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  • Updated 10.18.2021
  • Released 08.04.1998
  • Expires For CME 10.18.2024

Drug-induced delirium



Delirium is characterized by a reduction of the level of consciousness, and this is manifested clinically by disorientation. This article focuses on medications, which are considered the most common cause of delirium in the hospital setting. Anticholinergic agents are the leading cause of drug-induced delirium; these agents are also an important cause of drug-induced memory disorders. Pathogenesis of delirium is often multifactorial and may involve the interaction of precipitating factors with underlying patient vulnerability because of various risk factors. Awareness of the precipitating factors helps in the prevention of delirium. The article outlines diagnosis and general principles of management. Anticholinergic delirium is best managed by physostigmine, a cholinesterase inhibitor. Donepezil, also a cholinesterase inhibitor, is an effective choice in the management of anticholinergic drug-induced delirium.

Key points

• Delirium is an acute, transient disorder of higher nervous system function involving impaired consciousness and attention.

• Delirium can be drug-induced and is more common in the elderly.

• Various methods of management include supportive care and withdrawal of the offending drug.

• Anticholinergic delirium is the only form of delirium for which specific pharmacotherapy is available -- cholinesterase inhibitors.

Historical note and terminology

Delirium was 1 of the first mental disorders to be described and has been recognized for over 2000 years. The essential features of delirium were described by Hippocrates as phrenitis, referring to the transient mental disorder associated with physical illness and characterized by restlessness, insomnia, and disturbance of mood, perception, and “wit” (33). Celsius distinguished delirium from mania and depression. Galen differentiated between primary (idiopathic) and secondary symptomatic forms of the disorder. There was much speculation about the relationship of delirium to sleep and dreams from the 17th to the 19th centuries. Benjamin Rush thought that dream was a transient paroxysm of delirium and that delirium was a permanent dream (44). John Hunter described delirium as a diseased dream resulting from abnormally reduced awareness of the external world (21). Delirium was also considered as a point on the continuum between wakefulness and coma and described as "clouding of consciousness" (18). Delirium as a disorder of impaired consciousness was discussed by Hughling Jackson in terms of his hierarchical model of organization of the nervous system (24). The term "confusion" was introduced by the French and the German authors in the 19th century to describe inability to think with one's customary clarity and coherence, and the French psychiatric term delirie refers primarily to disordered thinking (05). The title of a monograph published in the United States refers to delirium as “acute brain failure” (33).

Historically, “acute encephalopathy” was the term used to describe unexpected change in mental status of a patient, but “delirium” is now defined by the Oxford English Dictionary as “an acutely disturbed state of mind characterized by restlessness, illusions, and incoherence that are occurring in intoxication, fever, and other disorders,” which was based on resemblance to delirium tremens (06). Delirium is now the accepted term for an acute, transient, global organic disorder of higher nervous system function involving impaired consciousness and attention. Delirium is further categorized as hypoactive or hyperactive. Hypoactive delirium is also referred to as “acute apathy syndrome” (46). There are more than 30 synonyms for delirium, which include the following terms: acute brain failure, toxic confusional state, psychosis associated with organic brain syndrome, postoperative encephalopathy, exogenous psychoses, reversible toxic confusional state, toxic delirious reaction, toxic encephalopathy, and toxic psychosis. Although these different terms may have been perceived as distinct clinical entities, evidence to support such distinctions is lacking. Substance-induced delirium can be due to exposure to a medication, toxin, or drug of abuse as well as to withdrawal from any of these. In addition to the Diagnostic and Statistical Manual of Mental Disorders, the International Statistical Classification of Diseases and Related Health Problems defines delirium (02; 23). To resolve the controversy about delirium and acute encephalopathy in the literature, and to generate consensus, an international, interdisciplinary panel of leading experts recommended the following terminology (52):

• The term acute encephalopathy refers to a rapidly developing (over less than 4 weeks, but usually within hours to a few days) pathophysiogical process in the brain. This is a preferred term.

• Acute encephalopathy can lead to a clinical presentation of subsyndromal delirium, delirium, or in case of a severely decreased level of consciousness, coma; all representing a change from baseline cognitive status.

• The term delirium refers to a clinical state characterized by a combination of features defined by diagnostic systems such as the DSM-5 in Table 1. This is a preferred term.

• The terms “acute confusional state,” “acute brain dysfunction,” and acute brain failure should not be used in addition to the terms delirium and acute encephalopathy.

• The term altered mental status is not synonymous with delirium and should not be used.

Delirium is a cognitive disorder, as are disturbances of memory, intellect, and behavior. This article will focus on drug-induced delirium.

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