Understanding and Managing Acute Agitation in Medical Settings

This resource discusses the medical management of acute agitation, covering the behavioral spectrum, differential diagnosis, non-pharmacologic and pharmacologic approaches, and case scenarios. Definitions of agitation, aggression, and violence are provided along with descriptions of component behaviors of agitation. A case study illustrates a patient's escalating agitation in a medical setting.

• Agitation management
• Behavioral spectrum
• Medical settings
• Pharmacologic approaches
• Acute care

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1. The Medical Management of Acute Agitation APM Resident Education Curriculum Revised 2019: Ariadna Forray, MD, Naomi Schmelzer, MD Original version: R. Scott Babe, M.D., Clinical Assistant Professor of Psychiatry, Western University of Health Sciences, Samaritan Mental Health, Corvallis, Oregon Thomas W. Heinrich, MD, Associate Professor of Psychiatry & Family Medicine, Chief, Psychiatric Consult Service at Froedtert Hospital, Department of Psychiatry & Behavioral Medicine, Medical College of Wisconsin Version of March 15, 2019 ACADEMY OF CONSULTATION-LIAISON PSYCHIATRY Psychiatrists Providing Collaborative Care Bridging Physical and Mental Health

2. Objectives Identify the behavioral spectrum of agitation Describe the broad differential diagnosis behind the symptoms of agitation and aggression. Apply non-pharmacologic and pharmacologic approaches to management of the agitated patient in the general medical setting. Academy of Consultation-Liaison Psychiatry 2

3. The Case A 47 year-old male with a history of substance use disorder and bipolar disorder along with morbid obesity, DM and COPD presents to the ED at 0200 after calling 911 and reporting chest pain. He is cooperative in the ED, but observed to be mumbling to himself and staring at staff suspiciously. He is given lorazepam 1mg PO to calm him. Since arriving to the floor to rule out an MI, he has become increasingly restless, irritable, and confrontational. He is increasingly uncooperative with medical care, then becomes verbally and physically threatening to the staff. His primary team calls a psychiatry consult for help managing these behaviors. 3 Academy of Consultation-Liaison Psychiatry

4. Definitions Agitation Excessive motor or verbal activity an emergent situation that is temporary, breaks the therapeutic alliance, and is in need of a prompt and immediate intervention (Garriga et al. 2016) Aggression Hostile, injurious, or destructive behavior. Can be verbal or physical. Violence Denotes physical aggression by people against other people 2 general types: Impulsive/reactive Instrumental/premeditated goal-oriented violence (Siever L. (2008) Neurobiology of aggression and violence. Am J Psychiatry 165: 429-42. Garriga M., Pacchiarotti, I., Kasper, S. et al. (2016) Assessment and Management of Agitation in Psychiatry: Expert consensus. World J Biol Psychiatry. 17, 170-185.) 4 Academy of Consultation-Liaison Psychiatry

5. Component Behaviors of Agitation Nonaggressive behaviors Restlessness (akathisia, fidgeting) Wandering Loud, excited speech Pacing or frequently changing body positions Inappropriate behavior (disrobing, intrusive, repetitive questioning) Aggressive behaviors Physical Combativeness, punching walls Throwing or grabbing objects, destroying items Clenching hands into fists, posturing Self-injury (repeatedly banging one s head) Verbal Cursing Screaming 5 Academy of Consultation-Liaison Psychiatry

6. Epidemiology There is little direct data on the prevalence, clinical impact, or financial consequences of agitation Behavioral emergencies responsible for 6% of all ED visits (Larkin et al 2005) 4.3 million psychiatric emergency visits/year (Marco and Vaughan, 2005) 21% (900,000) agitated patients with schizophrenia 13% (560,000) agitated patients with bipolar disorder 5% (210,000) agitated patients with dementia Larkin GL. et al. Trends in US Emergency Department Visits for Mental Health Conditions, 1992-2001. Psychiatric Services, June 2005. 56; 671-677. Marco, C. A., & Vaughan, J. (2005). Emergency management of agitation in schizophrenia. The American journal of emergency medicine, 23(6), 767-776. 6 Academy of Consultation-Liaison Psychiatry

7. Epidemiology Studies for health care workers California: 465 assaults per 100,000 hospital workers vs. 82.5 assaults per 100,000 for all workers (Peek-Asa et al 1997) Minnesota Nurses Study (Gerberich et al 2004): 13.2 per 100 persons per year for physical assaults 38.8 per 100 persons per year for non-physical assaults Greatest risk for persons working in/with: Long term care facility Intensive care Psychiatric unit Emergency department Geriatric patients Peek-Asa, C., Howard, J., Vargas, L., & Kraus, J. F. (1997). Incidence of non-fatal workplace assault injuries determined from employer's reports in California. Journal of Occupational and Environmental Medicine, 39(1), 44-50. Gerberich, S. G., Church, T. R., McGovern, P. M., Hansen, H. E., Nachreiner, N. M., Geisser, M. S., ... & Watt, G. D. (2004). An epidemiological study of the magnitude and consequences of work related violence: the Minnesota Nurses Study. Occupational and environmental medicine, 61(6), 495-503. Academy of Consultation-Liaison Psychiatry 7

8. Etiology of Agitation A. Disease-related: three major categories Psychiatric manifestations of general medical conditions Substance intoxication/withdrawal Primary psychiatric illness B. Instrumental: unlikely to benefit from medical intervention (e.g., criminal behavior) Consider short trial of verbal de-escalation Depending on severity, consider involving security or law enforcement These are not mutually exclusive 8 Academy of Consultation-Liaison Psychiatry

9. Etiology of Agitation: A Sample of the Varied Conditions that may Present with Pathologic Agitation Substance intoxication or withdrawal Bipolar disorder Major Depressive Disorder Psychosis PTSD Anxiety Disorders Personality Disorders Autism Intellectual Disability Dementia Huntington's disease Brain injury or trauma Delirium (Organic Brain Syndrome) Korsakoff s psychosis Brain tumors Seizure Hypoglycemia Stroke Thyroid disease Antisocial behavior 9 Academy of Consultation-Liaison Psychiatry

10. Etiology of Agitation: Medical Causes Head trauma Encephalitis, meningitis, other infection Encephalopathy (e.g., liver or renal failure) Environmental toxins Metabolic abnormalities (sodium, calcium, glucose) Hypoxia Thyroid disease Seizure (including post-ictal state) Toxic levels of medications Nordstrom, K., Zun, L. S., Wilson, M. P., Stiebel, V., Ng, A. T., Bregman, B., & Anderson, E. L. (2012). Medical evaluation and triage of the agitated patient: consensus statement of the American Association for Emergency Psychiatry Project BETA Medical Evaluation Workgroup. Western Journal of Emergency Medicine, 13(1), 3. 10 Academy of Consultation-Liaison Psychiatry

11. Etiology of Agitation: Delirium Diagnostic Features Disturbance of consciousness A change in cognition or development of perceptual disturbance Not accounted for by a dementia Disturbance develops over a short period of time and tends to fluctuate ( waxing and waning ) Caused by a general medical condition 11 Academy of Consultation-Liaison Psychiatry

12. Etiology of Agitation: Substances Substance intoxication Alcohol, cocaine, amphetamines, cannabis, ketamine, ecstasy, bath salts, inhalants Substance withdrawal Alcohol withdrawal delirium/DTs CNS effects of non-psychiatric medications (steroids) 12 Academy of Consultation-Liaison Psychiatry

13. Etiology of Agitation: Primary Psychiatric disorders Schizophrenia Bipolar Disorder Neurocognitive Disorder (Dementia) Personality Disorders Agitated depression Anxiety disorder Autism spectrum disorder 13 Academy of Consultation-Liaison Psychiatry

14. Etiology of Agitation: Common Triggers Akathisia from antipsychotic or antidepressant use Comorbid substance use or intoxication Poor impulse control or other comorbid cognitive deficits Chaotic or disruptive environment Medical illness Exacerbation of symptoms of primary illness Psychosocial trigger Garriga, M., Pacchiarotti, I., Bernardo, M., & Vieta, E. (2017). Psychiatric Causes of Agitation: Exacerbation of Mood and Psychotic Disorders. The Diagnosis and Management of Agitation, 126.. Academy of Consultation-Liaison Psychiatry 14

15. Etiology of Agitation: Schizophrenia Patients may present to the ED with acute psychosis Hallucinations Delusions Disorganized speech and/or behavior Lack of insight Bizarre behavior Fertile conditions for the development of agitation Psychosis and agitation have a reciprocal relationship 15 Academy of Consultation-Liaison Psychiatry

16. Etiology of Agitation: Schizophrenia Patients at highest risk for violence More suspicious and hostile More severe hallucinations Less insight into delusions Greater thought disorder Poor impulse control Risk factors for being targeted for violence by person with schizophrenia Parent or immediate family member Cohabitation Patient financially dependent on you Sachs, G. S. (2006). A review of agitation in mental illness: burden of illness and underlying pathology. The Journal of clinical psychiatry, 67, 5-12. 16 Academy of Consultation-Liaison Psychiatry

17. Etiology of Agitation: Personality Disorders Some personality disorders are more prone to agitation Decreased stress tolerance Poor impulse control E.g., Borderline personality disorder, Antisocial personality disorder 17 Academy of Consultation-Liaison Psychiatry

18. Etiology of Agitation: Major Neurocognitive Disorder Overall, the incidence of agitation is estimated to be between 60-80% (median 44%) (Bartels et al 2003) 50% become frankly physically aggressive 24% become verbally aggressive Burden of institutionalization Residents with dementia complicated by agitation have the highest 3-month rate of ED visits and greatest use of restraints (Sachs, 2006) Despite use of restraints, over 40% receive no psychiatric medications Bartels, S. J., Horn, S. D., Smout, R. J., Dums, A. R., Flaherty, E., Jones, J. K., ... & Voss, A. C. (2003). Agitation and depression in frail nursing home elderly patients with dementia: treatment characteristics and service use. The American journal of geriatric psychiatry, 11(2), 231-238. Sachs, G. S. (2006). A review of agitation in mental illness: burden of illness and underlying pathology. The Journal of clinical psychiatry, 67, 5-12 18 Academy of Consultation-Liaison Psychiatry

19. Etiology of Agitation: Dementia Agitation may be a final common pathway for the expression of Depression Anxiety Psychosis Pain Delirium While agitation may be of multifactorial etiology in patients with dementia, it is also true that many patients have only agitation as a target symptom for treatment (Madhusoodanan, 2001) Madhusoodanan, S. (2001). Introduction: antipsychotic treatment of behavioral and psychological symptoms of dementia in geropsychiatric patients.The American Journal of Geriatric Psychiatry, 9(3), 283-288. 19 Academy of Consultation-Liaison Psychiatry

20. Etiology of Agitation: Psychodynamic Perspectives A Psychodynamic framework can be used to complement treatment strategies - Helps temper counter-transference Psychodynamic perspectives of agitation and violence - In contemporary psychoanalytic thought, the capacity for aggression is innate and universal, aggressive behavior occurs in response to threats that the self perceives in relation to internal and external objects. - Crisis can be defined as an assault on the person s sense of self (Bernstein 2007) Yakeley, J. (2018). Psychodynamic approaches to violence. BJPsych Advances, 24(2), 83-92. Academy of Consultation-Liaison Psychiatry 20

21. Back to the Case (continued) Potential etiologies for our gentleman s growing agitation Substance intoxication or withdrawal Delirium Bipolar disorder Personality disorder 21 Academy of Consultation-Liaison Psychiatry

22. Assessment of Agitation Decisions regarding diagnostic tests must be made in the context of available history and physical examination Goal is to evaluate patient s risk for medical comorbidities Many questions involve forced decisions based on Assumptions Information available Diagnostic confidence Patient s individual risk factors 22 Academy of Consultation-Liaison Psychiatry

23. Assessment of Agitation For a patient with known diagnosis of schizophrenia presenting with behavioral features of typical decompensation: Expectant management is appropriate For patients with atypical features additional diagnostic tests may be required Atypical presentations Delirium History of trauma Overdose Headache Fever Diagnostic tests to consider Toxicology screens CT of brain BMP, CBC, and LFTs Urinalysis Endocrine tests Lumbar puncture 23 Academy of Consultation-Liaison Psychiatry

24. The Case (continued) Examination of the patient The patient is febrile with normal vitals Disheveled and malodorous Heart, lungs and abdomen are benign No tremor, diaphoresis, nystagmus or asterixis Mental status examination reveals: Appearance/behavior: middle-aged unkempt male in hospital johnny and socks, uncooperative, pacing the room, poor eye contact, posturing with fists Speech: spontaneous, loud, nonpressured, use of profane language Mood: I m lousy! , Affect: labile, irritable TP: tangential, TC: paranoia towards hospital staff, no SI/HI, no perceptual disturbances. Does not participate in formal cognitive exam questions. 24 Academy of Consultation-Liaison Psychiatry

25. The Case (continued) Laboratory evaluation of the patient CBC, BMP are normal except for a glucose of 211 LFTs are normal except for a low albumin TSH, B12, Folate, and RPR are also normal U/A is positive for glucose and trace ketones CT of head is read as negative EKG shows QTc < 400msec UDS and serum toxicology are negative Valproate, carbamazepine, and lithium levels are all negative 25 Academy of Consultation-Liaison Psychiatry

26. Before the Acute Intervention The staff on Med/Surg units are often less informed about what feelings and behaviors their actions may elicit in patients Studies indicate that staff training and education can change this lack of appreciation Psychiatric consultants should provide education about Establishing goals from the patient s perspective Interventions that support a structured setting Private or semi-private room Establish clear set of expectations with a written schedule Identify staff that are responsible for the patient s care Attempting to enlist the patient in the treatment, i.e. which route of medication has worked the best in the past as a choice which retains some patient control Academy of Consultation-Liaison Psychiatry 26

27. Goals of Intervention Acute agitation or a violent patient modifies the normal caregiver-patient relationship The first goal of treatment is to do only what is necessary to assure the safety of the patient and others while facilitating the resumption of more normal interpersonal relations Calming without over-sedation 27 Academy of Consultation-Liaison Psychiatry

28. Agitation Management Medical evaluation and triage Psychiatric evaluation Verbal de-escalation Environmental intervetions Psychopharmacologic interventions Use of seclusion/restraint Holloman Jr, G. H., & Zeller, S. L. (2012). Overview of Project BETA: best practices in evaluation and treatment of agitation. Western Journal of Emergency Medicine, 13(1), 1. Academy of Consultation-Liaison Psychiatry 28

29. Environmental Interventions Examples of effective non-pharmacological treatments Clearing the room Removing dangerous objects Having staff available as a show of force Close observation Calm conversation Decreasing sensorial stimulation 29 Academy of Consultation-Liaison Psychiatry

30. Communication/Behavioral Interventions Nonverbal Maintain a safe distance Maintain a neutral posture Do not stare; eye contact should convey sincerity Do not touch the patient Stay at the same height as the patient Avoid sudden movements Verbal Speak in calm, clear tone Personalize yourself Avoid confrontation; offer to solve the problem Onyike, C., & Lyketsos, C. (2011). Aggression and violence. Textbook of Psychosomatic Medicine: Psychiatric Care of the Medically, 101, 153-174.. 30 Academy of Consultation-Liaison Psychiatry

31. Communication/Behavioral Interventions Aligning Goals of Care Acknowledge the patient s grievance Acknowledge the patient s frustration Shift the focus to discussion of how to solve the problem Emphasize common ground Focus on the big picture Find ways to make small concessions Monitoring Intervention Progress Be acutely aware of progress Know when to disengage Do not insist on having the last word Onyike, C., & Lyketsos, C. (2011). Aggression and violence. Textbook of Psychosomatic Medicine: Psychiatric Care of the Medically Ill, 101, 153-174.. 31 Academy of Consultation-Liaison Psychiatry

32. Back to the Case (continued) You assist the team and the nursing staff: Clear the room Keep dangerous objects out of reach Call security You approach the patient using verbal de-escalation techniques that you have learned and practiced Despite these interventions the patient makes further threats, rips-off telemetry lines, and starts to pace with clenched fists while mumbling incoherently 32 Academy of Consultation-Liaison Psychiatry

33. A little bit of history 33 Academy of Consultation-Liaison Psychiatry

34. Serotonin-Dopamine Model of Regulation of Agitation Dynamic interaction between the amygdala, nucleus accumbens, and the prefrontal cortex Provides a basis for the response to certain medications Amygdala activation Serotonin Nucleus Accumbens Suppression Dopamine Released Prefrontal Cortex agitation Ryding et al. The role of dopamine and serotonin in suicidal behavior and aggression. Prog Brain Res 2008;172:307-15 34 Academy of Consultation-Liaison Psychiatry

35. Goals of Intervention Ideally pharmacotherapy for acute agitation should: Be easy to administer, non-traumatic Provide rapid tranquilization without excessive sedation Have a fast onset of action and a sufficient duration of action Have a low risk for significant adverse events and drug interactions 35 Academy of Consultation-Liaison Psychiatry

36. Goals of Intervention Definition of psychopharmacologic treatment endpoint: rapid tranquilization Calming process separate from total sleep induction Allows patient to participate in care Enables clinician to gather history, initiate a work-up, and begin treatment of unidentified conditions Better therapeutic endpoint Sleep is not the desired outcome It conflicts with goal of patient participation Has not been found to be essential to improvement in agitation or decrease in psychotic symptoms Vieta et al. Protocol for the management of psychiatric patients with psychomotor agitation. BMC Psychiatry 2017;17:328 36 Academy of Consultation-Liaison Psychiatry

37. Pharmacologic Considerations Ease of preparation/administration Rapid onset of action: IV > IM > PO Sufficient duration of effect Low risk of adverse reactions or drug interactions What is known about the patient s underlying condition(s)? Age Comorbid conditions Medication/other substance exposure Zeller et al. Systematic Reviews of Assessment Measures and Pharmacologic Treatments for Agitation. Clin Therapeutics 2010; 32:405-425 Academy of Consultation-Liaison Psychiatry 37

38. Pharmacologic Treatment Most important factors in medication selection Etiology of agitation Acute effect on behavioral symptoms Multiple means of administration Limited side effects Ease of administration Patient preference History of response Goal is a balance between effectiveness and tolerability Marder SR. A review of agitation in mental illness: treatment guidelines and current therapies. J Clin Psychiatry 2006;67:13-21 38 Academy of Consultation-Liaison Psychiatry

39. Pharmacologic Treatment Route of administration Oral (PO) administration Preferred if patient accepts Liquid or orally dissolving tablets Intramuscular (IM) administration Rapid elevation of plasma level Higher transient concentration Faster reduction in agitated behavior 39 Academy of Consultation-Liaison Psychiatry

40. Pharmacologic Treatment Route of administration (continued) Intravenous (IV) administration Similar to IM but more rapid elevation of plasma level Should be limited to when immediate tranquilization is essential Requires appropriate monitoring of vital signs for respiratory depression and cardiovascular compromise 40 Academy of Consultation-Liaison Psychiatry

41. Pharmacologic Treatment Most studies of pharmacologic treatment in agitation were done in patients with KNOWN psychiatric diagnosis No randomized, controlled studies have examined the use of medications in populations with Severe agitation Drug-induced agitation Significant medical comorbidity Results difficult to extrapolate to the undifferentiated agitated patient in the general ED or medical/surgical unit 41 Academy of Consultation-Liaison Psychiatry

42. Association for Emergency Psychiatry Recommendations Undifferentiated Agitation/Suspected intoxication with stimulant or withdrawal from alcohol/benzodiazepine Oral benzodiazepines (e.g. lorazepam 1-2 mg) Parenteral benzodiazepines (e.g. lorazepam 1-2 mg IM or IV) Acute intoxication with CNS depressant (e.g., alcohol) Avoid benzodiazepine if possible 1. Oral 1st generation antipsychotic (e.g. haloperidol 2-10 mg ) 2. Parenteral 1st generation antipsychotic (e.g. haloperidol 2-10 mg IM) Delirium (not associated with alcohol or benzodiazepine withdrawal) 1. Oral 2nd generation antipsychotic (e.g. risperidone 2 mg, olanzapine 5-10 mg) 2. Oral 1st generation antipsychotic (e.g. low dose haloperidol) 3. Parenteral 2nd generation antipsychotic (e.g. olanzapine 10 mg IM) 4. Parenteral 1st generation antipsychotic (e.g. haloperidol low dose IM or IV) Schizophrenia or Mania 1. Oral 2nd generation antipsychotic alone (e.g. risperidone 2 mg, olanzapine 5-10 mg) 2. Oral 1st generation antipsychotic (e.g. haloperidol 2-10 mg with benzodiazepine) 3. Parenteral 2nd generation antipsychotic (e.g. olanzapine 10 mg IM) 4. Parenteral 1st generation antipsychotic (e.g. haloperidol 2-10 mg IM) along with benzodiazepine (e.g. lorazepam 1-2 mg) Wilson M.P. et al. The Psychopharmacology of Agitation. Consensus Statement of the American Association for Emergency Psychiatry, Western J Emerg Med. 2012;13(1):26-34. 42 Academy of Consultation-Liaison Psychiatry

43. Benzodiazepines Benzodiazepines (BZDs) act by facilitating the activity of GABA GABA is a major inhibitory neurotransmitter Therapeutic effects appears linked to decreased arousal Little benefit for psychiatric symptoms other than anxiety Long history of use in the management of acute agitation Individually Combination with antipsychotics (except IM olanzapine) Preferred in a patient in whom agitation is secondary to alcohol or sedative withdrawal Zaman et al. Benzodiazepines for psychosis-induced aggression or agitation. Cochrane Database Syst Rev. 2017;12:Cd003079 43 Academy of Consultation-Liaison Psychiatry

44. Benzodiazepines Lorazepam Only BZD with complete and rapid IM absorption No involvement of P450 system IM or sublingual administration 60-90 minutes until peak plasma concentration 8-10 hour duration of effect 12-15 hour elimination half-life Studies suggest that lorazepam 2 mg is at least as effective as haloperidol in controlling acute agitation1-2 1Allen MH. Managing the agitated psychotic patient: a reappraisal of the evidence. J Clin Psychiatry 2000;61(S14):S1-S20 2Battaglia et al. Haloperidol, lorazepam, or both for psychotic agitation? A multicenter, prospective, double-blind, emergency department study. Am J Emerg Med 1997;15:335 340 44 Academy of Consultation-Liaison Psychiatry

45. Benzodiazepines Side effects Excessive sedation Additive with other CNS depressants Respiratory depression BZDs avoided in patients at risk for CO2 retention Paradoxical disinhibition More likely with high doses in patients with structure brain damage, mental retardation or dementia Ataxia 45 Academy of Consultation-Liaison Psychiatry

46. Typical Antipsychotics Dopamine antagonist Positive Antipsychotic Anti-agitation Negative Extrapyramidal symptoms (EPS) Neuroleptic Malignant Syndrome (NMS) Many authors consider typical antipsychotics the treatment of choice in acute agitation, especially in the setting of delirium 46 Academy of Consultation-Liaison Psychiatry

47. TypicalAntipsychotics Low potency Not recommended High potency - Haloperidol Virtually no anticholinergic properties Little risk of hypotension Does not suppress respiration Can be given IV Not FDA approved Fast acting Onset of action: 30 minutes Duration of action up to 12-24 hours Powney et al. Haloperidol for psychosis-induced aggression or agitation (rapid tranquillisation). Cochrane Database of Systematic Reviews 2012;11:CD009377 47 Academy of Consultation-Liaison Psychiatry

48. TypicalAntipsychotics Side effects Extrapyramidal symptoms Dystonia Akathisia Parkinson-like effects QTc prolongation Rare at low doses Haloperidol and droperidol with Black Box warnings Lower seizure threshold Low-potency > high-potency antipsychotics Powney et al. Haloperidol for psychosis-induced aggression or agitation (rapid tranquillisation). Cochrane Database of Systematic Reviews 2012;11:CD009377 48 Academy of Consultation-Liaison Psychiatry

49. Typical Antipsychotics Loxapine 5 10 mg, inhaled Inhaled Loxapine has been recently endorsed by FDA for treatment for agitation in Bipolar I disorder Efficacy supported in multiple trials when compared to placebo, has not been compared to other active medication Need to monitor for bronchospasm, especially in patients with asthma Owen RT. Inhaled loxapine: a new treatment for agitation in schizophrenia or bipolar disorder. Drugs of Today. 49(3):195-201, 2013 Garriga et al. Assessment and management of agitation in psychiatry: expert consensus. World J Biol Psychiatry 2016;17:86-128 Academy of Consultation-Liaison Psychiatry 49

50. Atypical Antipsychotics Major advance in psychiatry Broader spectrum of response Different side effect profile Less EPS and akathisia QTc concern remains Metabolic syndrome No randomized, controlled studies have examined the use of medications in populations with Severe agitation Drug-induced agitation Significant medical comorbidity 50 Academy of Consultation-Liaison Psychiatry

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