Key Points

• Nonpharmacologic management plans should be considered first when treating delirium.

• Indications for pharmacotherapy include delirium-induced behaviors that create a danger to the patient or others, or that interfere with necessary medical therapy.

• Fluctuating nature of delirium makes assessment of treatment efficacy difficult. Assessments must be objective and repeated frequently. Repeat assessment to judge drug efficacy should be consistent with time required for drug to reach steady state.

Treatment of delirium begins with maximized effort to apply strategies outlined in Box 48-5. Identifying and treating one or more potential causes of delirium are equally important (e.g., correcting fluid and electrolyte imbalance, treating an infection and discontinuing medications conferring risk). Many delirium-induced behaviors respond well to nonpharmacologic interventions. For example, a delirious elderly patient with repetitive vocalizations disturbing others should be managed by

Box 48-5 Prevention and Treatment Strategies for Delirium

1. Provide reassurance and education.

2. Optimize orientation. Minimize potentially ambiguous stimuli (e.g., overhead pager). Permit visitation (overnight family stay). Minimize room/facility transfers. Ensure consistent staff assignment. Provide clear instructions. Use frequent eye contact. Optimize vision and hearing. Optimize nutrition and fluid intake. Optimize pain management, Optimize mobility within patient's limitations, Minimize restraints and catheter use. Maximize independent function (e.g., grooming). Optimize sleep hygiene. Ensure consistent hour of retirement. Use bright light during day, with dark, quiet nights. Prevent nocturia.

Provide pre-retirement routine (warm milk/herb tea, relaxation techniques, back massage). Avoid sedative-hypnotics. Provide proactive medication management. Avoid drugs that typically cause delirium. Minimize polypharmacy.







Antiparkinsonian agents


Antineoplastic agents


Centrally acting antihypertensive agents


Mood stabilizers

Muscle relaxants

Nonsteroidal anti-inflammatory drugs Opioid analgesics Sedative-hypnotics

From American Medical Directors Association. Delirium and Acute Problematic Behavior Clinical Practice Guideline. Columbia, Md, AMDA, 2008.

protecting others from the noise, not by sedating the delirious patient. Having a family member or sitter stay with a restless patient is better than use of physical or chemical restraints.

Pharmacologic treatment becomes necessary when patients have delirium-induced behavior that makes them a danger to self or others, or that interferes with needed medical care (e.g., maintaining bed rest after major surgery, maintaining catheter integrity). Hypoactive delirium might warrant treatment to improve oral intake of food, fluids, and medication or to avoid the medical consequences of inactivity. Additionally, some patients will require treatment for the confusion or hallucinations causing anxiety and fear. Both agitation in hyperactive delirium and lethargy in hypoactive delirium increase the risk for malnutrition and dehydration, aspiration, pressure ulcerations, and deep venous thrombosis or pulmonary embolism. The goal of pharmacologic management should be correction of neurochemical abnormalities, not simply sedation.

No medications are approved by the U.S. Food and Drug Administration (FDA) for treatment of delirium. Benzodiazepines are first-line therapy in patients with delirium induced by alcohol and sedative withdrawal. Antipsychot-ics are generally considered the drugs of choice in patients with most other types of delirium requiring pharmaco-logic management. The mode of action for antipsychot-ics in delirium is probably antagonism of dopamine and the resultant increase in acetylcholine. The choice of anti-psychotic should be individualized based on suspected etiology, target symptoms, and patient susceptibility to adverse drug reactions (ADRs) because of age and comor-bid conditions. The profile of antipsychotics regarding risk of cardiovascular events and death, QTc prolongation, anticholinergic effects, sedation, hypotension, and resulting glucose intolerance and movement disorders must be considered when choosing a drug. Higher doses and longer duration of therapy increase the risk of ADRs, as do age, female gender, and preexisting mood disorders or dementia.

Delirious patients, particularly the elderly, often respond to fairly brief courses of low doses of antipsychotics, which decreases the chance of adverse side effects. Benzodiazepines are not recommended, but if used, low doses of short-half-life products (loratzepam, oxazepam) are preferred in elderly patients. Occasionally, methylphenidate is tried in hypoactive delirium. Delivery of medication to a delirious patient can be difficult; rapidly dissolving oral formulations are useful when cooperation with tablets or capsules is problematic. Depot injections of antipsychotics have no role in the treatment of delirium.

The fluctuating course of delirium makes evaluation of drug therapy difficult. Monitoring of mental status and behavior throughout the day using objective measures is required. The use of any of the recognized pharmacologic treatments for delirium risks further impairment of cognitive function, thereby confounding monitoring because the observer has little to differentiate an inadequate response to therapy (and need for uptitration), worsening of the delirium per se, or worsening of cognition from an adverse drug effect, compounding the original delirium.

When treating delirium, the family physician should employ nonpharmacologic strategies, medicate only when necessary, and use monotherapy. Adjust dose to age/body weight/composition and renal/hepatic function; avoid as-needed dosing; and titrate dose based on repeated objective assessments of delirium severity at intervals consistent with the time necessary for the drug to reach steady state. Treatment for 7 to 10 days after symptoms resolve is usual.


Benzodiazepines are indicated for the treatment of alcohol withdrawal seizures (SOR: A) but are not recommended for treatment of non-alcohol-related delirium (SOR: B) (Cochrane Review). Haloperidol (<3.5 mg/day), risperidone, and olanzapine are equally effective in treating delirium, with few adverse effects (Cochrane Review) (SOR: B).

Despite plausible theoretic arguments for efficacy, no convincing evidence supports the use of cholinesterase inhibitors for delirium (Cochrane Review) (SOR: B).

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