Acute Agitation Pharmacotherapy

Acute agitation is treated first by finding and correcting medical causes and by verbal de-escalation, and drugs are used only when behaviour is dangerous and de-escalation has failed. The aim is calm, not deep sedation, and the patient should be able to be assessed.

Medical causes. Hypoglycaemia, hypoxia, intoxication or withdrawal (alcohol, stimulants), infection including central nervous system infection and malaria, head injury, metabolic and endocrine disorders, and pain.

Rapid tranquillisation. Oral treatment is offered first, and intramuscular or intravenous drugs are used if refused or if the risk is high. Restraint should be brief and avoid the prone position.

By cause.

• Undifferentiated or psychosis: oral olanzapine, haloperidol with promethazine, or a benzodiazepine.

• Alcohol or sedative withdrawal, and stimulant intoxication: benzodiazepine (diazepam or lorazepam).

• Delirium in older adults: treat the cause, with the lowest dose of haloperidol or an alternative.

• Parkinson disease or Lewy body disease: lorazepam, and avoid haloperidol.

• Severe, dangerous agitation: ketamine or droperidol, where monitoring exists.

Avoid. Combining parenteral olanzapine with parenteral benzodiazepines within 1 hour, and haloperidol or droperidol when the QT interval is prolonged.

Special groups.

• Children: specialist care. Avoid routine sedation.

• Pregnancy: haloperidol or lorazepam at the lowest dose.

• Older adults: halve doses and monitor closely.

• East Africa: khat use can cause agitation and psychosis, and cerebral malaria and central nervous system infections must be excluded. Where only haloperidol and diazepam are available, give haloperidol 5 mg and intravenous diazepam 5 to 10 mg slowly, with monitoring.

• Lorazepam: 1 to 2 mg orally, intramuscularly or intravenously, repeated after 30 to 60 minutes. Maximum 4 mg in 24 hours in emergencies.

• Midazolam: 5 to 10 mg intramuscularly (2.5 to 5 mg in older adults).

• Diazepam: 5 to 10 mg intravenously slowly, repeated every 5 to 10 minutes as needed.

• Olanzapine: 10 mg orally, or 5 to 10 mg intramuscularly, maximum 20 mg in 24 hours.

• Haloperidol: 5 mg orally or intramuscularly, repeated after 30 to 60 minutes, maximum 20 mg in 24 hours (0.5 to 1 mg in older adults). Promethazine 25 to 50 mg intramuscularly can be added.

• Droperidol: 5 to 10 mg intramuscularly or intravenously, with ECG.

• Ketamine: 4 to 5 mg/kg intramuscularly, or 1 to 2 mg/kg intravenously, in monitored settings.

• Procyclidine: 5 to 10 mg intramuscularly for acute dystonia. Flumazenil 0.2 mg intravenously for reversal of benzodiazepine.

Monitoring. After parenteral drugs, record pulse, blood pressure, respiratory rate, oxygen saturation, temperature and sedation score every 15 minutes for the first hour, and then hourly until awake. Check an ECG when QT-prolonging drugs are used.

Stop rules. Stop doses as soon as the patient is calm, and do not give further doses without reassessment. Stop for respiratory depression, hypotension or dystonia.

Referral and escalation. Call senior and psychiatric help for continued agitation, need for repeated doses, intoxication needing airway support, and suspected neuroleptic malignant syndrome or serotonin toxicity.

Common errors. Sedating before finding a medical cause, combining several sedatives, using haloperidol in Lewy body disease, and missing hypoglycaemia or hypoxia.