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Current interventions for acute agitation are valuable but may come with trade-offs in clinical care

Coercive measures can have detrimental effects on patients, staff, and
overall resource utilization

Risk of physical harm1-3

  • Patient injuries
  • Staff injuries
  • Needlestick injuries

Risk of psychological harm4,5

  • Feeling violated, dehumanized, or
  • Mistrust and avoidance of their
    physician and the healthcare
    system overall
  • Retraumatization of past events

Greater healthcare resource utilization6-9

  • Greater number of staff required
    for “restraint” of the patient
  • Additional monitoring required for
    restrained or oversedated patients
  • Increased length of hospital stay
    and hospital readmission rate

Pharmacological options and associated safety considerations

While a number of pharmacological options exist to treat underlying neuropsychiatric disorders, very few of them are indicated specifically to treat agitation. Although they can be effective in reducing agitation in some patients, as with all products, there are important safety considerations.1,6,10


Increased risk of extrapyramidal side effects

QTc prolongation

Lowered seizure threshold


Central nervous system depression

restraint and sedation are still used

in up to 30%  of patients

admitted to an acute care setting12

There is a need for novel therapeutic approaches that can complement a cooperative de-escalation strategy, providing a safe option for agitated patients in need.1

HEAR Expert Perspectives ON intervention approaches

Dr. Scott Zeller,
Assistant Clinical Professor of
Psychiatry, University of

Dr. Les Zun,
Professor, Department of
Emergency Medicine, Chicago
Medical School*

*Dr. Zeller and Dr. Zun are acting on behalf of and are supported by BioXcel Therapeutics, Inc.


1. Ng AT, Zeller SL, Rhoades RW. Clinical challenges in the pharmacologic management of agitation. Prim Psychiatry. 2010;17(8):46-52. 2. Knox DK, Holloman GH. Use and avoidance of seclusion and restraint: consensus statement of the American Association for Emergency Psychiatry Project BETA Seclusion and Restraint Workgroup. West J Emerg Med. 2012;13(1):35-40. doi:10.5811/westjem.2011.9.6867 3. Holloman GH, Zeller SL. Overview of Project BETA: best practices in evaluation and treatment of agitation. West J Emerg Med. 2012;13(1):1-2. doi:10.5811/westjem.2011.9.6865 4. Wong AH, Ray JM, Rosenburg A, et al. Experiences of individuals who were physically restrained in the emergency department. JAMA Network Open. 2020;3(1):e1919381. doi:10.1001/jamanetworkopen.2019.19381 5. Strout TD. Perspectives on the experience of being physically restrained: an integrative review of the qualitative literature. Int J Ment Health Nurs. 2010;19(6):416-427. doi:10.1111/j.1447-0349.2010.00694.x 6. Zeller SL, Citrome L. Managing agitation associated with schizophrenia and bipolar disorder in the emergency setting. West J Emerg Med. 2016;17(2):165-172. doi:10.5811/westjem.2015.12.28763 7. Weiss AP, Chang G, Rauch SL, et al. Patient- and practice-related determinants of emergency department length of stay for patients with psychiatric illness. Ann Emerg Med. 2012;60(2):162-171. doi:10.1016/j.annemergmed.2012.01.037 8. Wilson MP, Brennan JJ, Modesti L, et al. Lengths of stay for involuntarily held psychiatric patients in the ED are affected by both patient characteristics and medication use. Am J Emerg Med. 2015;33(4):527-530. doi:10.1016/j.ajem.2015.01.017 9. Richmond JS, Berlin JS, Fishkind AB, et al. Verbal de-escalation of the agitated patient: consensus statement of the American Association for Emergency Psychiatry Project BETA De-escalation Workgroup. West J Emerg Med. 2012;13(1):17-25. doi:10.5811/westjem.2011.9.6864 10. Wilson MP, Pepper D, Currier GW, Holloman GH, Feifel D. The psychopharmacology of agitation: consensus statement of the American Association for Emergency Psychiatry Project BETA Psychopharmacology Workgroup. West J Emerg Med. 2012;13(1):26-34. doi:10.5811/westjem.2011.9.6866 11. Roppolo LP, Morris DW, Khan F, et al. Improving the management of acutely agitated patients in the emergency department through implementation of Project BETA (Best Practices in the Evaluation and Treatment of Agitation). JACEP Open. 2020;1(5):898-907. doi:10.1002/emp2.12138 12. Gaynes BN, Brown CL, Lux LJ, et al. Preventing and de-escalating aggressive behavior among adult psychiatric patients: a systematic review of the evidence. Psychiatr Serv. 2017;68(8):819-831. doi:10.1176/