Agitation and aggression

Agitation is excessive motor or verbal activity driven by internal tension, ranging from restlessness and pacing to purposeless, threatening or violent behaviour. Aggression is hostile verbal or physical behaviour directed at people or property. Together they are a behavioural emergency, with danger to the patient, staff and others. In a large share of patients they have a medical cause until proven otherwise.

Management has three steps. First, safety. Second, identify and treat the cause (hypoxia, hypoglycaemia, intoxication, withdrawal, delirium, head injury, infection, psychosis, mania). Third, calm the patient with the least restrictive means and avoid oversedation.

Definitions. Psychomotor agitation is inner restlessness with observable motor and verbal activity (pacing, wringing hands, inability to sit, pressured speech, shouting). Aggression is verbal (threats, abuse) or physical (hitting, kicking, throwing objects, weapons). Violence is physical force with intent to injure. Disturbed behaviour with risk of harm requires immediate action.

Classification by cause

• Medical and neurological (delirium, head injury, intracranial pathology, seizures and post ictal state, metabolic and endocrine disturbance, infection, pain, hypoxia, sepsis).
• Intoxication and withdrawal (alcohol, stimulants, hallucinogens, cannabis and synthetic cannabinoids, anticholinergics, sedative hypnotics, opioids, and novel psychoactive substances).
• Drug adverse effects (akathisia, serotonin syndrome, neuroleptic malignant syndrome, corticosteroids, anticholinergic toxicity, stimulants, dopamine agonists, levodopa, and disinhibition from benzodiazepines).
• Psychiatric (mania, schizophrenia and psychosis, agitated depression, anxiety and panic, posttraumatic stress disorder, personality disorder, and acute stress reaction).
• Dementia related (behavioural and psychological symptoms) and learning disability.
• Situational (pain, fear, unmet needs such as hunger, thirst, toileting, loud and crowded environment, language barrier, and perceived loss of control).

Severity

• The Richmond Agitation-Sedation Scale (RASS) scores +1 restless, +2 agitated (frequent non-purposeful movement), +3 very agitated (pulls tubes or catheters, aggressive), +4 combative (violent, immediate danger).
• The Behavioural Activity Rating Scale (score 1 to 7; 5 to 7 is agitated) is a second tool.
• The Broset Violence Checklist (confusion, irritability, boisterousness, verbal threats, physical threats, attacking objects; score 0 to 6) predicts violence in the next 24 hours: 0 low, 1 to 2 moderate, 3 or more high risk.

Mechanisms. Noradrenergic, dopaminergic and glutamatergic hyperactivity, reduced gamma aminobutyric acid inhibition (alcohol and benzodiazepine withdrawal), cholinergic deficiency (delirium), serotonergic excess (serotonin syndrome), frontal lobe disinhibition (head injury, dementia), and limbic hyperreactivity with perceived threat in psychosis and trauma.

Course. Agitation can rise quickly. A verbal and nonverbal build up is common before violence. Early de-escalation prevents most use of restraint and parenteral sedation. Restraint and oversedation carry risk of death from positional asphyxia, aspiration, hyperthermia and cardiac arrhythmia.

Key distinctions

• Acute onset, fluctuating attention and disorientation suggest delirium.
• Elevated mood, pressured speech and reduced sleep suggest mania.
• Hallucinations and suspiciousness in a clear sensorium suggest psychosis.
• Dilated pupils, tachycardia, hyperthermia and sweating suggest stimulant or serotonergic toxicity.
• Dry skin, urinary retention and hot flushed skin suggest anticholinergic toxicity.
• Restlessness within days of starting an antipsychotic is likely akathisia.

History (from the patient, family, police, ambulance staff and records)

• Onset, speed, trigger, previous episodes, and what has helped before. Whether the patient is known to services, with an advance statement or crisis plan.
• Intoxication and withdrawal: alcohol (last drink and daily amount), drugs (stimulants, cannabis, synthetic cannabinoids, opioids, benzodiazepines, hallucinogens), and caffeine. Collect empty containers and paraphernalia.
• Medication: antipsychotics (recent dose changes), antidepressants, anticholinergics, dopamine agonists, corticosteroids, antiepileptics, opioids, and sedatives. Adherence and recent stopping.
• Medical history: diabetes, epilepsy, head injury, stroke, dementia, thyroid disease, liver disease, HIV, infection symptoms (fever, dysuria, cough), recent surgery, pain, urinary retention and constipation.
• Psychiatric history: psychosis, bipolar disorder, depression, personality disorder, previous violence, suicide attempts and self harm.
• Risk history: weapons, previous assaults, threats, current targets, forensic history, safeguarding concerns, children at home, and pregnancy.
• Mental capacity and legal status. Whether the patient is arrested, brought by police, or has an advance refusal of treatment.

Observation and examination (while maintaining distance and safety)

• Appearance, level of alertness and orientation, speech, posture (clenched fists, staring), pacing, and proximity to exits.
• Vital signs: temperature (over 38 C or under 36 C), heart rate, blood pressure, respiratory rate, oxygen saturation, and capillary glucose.
• Head and neck: scalp wounds, bruising behind the ears, pupils (size, reactivity, nystagmus), mouth (tongue bite), and neck stiffness.
• Skin: sweating or dry, flushing, track marks, rash, and petechiae.
• Chest, abdomen and limbs: signs of injury or infection, distended bladder, and compartment tenderness.
• Neurological: tremor, clonus (inducible ankle clonus suggests serotonin syndrome), hyperreflexia, rigidity (neuroleptic malignant syndrome), focal signs, gait, and cranial nerves.
• Mental state: mood, thought content, delusions, hallucinations, orientation, attention (months of the year backwards), and insight.

Red flags (indicating a medical or neurological emergency)

• Reduced level of consciousness, new confusion or fluctuating attention (delirium).
• Hypoxia (saturation under 94%), hypoglycaemia (glucose under 4 mmol/L), hyperthermia (over 38.5 C), hypotension, tachycardia over 140 beats a minute, or shock.
• Head injury, scalp haematoma, seizure, vomiting, severe headache, neck stiffness or focal deficit.
• Signs of serotonin syndrome (clonus, hyperreflexia, hyperthermia, diarrhoea) or neuroleptic malignant syndrome (rigidity, fever, autonomic instability, raised creatine kinase).
• Anticholinergic toxidrome (hot, dry, red skin, dilated pupils, urinary retention, absent bowel sounds).
• Alcohol or benzodiazepine withdrawal with tremor, sweating, hallucinations or seizures.
• Hallucinogen or stimulant intoxication with hyperthermia, rhabdomyolysis or chest pain.
• Poisoning with paracetamol, salicylates or other agents.
• Wernicke encephalopathy (confusion, ataxia, ophthalmoplegia in a patient with alcohol use disorder or malnutrition).
• Meningitis, encephalitis, thyrotoxic storm, hepatic encephalopathy, uraemia.
• Pregnancy with hypertension (eclampsia) or the postpartum period (postpartum psychosis).
• Weapon access, targeted threats, or command hallucinations.
• Self harm, suicidal intent, or intentional overdose.

Special groups

• Children and adolescents: use calm explanation and carers, treat pain and hunger, use age specific doses, and exclude physical illness, trauma and intoxication.
• Pregnancy: left lateral position beyond 20 weeks, check for eclampsia and hypoglycaemia, avoid unnecessary benzodiazepines, and choose haloperidol or olanzapine if sedation is needed.
• Older adults and dementia: low dose drugs, delirium search, and care with falls. Antipsychotics carry stroke and mortality risk.
• Parkinson disease and Lewy body dementia: avoid haloperidol and risperidone (severe worsening of motor features and neuroleptic sensitivity).
• Learning disability and autism: sensory overload, communication difficulty, pain, and need for familiar carers.
• Region specific: language barriers, interpreter use, cultural views of restraint, and access to specialist units.

Delirium and organic causes

• Delirium (infection, drugs, metabolic, postoperative, urinary retention, constipation, pain).
• Traumatic brain injury and intracranial haemorrhage.
• Subarachnoid haemorrhage and stroke (frontal, right hemisphere).
• Encephalitis and meningitis, including herpes simplex encephalitis and autoimmune encephalitis (NMDA receptor).
• Seizure and postictal state; nonconvulsive status epilepticus.
• Brain tumour and normal pressure hydrocephalus.
• Hypoxia and hypercapnia.
• Hypoglycaemia and hyperglycaemic crisis.
• Hyponatraemia, hypernatraemia, hypercalcaemia, uraemia and hepatic encephalopathy.
• Thyrotoxicosis and thyroid storm; hypothyroidism.
• Sepsis, urinary tract infection, pneumonia, malaria, HIV related, syphilis.
• Wernicke encephalopathy and vitamin B12 deficiency.
• Cushing syndrome, adrenal crisis and phaeochromocytoma.
• Porphyria, Wilson disease, systemic lupus erythematosus.
• Pulmonary embolism, myocardial infarction and heart failure.
• Pain, urinary retention, faecal impaction, and unmet needs.
• Eclampsia.

Intoxication, withdrawal and drug induced

• Alcohol intoxication and withdrawal (including delirium tremens).
• Stimulant intoxication (cocaine, amphetamine, methamphetamine, cathinones, khat, MDMA).
• Synthetic cannabinoid and cannabis intoxication.
• Hallucinogen and dissociative drug effects (lysergic acid diethylamide, phencyclidine, ketamine).
• Anticholinergic toxicity (antihistamines, tricyclic antidepressants, benztropine, plants).
• Serotonin syndrome.
• Neuroleptic malignant syndrome and antipsychotic induced akathisia.
• Benzodiazepine and barbiturate withdrawal or paradoxical reaction.
• Opioid withdrawal.
• Corticosteroids, dopamine agonists, levodopa, antiepileptics, bupropion, isoniazid, and quinolone related.
• Salicylate, theophylline, carbon monoxide and organophosphate poisoning.

Psychiatric

• Acute mania or mixed episode.
• Schizophrenia, schizoaffective disorder and acute psychotic episode.
• Agitated or psychotic depression.
• Catatonia (excited form).
• Panic and severe anxiety.
• Posttraumatic stress disorder with dissociation.
• Personality disorder (emotionally unstable, antisocial) in crisis.
• Intermittent explosive disorder.
• Acute stress reaction and adjustment disorder.
• Conversion and dissociative states.
• Postpartum psychosis.

Neurodevelopmental, dementia and situational

• Dementia with behavioural and psychological symptoms.
• Autism spectrum disorder and intellectual disability with distress.
• Attention deficit hyperactivity disorder.
• Environmental or interpersonal conflict, and deliberate violence without mental illness.
• Pain and discomfort.

Step 1. Safety first. Ensure the safety of the patient, staff and others. Use a team of at least 3 trained staff, a clear exit, removal of weapons and potential weapons, and appropriate security. Only start investigations once the patient is safe to examine. Keep distance of about 2 arm lengths, stay at an angle and avoid blocking the exit.

Step 2. Rapid physical screen (do not wait for sedation). Check airway and breathing, oxygen saturation, temperature, pulse, blood pressure, respiratory rate, capillary glucose and level of consciousness, often by observation. Correct hypoglycaemia and hypoxia at once. When the patient allows, examine for head injury, toxidrome and focal deficit.

Step 3. Risk assessment. Use a structured tool such as the Broset Violence Checklist (confusion, irritability, boisterousness, verbal threats, physical threats, attacking objects), and document the history of violence, weapons and targets.

Step 4. Tests (after the patient is calm or sedated)

• Capillary glucose (immediate), venous blood gas with lactate, full blood count, urea, creatinine, electrolytes (sodium), calcium, magnesium, phosphate, liver tests, CRP, creatine kinase, and thyroid stimulating hormone.
• 12 lead ECG (QTc before and after antipsychotics or droperidol; arrhythmia in stimulant toxicity).
• Blood alcohol level, paracetamol and salicylate levels when overdose is possible, and urine or serum drug screen.
• Pregnancy test.
• Urinalysis and culture. Blood cultures if febrile.
• Chest radiograph if hypoxic or febrile.
• CT head for trauma, anticoagulation, focal signs, new severe headache, seizure, or no clear cause (before lumbar puncture).
• Lumbar puncture when meningitis or encephalitis is suspected (cell count, protein, glucose, culture, herpes simplex virus PCR, autoimmune antibodies), after imaging and with empirical aciclovir 10 mg/kg intravenously every 8 hours and ceftriaxone 2 g intravenously every 12 hours when delay is expected.
• Electroencephalogram when nonconvulsive status epilepticus is possible.
• Ammonia for suspected hepatic encephalopathy, vitamin B12 and folate, HIV and syphilis serology, and autoimmune screen directed by features.
• Delirium screening tool (4AT: score of 4 or more is possible delirium; Confusion Assessment Method).

Step 5. Interpretation. A raised creatine kinase after restraint is common and should be monitored for rhabdomyolysis and hyperkalaemia. Persistent tachycardia, hyperthermia and metabolic acidosis after struggle suggest serious physiological stress, and they need monitored care. A clear sensorium with typical psychotic or manic features and no physiological abnormality supports a primary psychiatric cause, but the diagnosis must be reviewed once the patient has calmed.

Limits. Urine drug screens miss many novel substances and do not show intoxication. Full cooperation is often impossible, so examination may be limited. Agitation can mask head injury, and sedation hides neurological change, so document neurological status before sedation and monitor afterwards.

Principle. Use the least restrictive effective measure in order: environment and verbal de-escalation, voluntary oral medicine, then parenteral rapid tranquillisation. Use physical restraint only as a last resort and for the shortest time, with a plan to treat the cause.

Immediate (non pharmacological)

• Move the patient to a quiet low stimulation space with a clear exit. Remove hazards.
• One leader speaks, with a calm, low, slow voice. Use a nonthreatening posture, a respectful distance and open hands.
• De-escalation technique: respect personal space, no provocation, concise simple language, listen, identify wants and feelings, agree where possible, set clear and reasonable limits, offer choices, and debrief later.
• Offer food, drink, toilet, pain relief, and a phone call. Reduce noise and crowds.
• Treat reversible triggers: oxygen to a saturation of 94 to 98% (88 to 92% in COPD with hypercapnia risk), analgesia, and a urinary catheter for retention.
• For glucose under 4 mmol/L give dextrose (20 g oral glucose, or 10% dextrose 150 to 200 mL intravenously over 15 minutes, or glucagon 1 mg intramuscularly).
• If a person with capacity declines treatment, continue de-escalation, and use legal powers only when criteria are met.

Restraint (last resort)

• Needs a trained team (at least 4 or 5), a team leader at the head, and all measures to protect the airway.
• Avoid the prone position, pressure on the neck, chest or abdomen, and prolonged restraint. Use supine or lateral position, and release as soon as the patient is calm.
• Monitor breathing, colour, consciousness and pulse continuously. Document the reason, duration and injuries.
• Restraint must not delay medication that allows early release.
• Mechanical restraint only under local legal and procedural controls, with one to one observation and monitoring every 15 minutes.

Pharmacological treatment (rapid tranquillisation)

Assess the cause and previous response. Check for contraindications, allergies, pregnancy, hepatic and renal function, cardiac disease and QT. Avoid giving two sedatives in quick succession. Prefer oral medicine if the patient accepts it. Give the smallest dose that is effective, and wait the proper interval before repeating.

Oral (first choice if the patient is cooperative)

• Lorazepam 1 to 2 mg orally, repeated after 45 to 60 minutes if needed (maximum 4 mg in 24 hours for emergencies in adults).
• Olanzapine 5 to 10 mg orally or orodispersible (maximum 20 mg daily in total).
• Risperidone 1 to 2 mg orally (maximum 6 mg daily; 4 mg in 24 hours acute).
• Haloperidol 5 mg orally (with lorazepam, to reduce extrapyramidal effects, where possible). Maximum 12 mg in 24 hours in antipsychotic naive patients; higher doses only under specialist direction.
• Diazepam 5 to 10 mg orally (alcohol withdrawal and stimulant toxicity).

Intramuscular (if oral treatment refused or ineffective, or immediate sedation is needed)

• Lorazepam 2 mg intramuscularly, repeated once after 30 to 60 minutes (maximum 4 mg in 24 hours). Preferred for undifferentiated agitation, stimulant toxicity and benzodiazepine or alcohol withdrawal. Monitor for respiratory depression.
• Olanzapine 5 to 10 mg intramuscularly (maximum 20 mg intramuscularly in 24 hours, and 30 mg total in 24 hours including oral doses). Do not give intramuscular olanzapine within 1 hour of an injectable benzodiazepine, because of cardiorespiratory depression and hypotension.
• Haloperidol 5 mg intramuscularly with promethazine 25 to 50 mg intramuscularly (maximum 12 mg haloperidol intramuscularly in 24 hours in antipsychotic naive patients). The promethazine reduces acute dystonia.
• Haloperidol needs ECG monitoring. Avoid it with known QTc over 450 ms in men or 470 ms in women, hypokalaemia, hypomagnesaemia, Parkinson disease or Lewy body dementia.
• Droperidol 5 to 10 mg intramuscularly or 2.5 to 5 mg intravenously (maximum 10 mg in a single dose), with ECG monitoring and a QTc under 450 ms. Onset 3 to 10 minutes.
• Midazolam 5 to 10 mg intramuscularly (0.07 to 0.1 mg/kg), or 2.5 to 5 mg intravenously slowly over 2 minutes, titrated to effect, with airway monitoring. Onset 5 to 15 minutes intramuscularly.
• Ketamine 4 to 5 mg/kg intramuscularly (or 1 to 2 mg/kg intravenously) in emergency departments with resuscitation capability, for severe agitation with immediate danger. Monitor for laryngospasm, hypersalivation, vomiting, and emergence reaction. Use only when expert staff are present.

Other drug directions

• Mania: olanzapine 10 mg orally or intramuscularly, or haloperidol 5 mg with lorazepam 2 mg. Avoid combining olanzapine with benzodiazepine intramuscularly within 1 hour.
• Schizophrenia and psychosis: olanzapine 10 mg, risperidone 2 mg orally, or haloperidol 5 mg with lorazepam 1 to 2 mg.
• Stimulant intoxication: benzodiazepines first, diazepam 5 to 10 mg intravenously (repeat every 5 to 10 minutes to effect, maximum 40 mg) or lorazepam 2 mg intravenously, with cooling. Avoid beta blockers. Add an antipsychotic only if psychosis persists after benzodiazepines.
• Alcohol withdrawal: diazepam 10 to 20 mg orally or intravenously every 1 to 2 hours until calm (symptom triggered, maximum 120 mg in 24 hours in specialist settings), or chlordiazepoxide 20 to 50 mg orally every 6 hours reducing over 5 to 7 days.
• Alcohol withdrawal, thiamine: 200 to 500 mg intravenously 3 times daily for 3 to 5 days before glucose when Wernicke encephalopathy is possible, then 100 mg orally daily. Replace magnesium and potassium.
• Delirium (not due to alcohol withdrawal): treat the cause. For distressing agitation or risk, haloperidol 0.5 to 1 mg orally or intramuscularly, repeated after 1 hour if needed (maximum 5 mg daily in older adults), or olanzapine 2.5 mg. Avoid benzodiazepines.
• Dementia: haloperidol 0.5 mg or risperidone 0.25 to 0.5 mg orally as a short course. Limit use to days to weeks.
• Avoid antipsychotics where the patient has Lewy body dementia or Parkinson disease. In these patients use quetiapine 12.5 to 25 mg or lorazepam 0.5 mg with caution.
• Anticholinergic toxicity: benzodiazepine for agitation, supportive care and cooling. Physostigmine 0.5 to 1 mg intravenously slowly over 5 minutes (maximum 2 mg) only by a toxicologist when the patient has no cardiac conduction defects or tricyclic overdose.
• Serotonin syndrome: stop serotonergic drugs, give lorazepam 1 to 2 mg intravenously or diazepam 5 to 10 mg, fluids and cooling. Give cyproheptadine 12 mg orally (via nasogastric tube if needed) then 2 mg every 2 hours while symptoms continue, then 8 mg every 6 hours (maximum 32 mg daily). Avoid antipsychotics and physical restraint.
• Neuroleptic malignant syndrome: stop the antipsychotic, give fluids, cooling and benzodiazepine, and consider dantrolene 1 to 2.5 mg/kg intravenously or bromocriptine 2.5 mg orally 3 times daily, in intensive care.
• Akathisia: reduce the antipsychotic dose, or give propranolol 10 to 20 mg orally 2 to 3 times daily, mirtazapine 15 mg at night, or benzatropine 1 to 2 mg orally or intramuscularly when dystonia is present.
• Agitation in pregnancy: haloperidol 5 mg or olanzapine 5 to 10 mg, lorazepam if needed after weighing risk, with left tilt.
• Children and adolescents: first line is de-escalation and addressing the cause. Drugs only by specialist: lorazepam 0.05 mg/kg orally (maximum 2 mg), or risperidone 0.25 to 0.5 mg orally, or olanzapine 2.5 to 5 mg.
• Kidney and liver impairment: halve doses of lorazepam (oxazepam is preferred in hepatic failure), olanzapine and haloperidol. Avoid repeated benzodiazepine doses in hepatic encephalopathy.

Monitoring after sedation. Check airway, breathing and circulation continuously in the first hour.

• Record oxygen saturation, respiratory rate, pulse, blood pressure, temperature and level of consciousness (RASS, aim for 0 to minus 2) every 5 to 15 minutes for the first hour, then hourly until ambulatory.
• Use continuous pulse oximetry and capnography where available. ECG if haloperidol, droperidol or high doses are used.
• Give oxygen if saturation under 94%. Keep the patient in the lateral position where possible.
• Flumazenil 200 micrograms intravenously over 15 seconds, then 100 micrograms every minute to a maximum of 1 mg, may reverse benzodiazepine induced respiratory depression (avoid in benzodiazepine dependence, seizure disorder and tricyclic overdose).
• For acute dystonia give procyclidine 5 to 10 mg intramuscularly or benzatropine 1 to 2 mg intramuscularly or intravenously.
• For hyperthermia, rhabdomyolysis (creatine kinase over 5 times upper limit), hyperkalaemia or acidosis, give intravenous fluids (isotonic crystalloid 1 to 2 litres in the first hour for adults, then 200 to 300 mL each hour to a urine output over 1 mL/kg each hour) and monitor.

Treat the cause. Antibiotics for infection, glucose, correction of electrolytes, antiepileptic treatment for seizures, withdrawal regimens, psychiatric treatment for mania and psychosis (olanzapine 10 mg daily, risperidone 2 mg daily, or haloperidol 2 to 5 mg daily, titrated), and review of drugs.

Debrief and documentation. Document the risk, events, the reasons for restraint or medicine, the doses, observations, injuries and capacity. Debrief the patient and staff. Report incidents. Review the care plan, advance statements and triggers to prevent recurrence.

Referral and escalation. Emergency psychiatry for primary psychiatric agitation, suicidal or homicidal ideation, and mania. Medicine or critical care for delirium with instability, toxic syndromes, and rhabdomyolysis. Neurosurgery for intracranial injury. Toxicology and poisons advice for unknown ingestion. Security, police liaison and safeguarding in line with local law. Social services and carers for dementia. Specialist addiction services for withdrawal.

Admission criteria. Persistent agitation needing parenteral sedation, abnormal vital signs, delirium, intoxication needing monitoring, head injury, rhabdomyolysis, serious withdrawal, suicidal or homicidal intent, psychosis or mania with risk, and unsafe discharge.

Discharge and follow up. Discharge only when sober, calm, oriented, physically well, no longer a risk, and with follow up arranged. Provide a written crisis plan, early review in 24 to 72 hours, carer involvement, and referral to community mental health, addiction or old age services.

Safety net advice: return or call emergency services for threats of violence, new confusion, hallucinations, suicidal thoughts, severe agitation, or inability to sleep for more than 2 nights with elevated mood.