2-Minute Consultation: Reversible Madness: Delirium in Older Patients

JANUARY 01, 2009
Tara Purvis, PharmD, and Robin Hieber, PharmD, BCPP

Dr. Purvis is a psychiatric pharmacy resident and Dr. Hieber is a clinical pharmacist at Western Missouri Mental Health Center in Kansas City.

Fifty years ago, the terms "everyman's psychosis" and "reversible madness" referred to a mental disorder to which everyone is susceptible— delirium, an acute confused state often overlooked by physicians.1

Up to 40% of hospitalized elderly patients experience delirium, one of the most preventable hospital-acquired adverse events.2,3 Failure to uncover the underlying etiology of delirium results in extended stays, increased costs, and increased morbidity and mortality.4,5

Delirium commences abruptly and encompasses a broad range of disturbances. These range from hyperactive to hypoactive states, with fluctuations in level of consciousness, attention, cognition (memory impairment, disorientation, language disturbance), and perception (visual/tactile hallucinations). Symptoms, including sleep pattern disturbance and psychomotor behavior, vary throughout the day and generally resolve within 10 to 12 days.4,6

The primary goal in management is to identify the underlying etiology and initiate immediate interventions to ensure patient safety. In elderly patients, delirium is commonly a result of acute illness or medication, the latter being the most common reversible cause.7 Half of all cases are missed by physicians; thus, pharmacists play a major role by recommending alternative treatment strategies and minimizing the use of high-risk medications (eg, anticholinergics, analgesics).8 See Table 11,9,10 for potential causes and treatment suggestions. Table 2 provides tips the pharmacist can implement to help prevent or treat delirium.

Table 1
Delirium Causes and Treatment Recommendations




Electrolyte imbalance


Endocrine disorders

Treat disorder

Neurologic disease

Treat underlying illness

Substance withdrawal

Treat withdrawal

Sleep deprivation

Optimize environmental cues for day/night, nonpharmacotherapy options for insomnia

Environmental changes

Provide familiar objects, moderate amount of stimuli, educate staff

Other illness(es)

Treat underlying illness(es)


High-Risk Medications
Tricyclic antidepressants
Dopamine agonists
Sedative hypnotics

Discontinue medication(s) or lower dose; recommend alternative with less deliriogenic risk

Low-Risk Medications
Cardiovascular agents
H2-receptor antagonists
Muscle relaxants

Discontinue medication(s) or lower dose; recommend alternative with less deliriogenic risk

Adapted from references 1,9,10.

Studies examining pharmacologic prevention investigated low-dose antipsychotic haloperidol, anticonvulsant gabapentin, and an acetylcholinesterase inhibitor (ACI), donepezil.11-13 No trial was overwhelmingly significant; therefore, using medication to prevent delirium is not currently recommended.4

Acute agitation with delirium may necessitate short-term pharmacologic treatment; however, if the cause of delirium is addressed, further intervention may not be necessary. Standard practice involves use of first-generation antipsychotics (primarily haloperidol).4,14-19 Using lower doses of haloperidol, between 0.5 and 4.5 mg/day, keeps extrapyramidal side effects to a minimum. The evidence for use of second-generation antipsychotics (eg, risperidone, olanzapine, quetiapine, ziprasidone) is expanding.4,20-32

A recent analysis of haloperidol versus risperidone, olanzapine, and quetiapine determined that all agents have similar efficacy in treatment of agitation in delirium.33 Second-generation anti-psychotics, especially olanzapine and quetiapine, are sedating, which may be beneficial in some situations. Choosing an agent should involve evaluating side effect profiles of each potential medication.

Current controversy exists regarding evidence that mortality is increased in elderly patients receiving antipsychotics.34-39 Clinical significance of these findings is under debate.

Table 2
Pharmacist's Role

Recognize and prevent polypharmacy

Identify potential medication causes

If applicable, recommend alternative therapy

Obtain blood levels when appropriate (eg, lithium, phenytoin)

Adjust dosages in renal or hepatic impairment

Actively participate in medication reconciliation

Recognize potential substance withdrawal

Other medications evaluated in delirium treatment include ACIs, benzodiazepines, and melatonin. Theoretically, ACIs reverse anticholinergic-induced delirium, although the evidence is limited to case reports.40 Benzodiazepines are to be avoided, except in cases of alcohol withdrawal. A study using alprazolam as treatment for delirium was terminated early due to worsening of delirium.14 A case report uses melatonin to treat delirium, although evidence supporting melatonin's role in delirium is limited.41


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