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Rivastigmine for the Treatment of Delirium—A Review

US Neurology, 2010;5(2):14-16 DOI: http://doi.org/10.17925/USN.2010.05.02.14

Abstract:

Delirium is a common disorder in hospitalized elderly patients. It is a complex neuropsychiatric syndrome with disturbance of consciousness, attention, cognition, and perception. Treatment is based on identification and correction of the underlying cause together with symptomatic treatment. Decreased cholinergic activity is often considered to be one of the essential features in the pathophysiology of delirium. Therefore, correction of this cholinergic deficiency appears to be a promising approach. In this article we describe the pathophysiology of delirium, the pharmacological properties of rivastigmine, and the use of rivastigmine in the prevention and symptomatic treatment of delirium.
Keywords: Delirium, acute confusional state, acetylcholine esterase inhibitors, rivastigmine, prevention, treatment
Disclosure: Gerwin Roks, MD, PhD, is a member of the Dutch advisory board of Novartis. The remaining authors have no conflicts of interest to declare.
Received: January 18, 2009 Accepted: September 21, 2009
Correspondence: Gerwin Roks, MD, PhD, Department of Neurology, St Elisabeth Hospital, PO Box 90151, 5000 LC Tilburg, The Netherlands. E: g.roks@elisabeth.nl

Delirium is a complex neuropsychiatric syndrome characterized by disturbances of consciousness, attention, cognition, and perception. It is a common condition with serious consequences. It is estimated that at admission 10–15% of elderly patients are delirious,1 and 10–40% become delirious during hospitalisation.2 Some groups of patients in particular seem to be at risk for developing a delirium. In postoperative hip fracture patients,3,4 hospitalized patients with dementia,5 patients with Parkinson’s disease,6 and acute stroke patients,7 high incidence figures have been reported. Recognition of delirium is very important as it is potentially reversible and because delirium is associated with increased duration of hospitalization, poor functional status, need for institutional care,8 and higher mortality rates.9

Treatment of delirium consists of three components: identification and correction of the underlying cause(s), environmental and supportive intervention, and symptomatic pharmacological treatment.10,11 With regard to pharmacological treatment, haloperidol is advocated as the drug of first choice and is most commonly used. However, there is some debate regarding the pharmacological treatment of delirium, and several other drugs are used. In this review we discuss the use of an acetylcholinesterase inhibitor, rivastigmine, which is a promising novel drug in the management of delirium.

Pathophysiology of Delirium

Given the clinical heterogeneity and the multifactorial nature of delirium, it is likely that multiple mechanisms play a role in the pathophysiology of delirium. Since delirium is often associated with infection and other conditions accompanied by stress, glucocorticoids and cytokines are considered to play key roles. Additionally, alterations in the release of neurotransmitter(s) appear to be important.

Stroke, infection, and pain can be considered as stress conditions and may lead to increased glucocorticoid production. In delirium, due to an abnormal shut-off of the hypothalamic–pituitary–adrenal axis,12 this increased glucocorticoid production is not adequately suppressed. This mechanism leads to increased plasma cortisol levels. Corticoids are known to affect mood and disturb attention and declarative memory.13,14 Therefore, hypercortisolism may be a mediator of delirium. In the early phase of stroke, hypercortisolism with decreased suppressibility of dexamethasone has been demonstrated.15–17

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Keywords: Delirium, acute confusional state, acetylcholine esterase inhibitors, rivastigmine, prevention, treatment