Agitation, aggression and rapid tranquillisation

• Agitation is an acute behavioural emergency in which arousal, restlessness and motor activity rise, and it can come from a medical illness, intoxication or withdrawal, or a psychiatric condition.
• De-escalation (one voice, space, calm body language, clear short messages) is treatment in its own right, not a prelude to medication.- The first clinical question is not "which drug?" but "is there a medical or substance cause that must be treated first?" New-onset agitation is assumed medical until shown otherwise. ^[2]
• If oral medication is possible it is preferred; if not, UK first-line rapid tranquillisation is intramuscular (IM) lorazepam on its own, or IM haloperidol plus IM promethazine, chosen to match the cause. ^[2]
• Restrictive interventions are measures of last resort, legally bounded and time-limited, and every use is followed by an immediate debrief and a formal external review within 72 hours.

By the end of this topic you should be able to:

1. Define agitation and distinguish it from aggression, and grade its severity using a simple activity scale.
2. Build a differential diagnosis of medical, substance and psychiatric causes, and triage a patient to the appropriate level of care.
3. De-escalate an agitated person using verbal and non-verbal techniques, and debrief afterwards.
4. Choose oral versus parenteral treatment, name first-line regimens, and give them safely with appropriate monitoring.
5. Apply the legal and ethical rules that govern restraint, seclusion and rapid tranquillisation in your jurisdiction.
6. Conduct an immediate post-incident debrief and a formal post-incident review, and use them to reduce future incidents.

This topic covers the clinical pathway from a person becoming agitated or aggressive through to recovery: recognition and triage, medical and substance causes, de-escalation, pharmacological treatment (oral first, then intramuscular rapid tranquillisation), safe restraint and seclusion, the legal framework, and post-incident review. It is a practical, safety-critical pathway rather than a single diagnosis, and it draws on the NICE guideline NG10 (2015, last reviewed 11 July 2024) for the UK legal and monitoring framework, the Royal College of Psychiatrists audit data on how rapid tranquillisation is actually used in UK services, and the BAP/NAPICU 2018 consensus and the American Association for Emergency Psychiatry Project BETA series for medication choice and non-pharmacological management ^[1][6][7]. ^[2]

Agitation is common in emergency and mental health settings, and staff safety is a real concern: workplace violence in these settings is frequent, and untreated severe agitation (for example excited delirium) can kill. Calming the person is therefore both a safety task and a therapeutic one. The aim of medication, when it is needed, is to produce calmness that allows assessment, not sleep ^[2].

The severity of activity is easy to grade with the Behavioural Activity Rating Scale (BARS), which does not require the person to answer questions: 4 is quiet and awake with a normal level of activity, 5 is signs of overt physical or verbal activity that settle with instruction, 6 is extremely or continuously active and not requiring restraint, and 7 is violent and requiring restraint. A score other than 4 should trigger clinical evaluation ^[3][4]. ^[6]

Before labelling behaviour as psychiatric, ask three questions in parallel: is there a medical cause, is there intoxication or withdrawal, and is this behaviour consistent with a known psychiatric illness? Collateral history from family, paramedics and police is invaluable in the first minutes, because an agitated person may be unable to give any history.

New-onset agitation is presumed to be medical until proven otherwise. A presentation inconsistent with a person's known psychiatric illness, or agitation beginning after the age of 45 with no psychiatric history, points strongly to a medical cause, because most psychiatric illnesses begin earlier ^[3].

Medical causes fall into recognisable groups:

• Head trauma (remember deceleration without direct head injury can cause brain injury), stroke, tumour, epilepsy (post-ictal state) and delirium.
• Infection (sepsis, meningitis, encephalitis; fever may be absent in the immunocompromised).
• Metabolic and cardiopulmonary: hypoglycaemia, hyperglycaemia, hypoxia, electrolyte disturbance, renal or hepatic encephalopathy, thyrotoxicosis.
• Toxins and medication: alcohol and other drug intoxication or withdrawal, anticholinergic toxicity, toxic levels of psychiatric or anticonvulsant medication, neuroleptic malignant syndrome, serotonin syndrome.
• Environmental exposure to toxins.

Delirium is the single most important medical cause to spot: it is a disturbance of attention and awareness with fluctuating cognition (memory, orientation, perception), developing over hours to days, and it signals an underlying medical or toxic process. Visual hallucinations are especially characteristic. Treating the agitation without treating the delirium misses the point, and antipsychotics or benzodiazepines may only mask it. Delirium from alcohol or benzodiazepine withdrawal is treated with a benzodiazepine; other delirium is best managed by correcting the cause, with short-term antipsychotic if immediate control is needed ^[2][3].

At triage, obtain vital signs, finger-stick glucose and oxygen saturation if possible. A complete set of vital signs, glucose and oxygenation should be part of the medical evaluation. Abnormal vital signs, abnormal examination findings, overt signs of intoxication or withdrawal, toxin exposure, decreased awareness with attentional problems, or new-onset agitation all indicate a medical cause. In a non-medical setting, any of the dangerous findings (airway, breathing or circulation problems, very high or low temperature, suspected head injury, seizure, severe dehydration, severe agitation at the top of the scale) should trigger immediate transfer to an emergency department. Directed laboratory testing and imaging, chosen for the most likely cause, are preferred to routine screening tests, which are often low yield ^[3].

De-escalation is a treatment in its own right and should be attempted before, and continued during, any restrictive intervention. It is often successful in less than 5 minutes, and even a series of a dozen repeated clinician-patient loops would take 10 minutes at most, so persistence is worthwhile before moving to coercion ^[4].

• Safety first for the person, staff and others in the area.
• Help the person manage emotion and regain control, rather than controlling them.
• Avoid restraint and coercive interventions that can escalate agitation.
• Use verbal and non-verbal skills: respect personal space, a calm and congruent demeanour, appropriate eye contact, and no provocation.
• Separate the person from others into a quiet area (not a seclusion room unless that is clinically indicated), keep staff from becoming isolated, and reduce environmental stimulation.
• One clinician speaks; orient, reassure, be concise (short sentences, simple words), repeat, and ask what the person wants.
• Agree where possible (agree with the truth, in principle, or with the odds) and agree to disagree where not.
• Set clear limits respectfully and coach the person on how to stay in control.
• Offer choices (including verbal, voluntary medication, oral versus injectable) and realistic kindness (food, drink, blankets), without promising what cannot be delivered.
• Be optimistic and provide hope with realistic time frames.
• Debrief both the person and the staff afterwards.
• Use objective scales such as BARS so that early escalation is not missed or ignored ^[1][4].

If a person can cooperate with taking oral medication, oral preparations are preferred over injections, and medication should be matched to the most likely cause of the agitation rather than used as a chemical restraint ^[2].

Oral medication is used in two ways here: as p.r.n. medication described in the care plan as part of a de-escalation strategy (p.r.n. medication on its own is not de-escalation), and as scheduled medication in the acute plan. The maximum daily dose, including routine, p.r.n. and rapid tranquillisation doses, must not inadvertently exceed the British National Formulary (BNF) maximum, and total antipsychotic exposure on the day of rapid tranquillisation must be counted, because a quarter of such episodes in UK practice push the day's antipsychotic dose to or above the high-dose threshold ^[1][6].

Oral options commonly used:

• Benzodiazepines (lorazepam is the dominant oral benzodiazepine in UK practice) are the commonest oral treatment, used in 60% of episodes in which only oral medication was given in the 2016 UK national audit; they help especially where anxiety, stimulant intoxication or alcohol/benzodiazepine withdrawal is the driver ^[2][6].
• Antipsychotics (haloperidol most commonly, then quetiapine and olanzapine) are used alone in only about 1 in 10 such oral episodes; antipsychotics are preferred when the agitation is psychosis-driven because they treat the underlying illness ^[2][6].
• Oral risperidone has the strongest evidence of the second-generation antipsychotics for safe and effective use in acute agitation, with smaller support for oral olanzapine ^[2].

Guide choice by the suspected cause (the same principle as for rapid tranquillisation below) ^{[2] [7]}.

In adults, NICE NG10 recommends:

• intramuscular lorazepam on its own, or
• intramuscular haloperidol combined with intramuscular promethazine. ^[6]

Choose between them using the person's preferences (including advance statements), physical health problems or pregnancy, possible intoxication, previous response and adverse effects, potential interactions, and the total daily dose prescribed and administered ^[1].

• If there is insufficient information to guide the choice, or the person has never taken antipsychotic medication, use IM lorazepam ^[1]. ^[2]
• If there is cardiovascular disease, a prolonged QT interval, or no ECG has been done, avoid IM haloperidol plus IM promethazine and use IM lorazepam instead ^[1].
• Benzodiazepines (especially lorazepam) are preferred where alcohol or benzodiazepine withdrawal may be contributing ^[2].
• Antipsychotics are preferred for psychosis-driven agitation. Second-generation agents with supportive data are preferred over haloperidol where an antipsychotic is indicated; oral risperidone or olanzapine first if cooperative, otherwise IM olanzapine or IM ziprasidone ^[2].
• In alcohol intoxication, antipsychotics (haloperidol has the longest track record) are preferred, because adding benzodiazepines risks dangerous sedation; distinguish intoxication from withdrawal, where benzodiazepines win ^[2].
• In delirium that is not due to alcohol or benzodiazepine withdrawal, second-generation antipsychotics are preferred, haloperidol is acceptable in low doses, and benzodiazepines are generally avoided because they can worsen delirium ^[2].
• Where the cause is unclear and the person is not psychotic, a benzodiazepine is first line; if psychotic features are present, an antipsychotic ^[2].

NICE NG10 does not itself publish fixed milligram doses; it defers to the BNF for exact licensed doses, and prescribing should be a single initial dose that is not repeated until its effect has been reviewed ^[1]. The "5 and 2" regimen widely used in UK inpatient practice (haloperidol 5 mg plus lorazepam 2 mg, both intramuscular) is named in the Royal College of Psychiatrists 2019 audit, which found it was the commonest combination even though the recommended combination (haloperidol plus promethazine) was rarely used. That audit also cited the Battaglia 1997 trial comparing haloperidol 5 mg IM, lorazepam 2 mg IM, and their combination for psychotic agitation, in which the combination required fewer further injections and had fewer extrapyramidal effects than haloperidol alone ^[6].

Observational data caution against high-dose sedation: initial intramuscular doses of haloperidol, droperidol or midazolam above 10 mg were associated with double the incidence of side effects (hypotension, oxygen desaturation) without more rapid or effective sedation ^[6]. Combining olanzapine with benzodiazepines is not currently recommended by the manufacturer and has been associated with decreased oxygen saturation in alcohol-intoxicated patients, so that combination should be avoided ^[2].

Intravenous haloperidol, although not an FDA-approved route, is used in some settings; if it must be given, the dose should be limited to 5 to 10 mg per day with continuous ECG monitoring, and both haloperidol and droperidol carry warnings about QT prolongation ^[2].

After rapid tranquillisation, monitor side effects, pulse, blood pressure, respiratory rate, temperature, hydration and level of consciousness at least every hour until there are no further concerns. Monitor every 15 minutes if the BNF maximum dose has been exceeded, or if the person appears asleep or sedated, has taken illicit drugs or alcohol, has a pre-existing physical health problem, or has been harmed by a restrictive intervention ^[1].

Resuscitation equipment (including an automated external defibrillator, bag-valve mask, oxygen, cannulas, intravenous fluids, suction and first-line resuscitation medicines, checked weekly) must be immediately available where restrictive interventions might be used, with staff trained in immediate life support and a doctor trained to use resuscitation equipment on call ^[1]. In the hour after rapid tranquillisation, UK audit data show the person was calm or asleep in about three of five episodes, but roughly a quarter remained extremely or continuously active, so reassessment and planning for the next step matter ^[6]. Each additional antipsychotic dose has a half-life of 20 hours or more, so frequent repeated doses risk accumulation; the effect of each dose is reviewed before any further dose ^[1][6].

Restraint is a last resort, after de-escalation and other preventive strategies (including p.r.n. medication) have failed and there is potential for harm if nothing is done, and de-escalation continues throughout. Staff should be trained together as teams with a clear lead. Restraints are never used to punish, humiliate or establish dominance, must be proportionate, the least restrictive option, for no longer than necessary, and must take account of physical health, frailty and age ^[1].

Safety rules for manual restraint (NICE NG10):

• Avoid taking the person to the floor; if it is unavoidable, use the supine (face-up) position where possible, or prone (face-down) only as briefly as necessary.
• Do not interfere with airway, breathing or circulation: no pressure on the rib cage, neck or abdomen, and do not obstruct the mouth or nose.
• Do not interfere with communication by obstructing the eyes, ears or mouth.
• Take extra care with people who are physically unwell, disabled, pregnant or obese.
• Preserve dignity and safety.
• Do not routinely use manual restraint for more than 10 minutes; consider rapid tranquillisation or seclusion instead. ^[1]
• Keep the level of force justifiable, appropriate, reasonable and proportionate, for the shortest time possible.
• One staff member leads throughout, with others supporting the head and neck, checking airway and breathing, and monitoring vital signs ^[1].

Physical health is monitored for as long as clinically necessary afterwards. Where restrictive interventions may be used, organisations should define the staff-to-patient ratio and minimum numbers of trained staff required ^[1].

Seclusion (involuntary confinement in a room or area from which the person cannot leave, used only for violent or self-destructive behaviour) and restraint require prior attempts at less restrictive measures and must be discontinued at the earliest possible time. In many systems a drug given only to control behaviour at a non-standard dose counts as a restraint, and least-restriction principles apply to all of these interventions ^[5].

A patient in seclusion or restraint must be evaluated face to face within 1 hour by a suitably trained clinician, with continuous observation and a review at least every 2 hours, and the seclusion room should be designed for visibility, safety, ventilation and access to toilet facilities ^[1][5].

Where seclusion is combined with rapid tranquillisation, proceed with caution, observe the person within eyesight by a trained member of staff, and reassess whether seclusion can end once the medication has taken effect ^[1].

This is a UK-focused guideline set (NICE NG10); law differs between jurisdictions, so local statutes and clinical advice must be followed. The same ethical principles recur across systems.

• Human rights and capacity. Restrictive interventions must comply with the Human Rights Act 1998 and the relevant rights under the European Convention on Human Rights. Unless a person is detained under mental health legislation or subject to a deprivation of liberty authorisation, restrictive interventions must not amount to a deprivation of liberty ^[1].
• Detention. Seclusion of adults is permitted only for people detained under the Mental Health Act 1983; if a non-detained person is secluded in an emergency, arrange an immediate mental health assessment under the Act ^[1].
• Advance planning. Check for advance decisions or statements about restrictive interventions as soon as possible (for example on admission) and respect them. If none exist, encourage the person to make one, including an understanding of the side-effect profiles of medicines used for rapid tranquillisation ^[1].
• Consent and confidentiality. Involve the person in decisions; where they cannot participate, review plans later and involve carers. In an emergency, revealing what is medically necessary to third parties without consent is generally considered ethical and legally defensible, and confidentiality does not stop a clinician receiving information from relatives ^[1][8].
• Working with police. Organisations should have locally agreed protocols for police in health settings and for health professionals in police cells ^[1].
• Staff training. Staff in settings where restrictive interventions could be used should be trained in the Human Rights Act 1998, the Mental Capacity Act 2005 and the Mental Health Act 1983, and in de-escalation and safe restraint techniques ^[1].

An incident is any event involving restraint, rapid tranquillisation or seclusion (but not observation). After every incident:

1. Once risks are contained, conduct an immediate post-incident debrief involving both a nurse and a doctor, addressing physical harm to anyone involved, ongoing risks, and the emotional impact on the person, witnesses and staff ^[1].
2. Use the ward's anticipation and reduction framework (team factors, environment, diagnosis, symptoms, personal factors, restrictive interventions that worked before) to identify quickly addressable factors and amend care and risk plans ^[1].
3. Give the person, witnesses and staff the opportunity to discuss the event in a supportive way once they have regained composure; allow the person to write their perspective in the notes and involve an advocate or carer if they agree ^[1].
4. Notify the service user experience monitoring unit, or equivalent group, to run the formal external post-incident review, led by a service user with staff from outside the ward, completed no later than 72 hours afterwards, using the same framework to examine physical and emotional impact on all involved ^[1].
5. Report to the trust board or governing body on violent incidents, restrictive interventions and learning gained ^[1].

• Older adults are vulnerable to medical causes (infection, metabolic problems) and to over-sedation; benzodiazepine choice should avoid accumulation.
• Children and adolescents (aged 13 to 17) and children aged 12 and under are covered by the same guideline but with weight- and age-appropriate dosing and greater emphasis on non-pharmacological methods; local paediatric guidance should be followed.
• Pregnancy should steer choice away from IM haloperidol plus promethazine towards IM lorazepam and involve obstetric and psychiatric input.
• Low-resource settings. Most cases can be managed without a laboratory: take a careful history and vital signs, do finger-stick glucose, look for infection and withdrawal, and remember that calming first enables assessment. De-escalation costs nothing; resuscitation equipment and a clear protocol for transfer are the critical investments. Where parenteral lorazepam or haloperidol is unavailable, seclusion and skilled observation plus rapid transfer become central, and one should not use unlicensed alternatives without local guidance.

• Agitation is an acute behavioural emergency on a continuum to aggression; many agitated people are not aggressive.
• Default to a medical cause until shown otherwise; new-onset agitation after age 45 strongly suggests one. ^[3]
• Delirium (fluctuating attention and awareness, often with visual hallucinations) is the most important medical cause and must be treated at its cause.
• De-escalation succeeds often and quickly and is treatment; one voice, safety, space, empathy, concise repetition, and offering choices are its core.
• p.r.n. medication is only part of de-escalation when used alongside verbal techniques, never alone.
• Oral treatment is preferred when possible, with oral benzodiazepines and antipsychotics chosen to match the cause.
• Rapid tranquillisation in adults (NICE NG10): IM lorazepam alone, or IM haloperidol plus IM promethazine, dosed as a single initial dose and reviewed before any repeat. ^[1]
• Avoid IM haloperidol plus promethazine when there is cardiovascular disease or a prolonged QT, or no ECG; use IM lorazepam instead.
• Benzodiazepines suit alcohol or benzodiazepine withdrawal and unknown non-psychotic causes; antipsychotics suit psychosis; delirium (other than withdrawal) is treated by correcting the cause, with second-generation antipsychotics or low-dose haloperidol if necessary.
• Do not combine olanzapine with benzodiazepines, and avoid benzodiazepines in alcohol intoxication.
• Restraint is a last resort, staffed and proportionate, avoided on the floor where possible, never applied to obstruct airway, breathing or circulation, and not routinely continued for more than 10 minutes.
• Drugs used only to control behaviour at a non-standard dose count as restraint in some systems.
• Seclusion requires detention under the Mental Health Act in UK practice and face-to-face review within 1 hour.
• Restrictive interventions must respect human rights and mental capacity law; police and advance statements matter.
• After every incident, an immediate nurse-and-doctor debrief and a formal external review within 72 hours are required.
• Monitor after rapid tranquillisation: at least every hour routinely, every 15 minutes if the maximum dose was exceeded or there are extra risks. ^[1]
• Count the total daily antipsychotic dose on the day of rapid tranquillisation.

Delirium; psychosis and schizophrenia; bipolar disorder and mania; substance use and alcohol dependence; neuroleptic malignant syndrome; serotonin syndrome; self-harm and suicide risk assessment; capacity and mental health law.