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Web audio at CurrentPsychiatry.com Dr. Brown talks about treatment options for acute

How to stabilize an acutely psychotic

In psychiatric emergencies, use a stepwise approach to provide safe, effective treatment

cute psychosis is a symptom that can be caused by many psychiatric and medical conditions. Psychotic Apatients might be unable to provide a history or par- ticipate in treatment if they are agitated, hostile, or violent. An appropriate workup may reveal the of the psychosis; secondary causes, such as medical illness and substance use, are prevalent in the emergency room (ER) setting. If the pa- tient has an underlying primary psychotic disorder, such as or , illness-specific intervention will help acutely and long-term. With agitated and uncooperative psy- chotic , clinicians often have to intervene quickly to ensure the safety of the patient and those nearby. This article focuses on the initial evaluation and treat- © DARREN KEMPER/CORBIS ment of psychotic patients in the ER, either by a psychiatric Hannah E. Brown, MD emergency service or a psychiatric consultant. This process Schizophrenia Fellow can be broken down into: Massachusetts General Harvard • or initial clinical assessment Boston, MA • initial psychiatric stabilization, including pharmaco- Joseph Stoklosa, MD logic interventions and agitation management Attending • diagnostic workup to evaluate medical and psychiat- McLean Hospital ric conditions Belmont, MA Instructor in • further psychiatric evaluation Harvard Medical School • determining safe disposition.1 Boston, MA Oliver Freudenreich, MD, FAPM Department of Psychiatry Triage determines the next step Massachusetts General Hospital Initial clinical assessment and triage are necessary to select Associate Professor of Psychiatry Harvard Medical School the appropriate immediate intervention. When a patient ar- Boston, MA rives in the ER, determine if he or she requires urgent medi- cal attention. Basic initial screening should include: Current Psychiatry 10 December 2012 • vital signs • finger stick blood glucose pharmacotherapy may limit the amount of • time spent in restraints. • signs or symptoms of intoxication or Medication choice depends on several withdrawal factors, including onset of action, available • signs of trauma (eg, neck ligature formulation (eg, IM, liquid, rapidly dis- marks, gunshot wounds, lacerations) solving), the patient’s previous medication • asking the patient to give a brief history response, side effect profile, or ad- leading up to the current presentation. verse reactions to medications, and medical A review of medical records may reveal .3 If a patient has a known psy- patients’ medical and psychiatric history chotic illness, it may be helpful to admin- and allergies. Collateral documentation— ister the patient’s regular or such as ambulance run sheets or police medication. Some medications, reports—may provide additional informa- such as lithium, are not effective in the acute tion. If no immediate medical intervention setting and should be avoided. Additionally, is warranted, determine if the patient can other than lorazepam or wait in an open, unlocked waiting area midazolam should not be administered IM or if he or she needs to be in an unlocked because of erratic absorption. Clinical Point area with a sitter, a locked open area, or a can be used for psy- Early signs of secluded room with access to restraints. chotic patients with or without agitation. In general, psychotic patients who pose Benzodiazepines may treat agitation, but are agitation include a threat of harm to themselves or oth- not specific for psychosis. can be restlessness, ers or cannot care for themselves because used to treat acute psychosis and has proven , decreased of their psychosis need locked areas or efficacy for agitation. Benzodiazepines can attention, and observation. decrease acute agitation and have efficacy inappropriate or similar to haloperidol, but with more seda- tion.5 A combination of lorazepam and halo- hostile behaviors Initial psychiatric stabilization peridol is thought to be superior to either Agitation is diagnostically unspecific medication alone.6 Lorazepam helps main- but can occur in patients with psychosis. tain sedation and decreases potential side Psychotic patients can become unpredict- effects caused by haloperidol. Consensus ably and impulsively aggressive and as- guidelines from 2001 and 2005 recommend saultive. Rapid intervention is necessary to combined haloperidol and lorazepam for minimize risk of bodily harm to the patient first-line treatment of acute agitation.3,7 and those around the patient. High-potency antipsychotics such as halo- often must make quick interventions peridol have an increased risk for extra- based on limited clinical information. It pyramidal symptoms (EPS), particularly is important to recognize early signs and acute dystonic reactions—involuntary, sus- symptoms of agitation, including: tained muscle contractions—in susceptible • restlessness (pacing, fidgeting, hand patients (eg, antipsychotic-naïve patients); wringing, fist clenching, posturing) consider starting diphenhydramine, 25 to • irritability 50 mg, or benztropine, 0.5 to 2 mg, to pre- • decreased attention vent EPS from high-potency antipsychotics • inappropriate or hostile behaviors.2 (Algorithm 1, page 12). Second-generation antipsychotics (SGAs) Pharmacologic interventions. The initial increasingly have been used for managing goals of pharmacologic treatment are to calm acute agitation in patients with an underly- Discuss this article at the patient without oversedation, thereby al- ing psychotic disorder. Guidelines from a www.facebook.com/ CurrentPsychiatry lowing the patient to take part in his or her 2012 American Association for Emergency care and begin treatment for the primary Psychiatry workgroup recommend using psychotic illness.3,4 Offering oral medications an SGA as monotherapy or in combina- first and a choice of medications may help a tion with another medication instead of patient feel more in control of the situation. haloperidol to treat agitated patients with Current Psychiatry If a patient has to be physically restrained, a known psychotic disorder.8 Clinical pol- Vol. 11, No. 12 11 Algorithm 1 Treating acute psychosis: Choosing pharmacologic agents

Acutely psychotic patient

Unknown cause of psychosis, Known or suspected underlying Acute psychosis no known history psychotic illness

• Initiate treatment with haloperidol (PO/IM/ • Continue treatment with previous IV): 0.5 mg to 5 mg + lorazepam (PO/IM/ antipsychotic IV): 0.25 to 2 mg OR • Consider adding benztropine (PO/IM/IV): 0.5 to 2 mg OR diphenhydramine (PO/ • Initiate treatment with a second- IM/IV): 25 to 50 mg to reduce likelihood generation antipsychotic: of acute dystonic reaction or other EPS • PO: olanzapine: 5 to 10 mg, • Can also consider PO risperidone: 0.5 to risperidone: 0.5 to 2 mg +/- Clinical Point 2 mg, risperidone + lorazepam (at doses lorazepam: 0.5 to 2 mg listed above), olanzapine (PO/IM/SL): • IM: olanzapine: 2.5 to 20 mg, IM ziprasidone and 2.5 mg to 20 mg, ziprasidone (IM):10 to ziprasidone:10 to 20 mg 20 mg OR olanzapine have *Interventions may be repeated if clinically indicated; benztropine, 1 mg, or diphenhydramine, 25 mg, usually • Haloperidol (PO/IM/IV): 0.5 to 5 mg + a relatively rapid provide sufficient EPS prophylaxis for 12 hours lorazepam (PO/IM/IV): 0.5 to 2 mg onset of action, *Interventions may be repeated if clinically indicated If acute mania is suspected: which makes them • Load with divalproex (Table)15,16 reasonable choices in the acute setting EPS: extrapyramidal symptoms; PO: by mouth; SL: sublingual

icy guidelines from the American College decreased within of Emergency Physicians recommend an- 2 hours of IM olanzapine administration.13 tipsychotic monotherapy for agitation and Both IM ziprasidone and olanzapine have initial treatment in patients with a known a relatively rapid onset of action (within 30 psychiatric illness for which antipsychotic minutes), which makes them reasonable treatment is indicated (eg, schizophrenia).9 choices in the acute setting. Olanzapine has For patients with known psychotic illness, a long half-life (21 to 50 hours); therefore, pa- expert opinion recommends oral risperi- tients’ comorbid medical conditions, such as done or olanzapine.3,8 The combination of cardiac abnormalities or hypotension, must oral risperidone plus lorazepam may be as be considered. If parenteral medication is re- effective as the IM haloperidol and IM lo- quired, IM olanzapine or IM ziprasidone is razepam combination.10 Patients who are recommended.8 IM haloperidol with a ben- too agitated to take oral doses may require zodiazepine also can be considered.3 parenteral medications. Ziprasidone, olan- Coadministration of parenteral olan- zapine, and aripiprazole are available in zapine and a can lead to IM formulations. Ziprasidone, 20 mg IM, severe orthostatic hypotension and cardiac is well tolerated and has been shown to be or respiratory and should be effective in decreasing acute agitation symp- avoided in geriatric patients.14 Finally, it is toms in patients with psychotic disorders.11 important to rule out presentations that may Olanzapine is as effective as haloperidol in worsen with antipsychotic treatment, in- decreasing agitation in patients with schizo- cluding (PCP) toxicity (could phrenia, with lower rates of EPS.12 In a dou- worsen dystonic reactions), anticholinergic ble-blind, placebo-controlled trial, psychotic , neuroleptic malignant syndrome Current Psychiatry 12 December 2012 symptoms in patients with schizophrenia or (NMS), or . Table Divalproex dosing for patients with acute psychosis and mania Initial dose Titration Acute Divalproex delayed-release: 750 mg/d Increase to clinical effectiveness or 15 mania Divalproex extended-release: 20 mg/kg/d maximum serum level of 125 µg/mL Exacerbation Divalproex: 15 mg/kg/d (in 2 doses) Increase to clinical effectiveness over 12 of days or maximum dosage of 30 mg/kg/d psychosis16

If a patient does not respond to the ini- Hypotension and bradycardia may oc- tial dose of a medication, the dose may be cur in patients treated with olanzapine; repeated. However, doses should not be re- however, these signs occur less frequently peated until a patient is so sedated that he or in agitated patients.18 Antipsychotic treat- she cannot take part in his or her care, or un- ment increases risk for EPS, including acute til he or she has developed significant EPS. dystonia, (subjective restlessness Clinical Point In addition to antipsychotics, consider with desire to move), and parkinsonism Verbal de-escalation loading with oral divalproex for patients (shuffling gait, resting tremor, rigidity and who are acutely psychotic in the context of bradykinesia), as well as NMS. should be attempted a manic episode (Table).15,16 Higher serum first; other divalproex levels—target serum levels >94 Nonpharmacologic interventions. Verbal interventions include μg/mL—are associated with greater effica- intervention to try to de-escalate an agitat- offering a meal or cy as measured by change from baseline in ed, psychotic patient should be attempted blanket to decrease Mania Rating Scale or Young Mania Rating first; however, this is not always possible. Scale scores compared with placebo.15 For Other behavioral interventions include of- the patient’s acutely psychotic schizophrenia patients, fering a meal, blanket, or pillow, or other there is evidence of benefit with initial comforting options to decrease the pa- treatment with divalproex combined with tient’s anxiety associated with psychosis.2 an SGA. In a randomized, double-blind However, if agitated psychotic patients study, patients treated with divalproex plus continue to display aggressive behaviors olanzapine or risperidone showed quicker and pose a risk of harm to themselves or initial resolution of psychotic symptoms those around them, physical restraints compared with olanzapine or risperidone should be considered because the clinician monotherapy, but no better long-term ben- must balance protecting the patient’s rights efit.16 Clinicians may consider this well- with others’ safety. If physical restraints are tolerated combination after an appropriate used, medication also should be adminis- medical workup. This finding of early ben- tered. Remove physical restraints as soon efit was not replicated with divalproex as safely possible; the Joint Commission has extended-release.17 established standards for minimizing harm when using physical restraints.19 and adverse reactions. Treatment with antipsychotics may cause QTc interval prolongation, which can lead Diagnostic workup to increased risk for torsades de pointes and Once a patient is medically stable in the ER, sudden death due to ventricular fibrillation. begin further workup of the etiology of the However, there have been few cases of tor- psychosis (Algorithm 2, page 14). All patients sades de pointes after oral haloperidol and should have a physical exam, provided they none with IM haloperidol compared with at are calm and in behavioral control. Monitor least 30 cases of torsades de pointes after IV vital signs; patients at risk of withdrawal haloperidol treatment. Torsades de pointes from substances should be monitored more after risperidone, olanzapine, or ziprasi- frequently. Although there is no established Current Psychiatry done treatment has not been reported.18 standard for “medical clearance” of a psy- Vol. 11, No. 12 13 Algorithm 2 Diagnostic workup of an acutely psychotic patient

Initial triage: • ABCs: airway, breathing, circulation • Vital signs Acute psychosis • Evidence of trauma • Signs or symptoms of acute intoxication or withdrawal • Presence of delirious process • Brief history of recent events

Not stable Stable

Emergent or urgent medical treatment In behavioral control

Clinical Point No Yes

Psychosis in a Yes Verbal or behavioral interventions with • Physical exam delirious patient may good effect • Monitoring vital signs be characterized No • Further psychiatric history by poorly formed • Diagnostic workup: Physical restraints + pharmacologic – Serum toxicology and visual interventions – Urine toxicology (see Algorithm 1, page 12) – Basic metabolic panel – – TSH (in some ER settings) • Consider in certain clinical settings: – MRI – EEG – LP

ER: emergency room; EEG: electroencephalography; LP: lumbar puncture; TSH: thyroid-stimulating hormone

chiatric patient,20 all patients should un- to distinguish between these 2 diagnoses. dergo basic laboratory tests, including basic Serial exams may help clarify the clinical metabolic panel, complete blood count, and picture. It is important to remember that pa- urine toxicology. The extent of the workup tients with a history of a psychotic disorder is determined by the clinical situation and may have a superimposed delirium. suspected cause of psychosis.21 In young patients (age 18 to 30) with new- If you suspect delirium, the underly- onset psychosis, consider drug-induced ing medical etiology must be identified psychosis; PCP, lysergic acid diethylamide, and treated. Up to 40% of hospitalized pa- and methamphetamine intoxication and tients with delirium may have psychosis.22 withdrawal can lead to psychotic presenta- Psychosis in a delirious patient may be tions. Additionally, comorbid substance use characterized by poorly formed delusions is common among patients with primary and visual hallucinations. Delirious pa- psychotic disorders. One study found 37% tients often are inattentive, easily distracted, of first-episode psychotic patients misused and disoriented, with a fluctuating clinical drugs or alcohol, similar to the lifetime rate course. Patients with psychosis generally of patients with chronic psychotic disor- do not have impaired attention and are alert ders.23,24 Check urine and serum toxicology with intact memory. However, acutely psy- screens and obtain relevant substance use chotic patients may be quite disorganized history. Brain MRI may be considered for Current Psychiatry 14 December 2012 and uncooperative, which makes it difficult patients with first presentation of psychosis; however, there is little evidence to support head CT imaging unless there is known Related Resources head trauma.25 Electroencephalography • Schwartz S, Weathers, M. The psychotic patient. In: Riba MB, Ravindranath D, eds. Clinical manual of emergency psy- and lumbar puncture can be considered if chiatry. Arlington, VA: American Psychiatric Publishing, Inc.; clinically indicated. 2010:115-140. • American Association for . http:// emergencypsychiatry.org. Further psychiatric evaluation Drug Brand Names Aripiprazole • Abilify Lorazepam • Ativan Obtaining a psychiatric history is neces- Benztropine • Cogentin Midazolam • Versed sary to determine the etiology of the acute Diphenhydramine • Benadryl Olanzapine • Zyprexa psychotic presentation. The timing and Divalproex • Depakote Risperidone • Risperdal Haloperidol • Haldol Ziprasidone • Geodon duration of psychotic symptoms are key. Lithium • Eskalith, Lithobid Acute symptom onset with fluctuating Disclosures course and impaired attention suggests Dr. Freudenreich receives grant or research support from a delirious process. A gradual decline in Beacon Health Strategies, Global , MGH functioning over several months to years Psychiatry Academy, Optimal , Pfizer Inc., and PsychoGenics. in a young person suggests a first episode Clinical Point Drs. Brown and Stoklosa report no financial relationship with of a psychotic disorder (eg, schizophre- any company whose products are mentioned in this article or Timing and duration nia). Drug is common among young with manufacturers of competing products. persons with a psychotic disorder and a of psychotic positive drug screen for a psychogenic symptoms are key; substance does not exclude a primary psy- gradual decline in chotic disorder. tion for containment and assurance of med- functioning suggests If a patient has a history of schizophre- ication adherence. Goals of inpatient care a first episode of a nia, , or psychotic depres- include initiating or resuming pharmaco- sion, acutely worsening psychosis may be logic treatment to reduce psychotic symp- psychotic disorder considered an acute or chronic presenta- toms and beginning the recovery process. tion. Even in patients diagnosed with a Response rates—defined as ≥20% improve- psychotic illness, it is necessary to deter- ment in total score on a psychopathol- mine the cause of symptom exacerbation. ogy scale such as the Positive and Negative Medication nonadherence (which can be Syndrome Scale—will vary, but can take ≥4 partial), substance use, psychosocial - weeks in some patients with first-episode ors, or underlying medical illness should schizophrenia.26 However, most patients be considered. Collateral information from will be stabilized and ready for discharge family or friends may be crucial to under- before 4 weeks. Family education and alli- standing a patient’s presentation. ance building with the patient and family are important during hospitalization.

Safe disposition References 1. Marco CA, Vaughan J. Emergency management of agitation Patients who pose a risk of harm to them- in schizophrenia. Am J Emerg Med. 2005;23(6):767-776. or others or who are so impaired 2. Freudenreich O. Emergency management of acute psychosis. In: Freudenreich O, ed. Psychotic disorders: a by their psychosis that they cannot care practical guide. New York, NY: Wolter Kluwer/Lippincott Williams & Wilkins; 2008:72-78. for themselves generally should be admit- 3. Allen MH, Currier GW, Carpenter D, et al; Expert Consensus ted to an inpatient psychiatric facility. For Panel for Behavioral Emergencies 2005. The expert consensus guideline series. Treatment of behavioral emergencies 2005. some psychotic patients who are agreeable J Psychiatr Pract. 2005;11(1 suppl):S5-S108. to treatment and not prone to , less 4. National Institute for Health and Clinical Excellence. Schizophrenia: core interventions in the treatment and restrictive settings—such as a crisis inter- management of schizophrenia in primary and secondary vention unit or respite facility—may be care. , United Kingdom: National Institute for Clinical Excellence; 2002. appropriate. A patient with first-episode 5. Allen MH. Managing the agitated psychotic patient: a reappraisal of the evidence. J Clin Psychiatry. 2000;61 psychosis could be admitted for further di- (14 suppl):S11-S20. agnostic clarification and treatment initia- 6. Battaglia J, Moss S, Rush J, et al. Haloperidol, lorazepam, tion. Manic patients often have no or both for psychotic agitation? A multicenter, prospective, double-blind, study. Am J Emerg Current Psychiatry into their illness and may need hospitaliza- Med. 1997;15(4):335-340. Vol. 11, No. 12 15 continued 7. Allen MH, Currier GW, Hughes DH, et al.; Expert Consensus 16. Casey DE, Daniel DG, Wassef AA, et al. Effect of Panel for Behavioral Emergencies. The expert consensus divalproex combined with olanzapine or risperidone in guideline series. Treatment of behavioral emergencies. patients with an acute exacerbation of schizophrenia. Postgrad Med. 2001;(Spec no):1-88. . 2003;28(1):182-192. 8. Wilson MP, Pepper D, Currier GW, et al. The 17. Casey DE, Daniel DG, Tamminga C, et al. Divalproex of agitation: consensus statement of ER combined with olanzapine or risperidone for American Association for Emergency Psychiatry project treatment of acute exacerbations of schizophrenia. BETA psychopharmacology workgroup. West J Emerg Med. Neuropsychopharmacology. 2009;34(5):1330-1338. 2012;13(1):26-34. 18. Currier GW, Allen MH, Bunney EB, et al. Safety of 9. Lukens TW, Wolf SJ, Edlow JA, et al.; American College medications used to treat acute agitation. J Emerg Med. of Emergency Physicians Clinical Policies Subcommittee 2004;27(4 suppl):S19-S24. (Writing Committee) on Critical Issues in the Diagnosis 19. The Joint Commission. Sentinel event alert. Preventing Acute psychosis and Management of the Adult Psychiatric Patient in the restraint deaths. Published November 18, 1998. http:// Emergency Department. Clinical policy: critical issues in the www.jointcommission.org/assets/1/18/SEA_8.pdf. diagnosis and management of the adult psychiatric patient in Accessed October 26, 2012 the emergency department. Ann Emerg Med. 2006;47(1):79-99. 20. Janiak BD, Atteberry S. Medical clearance of the psychiatric 10. Currier GW, Chou JC, Feifel D, et al. Acute treatment patient in the emergency department. J Emerg Med. of psychotic agitation: a randomized comparison of 2012;43(5):866-870. oral treatment with risperidone and lorazepam versus intramuscular treatment with haloperidol and lorazepam. 21. Freudenreich O, Schulz SC, Goff DC. Initial medical work- J Clin Psychiatry. 2004;65(3):386-394. up of first-episode psychosis: a conceptual review. Early Interv Psychiatry. 2009;3(1):10-18. 11. Daniel DG, Potkin SG, Reeves KR, et al. Intramuscular (IM) ziprasidone 20 mg is effective in reducing agitation 22. Webster R, Holroyd S. Prevalence of psychotic symptoms in associated with psychosis: a double-blind, randomized trial. delirium. Psychosomatics. 2000;41(6):519-522. Psychopharmacology (Berl). 2001;155(2):128-134. 23. Cantwell R, Brewin J, Glazebrook C, et al. Prevalence of Clinical Point 12. Wright P, Birkett M, David SR, et al. Double-blind, placebo- substance misuse in first-episode psychosis. Br J Psychiatry. controlled comparison of intramuscular olanzapine and 1999;174:150-153. intramuscular haloperidol in the treatment of acute agitation 24. Green AI, Tohen MF, Hamer RM, et al. First episode Even in patients in schizophrenia. Am J Psychiatry. 2001;158(7):1149-1151. schizophrenia-related psychosis and substance use 13. Kapur S, Arenovic T, Agid O, et al. Evidence for onset of disorders: acute response to olanzapine and haloperidol. diagnosed with a antipsychotic effects within the first of treatment. Schizophr Res. 2004;66(2-3):125-135. psychotic illness, Am J Psychiatry. 2005;162(5):939-946. 25. Goulet K, Deschamps B, Evoy F, et al. Use of brain 14. Marder SR, Sorasburu S, Dunayevic E, et al. Case reports of imaging (computed tomography and magnetic it is necessary to postmarketing adverse event experiences with olanzapine resonance imaging) in first-episode psychosis: review intramuscular treatment in patients with agitation. J Clin and retrospective study. Can J Psychiatry. 2009;54(7): determine the Psychiatry. 2010;71(4):433-441. 493-501. 15. Allen MH, Hirschfeld RM, Wozniak PJ, et al. Linear 26. Perkins DO, Gu H, Boteva K, et al. Relationship between cause of symptom relationship of valproate serum concentration to response duration of untreated psychosis and outcome in first- and optimal serum levels for acute mania. Am J Psychiatry. episode schizophrenia: a critical review and meta-analysis. exacerbation 2006;163(2):272-275. Am J Psychiatry. 2005;162(10):1785-1804.

Bottom Line Acute psychosis has many possible causes, including psychiatric illness, medical conditions, and . An appropriate workup and treatment are key to stabilize and ensure the safety of an acutely psychotic patient in the emergency setting. Consider pharmacotherapy, such as haloperidol, second- generation antipsychotics, and benzodiazepines, and other interventions such as Current Psychiatry 16 December 2012 de-escalation.