Definition of Drug-Induced Cognitive Impairment in the Elderly

Donna M. Lisi, PharmD, BCPS, BCPP, CGP, FASCP


June 14, 2000

In This Article


Diagnostic criteria for delirium in the Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV), are divided into 5 categories based on the possible etiology of the syndrome, ie, whether it is thought to be attributable to: a general medical condition, substance intoxication, substance withdrawal, multiple etiologies, or not otherwise specified. For "Substance Intoxication Delirium," the criteria state that there is evidence from the history, physical examination, or laboratory findings of either disturbances in consciousness with reduced ability to focus, sustain, or shift attention OR that there is a change in cognition or the development of a perceptual disturbance that is not better accounted for by a preexisting, established, or evolving dementia AND that these symptoms develop during the substance intoxication AND that medication use is etiologically related to the disturbance. For "Substance Withdrawal Delirium," the symptomatology must present during or shortly after the removal of the drug. "Delirium due to Multiple Etiologies" considers the possibility that there may be more than 1 cause of the delirium, eg, drugs and the underlying medical condition. If the cause of delirium is not addressed by any of the above categories (eg, sensory deprivation), it is considered "Not Otherwise Specified."[3]

Criteria used to define drug-induced delirium in one study protocol included the following: the drug in question had central nervous system (CNS) effects; a toxic level was documented, or there was improvement with dose reduction or cessation; and the time course of mental status change coincided with the period of drug use. This definition excluded the presence of alcohol and drug withdrawal.[4]

Other terms that have been used synonymously with delirium are transient cognitive impairment, acute brain failure, exogenous psychosis, toxic confusional state, toxic delirious reaction, toxic encephalopathy, toxic psychosis, senile delirium, acute brain syndrome, pseudosenility, clouded states, neurotoxicity, reversible dementia, intensive care unit psychosis, postsurgery psychiatric syndrome, metabolic encephalopathy, psychosis associated with organic brain syndrome, postoperative delirium, and postoperative encephalopathy.[5,6,7,8,9]

Delirium, which is also known as an acute confusional state, is a syndrome characterized by disturbance in consciousness (ie, reduced clarity of awareness of the environment), change in cognition including alteration in attention, disorganized thinking, disturbed psychomotor activity, and abnormal sleep-wake cycle.[1,6] According to DSM-IV, the essential feature of delirium is a disturbance of consciousness that is accompanied by a change in cognition that cannot be better accounted for by a preexisting or evolving dementia. This disturbance in consciousness results in altered awareness of the environment and the inability to focus, sustain, or shift attention appropriately. This change in consciousness is associated with cognitive abnormalities (which may include memory impairment, disorientation, or language disturbance such as inability to name objects or to write) or the development of perceptual disturbance (which may include misinterpretations, illusions, or hallucinations). Additional characteristic features of delirium are its development over a brief period of time and that it has a fluctuating course. Disturbances in orientation and thinking as well as bizarre psychomotor behavior are possible. These behaviors may manifest as stupor or as severe agitation with the patient trying to pull out intravenous catheters or trying to leave the facility.

Delirium is estimated to occur in 14% to 56% of hospitalized elderly patients.[10] About 15% of elderly have delirium upon admission to the hospital.[8] About 10% to 30% of hospitalized medical and surgical patients are experiencing delirium at any given time,[8,11] and 25% to 55% of elderly who are asymptomatic on admission develop confusion during their hospital course.[5] Once delirium develops, it is associated with a 10% to 75% mortality rate, although death may be related more to advanced age and severity of illness than to delirium per se. Unfortunately, 32% to 80% of delirious patients are not diagnosed properly. In the elderly, this may be an especially important problem since symptoms may falsely be attributed to dementia or senescence and because they may manifest as the hypoactive form of delirium, which is characterized by lethargy and decreased activity. Patients may also demonstrate a mixed form of delirium having elements of both the hyper-and hypoactive states. This mixed state may be the most common presentation of delirium.[10,12,13,14] Francis and associates[4] found that less than half of the delirious older patients in their study demonstrated disruptive behaviors, hallucinations, or delusions. Rather, somatic features such as incontinence were the problems most frequently associated with the onset of delirium.

Another problem that may occur in the elderly is the persistence of symptoms even once the underlying condition is addressed and the patient is discharged from the hospital. About one fifth of patients may have residual symptoms of the delirium present even 6 months postdischarge.[10] The risk for elderly patients of either dying or of being transferred to an institutional care setting may be especially high following the first 6 months after discharge from the hospital. Patients who succumb to these outcomes demonstrate more cognitive and functional impairment. Cognitive impairment may outlast the acute syndrome. Up to 55% of those who experience delirium may have permanent cognitive impairment, which may be a harbinger for the onset of dementia.[15] Delirium may serve as a marker of future cognitive and functional impairment.[13] The likelihood of developing delirium appears to be inversely related to a patient's physiological reserve capacity.

Delirium occurs in 25% to 40% of all patients with cancer and up to 85% of patients who are in the terminal phase of the disease. This alteration in mental status may be attributable to both the underlying condition as well as to the cancer treatment utilized. Yet, there is a paucity of data on the cognitive side effects of cancer treatments used among older adults.[5]

Surgical patients may be especially at risk for developing cognitive impairment. Postoperative delirium in the elderly occurs in 10% to 61% of those aged 65 or older. Orthopaedic patients are more likely to experience delirium than those undergoing general surgery. Delirium develops in 44% to 55% of hip surgery patients vs 10% to 14% of general surgery patients. Even patients undergoing cataract surgery are at risk. In the coronary and intensive care units, between 2% and 30% of patients experience delirium.[8,13,16]

Medications are the most common reversible cause of delirium. It is estimated that medications contribute to 22% to 39% of all cases of delirium.[10] A recent study involving older hospitalized adults found that the most likely primary cause of delirium in their study population was medication use.[17]


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