacological treatment.

These therapeutic approaches should always be chosen as a treatment of last resort.

When isolation is necessary, a specially equipped isolation room with protective walls and doors should be used to ensure stimulation reduction and patient safety.

Physical restraint is a procedure in which approved mechanical restraint devices are used to limit the physical mobility of the patient. Physical restraint is indicated for patients who exhibit behaviors that are dangerous to themselves or others, whose agitation cannot be controlled pharmacologically, and/or who require temporary restraint to receive appropriate treatment. Physical restraint should be considered exceptional and a last resort when other strategies have failed as this approach may result in negative outcomes for the patient (including negative effects on physical and mental health). From the beginning of this process, the patient should be informed about the reason for the restraint and given a further opportunity to comply with alternative treatment options. It should be explained that restraint is not a punishment but is intended to ensure the patient’s safety ⁶⁸.

CONCLUSIONS

Psychomotor agitation and aggression is a delicate and current issue. It represents an emergency in the medical field, even before the psychiatric one. Being aware of the risk of aggression is the first step in initiating procedures to prevent it.

It is important to know that not only psychiatric pathology is related to aggression, but many other causes can be the basis of violent behaviour in emergency care settings. Knowing how to promptly recognize the etiology of aggression can reduce the risk of its presentation, allowing timely actions to be implemented to resolve the cause of the problem. It would also be useful to reinforce intervention and management protocols for aggression in the medical setting, both to prevent injuries to healthcare workers and to reduce the incidence of self-harming in the patient. It is therefore hoped that standardized protocols and clinical support tools for the management of episodes of psychomotor agitation in emergency situations will be soon achieved.

Another important objective is to implement prevention and information programs and at the same time to facilitate the complex relationship between healthcare workers, patients or their families, which can lead to episodes of aggression, for example through organizational procedures aimed at improving the provision of healthcare services and perhaps even reducing waiting times.

Our study shares some limitations encountered in other narrative reviews: they are not often reproducible, related to the influence of the authors and setting on screening, sampling, and analysis. In particular, our review does not include an exhaustive search of all possible evidence on the topic; nonetheless, it aims at providing a flexible yet rigorous approach for knowledge synthesis, which would be useful to many educators and researchers, also as a basis for future studies.

Conflict of interest statement

The authors declare no conflict of interest.

Funding

None.

Ethical consideration

None.

Authors’ contributions

S.P.: conceptualization, writing—original draft preparation, review & editing, supervision; F.G.: writing—original draft preparation; V.A. review; A.C. review; A.B. review; G.C. review & editing, supervision, project administration.

Figures and tables

FIGURE 1. Algorithm for the initial identification and first steps in the management of the patient with psychomotor agitation (adapted from Vieta et al., 2017) ⁵⁵.

FIGURE 2. Algorithm for the selection of appropriate pharmacological agents, guided by the underlying cause and severity of agitation (adapted from Vieta et al., 2017) ⁵⁵.

TABLE I. Psychiatric disorders associated with agitation and violent behavior.

Agitation	Both agitation and aggression	Aggression
Psychiatric, psychopathological and psychological conditions
	Schizophrenia and psychotic disorders
	Mania
Agitated depression
Anxiety disorder (acute anxiety, panic attack)
	Post-traumatic stress disorders and other trauma- and stressor- related disorders
	Borderline personality disorders and other personality disorders
		Antisocial personality disorder
		Paraphilias
		Intermittent explosive disorder and other disruptive, impulse control, and conduct disorders
	Emotional response (fear, anger) to acute stressors in non-clinical individuals
Neurodevelopmental disorders
	Intellectual disability
	Autism spectrum disorder
	Attention deficit hyperactivity disorder
Substance use/intoxication/withdrawal
	Alcohol
	Cocaine and amphetamines
	Ecstasy
	Phencyclidine
	Steroids
	Other substances
Neurocognitive disorders
	Dementia
	Delirium/confusional state
Adapted from Penders et al., 2013 4; Rosell and Siever, 2015 5.

TABLE II. Medical disorders associated with agitation and violent behavior.

Neurologic illnesses Brain infections such as encephalitis, meningo encephalitis Head injury with intracerebral, subarachnoid or subdural haematoma Cerebral infarction Seizure disorders (interictal, post ictal or temporal lobe epilepsy) Hepatic encephalopathy Huntington’s disease Parkinson’s disease due to levodopa toxicity Wilson’s disease

Endocrinopathies Thyrotoxicosis Hypothyroidism Cushing’s syndrome Hyper parathyroidism

Metabolic disorders Hypoglycemia Hypoxia Electrolyte imbalance Hypocholesterolemia

Infections AIDS Syphilis Tuberculosis

Vitamin deficiencies Folic acid Niacin Pyridoxine Vitamin B 12

Temperature distubrances Hyperthermia Hyhpothermia

Adapted from Penders et al., 2013 4; Rosell and Siever, 2015 5

TABLE III.

Class	Drug	Mode of Admin	Dose Range (mg)	Adverse Effects	Contraindications	Treatment Associations and Recommendations
FGA	Haloperidol	IM, IV	5–30 (IM), 5–20 (IV)	NMS • Extrapyramidal side effects Torsade de pointes QT prolongation Falls Torsade de pointes Cardiac arrest Sudden death	○ Severe cardiovascular disorders ○ History of seizures EEG abnormalities ○ Dementia-related psychosis ○ Parkinson’s disease ○ Haloperidol hypersensitivity	Lorazepam, promethazine, or diphenhydramine (low risk of NMS) FGAs should only be administered during pregnancy if the benefit clearly outweighs the potential risk to the fetusUse with caution in patients <17 years of age
FGA	Chlorpromazine	IM, IV	50–150 (IM), 25–50 (IV)	Hypotension Falls Pain at the site of injection NMS Extrapyramidal side effects Alpha-adrenergic effects Prolonged unconsciousness Sudden death (for high doses)	○ History of seizures ○ Dementia-related Psychosis
FGA	Loxapine	Inhalation	9.1–18.2	Extrapyramidal side effects	○ Asthma ○ COPD
FGA	Zuclopenthixol Acetate	IM	50–150	Fatal cardiac events, Sudden death	○ Patients requiring immediate effect onset ○ (delayed onset of about 8 h) ○ Children and adolescents
FGA	Promazine	IM	50–300	Hypotension, Somnolence, Dizziness, Paralytic ileus, Ketoacidosis, NMS	○ Coma ○ Bone marrow depression ○ Pheochromocytoma ○ Central nervous system depression	In children ≥12 years and adolescents, dosage should not exceed 0.25–0.50 mg/kg
BDZ	Lorazepam	IM, IV	2–8 (IM, IV)	Respiratory depression, Ataxia, Excessive sedation, Memory impairment, Paradoxical disinhibition	○ Intra-arterial administration ○ Use in neonates or infants ○ Acute narrow-angle glaucoma ○ Severe respiratory insufficiency ○ Alcohol dependence and abuse ○ Sleep apnea	Oral risperidone Use lower dosages in children and adolescents Drug of choice for psychomotor agitation in epilepsy
BDZ	Diazepam	IV	10–40	Respiratory depression, Ataxia, Excessive sedation, Memory impairment, Paradoxical disinhibition	○ Intra-arterial administration ○ Use in neonates or infants ○ Acute narrow-angle glaucoma ○ Severe respiratory insufficiency ○ Alcohol dependence and abuse ○ Sleep apnea	Use lower dosages in children and adolescents Useful for psychomotor agitation in epilepsy
Anticonvulsant	Sodium Valproate	IV	400–1200	Increased liver enzymes, Hepatotoxicity, Excessive sedation, Ataxia	○ Intra-arterial administration ○ Use in neonates or infants ○ Hepatic disorders Porphyria ○ Coagulopathies ○ Pregnancy and breastfeeding ○ Mitochondrial disorders such as Alpers-Huttenlocher syndrome	IV sodium valproate doesn’t have direct psychiatric indications in the product label Useful for psychomotor agitation in epilepsy
Atypical Antipsychotic	Aripiprazole	IM	10–30	Low risk of extrapyramidal effects, Cardiovascular effects	Cardiovascular disorders	Lorazepam The safety and efficacy of aripiprazole injection have not been established in subjects ≥17 years
Atypical Antipsychotic	Olanzapine	IM	10–20	Hypotension Bradycardia Cardiorespiratory depression	○ Substance or alcohol abuse ○ Contraindicated in association with benzodiazepine	Administration with BDZ. isn’t recommended due to safety considerations. The safety and efficacy of olanzapine injection have not been established in subjects ≥17 years
Atypical Antipsychotic	Ziprasidone	IM	10–40	DRESS	Cardiovascular disorders	Safety and efficacy not established in subjects ≥17 years