Assessment and Management of Acute Agitation

Assessment and Management of Acute Agitation Medical Writer: Haifa Kassis, MD Introduction The DSM-5 defines psychomotor agitation as an excessive motor activity associated with a feeling of inner tension. 1 Aggression may not be the key feature of agitation, but when severe, agitation can lead to violence. 2 Acute agitation in patients with psychiatric disorders, such as schizophrenia and mood disorders, is common and can occur in any clinical settings, including emergency departments (ED), outpatient psychiatric settings, and inpatient hospitalizations. 3 In the United States, around 1.7 million ED visits every year involve symptoms of agitation, 4 and approximately 10% of patients treated by psychiatric emergency services are at risk of becoming agitated or violent. 5 In a survey among psychiatry residents, 36% reported being assaulted by patients during training; however, only a third of those residents reported being adequately trained in managing possibly violent patients. 6 Educational activities are essential to improve the ability of psychiatrists to effectively manage symptoms of agitation and to reduce the risks of physical injury to themselves and their patients. In this article, we highlight the available recommendations regarding the assessment and management of agitation in psychiatry. Etiology and Differential Diagnosis The differential diagnosis of agitation is wide and includes both medical and psychiatric conditions. 7 As a general rule, causes of agitation can be divided into three major categories: a general medical condition (infections, metabolic derangements, brain disorders, systemic organ failure, etc), substance (alcohol or other drugs of abuse) intoxication or withdrawal, or a primary psychiatric illness (psychosis, manic episode, agitated depression, anxiety disorder, personality disorder, etc). 8 To narrow the differential diagnosis, the initial steps in the assessment of agitation symptoms should include attempts to obtain vital signs, medical and psychiatric history, and general assessment of the patient s behavior. 8 In a patient without a known history of a psychiatric disorder, acute agitation should be considered to be secondary to a general medical condition until proven otherwise. 3 Copyright Crisp Writing, LLC Page 1

Aggression Risk Assessment Avoiding escalation of agitation into violence relies on the identification of individuals at risk. Research into this area is limited; however, several variables, including a history of violent behaviors, nonvoluntary admission, extended length of hospital stay, impulsiveness, hostility, and aggressive speech are commonly associated with violence in psychiatric settings. 9 Several objective assessment scales have been developed to help clinicians estimate the risk of aggression or violence in agitated patients with psychiatric disorders. 3 Generally, these tools evaluate a number of demographic, behavioral, and clinical variables to predict violent behaviors: The Brøset Violence Checklist (BVC), a 6-item checklist that can be used to help predict imminent violent behavior within the next 24 hours in inpatient psychiatric settings. 10 The Historical, Clinical, Risk Management-20 (HCR-20), a 20-item assessment tool that can help predict the potential for aggression or violence in patients undergoing acute episodes of a major psychiatric disorder. 11 The McNiel-Binder Violence Screening Checklist (VSC), a 5-item scale designed to assess the risk for aggression or violence in patients with psychiatric disorders who were recently admitted to short-term inpatient units. 12 Management Studies examining the best methods for management of agitation are limited. The available literature, which is largely based on recommendations and expert consensus, has classified four methods for managing symptoms of agitation: environmental modifications, verbal de-escalation techniques, physical restraints, and pharmacological interventions. 13 Environmental Modifications. Clinicians cannot de-escalate the situation if they don t feel safe. The primary initial concern of management is to ensure the safety of the agitated patient, the medical team, and all other persons in the nearby environment. 14 To decrease the likelihood of violence, several environmental modifications by healthcare providers are recommended; for example, removal of any items that could be potentially thrown, avoiding extremely loud or uncomfortable physical environment, and ensuring access to exits for both the patient and staff. 3,15 Copyright Crisp Writing, LLC Page 2

Verbal De-escalation. Noncoercive techniques such as verbal de-escalation should be usually attempted before physical restraints or medications are used, especially in agitated but cooperative patients. 16 The American Association for Emergency Psychiatry De-escalation Workgroup recommends that all medical staff should be trained in verbal de-escalation techniques. The workgroup has also outlined 10 key recommendations for verbal deescalation 15 : 1. Respect the patient s and your personal space and maintain a safe distance 2. Avoid any direct or indirect provocation 3. Establish the identity of one person who will be verbally interacting with the patient 4. Choose simple and concise language and persistently repeat your message to the patient 5. Identify the needs, wants, and feelings of the patient 6. Be an active listener and show interest in the patient s standpoint 7. Try to find points to agree about with the patient or agree to disagree 8. Reasonably and respectfully establish the working conditions (eg, violence cannot be tolerated) and gently teach the patient how to stay in control 9. Propose alternatives to violence and provide hope 10. To alleviate the traumatic nature of any involuntary intervention and to prevent future escalation, debrief the patient and staff after the intervention If verbal de-escalation fails and agitation symptoms escalate to aggression, the use of physical restraints and medications may be considered; however, if only minor violent behaviors occur (eg, punching the wall), the medical staff may attempt to continue the verbal de-escalation while increasing the consequences of violating the working conditions. 15 Physical Restraints. The use of restrains or seclusion may have deleterious psychologic and physical effects on the patient and the medical team 17 ; therefore, restraints are never indicated for convenience or punishment. 13 The Joint Commission on Accreditation of Healthcare Organizations (JCAHO) mandated in 2000 that physical restraints or seclusion can only be used in an emergency when other noncoercive attempts to manage agitation have failed and there is imminent risk of harm to a patient or others. 8 Physical restraints should be used carefully and humanely as a last resort. 18 Ideally, the institution would have a protocol and training programs in place to guide the staff in how to properly apply physical restraints. Copyright Crisp Writing, LLC Page 3

Once verbal de-escalation fails, the interviewer should leave the examination room and call for assistance from the restraint team. 13 After the patient is physically restrained, efforts for verbal de-escalation should resume, and medications to calm the patient should be administered. 3 It is also essential that all patients in restraint be monitored to prevent complications. Pharmacological Interventions. Three classes of medications are generally used to manage acute agitation: benzodiazepines, first generation (typical) antipsychotics, and second generation (atypical) antipsychotics. 19 Effective drugs are usually fast acting and can be given orally or intramuscularly (IM). Intravenous (IV) formulations might be difficult to administer because of the need for an IV line access. 1. Benzodiazepines Benzodiazepines modulate γ-aminobutyric acid (GABA) neurotransmission. They are recommended for agitation due to substance intoxication or withdrawal and when there is no specific treatment for the psychiatric disorder causing agitation (eg, personality disorder). 20,21 Lorazepam acts rapidly and has a short half-life. It can be administered IV or IM at 0.5 to 2 mg. 22,23 In a double-blind prospective trial, lorazepam (2 mg IM) was as effective as haloperidol (5 mg IM) in reducing psychotic disruptive behavior and resulted in significantly less extrapyramidal symptoms. 24 Midazolam is usually given at 2.5 to 5 mg IV or IM. 25 It has a significantly shorter time to onset of sedation than lorazepam (5 to 15 minutes versus 1 to 1.5 hours), but a shorter duration of action (one to two hours versus 8 to 10 hours). 14 In a randomized doubleblind trial, midazolam (5 mg IV) provided a more rapid sedation of severely agitated patients than lorazepam (2 mg IM) or haloperidol (5 mg IM) with no difference in sedation efficacy. 26 Patients who are agitated but cooperative may be given lorazepam or midazolam orally at the same doses mentioned above. 7 Because of increased risk for respiratory depression, clinicians must be vigilant in monitoring the respiratory function of patients treated with benzodiazepines. 27 Excessive sedation is another significant concern. 22 2. First generation (typical) antipsychotics Typical antipsychotics have been used as the mainstay treatment for agitation for many years. Due to its known efficacy, haloperidol has been typically used as first-line therapy and is usually the comparator drug against which new medications for agitation are evaluated. 14 Copyright Crisp Writing, LLC Page 4

Typical antipsychotics are believed to reduce agitation through inhibition of dopaminergic transmission. 28 Haloperidol can be given IM, IV or orally at 2.5 to 10 mg and its onset of action is within 15 to 60 minutes. The dose should be adjusted in the elderly. 29 Droperidol has a shorter half-life than Haloperidol and can be given IM or IV at 2.5 to 5 mg. Its onset of action ranges from 15 to 30 minutes. 30 The most common adverse effects of typical antipsychotics are extrapyramidal symptoms, which may be prophylactically prevented or treated with anticholinergics. 22 Because of their potential to induce quinidine-like QT prolongation that may result in fatal cardiac arrhythmias (torsades de pointes), haloperidol and droperidol were given the so-called black box warnings from the FDA. 31 If possible, typical antipsychotic drugs should be avoided in cases of alcohol or benzodiazepine withdrawal, seizures, and in pregnant patients. 13 Benzodiazepines and typical antipsychotics can be given as combination therapies to sedate highly agitated patients. Commonly used combinations include lorazepam (2 mg IV or IM) with haloperidol (5 mg IM or IV) or midazolam (5 mg IV or IM) with droperidol (5 mg IV or IM). 32,33 3. Second generation (atypical) antipsychotics Experience with atypical antipsychotics to control agitation is growing. These drugs act on serotonergic and dopaminergic receptors and cause less extrapyramidal adverse effects than typical antipsychotics. 34 Some consensus guidelines recommend atypical antipsychotics as first-line therapy for acute agitation in schizophrenia. 8 Olanzapine can be given IM (2.5 to 10 mg) or orally (5 to 20 mg) and has an onset of action of 15 to 45 minutes. 35 Randomized double-blind trials have shown efficacy and safety of IM olanzapine in treating agitation due to acute mania 36 or schizophrenia. 37 Parenteral benzodiazepines should be avoided in patients receiving IM olanzapine because of increased risk for hypotension. 14 Risperidone is not available in a fast-acting IM formulation, but can be given orally (1 to 2 mg) and controls agitation secondary to psychosis rapidly. 38 Copyright Crisp Writing, LLC Page 5

Ziprasidone is available in oral and IM formulations and is typically administered IM at 10 to 20 mg. 14 Caution is warranted when given to patients with renal disease because its excipient cyclodextrin is cleared by renal filtration. Cyclodextrin accumulation may be toxic to the liver and kidneys. 14 Atypical antipsychotics also increase the risk for QT prolongation to some degree. Ziprasidone carries a higher risk than other typical and atypical antipsychotics and is contraindicated in patients with known history of QT prolongation or recent myocardial infarction. 39 Conclusion Agitation is a common scenario in clinical psychiatry. To prevent violence, clinicians are encouraged to use noncoercive measures (environmental modifications, verbal de-escalation, and oral medications) to calm agitated patients. Physical restraints and rapid sedation with benzodiazepines or antipsychotics may be necessary in highly agitated or violent patients. References 1. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. 5th ed. Arlington, VA: American Psychiatric Association; 2013. 2. Nordstrom K, Allen MH. Managing the acutely agitated and psychotic patient. CNS Spectr. 2007;12(10 Suppl 17):5-11. 3. Garriga M, Pacchiarotti I, Kasper S, et al. Assessment and management of agitation in psychiatry: Expert consensus. World J Biol Psychiatry. 2016;17(2):86-128. 4. Allen MH, Currier GW. Use of restraints and pharmacotherapy in academic psychiatric emergency services. Gen Hosp Psychiatry. 2004;26(1):42-49. 5. Huf G, Alexander J, Gandhi P, Allen MH. Haloperidol plus promethazine for psychosisinduced aggression. Cochrane Database Syst Rev. 2016;2016(11). 6. Schwartz TL, Park TL. Assaults by patients on psychiatric residents: A survey and training recommendations. Psychiatr Serv. 1999;50(3):381-383. 7. Yildiz A, Sachs GS, Turgay A. Pharmacological management of agitation in emergency settings. Emerg Med J. 2003;20(4):339-346. Copyright Crisp Writing, LLC Page 6

8. Allen MH, Currier GW, Carpenter D, Ross RW, Docherty JP. The expert consensus guideline series. Treatment of behavioral emergencies 2005. J Psychiatr Pract. 2005;11 Suppl 1:5-108. 9. Hankin CS, Bronstone A, Koran LM. Agitation in the inpatient psychiatric setting: a review of clinical presentation, burden, and treatment. J Psychiatr Pract. 2011;17(3):170-185. 10. Almvik R, Woods P, Rasmussen K. Assessing risk for imminent violence in the elderly: The Brøset violence checklist. Int J Geriatr Psychiatry. 2007;22(9):862-867. 11. Douglas KS, Guy LS, Weir J. HCR-20 violence risk assessment scheme: overview and annotated bibliography. Simon Fraser Univ. 2005. 12. McNiel DE, Binder RL. The relationship between acute psychiatric symptoms, diagnosis, and short-term risk of violence. Hosp Community Psychiatry. 1994;45(2):133-137. 13. Petit JR. Management of the acutely violent patient. Psychiatr Clin North Am. 2005;28(3):701-711. 14. Schleifer JJ. Management of acute agitation in psychosis: an evidence-based approach in the USA. Adv Psychiatr Treat. 2011;17:91-100. 15. Richmond J, Berlin J, Fishkind A, 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. 16. Price O, Baker J, Bee P, Lovell K. Learning and performance outcomes of mental health staff training in de-escalation techniques for the management of violence and aggression. Br J Psychiatry. 2015;206(6):447-455. 17. Fisher WA. Restraint and seclusion: A review of the literature. Am J Psychiatry. 1994;151(11):1584-1591. 18. Buckley PF, Noffsinger SG, Smith DA, Hrouda DR, Knoll IV JL. Treatment of the psychotic patient who is violent. Psychiatr Clin North Am. 2003;26(1):231-272. 19. Marder SR. A review of agitation in mental illness: Treatment guidelines and current therapies. J Clin Psychiatry. 2006;67(Suppl 10):13-21. Copyright Crisp Writing, LLC Page 7

20. Allen MH, Currier GW, Hughes DH, et al. The expert consensus guideline series. Treatment of behavioral emergencies. Postgrad Med. 2001:1-88. 21. Mayo-Smith MF, Beecher LH, Fischer TL, et al. Management of alcohol withdrawal delirium. An evidence-based practice guideline. Arch Intern Med. 2004;164(13):1405-1412. 22. Battaglia J. Pharmacological management of acute agitation. Drugs. 2005;65(9):1207-1222. 23. Zeller SL, Rhoades RW. Systematic reviews of assessment measures and pharmacologic treatments for agitation. Clin Ther. 2010;32(3):403-425. 24. Salzman C, Solomon D, Miyawaki E, et al. Parenteral lorazepam versus parenteral haloperidol for the control of psychotic disruptive behavior. J Clin Psychiatry. 1991;52(4):177-180. 25. Mendoza R, Djenderedjian AH, Adams J, Ananth J. Midazolam in acute psychotic patients with hyperarousal. J Clin Psychiatry. 1987;48(7):291-292. 26. Nobay F, Simon BC, Levitt MA, Dresden GM. A prospective, double-blind, randomized trial of midazolam versus haloperidol versus lorazepam in the chemical restraint of violent and severely agitated patients. Acad Emerg Med. 2004;11(7):744-749. 27. Battaglia J, Moss S, Rush J, et al. Haloperidol, lorazepam, or both for psychotic agitation? A multicenter, prospective, double-blind, emergency department study. Am J Emerg Med. 1997;15(4):335-340. 28. Altamura AC, Sassella F, Santini A, Montresor C, Fumagalli S, Mundo E. Intramuscular preparations of antipsychotics: Uses and relevance in clinical practice. Drugs. 2003;63(5):493-512. 29. Inouye SK, Westendorp RGJ, Saczynski JS. Delirium in elderly people. Lancet. 2014;383(9920):911-922. 30. Thomas H, Schwartz E, Petrilli R. Droperidol versus haloperidol for chemical restraint of agitated and combative patients. Ann Emerg Med. 1992;21(4):407-413. 31. Meyer-Massetti C, Cheng CM, Sharpe BA, Meier CR, Guglielmo BJ. The FDA extended Copyright Crisp Writing, LLC Page 8

warning for intravenous haloperidol and torsades de pointes: How should institutions respond? J Hosp Med. 2010;5(4). 32. Chan EW, Taylor DM, Knott JC, Phillips GA, Castle DJ, Kong DCM. Intravenous droperidol or olanzapine as an adjunct to midazolam for the acutely agitated patient: A multicenter, randomized, double-blind, placebo-controlled clinical trial. Ann Emerg Med. 2013;61(1):72-81. 33. Huang CLC, Hwang TJ, Chen YH, et al. Intramuscular olanzapine versus intramuscular haloperidol plus lorazepam for the treatment of acute schizophrenia with agitation: An open-label, randomized controlled trial. J Formos Med Assoc. 2015;114(5):438-445. 34. Marco CA, Vaughan J. Emergency management of agitation in schizophrenia. Am J Emerg Med. 2005;23(6):767-776. 35. Battaglia J, Lindborg SR, Alaka K, Meehan K, Wright P. Calming versus sedative effects of intramuscular olanzapine in agitated patients. Am J Emerg Med. 2003;21(3):192-198. 36. Meehan K, Zhang F, David S, et al. A double-blind, randomized comparison of the efficacy and safety of intramuscular injections of olanzapine, lorazepam, or placebo in treating acutely agitated patients diagnosed with bipolar mania. J Clin Psychopharmacol. 2001;21(4):389. 37. Wright P, Birkett M, David SR, et al. Double-blind, placebo-controlled comparison of intramuscular olanzapine and intramuscular haloperidol in the treatment of acute agitation in schizophrenia. Am J Psychiatry. 2001;158(7):1149-1151. 38. Rund DA, Ewing JD, Mitzel K, Votolato N. The use of intramuscular benzodiazepines and antipsychotic agents in the treatment of acute agitation or violence in the emergency department. J Emerg Med. 2006;31(3):317-324. 39. Glassman AH, Bigger J. Antipsychotic drugs: Prolonged QTc interval, torsade de pointes, and sudden death. Am J Psychiatry. 2001;158(11):1774-1782. Copyright Crisp Writing, LLC Page 9