Agitation

Agitation is a nonspecific constellation of behaviors seen in various treatment settings. Agitated individuals can be dangerous to themselves and others, making agitation an emergency. Acute presentations of agitation can include restlessness, inability to stay calm, paranoia, suspiciousness, irritability, hostility, confusion, disorientation, inability to communicate, changes in vital signs, and violent behavior. Agitation can have a multifactorial etiology that is often difficult to identify. Individuals with agitation may present in various settings, including emergency departments, medical units, intensive care units (ICUs), inpatient psychiatry units, outpatient clinics, and long-term care facilities. Approaches to understanding and managing agitation can vary depending on the setting, individual factors, clinician experience, and the underlying etiology.  Multiple definitions have been offered for agitation, reflecting the complexity of this syndrome. The 5th ed.;Text Revision () characterizes agitation as "the inability to sit still, pacing, handwringing; or pulling or rubbing of the skin, clothing, or other objects" and as "disruptive motor or vocal activity." In their evaluation of a new drug application for the treatment of agitation on May 11, 2023, the United States Food and Drug Administration (FDA) Center for Drug Evaluation and Research described agitation as including "symptoms ranging from pacing and restlessness to verbal and physical aggression." The International Experts' Meeting on Agitation in 2016 noted that a consensus on the definition of agitation does not exist and formulated a practical description of agitation as "a state where patients cannot remain still or calm, characterized by internal features such as hyperresponsiveness, racing thoughts, and emotional tension; and external ones, mainly motor and verbal hyperactivity, and communication impairment."  In dementia, it is helpful to conceptualize aggressive and agitated behavior as " that manifests in response to a stimulus in the patient's internal or external environment."  Agitation can be distinguished from aggression. In individuals with dementia, agitation is described as "a constellation of symptoms, including pacing, aimless wandering, performing repetitious mannerisms, and general restlessness," whereas aggression encompasses "both verbal and physical behavior, such as hitting, kicking, pushing, throwing or tearing things, spitting, biting, scratching, destroying property, grabbing people or objects away from others, hurting oneself or others, making sexual advances, cursing, and screaming."  In the broader population, acute agitation is characterized as "a state of unease or inner tension with or without excessive motor activity," while aggression is the "behavioral expression of severe agitation with the potential to cause harm to oneself or others."  As the definition and use of the term "agitation" vary, the clinical team should attempt to identify patient-specific behaviors to clarify how agitation is defined for each individual patient. Reaching a consensus on this definition will help direct the management plan effectively.  In a study of patients with dementia, aggressive behavior was defined as "an overt act involving the delivery of noxious stimuli to (but not necessarily aimed at) another object, organism, or self, which is clearly not accidental."  In this population, the prevalence of verbal aggression was 89%, while physical aggression and destructive behavior were 61% and 25%, respectively. Verbal aggression was found to persist for about 2 years, and 67% of individuals with verbal aggression remained verbally aggressive until near death. Physical aggression was found to be self-limiting, lasting for only 1 year. Intimate care was identified as the primary factor precipitating aggressive behavior, with hallucinations and delusions as secondary contributors.  The proposed hypothesis for this association is that misinterpretation of the environment leads to the perception of intimate care as a threat. This hypothesis is supported by the finding that most aggressive behavior was directed toward a group, primarily primary caregivers. Aggressive behavior resembled the patient's premorbid behavior (behavior before dementia diagnosis) in only 3% of cases. In contrast, 43% of individuals displayed aggression as an "exaggeration of premorbid behavior," while 53% exhibited aggression that was "quite different from premorbid behavior." Aggressive behavior was found to cease before death, with the hypothesized mechanism being progressive cognitive impairment. This impairment likely leads to reduced awareness of the environment and a diminished perception of intimate care as a threat.