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Home , Akathisia

Management of the Violent Recised from: Patient Jennifer Richman MD Assistant Professor APM Resident Education Curriculum University of Rochester School of Medicine R. Scott Babe, M.D. Medical Director of the Inpatient Psychiatric Consultation Liasion Service Clinical Assistant Professor of Psychiatry Medical Director of the Telepsychiatry Program Western University of Health Sciences Samaritan Mental Health Corvallis, Oregon Thomas W. Heinrich, M.D. Updated Associate Professor of Psychiatry & Family Medicine Fall 2013: Chief, Psychiatric Consult Service at Froedtert Hospital Paula Zimbrean, M.D. Department of Psychiatry & Behavioral Medicine Karina Uldall M.D., M.P.H. Medical College of Wisconsin ACADEMY OF PSYCHOSOMATIC MEDICINE ACADEMY OF PSYCHOSOMATIC MEDICINE Psychiatrists Providing Collaborative Care for Physical and Mental Health Psychiatrists Providing Collaborative Care for Physical and Mental Health 1

Objectives The Case

. Identify the principles of the “cycle of violence.” . A 47 year‐old male with a history of substance abuse and . Describe the broad behind the bipolar disorder along with morbid obesity, DM and COPD symptoms of agitation and . presents to the ED at 0200 after calling 911 and reporting chest . Apply nonpharmacologic and pharmacologic pain. approaches to management of the agitated patient in . Initially cooperative in the ED, but the staff indicate that he has the general medical setting. been mumbling to himself and starring at them suspiciously. They gave him some to “calm” him. . Since arrival to the floor to r/o MI he has been becoming increasingly irritable, confrontational and restless. Eventually he starts to become uncooperative with care and then verbally and physically threatening to the staff. . They call a psychiatry consult for “HELP!!!!”

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1 Definitions Component Behaviors of Agitation . Aggressive behaviors . Agitation – Physical – Excessive motor or verbal activity . Fighting . Throwing things . Grabbing objects . Aggression . Destroying items – Actual noxious behavior that can be verbal, physical against – Verbal objects, or physical against people . Cursing . Screaming . Violence . Nonaggressive behaviors – Denotes physical aggression by people against other people – Restlessness (akathisia, restlessness) – Wandering (Citrome and Volavka, 2002) – Inappropriate behavior (disrobing, intrusive, repetitive questioning)

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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) . Marco and Vaughn (2005) – 4.3 million psychiatric emergency visits/year . 21% (900,000) agitated patients with . 13% (560,000) agitated patients with bipolar . 5% (210,000) agitated patients with

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2 Epidemiology Etiology of Agitation

. Studies for health care workers . A. Disease‐related: three major categories – California: – Psychiatric manifestations of general medical conditions . 465 assaults per 100,000 hospital workers vs. 82.5 assaults per – Substance intoxication/withdrawal 100,000 for all workers (Peek‐Asa et al 1997) – Primary psychiatric illness – Minnesota Nurses Study (Gerberich et al 2004): . 13.2 per 100 persons per year for physical assaults . B. No “disorder”; unlikely to benefit from medical . 38.8 per 100 persons per year for non‐physical assaults intervention (e.g., criminal behavior) . Greatest risk for persons working in/with: – consider calling security or the police, depending on the . Long term care facility severity . Intensive care . Psychiatric unit . Not mutually exclusive . Emergency department . Geriatric patients

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Etiology of Agitation: A Sample of the Varied Conditions Etiology of Agitation: Medical Causes that may Present with Pathologic Agitation . Dementia . Bipolar disorder . Head trauma . Hypoxia . Huntington's disease . Substance intoxication or . , , . Thyroid disease withdrawal . Brain injury other infection . . . Psychosis Organic brain syndrome . , liver or . Toxic levels of (delirium) . Premenstrual dysphoric renal failure . disorder Korsakoff’s psychosis . Environmental toxins . Brain tumors . PTSD . Metabolic abnormalities . . Panic disorder and GAD Mental retardation (sodium, calcium, glucose) . Autism . Antisocial personality . disorder disorder (Nordstrom et al. Medical Evaluation . and Triage of the Agitated Patient. . Major depression Borderline personality disorder Western J Emergency Med 2012; 1:3‐ . Dysthymia 10.) . ADD Academy Of Psychosomatic Medicine 11 Academy Of Psychosomatic Medicine 12

3 Etiology of Agitation: Medical condition Etiology of Agitation: Substances

–Delirium . Substance intoxication (ETOH, cocaine, . Disturbance of consciousness amphetamines, ketamine, bath salts, inhalants) . A change in cognition or development of perceptual disturbance . Substance withdrawal (ETOH withdrawal . Not accounted for by a dementia delirium/DTs) . Disturbance develops over a short period of time and tends to fluctuate . Caused by a general medical condition . CNS effects of non‐psychiatric medications (steroids)

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Etiology of Agitation: Primary Psychiatric disorders Etiology of Agitation: Schizophrenia

–Acutely, patients may present to the ED with acute psychosis –Schizophrenia . Hallucinations –Bipolar . Delusions . Disorganized speech and/or behavior –Dementia . Lack of insight –Personality Disorders . Bizarre behavior –Fertile conditions for the development of agitation . Psychosis and agitation have a reciprocal relationship

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4 Etiology of Agitation: Schizophrenia Etiology of Agitation: Personality Disorders

–Patients at highest risk for violence . More suspicious and hostile –Some personality disorders are more prone to . More severe hallucinations agitation . Less insight into delusions . Decreased stress tolerance . Greater thought disorder . Poor impulse control . Poor impulse control –Borderline personality disorder –Risk factors for becoming a target –Antisocial personality disorder . Parent or immediate family member . Cohabitation . Patient financially dependent on you

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Etiology of Agitation: Dementia Etiology of Agitation: Dementia

–Agitation may be a final common pathway for the –Overall, the incidence of agitation is estimated to be expression of… between 60‐80% (median 44%) (Bartels et al 2003) . Depression . 50% become frankly physically aggressive . . 24% become verbally aggressive . Psychosis –Burden of institutionalization . Pain . Residents with dementia complicated by agitation have . Delirium the highest 3‐month rate of ED visits and greatest use of – While agitation may be of multifactorial etiology in patients restraints (Sachs, 2006) with dementia, it is also true that many patients have only agitation as a target symptom for treatment (Madhusoodanan, . Despite use of restraints, over 40% receive no psychiatric 2001) medications

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5 Etiology of Agitation The Case (continued)

. Potential etiologies for our gentleman’s growing . Psychodynamic perspectives of agitation and violence agitation – “…motive or cause of violent behavior is the wish to ward off or eliminate feelings of shame and humiliation [ego integrity]…” (Hodas, –Substance intoxication 2004) –Bipolar disorder – Crisis can be defined as an assault on the person’s sense of self (Bernstein, 2007) –Personality disorder – Violence is often in response to blocking of demands or loss of control (Bernstein, 2007) –Delirium

. A psychological understanding of aggressive behavior can help temper counter‐transference

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Assessment of Agitation Assessment of Agitation –Decisions regarding diagnostic tests must be made . For a known schizophrenic with typical behavioral features – Expectant management is appropriate in the context of available history and physical . For patients with atypical features additional diagnostic tests examination may be required – Atypical presentations –Goal is to evaluate patients at risk for medical . Delirium comorbidities . History of trauma . Overdose –Many questions involve forced decisions based . on… . Fever – Diagnostic tests to consider . Assumptions . Toxicology screens . Information available . CT of brain . Diagnostic confidence . BMP, CBC, and LFTs . Urinalysis . Patient’s individual risk factors . Endocrine tests . Lumbar puncture Academy Of Psychosomatic Medicine 23 Academy Of Psychosomatic Medicine 24

6 The Case (continued) The Case (continued)

. Examination of the patient . Laboratory evaluation of the patient – The patient is febrile with normal vitals – CBC, BMP are normal except for a glucose of 211 – Malnourished, disheveled, and stinky – LFTs are normal except for a low albumin – Heart, lungs and abdomen are benign – TSH, B12, Folate, and RPR are also normal – No or asterixis – U/A is positive for glucose and trace – Mental status/state examination reveals… – CT of head is read as “negative” – EKG shows QTc < 400msec – UDS and serum toxicology are negative – VPA, carbamazepine, and lithium are all negative

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Before the Acute Intervention Goals of Intervention

. The staff on Med/Surg units are often less informed about what feelings and behaviors their actions may elicit in patients . Acute agitation or a violent patient modifies the . Studies indicate that staff training and education can change normal caregiver‐patient relationship this lack of appreciation . The first goal of treatment is to do only what is . Psychiatric consultants can provide education about necessary to assure the safety of the patient and – Establishing goals from the patients perspective others while facilitating the resumption of more – Interventions that support a structured setting normal interpersonal relations . Private or semi‐private room – Calming without over‐sedation . Establish clear set of expectations with a written schedule . Identify staff that are responsible for the patients care – Attempting to enlist the patient in the treatment, i.e. which route of has worked the best in the past as a “choice” which retains some patient control

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7 Agitation Management Environmental Interventions

. Medical evaluation and triage . Examples of effective non‐pharmacological treatments . Psychiatric evaluation – Clearing the room . Verbal de‐escalation – Removing dangerous objects – Having staff available as a “show of force” . Psychopharmacologic interventions – Close observation . Use of seclusion/restraint – Calm conversation – Decrease sensorial stimulation (Project BETA: Best practices in Evaluation and Treatment of Agitation, Western J Emergency Med 2012; 1:1‐2)

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Communication/Behavioral Interventions Communication/Behavioral Interventions

. Nonverbal . Aligning Goals of Care – Maintain a safe distance – Acknowledge the patient’s grievance – Maintain a neutral posture – Acknowledge the patient’s frustration – Do not stare; eye contact should convey sincerity – Shift the focus to discussion of how to solve the problem – Do not touch the patient – Emphasize common ground – – Stay at the same height as the patient Focus on the big picture – Find ways to make small concessions – Avoid sudden movements . Monitoring Intervention Progress . Verbal – Be acutely aware of progress – Speak in calm, clear tone – Know when to disengage – Personalize yourself – Do not insist on having the last word – Avoid confrontation; offer to solve the problem (APA Textbook of Psychosomatic (APA Textbook of Psychosomatic Medicine, 2nd ed. Edited by James L. Medicine, 2nd ed. Edited by James L. Levenson. 2011) Levenson. 2011) Academy Of Psychosomatic Medicine 31 Academy Of Psychosomatic Medicine 32

8 The Case (continued) Serotonin‐ Model of Regulation of Agitation . You and the nursing staff . Dynamic interaction between the amygdala, nucleus – Clear the room accumbens, and the prefrontal cortex – Keep dangerous objects out of reach – Call security Amygdala Serotonin . You attempt to approach the patient using everything you activation Nucleus learned in this amazing talk Accumben s . Despite these great interventions the patient makes further threats, rips‐off telemetry lines, and starts to pace with Dopamine Released Suppression clenched fists while mumbling incoherently Prefrontal Cortex

agitation Provides a basis for the response to certain medications (Ryding et al, 2008) Academy Of Psychosomatic Medicine 33 Academy Of Psychosomatic Medicine 34

Goals of Intervention Pharmacologic Considerations

. Definition of psychopharmacologic treatment . Ease of preparation/administration endpoint (rapid tranquilization) . Rapid onset of action: IV > IM > PO . Sufficient duration of effect – Sleep . . Conflicts with goal of patient participation Low risk of adverse reactions or drug interactions . Has not been found to be essential to improvement in agitation or decrease in psychotic symptoms . What is known about the patient’s underlying condition(s)? – Tranquillization – Age . Calming process separate from total sleep induction – Comorbid conditions . Allows patient to participate in care – Medication/other substance exposure . Enables clinician to gather history, initiate a work‐up, and begin treatment of unidentified conditions (Zeller et al, Systematic Reviews of Assessment Measures and Pharmacologic Treatments for Agitation. Clin Therapeutics 2010; . Better therapeutic endpoint 32:405‐425)

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9 Pharmacologic Treatment Pharmacologic Treatment

. Most important factors in medication selection (Marder, . Route of administration 2006, Allen et al, 2005) – Etiology of agitation –Oral administration – Acute effect on behavioral symptoms . Preferred if patient accepts – Multiple means of administration . Liquid or orally dissolving tablets – Limited side effects –Intramuscular administration – Ease of administration . Rapid elevation of plasma level – Patient preference . Higher transient concentration – History of response . Faster reduction in agitated behavior . Goal is a balance between effectiveness and tolerability

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Association for Emergency Psychiatry Pharmacologic Treatment Recommendations . . Most studies of pharmacologic treatment in agitation . No Data/Suspect Intoxication were done in patient with KNOWN psychiatric – or benzodiazepines + diagnosis . No randomized, controlled studies have examined the . use of medications in populations with… Schizophrenia or Mania – Severe agitation –olanzapine alone orally – Drug‐induced agitation – alone or + orally – Significant medical comorbidity –haloperidol +benzodiazepine orally . Results difficult to extrapolate to the undifferentiated –olanzapine alone if IM required agitated patient in the general ED or med/surg unit . (Allen MH et al, for the Expert Consensus Panel for Behavioral Emergencies 2005. The expert consensus guideline series. Treatment of behavioral emergencies 2005. J Psychiatr Pract. 2005;11(Suppl 1):5–108)

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10 Benzodiazepines Benzodiazepines

–BZDs act by facilitating the activity of GABA . Lorazepam . GABA is a major inhibitory neurotransmitter – Only BZD with complete and rapid IM absorption –Therapeutic effects appears linked to decreased – No involvement of P450 system . Little benefit for psychiatric symptoms other than – IM or sublingual administration anxiety . 60‐90 minutes until peak plasma concentration –Long history of use in the management of acute . 8‐10 hour duration of effect agitation . 12‐15 hour elimination half‐life . Individually – . Combination with Studies suggest that lorazepam 2mg is at least as effective . Preferred in a patient in whom agitation is secondary to as haloperidol in controlling acute agitation alcohol or sedative withdrawal

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Benzodiazepines Typical Antipsychotics

. Side effects – – Excessive sedation . Positive . Additive with other CNS depressants . . Antiagitation – Respiratory depression . Negative . BZDs avoided in patients at risk for CO2 retention . (EPS) – Paradoxical disinhibition . Neuroleptic Malignant Syndrome (NMS) . More likely with high doses in patients with structure –Many authors consider typical antipsychotics the brain damage, mental retardation or dementia treatment of choice in acute agitation – Ataxia

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11 Typical Antipsychotics Typical Antipsychotics . Low potency – Not recommended . . High potency ‐ haloperidol Side effects – Virtually no properties – Extrapyramidal symptoms – Little risk of hypotension . – Does not suppress respiration . Akathisia – Can be given IV . Parkinson‐like effects . Not FDA approved – QTc prolongation – Little cardiotoxicity . Concern of QTc prolongation . Rare at low doses – Fast acting . Haloperidol and droperidol with “Black Box” warnings . Onset of action: 30 minutes – Lower seizure threshold . Duration of action up to 12‐24 hours . Low‐potency > high‐potency antipsychotics . (Powney MJ. Adams CE. Jones H. Haloperidol for psychosis‐ induced aggression or agitation (rapid tranquillisation). [Review] Cochrane Database of Systematic Reviews. 11:CD009377, 2012)

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Typical Antipsychotics: Loxapine Atypical Antipsychotics

. Inhaled Loxapine has been recently endorsed by FDA –Major advance in psychiatry for treatment for agitation in Bipolar I disorder . Broader spectrum of response . Need to monitor for bronchospasm, especially in . Different side effect profile . patients with asthma Less EPS and akathisia . QTc concern remains . Metabolic syndrome . (Owen RT. Inhaled loxapine: a new treatment for agitation in schizophrenia or bipolar disorder. Drugs of Today. 49(3):195‐201, –No randomized, controlled studies have examined 2013 Mar) the use of medications in populations with… . Severe agitation . Drug‐induced agitation . Significant medical comorbidity

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12 Atypical Antipsychotics Atypical Antipsychotics – Risperidone . Oral solution . Oral tablet . Risperidone (Currier and Simpson 2001, Currier et al 2004) . Oral tablet, disintegrating – Olanzapine – 2 studies have compared have compared . Intramuscular . Oral risperidone concentrate 2mg + oral lorazepam 2mg . Oral tablet . Oral tablet, disintegrating . IM haloperidol 5mg + IM lorazepam 2mg – Quetiapine . The two interventions were equally effective at . Oral tablet reducing agitation at 30, 60, and 120 minutes – . Intramuscular – So… In agitated patients willing to take oral medication and . Oral tablet comply with treatment, the combination of oral risperidone – and lorazepam appears to be acceptable . Intramuscular . Oral solution . Oral tablet . Oral tablet, disintegrating

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Atypical Antipsychotics Atypical Antipsychotics

. Olanzapine . Olanzapine – IM dose range of 5‐10mg – Adverse events . Maximum of 30mg/day . Concern of orthostasis . 15‐45 minutes until peak plasma concentration . Long‐term use has been associated with the development of metabolic syndrome . 21‐54 hour elimination half‐life . IM olanzapine should NOT be administered with BZDs – PO dose range 5‐10mg or CNS depressants given reports of adverse events and . 24‐54 hour elimination half‐life 8 deaths in Europe . 1‐3 hours until peak plasma concentration, but benefits . Patients were also suffering from medical often occur in less time comorbidities . Cardiopulmonary depression, hypotension, and bradycardia reported

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13 Atypical Antipsychotics Atypical Antipsychotics

. Ziprasidone . Ziprasidone – First atypical with an IM formulation – Adverse events – IM dose range of 10‐20mg . QTc interval prolongation . 10mg q2 hour . Appears to prolong the QTc to a greater degree than . 20mg q4 hour haloperidol, risperidone, or olanzapine . Maximum of 40mg IM/day . No clinically relevant ECG changes observed in – 30‐40 minutes to peak plasma concentrations agitation studies . . 9x faster than oral administration Somnolence, nausea, and dizziness were the most common reported in the agitation studies – 2‐4 hour elimination half‐life – 4‐6 hour duration of effect

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Atypical Antipsychotics Atypical Antipsychotics

. Aripiprazole . Quetiapine – Newest – 1‐3 hours to peak plasma concentrations – It is unique in that it is a partial dopamine agonist – Very low risk of EPS . Decreases dopamine in hyper‐dopaminergic areas of the brain . Increases dopamine in hypo‐dopaminergic areas of the brain – Sedation and orthostasis are side effects – IM Aripiprazole has been found effective in the management – 1 open‐labeled pilot study (N=20) (Currier et al, 2006) of agitation in psychiatric illness . 100mg (N=7), 150mg (N=6), or 200mg (N=7) – Recommended IM dose is 9.75mg administered . Fair efficacy in reducing agitation over 120 minutes . (Gonzalez D. Bienroth M. Curtis V. Debenham M. Jones S. Pitsi D. . No clear dose‐response pattern George M. Consensus statement on the use of intramuscular aripiprazole for the rapid control of agitation in bipolar mania and . 40% exhibited orthostasis by 120 minutes Schizophrenia.Current Medical Research & Opinion. 29(3):241‐50, . 6 subjects were asleep at 120 minutes 2013 Mar)

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14 Combination Therapy Combination Therapy

– individual medications can be targeted to the different components of agitation . Most common combination . Anxiety and arousal  benzodiazepine – Haloperidol 5mg IM . Psychosis  antipsychotic – Lorazepam 2mg IM – – combining medications at low doses may reduce individual Benefits side effects (decrease Cmax), while obtaining desired effect . Faster reduction in agitation . – specific prevention of side effects while combining anti‐ Less injections required agitation effect . Simple to administer . . e.g., Haloperidol + Dipheniramine Lower incidence of EPS

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Combination Therapy Cost

. Side effects Lorazepam Haloperidol Ziprasidone Olanzapine – Overall, very well tolerated 2 mg IM 5 mg IM 20 mg IM 10 mg IM – Side effect profiles of both the BZDs and antipsychotics apply $1.28 $7.49 $12.25 $27.25 – Excess sedation most common adverse reaction Number of injections 1 (42%) or 1 (76%) . However, recent studies suggest sedation rates appear similar to lorazepam treatment alone required (clinical trial 2 (37%) data) . (Wilson MP. MacDonald K. Vilke GM. Feifel D. A comparison of the safety of olanzapine and haloperidol in combination with benzodiazepines in emergency department patients with acute agitation. Journal of Emergency Medicine. 43(5):790‐7, 2012 Nov)

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15 Summary for Acute term Summary for Acute Term(cont.)

Medication Class Medication Dosing Side Effects/Considerations Can cause hypotension. Benzodiazepine Alprazolam Only available PO; initial dose is 0.5-4 Paradoxical reactions can be seen in Atypical antipsychotics Risperidone PO, orally disintegrating tablet (OTD), No IM form is available. mg/day character-disordered patients and can Starting dose 0.5-2 mg acutely worsen symptoms in the elderly. Offers calming effect with treatment of underlying condition. Diazepam PO, IM, IV; start at 5 mg Calming/sedating effect with rapid Orthostatic hypotension with reflex onset; however, use cautiously with tachycardia. elderly patients because of the drug's Increased risk of in the elderly with long half-life. CVD. Lorazepam PO, SL, IM, IV; start at 1 mg, moderate No active metabolites; therefore, there is Olanzapine PO, OTD, IM; Useful in patients with poor reaction to half-life (10-20 hr) a small risk of drug accumulation. Starting dose 2.5-5 mg, max 30 mg/24 hr haloperidol. Metabolized only via gluconuronidation; Calming medication with treatment of therefore, it can be used in most patients underlying disorder. with impaired hepatic function. Avoid IM combination with lorazepam. Drug of choice within this class due to Increased risk of stroke in the elderly with CVD. moderately long half-life. Ziprasidone PO, IM Use caution in patients with preexisting QT Typical antipsychotics Haloperidol PO, IM, IV; start at 5-10 mg IM, IV* High-potency neuroleptic with favorable prolongation. side-effect profile and cardiopulmonary Max of 40 mg/24 hr of IM formulation Less sedating medication; therefore, good * IV formulation is not FDA approved safety. choice if desire tranquilization without IV form less likely to cause EPS. sedation. ECG monitoring needed to assess Aripiprazole PO, IM, OTD Akathisia risk. torsades de pointes or QTc prolongation. 9.5mg IM Less sedating than other medications Risk of NMS increases in patients who Increased risk of stroke in the elderly are poorly hydrated, restrained, and kept Combinations Haloperidol, lorazepam, , or 5 mg IM, 2 mg IM, 50 mg IM, 1 mg IM Most commonly used in the acute setting. in poorly aerated rooms while given large doses of antipsychotics. Frequent Young athletic men are at increased risk for dystonia. vital sign checks and testing for Akathisia must be considered if agitation muscular rigidity are recommended. increases after administration.

CVD, Cardiovascular disorder; ECG, electrocardiogram; EPS, extrapyramidal symptoms; IM, intramuscular; IV, intravenous; NMS, CVD, Cardiovascular disorder; ECG, electrocardiogram; EPS, extrapyramidal symptoms; IM, intramuscular; IV, intravenous; NMS, neuroleptic neuroleptic malignant syndrome; PO, per os (by mouth, orally); PR, per rectum; SL, sublingual. malignant syndrome; PO, per os (by mouth, orally); PR, per rectum; SL, sublingual. Adapted from Allen M, Currier G, Carpenter D: The expert consensus guideline series: treatment of behavioral emergencies, J Psychiatr Pract 11:1‐112, 2005. Adapted from Allen M, Currier G, Carpenter D: The expert consensus guideline series: treatment of behavioral emergencies, J Psychiatr Pract 11:1‐112, 2005. Stern, T, et. al. 200861 Stern, T, et. al. 200862

Disposition Special Population: ICU patients

. Disposition depends on etiology of agitation and . Mechanically ventilated ICU patients analgesia and sedation current condition are recommended – Delirium  General medical hospital . Dexmedetomidine, rather than benzodiazepines – Psychosis  Psychiatric admission . No evidence haloperidol decreases the duration of delirium – Don’t have a clue  General medical hospital to determine . Atypical antipsychotics may decrease the duration of delirium cause of agitation in ICU patients

. (Riker RR. Fraser GL. The new practice guidelines for pain, agitation, and delirium. Am J Critical Care. 22(2):153‐7, 2013 Mar)

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16 Recommended Readings Special Population: Weaning of Ventilation . Marder SR. A review of agitation in mental illness: treatment guidelines and current therapies. J Clin Psychiatry. 2006;67 . Dexmedetomidine (alpha 2 adrenergic sedative) (Suppl 10):13‐21. –Better than midazolam (VS, time intubated) . Citrome L. Interventions for the treatment of acute agitation. . (Ricker et al, 2009) CNS Spectr. 2007; 8 (Suppl 11):8‐12. –Better than haloperidol (time intubated, LOS) . Ryding E, Lindström M, Träskman‐Bendz L. The role of . (Reade et al, 2009) dopamine and serotonin in suicidal behaviour and aggression. Prog Brain Res. 2008;172:307‐15. . 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.

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