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Management Strategies for Agitation Associated with Schizophrenia and Bipolar Disorder

Providers Perspective
Faculty Perspectives: The Spectrum of Agitation Associated with Schizophrenia and Bipolar Disorder

Agitation, consisting of excessive motor and/or verbal activity and often accompanied by psychological distress, is a common manifestation of a number of medical and psychiatric disorders. Project BETA (Best Practices in Evaluation and Treatment of Agitation) is an effort by the American Association for Emergency Psychiatry to establish useful guidance for managing agitation. Information regarding best practices for the medical evaluation and triage of the agitated patient, psychiatric evaluation of the agitated patient, verbal de-escalation of the agitated patient, psychopharmacologic approaches to agitation, and the use and avoidance of seclusion and restraint, are outlined in a series of open-access papers in the February 2012 issue of the Western Journal of Emergency Medicine.1

An often overlooked consideration, especially in a patient with a psychiatric disorder, is the possibility of an underlying medical condition that causes a change in behavior.2 Ruling out delirium is especially important because treatment will need to be directed at the underlying cause of the delirium, whether the cause is infectious, toxic, metabolic, or another. Evidence of delirium may include a sudden onset, an altered sensorium, and altered or labile vital signs.3

Substance abuse may contribute to agitation and is often comorbid with major mental disorders, such as schizophrenia and bipolar disorder.4,5 In the past, the use of phencyclidine was regarded as a common problem in urban emergency departments; a more recent development has been the use of designer drugs, recognized on the street as bath salts or synthetic cathinones in scientific literature.6 These agents are inexpensive and relatively easy to obtain, and although they may mimic somewhat the psychomimetic properties of older drugs of abuse, they are often associated with highly toxic effects, including altered liver function.7 Individuals who are under the influence of synthetic cathinones may be disoriented and highly agitated, and also have dilated pupils, nystagmus, and abnormal motor movements. Intoxication can mimic a psychiatric disorder and can complicate a differential diagnosis.7 The optimal treatment of agitation needs to be instituted quickly to prevent further escalation into aggressive and potentially violent behavior.8 Pharmacologic treatment should be directed at the underlying cause. In the case of uncomplicated psychosis, where an underlying medical problem or delirium is not a relevant consideration, use of an antipsychotic is recommended for the treatment of agitation.9

Until recently, to achieve as rapid a response as possible, intramuscular formulations of antipsychotics have been the preferred route of administration. Some of the atypical antipsychotic agents have a robust antiagitation action,10 as well as advantageous safety profiles regarding extrapyramidal side effects, particularly acute dystonic reactions and akathisia when compared with typical antipsychotics.11 This is critically important because the occurrence of an acute dystonic reaction will fracture a therapeutic alliance, and akathisia is often confused for psychotic agitation, leading to therapeutic misadventures.

A more recently available option for the treatment of agitation associated with schizophrenia and bipolar I disorder that was approved by the US Food and Drug Administration (FDA) is an orally inhaled antipsychotic agent with clinically relevant serotonin 5-HT2A receptor antagonism-a property that is common to second-generation antipsychotic agents.12 In clinical trials, this inhaled antipsychotic drug was well-tolerated regarding extrapyramidal effects.12 Because this drug is administered through inhalation rather than injection, it may be perceived as less coercive and thus accepted more readily. Concerns about the risk of bronchospasm obligates clinicians to screen patients for pulmonary disease and to monitor patients after drug administration.2

The efficacy of this inhaled antipsychotic agent is on par with the other FDA-approved agents (ie, intramuscular antipsychotic agents and benzodiazepines).12 Although not FDA approved for the treatment of agitation, a sublingual antipsychotic agent may be an alternative option for the treatment of patients with agitation.13

1. Holloman GH Jr, Zeller SL. Overview of Project BETA: Best practices in Evaluation and Treatment of Agitation. West J Emerg Med. 2012 Feb;13:1-2.
2. Nordstrom K, Zun LS, Wilson MP, et al. Medical evaluation and triage of the agitated patient: consensus statement of the American Association for Emergency Psychiatry Project Beta Medical Evaluation Workgroup. West J Emerg Med. 2012;13:3-10
3. Stern TA, Celano CM, Gross AF, et al. The assessment and management of agitation and delirium in the general hospital. Prim Care Companion J Clin Psychiatry. 2010;12:PCC.09r00938.
4. Alderfer BS, Allen MH. Treatment of agitation in bipolar disorder across the life cycle. J Clin Psychiatry. 2003;64(suppl 4):3-9.
5. Dixon L. Dual diagnosis of substance abuse in schizophrenia: prevalence and impact on outcomes. Schizophr Res. 1999;35(suppl):S93-S100.
6. Capriola M. Synthetic cathinone abuse. Clin Pharmacol. 2013;5:109-115.
7. Prosser JM, Nelson LS. The toxicology of bath salts: a review of synthetic cathinones. J Med Toxicol. 2012;8:33-42.
8. Citrome L, Volavka J. The psychopharmacology of violence: making sensible decisions. CNS Spectr. 2014;19:411-418.
9. Schleifer JJ. Management of acute agitation in psychosis: an evidence-based approach in the USA. Adv Psychiatr Treat. 2011;17:91-100.
10. Citrome L. Comparison of intramuscular ziprasidone, olanzapine, or aripiprazole for agitation: a quantitative review of efficacy and safety. J Clin Psychiatry. 2007;68:1876-1885.
11. Muench J, Hamer AM. Adverse effects of antipsychotic medications. Am Fam Physician. 2010;81:617-622.
12. Citrome L. Addressing the need for rapid treatment of agitation in schizophrenia and bipolar disorder: focus on inhaled loxapine as an alternative to injectable agents. Ther Clin Risk Manag. 2013;9:235-245.
13. Pratts M, Citrome L, Grant W, et al. A single-dose, randomized, double-blind, placebo-controlled trial of sublingual asenapine for acute agitation. Acta Psychiatr Scand. 2014;130:61-68.

Last modified: August 30, 2021