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Cancer. 2002 Mar 15;94(6):1836-53.

The panorama of opioid-related cognitive dysfunction in patients with cancer: a critical literature appraisal.

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Edmonton Palliative Care Program and Division of Palliative Care Medicine, Department of Oncology, University of Alberta, Edmonton, Alberta, Canada.



Opioids have an essential role in the management of pain in cancer patients, particularly those with advanced disease. Cognitive dysfunction is a recognized complication of opioid use. However, misconceptions and controversy surround the nature and prevalence of its occurrence. A projected increase in the aging cancer population highlights the need for a better understanding of this phenomenon.


A critical appraisal of the literature evidence in relation to the pattern, pathophysiology, assessment, impact, and management of cognitive dysfunction due to opioid use in cancer pain management is given.


Studies in cancer patients with less advanced disease reveal subtle evidence of cognitive impairment, largely related to initial dosing or dose increases. In advanced cancer, opioid-induced cognitive dysfunction usually occurs in the form of delirium, a multifactorial syndrome. The presence of both cognitive impairment and delirium frequently is misdiagnosed or missed. Potential risk factors include neuropathic and incidental pain, opioid tolerance, somatization of psychologic distress, and a history of drug or alcohol abuse. Elevation of opioid metabolites with renal impairment may contribute to cognitive dysfunction. Recognition of opioid-related cognitive dysfunction is improved by objective screening. Successful management requires either dose reduction or a change of opioid, in addition to addressing other reversible precipitants such as dehydration or volume depletion.


Opioid-related cognitive dysfunction tends to be subtle in the earlier stages of cancer, whereas delirium, a more florid form with behavioral disturbance is likely to be present in the advanced cancer population. In patients with advanced disease, an optimal management approach requires careful clinical assessment, identification of risk factors, objective monitoring of cognition, maintenance of adequate hydration, and either dose reduction or switching to a different opioid.

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