No convincing evidence from one trial of the efficacy of cholinesterase inhibitors for delirium

Delirium is a confusional state that is associated with physical illness. Its characteristic features are rapid onset, altered consciousness, reduced attention and global cognitive impairment. Other symptoms are hallucinations (particularly visual hallucinations), disturbed sleep pattern and agitation. Delirium is commonly found in hospital patients and is associated with longer admissions, poor functioning level, persistent cognitive impairment and need for institutional care. Delirium is therefore an important syndrome to recognise and treat. The one included trial, of donepezil compared with placebo in 15 patients, showed no statistically significant difference in length of delirium. No other outcomes were measured.

Authors' conclusions: 

There is currently no evidence from controlled trials that donepezil is effective in the treatment of delirium. Further trials using cholinesterase inhibitors for the treatment of delirium are needed.

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Delirium is now the preferred term to describe acute confusional states. It is experienced by 10 to 30% of all hospital inpatients. Delirium is potentially reversible and is related to several adverse outcomes, including increased hospital length of stay, poor functional status, persistent cognitive impairment, need for institutional care and probably mortality. Disruption of the cholinergic system has been proposed as a key mechanism of delirium. Cholinesterase inhibitors enhance the cholinergic system and there have been reports that they might be beneficial in treating delirium.


To assess the efficacy and safety of cholinesterase inhibitors in the treatment of delirium.

Search strategy: 

The Cochrane Dementia and Cognitive Improvement Group's Register of Clinical Trials (which includes records from MEDLINE, EMBASE, PsycINFO, CINAHL, CENTRAL, LILACS and other databases) was searched for relevant randomised controlled trials using the terms: donepezil or aricept, galantamine or reminyl, rivastigmine OR exelon and tacrine OR cognex on 19 April 2005. As this Specialised Register only contains trials relating to dementia and cognitive impairment, in addition all years of MEDLINE, EMBASE, PsycINFO and CINAHL were searched for trials of cholinesterase inhibitors for delirium in non-demented people.

Selection criteria: 

Unconfounded, blinded randomised controlled trials, published or unpublished in which treatment with cholinesterase inhibitors was administered and compared with alternative interventions in patients with delirium are included.

Data collection and analysis: 

Two reviewers (RO, SK) independently assessed the quality of the studies according to parameters such as randomisation, blinding and how dropouts were managed. Each cholinesterase inhibitor was to be examined separately and together as a group.

The primary outcome measures of interest are length of delirium, severity of delirium and presence and severity of behavioural symptoms (e.g. agitation and hallucinations). Other outcomes of interest include: cognition, need for institutionalisation, length of hospital admission and adverse effects.

Main results: 

There was one included trial of donepezil compared with placebo in 15 patients. No significant difference between the treatment and placebo groups was found in the duration of delirium. The mean duration of postoperative delirium for the donepezil group was 1.0 day (Standard Error 0.0) while for the placebo group it was 1.3 days (Standard Error 0.19). No other outcomes were measured for the patients who developed delirium.

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