Pharmacological Management of Acute Agitation

Acute agitation represents a transient but potentially dangerous escalation of psychomotor activity, emotional arousal and disinhibition that can arise in a range of medical, psychiatric and toxicological contexts. Pharmacological intervention aims to restore patient safety and prevent injury to staff or bystanders by combining rapid onset of action with a favourable tolerability profile. Traditional approaches have employed first-generation antipsychotics and benzodiazepines, often delivered via intramuscular injection to ensure prompt bioavailability when oral administration is not feasible. In recent years, the therapeutic armamentarium has expanded to include second-generation antipsychotics, non-invasive formulations such as inhaled or intranasal preparations and the dissociative anaesthetic ketamine, each offering distinct pharmacodynamic advantages. Clinicians must tailor their choice of agent and route of administration to the probable aetiology of agitation—be it delirium, substance intoxication, psychotic exacerbation or organic brain disorder—while balancing speed of tranquillisation against risks of sedation, respiratory depression or cardiovascular effects. Innovations in delivery mode and evidence-based protocols have refined dosing strategies to reduce coercion, improve patient experience and streamline care pathways in both prehospital and emergency department settings. A growing focus on safety monitoring—particularly cardiac repolarisation surveillance—and on protocols that prioritise the least restrictive yet effective intervention reflects an evolving paradigm in which pharmacological management is integrated with de-escalation techniques and multidisciplinary teamwork to achieve optimal outcomes.

Research from Nature Portfolio

No recent Nature Portfolio content available.

Pharmacological Management of Acute Agitation publication trend

The graph below shows the total number of articles in pharmacological management of acute agitation across all publications each year (not limited to Nature Index journals).

Technical terms

Acute agitation: A transient state of heightened psychomotor activity, irritability and emotional arousal requiring urgent management.

Rapid tranquilisation: The prompt administration of sedative or antipsychotic medication to mitigate risk and restore calm in an agitated individual.

Intramuscular sedation: Delivery of sedative agents via intramuscular injection for rapid systemic absorption when oral routes are impractical.

Benzodiazepines: A class of anxiolytic and sedative drugs that potentiate GABAergic transmission to reduce agitation and anxiety.

First-generation antipsychotics: Dopamine D2 receptor antagonists traditionally used for rapid tranquillisation, often associated with extrapyramidal side effects.

QT prolongation: An extension of the cardiac ventricular repolarisation interval on ECG that increases the risk of torsades de pointes and related arrhythmias.

References

1. The Psychopharmacology of Agitation: Consensus Statement of the American Association for Emergency Psychiatry Project BETA Psychopharmacology Workgroup. Western Journal of Emergency Medicine (2012).
2. Prehospital Use of IM Ketamine for Sedation of Violent and Agitated Patients. Western Journal of Emergency Medicine (2014).
3. Revisiting loxapine: a systematic review. Annals of General Psychiatry (2015).
4. The Incidence of QT Prolongation and Torsades des Pointes in Patients Receiving Droperidol in an Urban Emergency Department. Western Journal of Emergency Medicine (2020).
5. Ketamine Safety and Use in the Emergency Department for Pain and Agitation/Delirium: A Health System Experience. Western Journal of Emergency Medicine (2020).
6. 1st International Experts’ Meeting on Agitation: Conclusions Regarding the Current and Ideal Management Paradigm of Agitation. Frontiers in Psychiatry (2018).