Assessment and Management of Agitation in Consultation-Liaison Psychiatry.

AGITATION, AGGRESSION, AND VIOLENCE: AN OVERVIEW

Agitation is a complex topic, not only in definition but also in administration. It is a state of motor and cognitive hyperactivity marked by inappropriate or excessive verbal or motor activity, as well as emotional excitement.[1] According to Garriga et al., agitation is described as “excessive physical or verbal activity, a temporary emergent scenario that fractures the therapeutic partnership and necessitates prompt and immediate action”.[2] Agitation is defined by the Diagnostic and Statistical Manual of Mental Disorders (DSM-5)[3] as “There is a link between excessive motor activity and a feeling of inner stress. Pacing, fidgeting, wringing of hands, pulling of garments, and reluctance to sit still are examples of nonproductive and repetitive actions” (DSM -5). Agitation is also defined as a spectrum of physical, verbal, and emotional arousal symptoms ranging from minor to severe.[4] Table 1 summarizes the main behavioral components of Agitation, which are separated into nonaggressive and aggressive actions.

Table 1

Component behaviours of agitation

Nonaggressive behaviors	Aggressive behaviors
Restlessness (akathisia, fidgeting)	Physical
Wandering	Combativeness, punching walls
Loud, excited speech	Throwing or grabbing objects, destroying items
Pacing or frequently changing body positions	Clenching hands into fists, posturing
Inappropriate behavior (disrobing, intrusive, repetitive questioning)	Self-injury (repeatedly banging one’s head)
	Verbal
	Cursing
	Screaming

Because there is little systematic research in this field, determining the prevalence of acute agitation episodes will be complicated; however, this is a typical emergency seen in emergency rooms, triages, and inpatient facilities. Inpatient, outpatient, and emergency therapeutic settings all have different rates of agitation episodes. It ranges from 10.5%[5] to 52%.[6] It may be higher in emergency clinical settings. Involuntary medication, physical constraint, and seclusion may be used unnecessarily due to ineffective early detection and management of agitation. As agitation is linked to high-risk aggression and violence, early detection of Agitation in a therapeutic environment is critical. In a clinical context, this is critical to protect the patient’s, family’s, and healthcare staff’s safety. Well-developed standardized and appropriate procedures and algorithms can assist healthcare providers in identifying patients at risk of Agitation and assessing and detecting their agitation.[27] Martnez-Raga et al. also discuss the preliminary identification of agitation symptoms, which are all listed in Table 2.[8]

Table 2

Signs for preliminary identification of agitation

Inability to stay calm or still

Motor and verbal hyperactivity and hyperresponsiveness

Emotional tension

Difficulties in communication

As health care facilities are not equipped with skilled healthcare professionals (HCPs), and due to ethical/legal concerns on the various management processes, identification and management of the agitated patient in consultation-liaison are vital. Aggression, aggressive, harmful, or destructive behavior, and physical violence in consultation-liaison settings can impair the established therapeutic environment and rapport with a patient, both directly and indirectly. As a result, evaluating and disseminating empirically determined best practices for diagnosing and managing agitation that is culturally acceptable to patients, carers, and HCPs and economically cost-effective to the healthcare system becomes crucial.

It is critical to understand the etiopathogeneses of agitation, subsequent risk, and predisposition to physical aggression and violence. The etiology of agitation can be divided into two categories, neither of which is mutually exclusive:

Disease-related

In this case, the source of Agitation is a diagnosable disease, which can be either a medical or mental health problem.

Psychiatric symptoms of nonpsychiatric illnesses

Substance abuse due to intoxication or withdrawal

Psychiatric disease (primary).

Behavioral

Agitation results from a person’s actions rather than a medical or mental condition symptom. This grouping is unlikely if patients gain from medical intervention (e.g., anti-social behavior, criminal behavior). A quick verbal de-escalation trial is considered under these circumstances. Depending on the severity of the agitation, security or law enforcement may be considered. Table 3 lists several different etiologies. Past episodes of aggression/violence, a diagnosis of schizophrenia, the presence of impulsivity/hostility, more extended hospitalization, and involuntary hospitalization are all individual characteristics that consistently increase the risk of physical violence among agitated patients in psychiatric inpatient settings.

Table 3

Etiology of agitation

Primary psychiatric conditions	Medical conditions
Delirium	Head injury
Dementia	CNS infections- meningitis, encephalitis
Substance intoxication (alcohol, cannabis, cocaine, stimulants, hallucinogens, inhalants)	Encephalopathies (hepatic, renal, etc.)
Substance withdrawal (alcohol delirium)	Brain tumors/metastases
Schizophrenia	Stroke
Bipolar affective disorder	Wernicke-korsakoff’s psychosis
Agitated depression	Metabolic abnormalities (electrolytes, glucose, calcium, etc.)
Anxiety disorder	Hypoxia
Personality disorder-antisocial	Toxins/poisoning
Autism/intellectual disability	Hormonal (thyroid dysfunction)
Posttraumatic stress disorder	Seizure (postictal state)
	Adverse effects/toxicity of mediations

CNS – Central nervous system

ASSESSMENT, EVALUATION, AND APPROACH TO AGITATION

Assessing and evaluating Agitation for medical and psychological causes in therapeutic settings is critical. These three aspects must be highlighted by healthcare personnel during the examination of an intensely agitated patient:

The patient’s, caregivers, and healthcare workers’ safety

Prompt detection or exclusion of life-threatening medical and psychological conditions

A comprehensive differential diagnosis is considered to discover or rule out other common etiologies.

The safety of patients and employees remains at the top of the priority list. The other technique should be adapted to the patient’s level of agitation and the threat level they pose. Regardless of this strategy, it is important to note that any patient, regardless of their initial level of Agitation, is vulnerable to escalation, Agitation, and aggression under the right circumstances. If warning indicators [Table 4] are recognized during the initial evaluation, the physician and team can anticipate agitation/violence.

Table 4

The signs of impending violence[10]

Provocative behavior

Angry demeanor, fixed gaze, avoidance of gaze, hostile facial expression

Loud, excited, aggressive speech

Tense posturing (e.g., gripping arm rails tightly, clenching fists)

Pacing or frequently changing body position

Aggressive acts (e.g., pounding walls, throwing objects, hitting oneself)

Behaviour of looking for an escape

Physical signs of stress (e.g., hyperventilation, sweating, tremor)

The following are universal safeguards must be observed during the initial evaluation:

Searching and disarming of patients on a regular, non-confrontational, and nondiscriminatory basis[9]

Interviewing in a calm, quiet, private, but non-isolated environment[1011]

Objects that could be used as weapons are not allowed in the environment[1011]

The history and physical examination, which will lead the future evaluation and intervention procedure, can be considered once arrangements for an optimum assessment environment and safety measures have been observed.[12] Any agitation is invariably assigned to psychiatric causes by physicians (anchoring bias), and this bias may induce clinicians to miss or disregard other relevant evidence that could indicate life-threatening illnesses or injuries (confirmation bias).[13] As a result, a thorough history and physical examination can help to reduce bias in clinical decision-making. The primary goal at this stage is to rule out a medical or physical cause for the patient’s symptoms and treat them properly.[1415]

If patients are cooperative and just slightly agitated, they can describe the circumstances of their presentation, including triggers and appropriate actions. If patients are agitated and unwilling to cooperate, additional sources of information such as friends or family members, attendants, nursing staff, and papers can be used. As shown in Table 5, certain vital information must be acquired from accessible sources.

Table 5

Critical information which must be part of the history of presenting illness

Timing of agitation

Nature of agitation

Concomitant substance use

Medication details: changes, new medicines, stopped any medicine

Noncompliance to medications

Other medical conditions

DIFFERENTIAL DIAGNOSIS OF ACUTE AGITATION

The amount of agitation in an acutely agitated patient can range from non-agitation (average level of activity) to severe Agitation, and it is often dynamic in response to stimulations and interventions (verbal de-escalation or medications). Table 6 shows the standard differentials that can be examined.

Table 6

Common and potentially life-threatening aetiologies of the acutely agitated patient[16]

Toxicological	Metabolic
Alcohol intoxication or withdrawal	Hypoglycemia
Stimulant intoxication	Hyperglycemia/diabetic ketoacidosis
Other drugs or drug reactions	Hypoxia
Neurologic	Hyper/hyponatremia
Stroke	Other medical conditions
Intracranial lesion (e.g., hemorrhage, tumor)	Hyperthyroidism/thyroid storm
CNS infection	Shock syndromes
Seizure disorder	AIDS
Dementia	Hypothermia or hyperthermia
Psychiatric
Psychosis
Schizophrenia
Paranoid delusional disorder
Personality disorder
Antisocial behavior

CNS – Central nervous system; AIDS – Acquired immune deficiency syndrome

SMART MEDICAL CLEARANCE PROTOCOL (SMART)

Standardized screening protocols have been created to guide focused medical assessments and applied in some situations to help make quick decisions. The SMART Medical Clearance Approach (SMART), developed by Dr. Seth Thomas and colleagues, is one such protocol, as depicted in Figure 1. This can be tailored to meet the specific clinical demands of the practice.

Figure 1

SMART medical clearance form

PSYCHIATRIC EVALUATION OF AGITATION

The medical and psychiatric evaluations of agitation are complementary. Initial exploration – history of current disease, Psychiatric status examination (PSE), working diagnosis, differential diagnosis, risk assessment, completion of psychiatric history, and any definite diagnosis will be on the same agenda for both psychiatric and medical evaluations. Figures 2 and 3 show the evaluation algorithm.

Figure 2

Initial assessment of agitated patient. (*) - ICU - Intensive care unit, HDU - High dependency unit

Figure 3

Diagnostic evaluation

INTERVENTION

As a first thing to do, the psychiatrist should discuss with referring unit/clinician and explain/educate about the need of:

Intervention goals are from the individual patient’s perspective

Need of a structured setting to ensure proper evaluation/interventions

Privacy: room (private/semi-private)

A realistic and clear set of expectations with a written schedule

Staff who is responsible for the individual patient’s care

Attempt and enlist the patient in the treatment, i.e., past good response to the type of medication, total dose received side/adverse effects, and route of administration.

Attempting to engage the patient in the treatment, based on the patient’s previous positive reaction to the type of medication, total dose received side/adverse effects, and mode of administration.

GOALS OF INTERVENTION

The primary purpose is to keep patients and others safe. Collecting samples for laboratory evaluations, establishing rapport, arriving at a provisional diagnosis, facilitating the resumption of the treating team-patient relationship, calming the patient without sedation, and co-management with a medical/surgical team are all goals to be met during the process. Table 7 lists a few general guidelines to follow while dealing with Agitation.

Table 7

General recommendations in managing agitation

Initial attempts should identify the most likely cause of agitation and establish a provisional diagnosis and specific medication for the diagnosed cause/condition. Medications as restraint can be discouraged initially before arriving at any provisional diagnosis

Nonpharmacologic methods of interventions should be considered. Environmental modifications to reduce stimulation (low lighting, quiet room) and verbal de-escalation have to be considered, if possible, before medications

Medications sold calm the patient rather than induce sleep

Patient should be kept in the loop of proceedings, even if the patient is agitated. E.g., convey the need for restraints, choice of medication, selection of room/ward, check for preference of route of medicine administration, duration of conditions, etc.

If the patient is cooperative to take oral medicines, then oral medication can be preferred based on resources available for managing any acute exacerbation

MANAGEMENT OF AGITATION

Agitation management begins during the evaluation process; instead, both will co-occur. The steps for dealing with Agitation are as follows: (Hollman and Jeller, 2012)

Medical assessment and triage

Psychiatric assessment

Communication/behavioral Interventions and Verbal De-escalation [Table 8]

Table 8

Communication/behavioural interventions[18]

Nonverbal	Verbal
Maintain a safe distance	Speak in a calm, more transparent tone
Maintain a neutral posture	Personalize yourself
Do not stare; the eye contact should convey sincerity	Avoid confrontation; offer to solve the problem
Do not touch the patient
Stay at the same height as the patient
Avoid any sudden movements
Aligning goals of care	Monitoring intervention progress
Acknowledge the patient’s grievance	Be acutely aware of progress
Acknowledge the patient’s frustration	Know when to disengage
Shift the focus to a discussion of how to solve the problem	Do not insist on having the last word
Emphasize common ground
Focus on the big picture
Find ways to make small concessions

Interventions in the environment

Psychopharmacological therapy

Use of restraint/seclusion

Coordination with the medical and surgical teams

ENVIRONMENTAL INTERVENTIONS

Environmental interventions will focus on reducing patient sensory stimulation and establishing a safe atmosphere for patients, assisting clinicians in clinical observation, and assuring the patient’s and healthcare workers’ safety. Clearing the space, eliminating harmful objects, having personnel on hand as a “show of force,” close observation, calm dialogue, and lowering the sensory intensity are just a few examples.

RESTRAINTS FOR MEDICAL REASONS

For centuries, medical restraint and isolation have been used in medical and mental settings. Medical restraints have a long history and have developed through time in legal settings.[17] If the patient is unable to assent, written informed consent from the patient and a family member, or solely a family member/legal guardian, must be obtained in the presence of two witnesses. It is essential to know how long medical constraints will last. Every time restrictions are utilized, this should be done. Medical restraints should not be used as a form of punishment or discipline, as a substitute for less restrictive measures, or as a precaution when there is insufficient nursing/healthcare personnel, to name a few examples. Local algorithms can be created to assess when medical restraint can be employed based on the institution’s needs. Figure 4 depicts an example algorithm. Table 9 details the indications and contraindications for medical restraints. Table 10 shows the negative results associated with constraints.

Figure 4

Algorithm to use medical restraint

Table 9

Indications and contraindications for medical restraints and seclusion

Indications	Contraindications
Risk of imminent harm to self	Unstable medical condition
Risk of imminent harm to others	Severe drug reaction or overdose
Serious destruction to the environment	Punishment
	Staff convenience
Patient’s voluntary reasonable request	If experienced by the patient as positive
Decrease sensory overstimulation*	reinforcement for violence or disruptive behavior
Only for seclusion*

*Only for seclusion

Table 10

Adverse outcomes related to medical restraints

Patient-related adverse events	Staff-related adverse events
Asphyxiation	Spit upon
Choking/aspiration	Fracture or skin injury
Dehydration	Eye injury
Joint injuries	Permanent disability
Blunt chest trauma	Adverse emotional reactions (e.g., sadness, guilt, self-reproach, retribution)
Skin problems (e.g., Bruising)
Cardiac arrest/death
Rhabdomyolysis
Thrombosis (e.g., PE, DVT)
Escaping restraint
Escalating agitation
Re-traumatization
Emotional distress
Feelings of humiliation, fear, dehumanization, isolation, being ignored

PE – Pulmonary embolism; DVT – Deep vein thrombosis

ALTERNATIVE MEDICAL RESTRAINTS: PHYSICAL, CHEMICAL, ENVIRONMENTAL, AND SECLUSION

Physical

Hand straps, limb ties, belts, straitjackets, cloth body holders, four-point restraints, tucked securely in bedsheets, bedside rails, and mittens/gloves to avoid scratching are examples of physical restraints. Table 11 lists the elements to consider before employing physical restraints.

Table 11

Factors to be considered before the physical restraints

• What are the objectives of physical restraint?

• What are the risks associated with particular physical restraint?

• Management plan of specific anticipated risks associated with the particular restraint plan

• Consensus about the exact timing of using a specific physical restraint

• Patient-specific risk factors: age, gender, degree of cooperation, possible intoxication, any medications given, presence of cardiovascular, respiratory, neurological, or musculoskeletal disorders

• Any specific risk factors that may increase the patient’s risk of harm during restraint?

• Vulnerability to significant psychological trauma, especially for minors and the elderly

• Any cultural connotations

• Availability of emergency medicines, oxygen, required medical equipment

Chemical

These mainly consist of antipsychotics and benzodiazepines, given orally or intravenously depending on the severity of agitation. These are usually not part of the patient’s continuing treatment plan, and they are primarily intended to limit the patient’s conduct.

Environmental

This includes preventing the patient from moving freely on the premises to guarantee the patient’s and others’ safety. This may be a locked ward.

Seclusion

Entails isolating the patient in a room or area with the doors shut, preventing them from leaving.

MEDICAL RESTRAINT ORDER

The cause for the restriction, the duration of the medical restraint, the type of confinement, and the monitoring schedule should all be included in the medical restraint order. Nutrition, hydration, elimination, hygiene, range of motion, and circulation are all essential needs that must be met for the patient. In addition, the file should include the following documentation: a clinician’s order, an initial assessment by the resident doctor/duty doctor, and an in-person evaluation by the consultant as soon as possible, alternatives that were considered and tried, patient monitoring and outcomes of interventions used, periodic re-assessments for vitals and progress of agitation and physical condition, and psychoeducation of the patient and family member about the medical restraint provided.

The personnel in charge of physical restraint should be given specific instructions, as shown in Table 12.

Table 12

Instructions to the staff carrying physical restraint

Before physical restraint

Know the steps and plan clearly

Adheres to the plan discussed to execute the use of physical restraint safely. Ensure that mechanical and postural factors should not interfere in breathing or circulation: e.g., to avoid prone restraint or any other position where the patient’s head or trunk is bent towards their knees

During the physical restraint

Physical force used should be as per the necessity and in a reasonable manner

To avoid excessive physical force or verbal aggression

Ensure and monitor ABC all the time: Airway, Breathing, Circulation

Consciousness and body alignment have to be monitored by the clinician

Do not put direct pressure on the neck, chest/thorax, back, or pelvic area

Nurse/resident doctors/duty doctors must observe for physical or mental distress indications and ensure that clinical concerns are timely and appropriately escalated and appropriate intervention is provided

Specifically, monitor patients who have received intramuscular or intravenous medication within an hour before (or during) the use of physical restraint

On period reviews, if necessary, physical restraint positions can be changed as per the need and safety of the patient

Discontinue physical restraint as soon as it is no longer required

Risk assessment of continuing or discontinuing the physical restraint needs to be continuously assessed and balanced

Postrestraint debriefing

After the physical restraint ends and the patient is cooperative, a debriefing session with the patient and the patient’s caretakers must be conducted. This is done

To ensure open discussion about the events that led to the use of physical restraint

To discuss the patient’s experience of events and physical restraint

To allow the patient to clarify any doubts or seek more details

To provide an opportunity to identify the risk factors and plan strategies for the prevention of the need for physical restraint

DOCUMENTATION DURING RESTRAINT

Accurate and complete documenting of restraint episodes is required for adequate and improved care. It will start with the cause for the constraint, and the patients and family member’s/legal representatives’ informed permission. The documentation should include the patient’s mental status, details of medical restraints used and where they were used, vitals, airway/breathing/circulation, condition of limbs, range of motion in limbs, notes on skin care-change of posture, sponge bath, etc., liquids, food, and toileting offered. Appendix 1 is a sample medical restraint flowsheet.

APPENDIX

Appendix 1
Medical restraint flowsheet
I. Patient’s details
Name: Age: Gender: Male/female/others Hosp. No.
II. Clinician’s order
Name: Dr. Date: Time:
a. Doctor’s Orders (orders must be renewed every 12–24 h based on the practice)
1.
2.
3.
b. Initial Order
Start: Date/time
End: Date/time
c. Repeat order
Start: Date/time
End: Date/time
III. Alternatives attempted before initiation of medical restraints (check all that apply)
□Re-orient patient to time/date/place/person and/or situation
□Move patient closer to the nurses’ station
□Conceal lines/tubes/devices
□Minimize stimulation
□Reevaluate need for lines and tubes
□Appropriate diversional activities
□Repositioning
□Pain and sedation intervention
□Other
IV. Indication for using medical restraints
□Pulling lines
□Pulling tubes
□Removal of equipment
□Removal of dressing
□Inability to respond to direct requests or follow instructions
□Other
V. Type and details of medical restraints applied (Tick all that applies)
Wrists: Both/right only/left only
Legs: Both//right only/left only
Gloves/mittens: Both//right only/Left only
Waist Belt: Yes/No
Side railings: Yes/No
VI. Psycho-education of the patient
a. Informed the patient about the need and alternatives for medical restraints. Yes/No
b. Periodically patient has explained the behavior required to discontinue the restraint until an understanding was evidenced. Yes/No
Nurse’s name and sign Date and time
Doctor’s name and sign Date and time

ALTERNATIVES TO RESTRAINT

According to,[19] about 90% of emergency departments consider employing an alternative before restricting. The most popular strategy is the one-on-one verbal discourse, followed by a time-out or pastoral care. Konito et al. propose three common alternatives:[2021]

Interventions by nurses – The simple presence of nursing staff around the clock and regular staff talks with the patients will keep them engaged and reduce the likelihood of hostility

Multi-professional agreements involving patients – It was discovered that agreements between physicians, nursing staff, and patients about medications, dosage, ward difficulties, and restraint and seclusion criteria would encourage patients to participate in the treatment process, making them more cooperative and less aggressive

The use of authority/power, whether in the form of ward staff strength or a person with authority, such as a clinician or a senior nurse - presence or a conversation with the authority will aid in managing the violence without the need for restraint.

PHARMACOTHERAPY

Despite these efforts, the patient continues to threaten, toss things, pace, and make hitting gestures, prompting medication use. However, medication preparation should be done at all times. Each hospital ward should have a crash cart with the psychotropics needed for sedation. Security guards should be alerted before the start of the assessment so that they are ready to help right away.

GOALS OF PHARMACOTHERAPY

Pharmacotherapy for acute agitation should, in theory, include the following:

Be non-traumatic and straightforward to use

Have a quick beginning of an action (rapid tranquilization) and last long enough without causing severe sedation

Have a low or no risk of severe side effects and drug interactions.

Rapid tranquilization should be the goal of psychopharmacologic treatment[7]

Calming process separate from total sleep induction

Allows the patient to participate in the care

Helps the clinician to collect history, start a work-up, and initiate the treatment of unidentified conditions

Better therapeutic endpoint

Sleep induction is not the desired outcome.

It conflicts with the goal of participation by the patient

It may not be essential for the improvement in the agitation or decrease in the psychotic symptoms.

PHARMACOLOGIC CONSIDERATIONS

The drugs used to treat agitation should be kept in the crash cart. These should be simple to store. It will help if these can be reconstituted and administered quickly. Furthermore, these drugs should have a quick onset of effect. When using the parenteral method, the same medicine may act quickly. The treating team must decide the route of administration based on the severity of the agitation. In general, intravenous administration delivers drugs quickly, and the beginning of action is quicker than when pharmaceuticals are injected intramuscularly or orally. Intravenous formulations are preferred in cases of acute agitation. The medication should be adequate for a long time after being given. The drug supplied should have few side effects and no interactions with other medications. Table 13 lists the elements to consider while selecting drugs. Pharmacological intervention algorithm is given in Figure 5.

Table 14

Medications used in managing agitation

	Initial dose (mg)	Tmax* (min)	Can repeat (h)	Maximum dose (per 24 h), mg
Oral
Risperidone	2	1 h	2	6
Olanzapine	5-10	6 h	2	20
Haloperidol	5	30-60	15 m	20
Lorazepam	2	20-30	2	12
IM
Olanzapine	10	15-45	20 m	30
Haloperidol	5	30-60	15 m	20
Lorazepam	2	20-30	2	12
Ziprasidone	10-20	15	10 mg q 2 h	40
			20 mg q 4 h
>Aripiprazole	9.75	1 h	2	30
IV
Haloperidol	5	Immediate	4	10
Lorazepam	2	Immediate	2	12

Maximum doses can vary depending on the outcome. q 2 h – Every 2 hours; q 4 h – Every 4 hours, IM – Intramuscular; IV – Intravenous

Figure 5

Pharmacological intervention

EMERGENCY PSYCHIATRY/AGITATION PHARMACOLOGICAL PREPARATION SALIENT INFORMATION

Combination therapy

Medications can be chosen to target to manage different components of agitation

Anxiety and increased arousal, to use benzodiazepine

Psychotic symptoms, use of antipsychotic.

To reduce the side effects combining medications at low doses will help while obtaining the desired effect

Most common combination

Haloperidol 5 mg IM

Lorazepam 2mg IM.

Benefits

Faster reduction in agitation

Fewer injections required

Simple to administer

Lower incidence of EPS.

Side effects

Overall, very well tolerated

The most common adverse reaction is excess sedation.

Recent studies suggest sedation rates appear similar to lorazepam treatment alone.

Special population: Intensive care unit patients

Mechanically ventilated intensive care unit (ICU) patients: analgesia and sedation are recommended

Atypical antipsychotics can reduce the duration of delirium in ICU patients

Special population: Weaning of ventilation

Dexmedetomidine (alpha 2 adrenergic sedative).

Better than midazolam (hypertension and tachycardia, time intubated)[1]

Better than haloperidol (time intubated, length of stay).

Association for emergency psychiatry recommendations are outlined in Table 14.

Table 15

Use of benzodiazepines and typical antipsychotics in agitation

Medication class	Medication	Dosing	Side effects/considerations
Benzodiazepine	Alprazolam	Only available PO	Paradoxical reactions can be seen in character-disordered patients and can worsen symptoms in the elderly
		Initial dose is 0.5-4 mg/day
	Diazepam	PO, IM, IV	Calming/sedating effect with rapid onset
		Start at 5 mg	Use cautiously with elderly patients because of the long half-life
	Lorazepam	PO, SL, IM, IV	There are no active metabolites; therefore, there is a small risk of drug accumulation
		Start at 1 mg, moderate half-life (10-20 h)	Metabolized only via glucuronidation; therefore, it can be used in most patients with impaired hepatic function
			Drug of choice within this class due to the moderately long half-life
Typical antipsychotics	Haloperidol	PO, IM, IV	High-potency neuroleptic with favorable side-effect profile and cardiopulmonary safety
		Start at 5-10 mg IM, IV	IV form less likely to cause EPS
			ECG monitoring is needed to assess torsades de pointes or QTc prolongation
			NMS risk increases in poorly hydrated, restrained, and kept in poorly aerated rooms while given large doses of antipsychotics
			Frequent vital sign checks and testing for muscular rigidity are recommended
			Can cause hypotension

Adapted from Allen M, Currier G, Carpenter D: The expert consensus guideline series: treatment of behavioral emergencies, J Psychiatr Pract 11:1-112, 2005. CVD – Cardiovascular disorder; ECG – Electrocardiogram; EPS – Extrapyramidal symptoms; IM – Intramuscular; IV – Intravenous; NMS – Neuroleptic malignant syndrome; PO – Per os (by mouth, orally); SL – Sublingual; PR – Per rectum

The role of benzodiazepines and antipsychotics is shown in Tables 15 and 16.

Table 16

Use of benzodiazepines and typical antipsychotics in agitation

Medication class	Medication	Dosing	Side effects/considerations
Atypical antipsychotics	Risperidone	PO, OTD	No IM form is available
		Starting dose 0.5-2 mg acutely	Offers calming effect with the treatment of the underlying condition
			Orthostatic hypotension with reflex tachycardia
			Increased risk of stroke in the elderly with CVD
	Olanzapine	PO, OTD, IM	Useful in patients with poor reaction to haloperidol
		Starting dose 2.5-5 mg, maximum 30 mg/24 h with doses 2-4 h apart	Calming medication with the treatment of the underlying disorder
	Aripiprazole	PO, OTD	Akathisia risk
		Starting PO dose 5-10 mg, maximum 30 mg/day (currently IM formulation only for extended-release maintenance therapy)	Less sedating than other medications
			Increased risk of stroke in the elderly
			Good choice for patients with QT interval prolongation
Combinations	Haloperidol, lorazepam, diphenhydramine, or benzatropine	5 mg IM, 2 mg IM, 50 mg IM, 1 mg IM	Most commonly used in the acute setting
			Young athletic men are at increased risk for dystonia
			Akathisia must be considered if agitation increases after administration

PO – Per os (by mouth, orally); OTD – Orally disintegrating tablet; IM – Intramuscular; CVD – Cardiovascular disorder

CONCLUSION

This article includes a comprehensive discussion of the etiology, evaluations, treatment options, current international accepted agitation management practice, and practical guidance for physicians treating Agitation in inpatient psychiatric and consultation-liaison settings. Agitation should be recognized early using warning signals, and nonpharmacological therapies should be used to deescalate the patient’s agitation, according to internationally accepted agitation management practice. If these tactics do not work, recommendations suggest using medical restraint to calm patients rather than sedating them too quickly. The doctor must decide whether to use a medical restraint order that is non-invasive and simple to use, has a quick onset, successfully calms the patient without sedating them unduly, and treats the patient’s agitation. Medical staff must be trained through mock drills in addition to medical restraint orders and alternatives to ensure best practice. Along with that, documentation and monitoring of the patient’s continued need for medical restraints, mental status, details of medical restraints used and location of restraints, vitals, airway/breathing/circulation, condition of limbs, range of motion in limbs among patients on medical restraint orders, and the alternative is necessary to ensure adequate care and follow the best practice, which is socio-culturally acceptable, suitable, and legally accepted for low-intensity medical restrain.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

Table 13

Factors to be considered while choosing medications

• Patient’s details: Age, gender, comorbid medical conditions, substance use, allergies

• Agitation details: Cause, presentation

• Pharmacological considerations: Route of administration, rapidity of action, duration of action, adverse effects and interaction with other medications, past good response to any particular psychotropic

• Monitoring facilities: Airway, breathing, and circulation monitoring facilities; crash cart for any medical emergency, availability of ICU and ventilator

• Patient’s preference of route of administration

• Route of administration

• Oral: Tablets or syrups can be preferred if the patient accepts

• IM: Helps in rapid elevation of drug plasma levels and faster onset of action, leading to an immediate reduction in agitation

• IV administration should be preferred when rapid restraint is essential

• IM – Intramuscular; IV – Intravenous; ICU – Intensive care units

Medical restraint flow sheet contd…

VII. Patient’s monitoring chart

In the first hour, observation checks are done every 15 min, then hourly

•15 min: Time_______ Behavior (**See Key)___________ Initials____________

•30 min: Time_______ Behavior (**See Key)___________ Initials____________

•45 min: Time_______ Behavior (**See Key)___________ Initials____________

•60 min: Time_______ Behavior (**See Key)___________ Initials____________

Time (hours)	7	8	9	10	11	12	1	2	3	4	5	6	7	8	9	10	11	12	1	2	3	4	5	7
Observation check
(**See Key) Q1h
Circulation/skin check
Q2h
Food/fluids
Q2h
Elimination (or F for Foley in place)
Q2h
Range of Motion
Q2h
Change in type or number of Restraint (*See Key) Q1h
Staff initials
Key: *Restraints	**Observed Behavior (May use more than one)
NC=No change	CF – Confused; AG – Agitated; VA – Verbally abusive; TF – Tearful; JC – Hallucination; DL – Delusional; A – Patient asleep; SD – Sedated; SB – Subdued; CA – Calm; CO – Cooperative; O – Other
↑3=Increase to 3pt
↑4=Increase to 4pt
↓1=Decrease to 1pt
↓2=Decrease to 2pt
↓3=Decrease to 2pt

Table investigations and rationale

Investigation	Rationale
Haemogram: Hb, TC, DC, ESR, Platelets, Indices	To evaluate infective etiology, anemia
RFT: Urea, creatinine, sodium, potassium	To evaluate renal causes and electrolyte imbalances
LFT: Total/direct bilirubin, AST, ALT, ALP, GGT, total protein, albumin, globulin, A/G ratio	To evaluate hepatic causes, acute/chronic liver disease, hepatic encephalopathy
TFT: T3, T4, TSH	To evaluate thyroid etiology
Sugars: RBS, FBS, PPBS, HBA1C	Hypoglycemia/hyperglycemia related causes
Urine complete analysis, microscopy, and urine drug screening	For detection of substances
Serum toxicology	Based on the history
Drug levels	If on valproic acid, lithium, carbamazepine, phenytoin, and toxicity is suspected
Ultrasound abdomen and pelvis	Based on history and indication: Blunt trauma abdomen
12-Lead ECG	For cardiac causes and cardiac monitoring for medication-related changes
CT/MRI brain/part of the interest	As per the history and indication
Lumbar puncture and EEG	As per the indication

Hb – Hemoglobin; HBA1C – Hb A1C; AST – Aspartate transaminase; ALT – Alanine aminotransferase; FBS – Fasting blood sugar; CT – Computed tomography; MRI – Magnetic resonance imagin

Association for Emergency Psychiatry Recommendations

Situation	Preferences
Undifferentiated agitation/suspected intoxication with stimulant or withdrawal from alcohol/benzodiazepine	Oral benzodiazepines (e.g., lorazepam 1-2 mg)
	Parenteral benzodiazepines (e.g., lorazepam 1-2 mg IM or IV)
Acute intoxication with CNS depressant (e.g., alcohol)	Avoid benzodiazepine if possible
	Oral 1st generation antipsychotic (e.g., haloperidol 2-10 mg)
	Parenteral 1st generation antipsychotic (e.g., haloperidol 2-10 mg IM)
Delirium (not associated with alcohol or benzodiazepine withdrawal)	Oral 2nd generation antipsychotic (e.g., risperidone 2 mg, olanzapine 5-10 mg)
	Oral 1st generation antipsychotic (e.g., low dose haloperidol)
	Parenteral 2nd generation antipsychotic (e.g., olanzapine 10 mg IM)
	Parenteral 1st generation antipsychotic (e.g., haloperidol low dose IM or IV)
Schizophrenia or mania	Oral 2nd generation antipsychotic alone (e.g., risperidone 2 mg, olanzapine 5-10 mg)
	Oral 1st generation antipsychotic (e.g., haloperidol 2-10 mg with benzodiazepine)
	Parenteral 2nd generation antipsychotic (e.g., olanzapine 10 mg IM)
	Parenteral 1st generation antipsychotic (e.g., haloperidol 2-10 mg IM) along with benzodiazepine (e.g., lorazepam 1-2 mg)

CNS – Central nervous system; IV – Intravenous

Salient pharmacological features of benzodiazepines

Class/molecule	Pharmacological features
Benzodiazepines	Act by facilitating the activity of GABA, which is a major inhibitory neurotransmitter
	Therapeutic effects due to decreased arousal
	Target symptom anxiety
	Can be used alone or in combination with antipsychotics
	Preferred in a patient in whom agitation is secondary to alcohol or sedative withdrawal
	Side effects to consider
	Excessive sedation; added sedation when combined with CNS depressant
	Respiratory depression; to avoid in patients with risk for CO2 retention
	Paradoxical disinhibition in high doses in patients with structural brain damage, mental retardation, or dementia
	Ataxia
Typical antipsychotics (FGA)	Dopamine antagonist
	Advantageous effects: as antipsychotic and for agitation
	Preferred in acute agitation
	Low potency FGA: Not recommended
	High potency FGA (haloperidol): virtually no anticholinergic properties, little risk of hypotension, no respiratory depression, can be given IV, the onset of action is within 30 min and lasts up to 12-24 h
	Side effects to consider
	EPS
	Neuroleptic Malignant Syndrome (NMS)
	Dystonia
	Akathisia
	Parkinson-like effects
	QTc prolongation
	May lower the seizure threshold
Atypical antipsychotics (SGA)	Broader spectrum of response
	Different side effect profile
	Fewer EPS and akathisia
	QTc concern remains
	Metabolic syndrome on prolonged use
	Olanzapine
	IM dose range of 5-10 mg
	Maximum of 30 mg/day
	15-45 min until peak plasma concentration
	21-54 h elimination half-life
	Oral dose range 5-10 mg and flexible-dose up to 40 mg/day
	Risperidone
	1–6 mg PO or ODT
	Oral risperidone concentrate 2 mg+oral lorazepam 2 mg equivalent to IM haloperidol 5mg+IM lorazepam 2 mg
	Oral risperidone 2 mg equally effective as oral haloperidol 5 mg
	Risk of EPS
	Aripiprazole
	Partial dopamine agonist
	Oral aripiprazole 15 mg as effective as oral olanzapine 20 mg
	Low risk for QT interval prolongation (<1%)
	Quetiapine
	25 mg onwards up to 400 mg
	1–3 h to peak plasma concentrations
	Shallow risk of EPS
	Sedation and orthostasis are side effects

FGA – First generation antipsychotics; EPS – Extrapyramidal symptoms; SGA – Second generation antipsychotics; CNS – Central nervous system; IV – Intravenous