Drug-induced delirium

K K Jain MD (

Dr. Jain is a consultant in neurology and has no relevant financial relationships to disclose.

Originally released August 4, 1998; last updated November 5, 2020; expires November 5, 2023


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” (Lipowski 1980). 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 (Rush 1812). John Hunter described delirium as a diseased dream resulting from abnormally reduced awareness of the external world (Hunter 1835). Delirium was also considered as a point on the continuum between wakefulness and coma and described as "clouding of consciousness" (Greiner 1817). Delirium as a disorder of impaired consciousness was discussed by Hughling Jackson in terms of his hierarchical model of organization of the nervous system (Jackson 1932). 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 (Berrios 1981).

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 (Bleck 2018). 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” (Schieveld and Strik 2018). 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. 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.

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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