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Paula Trzepacz, M.D., Chair
William Breitbart, M.D.
John Franklin, M.D.
James Levenson, M.D.
D. Richard Martini, M.D.
Philip Wang, M.D., Dr.P.H. (Consultant)
Originally published in May 1999. A guideline watch, summarizing significant developments in the scientific literature since publication of this guideline, may be available.
This practice guideline seeks to summarize data regarding
the care of patients with delirium. It begins at the point where
the psychiatrist has diagnosed a patient as suffering from delirium
according to the DSM-IV criteria for the disorder. The purpose of
this guideline is to assist the psychiatrist in caring for a patient
with delirium.
Psychiatrists care for patients with delirium in many different
settings and serve a variety of functions. In many cases, a psychiatrist
will serve as a consultant to the attending physician and will not
have primary responsibility for the patient. This guideline reviews
the treatment that patients with delirium may need. The psychiatrist
should either provide or advocate for the appropriate treatments. In
addition, many patients have comorbid conditions that cannot be
described completely with one DSM diagnostic category. Therefore,
the psychiatrist caring for patients with delirium should consider,
but not be limited to, the treatments recommended in this practice
This practice guideline was developed under the auspices of
the Steering Committee on Practice Guidelines. The process is detailed
in the Appendix to this volume. Key features of the process include the
a comprehensive literature
review (description follows) and development of evidence tables;
initial drafting by a work group that included psychiatrists
with clinical and research expertise in delirium;
the production of multiple drafts with widespread review,
in which 12 organizations and over 83 individuals submitted comments
(see section VI);
approval by the APA Assembly and Board of Trustees;
planned revisions at 3- to 5-year intervals.
A computerized search of the relevant literature from MEDLINE,
PsycINFO, and EMBASE was conducted.
The first literature search was conducted by searching MEDLINE
for the period 1966 to April 1996 and used the keywords "organic
mental disorders," "psychotic," "delirium," "delusions," "acute organic
brain syndrome," "alcohol amnestic disorder," "psychoses," "substance-induced," and "intensive
care psychosis" with "haloperidol," "droperidol," "antipsychotic
agents," "physostigmine," "tacrine," "cholinergic
agents," "benzodiazepines," "thiamine," "folic
acid," "vitamin b 12," "vitamins," "morphine," "paralysis," "electroconvulsive
therapy," "risperidone," and "neuroleptic malignant
syndrome." A total of 954 citations were found.
A second search in MEDLINE was completed for the period 1995
to 1998 and used the key words "delirium," "dementia," "amnestic," "cognitive
disorders," and "delusions" with "haloperidol," "droperidol," "antipsychotic
agents," "physostigmine," "tacrine," "cholinergic
agents," "benzodiazepines," "vitamins," "morphine," "paralysis," "electroconvulsive
therapy," "risperidone," and "neuroleptic
malignant syndrome." A total of 1,386 citations were found.
The literature search conducted by using PsycINFO covered
the period 1967 to November 1998 and used the key words "delirium" and "treatment
& prevention" with "psychosocial," "behavioral," "restraint," "seclusion," "isolation," "structure," "support," "sensory
deprivation," "orient," "reorient," and "delirium
tremens." A total of 337 citations were found.
An additional literature search was conducted by using EMBASE
for the period 1985 to November 1998 and used the key word "delirium" with "vitamins," "morphine," "paralysis," "electroconvulsive therapy," and "neuroleptic
malignant syndrome." A total of 156 citations were found.
The following executive summary is intended to provide an
overview of the organization and scope of recommendations in this
practice guideline. The treatment of patients with delirium requires
the consideration of many factors and cannot be adequately reviewed
in a brief summary. The reader is encouraged to consult the relevant
portions of the guideline when specific treatment recommendations
are sought. This summary is not intended to stand on its own.
Each recommendation is identified as falling into one of three
categories of endorsement, indicated by a bracketed Roman numeral
following the statement. The three categories represent varying
levels of clinical confidence regarding the recommendations:
[I] Recommended
with substantial clinical confidence.
[II] Recommended
with moderate clinical confidence.
[III] May be recommended on the basis
of individual circumstances.
Delirium is primarily a disturbance of consciousness, attention,
cognition, and perception but can also affect sleep, psychomotor
activity, and emotions. It is a common psychiatric illness among
medically compromised patients and may be a harbinger of significant morbidity
and mortality. The treatment of patients with delirium begins with
an essential array of psychiatric management tasks designed to provide
immediate interventions for urgent general medical conditions, identify
and treat the etiology of the delirium, ensure safety, and improve
the patient's functioning. Environmental and supportive
interventions are also generally offered to all patients with delirium
and are designed to reduce factors that may exacerbate delirium,
to reorient patients, and to provide them with support. Somatic interventions
largely consist of pharmacologic treatment with high-potency antipsychotic medications.
Other somatic interventions may be of help in particular cases of
delirium due to specific etiologies or with particular clinical
Psychiatric management is an essential feature of treatment
for delirium and should be implemented for all patients with delirium [I].
The specific tasks that constitute psychiatric management include
the following: coordinating the care of the patient with other clinicians; identifying
the underlying cause(s) of the delirium; initiating immediate interventions
for urgent general medical conditions; providing treatments that
address the underlying etiology of the delirium; assessing and ensuring
the safety of the patient and others; assessing the patient's
psychiatric status and monitoring it on an ongoing basis; assessing
individual and family psychological and social characteristics;
establishing and maintaining a supportive therapeutic stance with
the patient, the family, and other clinicians; educating
the patient, family, and other clinicians regarding the
illness; and providing postdelirium management to support the patient
and family and providing education regarding risk factors for future episodes.
These interventions are generally recommended for all patients
with delirium [I]. Environmental interventions
are designed to reduce or eliminate environmental factors that exacerbate
delirium. They include providing an optimal level of environmental
stimulation, reducing sensory impairments, making environments more
familiar, and providing environmental cues that facilitate orientation.
Cognitive-emotional supportive measures include providing patients
with reorientation, reassurance, and information concerning delirium
that may reduce fear or demoralization. In addition to providing
such supportive interventions themselves, it may be helpful for
psychiatrists to inform nursing staff, general medical physicians, and
family members of their importance.
The choice of somatic interventions for delirium will depend
on the specific features of a patient's clinical condition,
the underlying etiology of the delirium, and any associated comorbid
conditions [I]. Antipsychotic medications are
often the pharmacologic treatment of choice [I].
Haloperidol is most frequently used because it has few anticholinergic
side effects, few active metabolites, and a relatively small likelihood
of causing sedation and hypotension. Haloperidol may be administered orally,
intramuscularly, or intravenously and may cause fewer extrapyramidal
symptoms when administered intravenously. Haloperidol can be initiated
in the range of 1–2 mg every 2–4 hours as needed
(0.25–0.50 mg every 4 hours as needed for elderly patients),
with titration to higher doses for patients who continue to be agitated.
For patients who require multiple bolus doses of antipsychotic medications,
continuous intravenous infusions of antipsychotic medication may
be useful (e.g., haloperidol bolus, 10 mg i.v., followed by continuous
intravenous infusion of 5–10 mg/hour; lower doses
may be required for elderly patients). For patients who require
a more rapid onset of action, droperidol, either alone or followed
by haloperidol, can be considered. Recently some physicians have
used the newer antipsychotic medications (risperidone, olanzapine,
and quetiapine) in the treatment of patients with delirium. Patients
receiving antipsychotic medications for delirium should have their
ECGs monitored [I]. A QTc interval greater than
450 msec or more than 25% over baseline may warrant a cardiology
consultation and reduction or discontinuation of the antipsychotic medication.
Benzodiazepine treatment as a monotherapy is generally reserved
for delirium caused by withdrawal of alcohol or sedative-hypnotics [I].
Patients with delirium who can tolerate only lower doses of antipsychotic
medications may benefit from the combination of a benzodiazepine
and antipsychotic medication [III].
Other somatic interventions may be considered for patients
with delirium who have particular clinical conditions or specific
underlying etiologies. Cholinergics such as physostigmine may be useful
in delirium known to be caused specifically by anticholinergic
medications [II]. Paralysis, sedation, and mechanical
ventilation may be required for agitated patients with delirium
and hypercatabolic conditions [III]. Palliative
treatment with opiates may be needed by patients with delirium for
whom pain is an aggravating factor [III]. Multivitamin
replacement should be given to patients with delirium for whom there
is the possibility of B vitamin deficiencies (e.g., those who are
alcoholic or malnourished) [II].
The essential features of delirium include disturbances of
consciousness, attention, cognition, and perception. The disturbance
develops over a short period of time (usually hours to days) and
tends to fluctuate during the course of the day. Following are the
DSM-IV criteria for delirium (1):
Disturbance of consciousness
(i.e., reduced clarity of awareness of the environment) with reduced
ability to focus, sustain, or shift attention.
A change in cognition (such as memory deficit, disorientation,
language disturbance) or the development of a perceptual disturbance
that is not better accounted for by a preexisting, established,
or evolving dementia.
The disturbance develops over a short period of time
(usually hours to days) and tends to fluctuate during the course
of the day.
According to DSM-IV, delirium frequently represents a sudden
and significant decline from a previous level of functioning and
cannot be better accounted for by a preexisting or evolving dementia.
There is usually evidence from the history, physical examination,
or laboratory tests that the delirium is a direct physiological
consequence of a general medical condition, substance intoxication
or withdrawal, use of a medication, toxin exposure, or a combination
of these factors. The disorders included in the DSM-IV delirium
section have a common symptom presentation of a disturbance in consciousness
and cognition but are differentiated by etiology:
Delirium due to a general medical condition.
Substance-induced delirium.
Delirium due to multiple etiologies.
Delirium not otherwise specified.
The disturbance in consciousness or arousal can be manifested
by a reduced clarity or awareness of the environment that does not
reach the level of stupor or coma. In addition, the ability to focus, sustain,
or shift attention is frequently impaired and may result in the
patient's being easily distracted.
There is also an accompanying decline in other areas of cognition.
Cognitive deficits can include memory and visuoconstructional impairment,
disorientation, or language disturbance. Memory impairment is most
commonly evident in recent memory. Disorientation is usually manifested
as disorientation to time (e.g., thinking it is morning in the middle
of the night) or place (e.g., thinking one is at home rather than
in the hospital). Disorientation to other persons occurs commonly,
but disorientation to self is rare. It may be difficult for the
clinician to fully assess cognitive function because the patient
is inattentive and incoherent. Obtaining information from the medical
chart, medical staff, and other informants, particularly family
members, is often helpful in these circumstances.
Dysarthria is a frequent speech and language disturbance,
and dysnomia (i.e., impaired ability to name objects), dysgraphia
(i.e., impaired ability to write), or even frank aphasia may be
Perceptual disturbances may include misinterpretations, illusions,
or hallucinations. For example, the patient may see the nurse mixing
intravenous solutions and conclude the nurse is trying to poison him
or her (misinterpretation); the folds of the bedclothes may appear
to be animate objects (illusion); or the patient may see a group
of people around the bed when no one is actually there (hallucination). Although
visual misperceptions and hallucinations are most common in delirium,
auditory, tactile, gustatory, and olfactory misperceptions or hallucinations
can also occur. Misperceptions range from simple and uniform to
highly complex. A patient with delirium may have a delusional conviction
of the reality of a hallucination and exhibit emotional and behavioral
responses consistent with the hallucination's content.
Other commonly associated features of delirium include disturbances
of sleep, psychomotor activity, and emotion. Disturbances in the
sleep-wake cycle observed in delirium include daytime sleepiness,
nighttime agitation, and disturbances in sleep continuity. In some
cases, complete reversal of the night-day sleep-wake cycle or fragmentation
of the circadian sleep-wake pattern can occur.
Delirium is often accompanied by disturbed psychomotor activity.
Lipowski (2, 3) clinically described two subtypes of delirium
based on psychomotor activity and arousal levels. These delirium subtypes
included the "hyperactive" (or agitated, hyperalert)
subtype and the "hypoactive" (lethargic, hypoalert)
subtype. Others have included a "mixed" delirium
subtype with alternating features of both. Ross et al. (4) suggested
that the hyperactive form is more often characterized by hallucinations, delusions,
agitation, and disorientation, while the hypoactive form is characterized
by confusion and sedation and is less often accompanied by hallucinations,
delusions, or illusions. Comparable levels of cognitive impairment
have been observed with both motor subtypes.
The delirious individual may also exhibit emotional disturbances,
such as anxiety, fear, depression, irritability, anger, euphoria,
and apathy. There may be affective lability, with rapid and unpredictable shifts
from one emotional state to another.
Depending on the etiology, delirium can be associated with
a number of nonspecific neurological abnormalities, such as tremor,
myoclonus, asterixis, and reflex or muscle tone changes. For example, nystagmus
and ataxia may accompany delirium due to medication intoxications;
cerebellar signs, myoclonus, and generalized hyperreflexia may be
seen with lithium intoxication; cranial nerve palsies may occur
with Wernicke's encephalopathy; and asterixis may be observed
with renal or hepatic insufficiency. The background rhythm seen
on EEG is typically abnormal, usually showing generalized slowing.
However, in alcohol or sedative-hypnotic withdrawal, the EEG usually
shows fast activity. In addition, laboratory findings that are characteristic
of associated or etiological general medical conditions (or intoxication
or withdrawal states) may be seen.
The differential diagnosis of patients with features of delirium
is discussed in the delirium section of DSM-IV. The most common
issue in differential diagnosis is whether the patient has dementia
rather than delirium, has delirium alone, or has a delirium superimposed
on a preexisting dementia. Cognitive disturbances, such as memory
impairment, are common to both delirium and dementia; however, the patient
with dementia usually is alert and does not have the disturbance
of consciousness or arousal that is characteristic of delirium.
The temporal onset of cognitive deficit symptoms and the temporal
course and reversibility of cognitive impairments are helpful in
distinguishing between delirium and dementia. The severity of delirium
symptoms characteristically fluctuates during a 24-hour period,
while dementia symptoms generally do not. Information from medical
records, other caregivers, and family members may be helpful in
determining whether a dementia was present before the onset of a
The prevalence of delirium in the hospitalized medically ill
ranges from 10% to 30%. In the hospitalized
elderly, the delirium prevalence ranges from 10% to 40% (2).
As many as 25% of hospitalized cancer patients (5) and
30%–40% of hospitalized AIDS patients
(6) develop delirium. As many as 51% of postoperative patients
develop delirium (7), and up to 80% of patients with terminal
illnesses develop delirium near death (8). Patients who have just
had surgery, particularly cardiotomy, hip surgery, or a transplant,
and patients with burns, dialysis, or central nervous system lesions
are at increased risk for delirium.
Some patients manifest subclinical delirium or prodromal symptoms
such as restlessness, anxiety, irritability, distractibility, or
sleep disturbance in the days before the onset of overt delirium. Prodromal
symptoms may progress to full-blown delirium over 1–3 days.
The duration of symptoms of delirium has been reported to range
from less than 1 week to more than 2 months (9–14). Typically the
symptoms of delirium resolve within 10–12 days; however,
up to 15% of patients with delirium have symptoms that
persist for up to 30 days and beyond (10). Elderly patients with
delirium may be more likely to have a prolonged course, with symptom
durations frequently exceeding 1 month (11, 12).
While the majority of patients recover fully, delirium may
progress to stupor, coma, seizures, or death, particularly if untreated.
Full recovery is less likely in the elderly, with estimated
rates of full recovery by the time of discharge varying from 4% to
40% (9, 15). Persistent cognitive deficits are also quite
common in elderly patients recovering from delirium, although such
deficits may be due to preexisting dementia that was not fully appreciated
(9). Similarly, in a study of delirium in AIDS patients Fernandez
et al. (16) found that only 27% had complete recovery of
cognitive function, possibly because of underlying AIDS dementia.
Delirium in the medically ill is associated with significant
morbidity. Medically ill patients, particularly the elderly, have
a significantly increased risk of developing complications, such
as pneumonia and decubitus ulcers, resulting in longer hospital
stays (17, 18). In postoperative patients, delirium is a harbinger
of limited recovery and poor long-term outcome. Patients who develop delirium,
particularly after orthopedic surgery, are at increased risk for
postoperative complications, longer postoperative recuperation periods,
longer hospital stays, and long-term disability (19, 20). Seizures
may occur in delirium, particularly among patients with alcohol
or sedative-hypnotic withdrawal, cocaine intoxication, head trauma,
hypoglycemia, strokes, or extensive burns (21).
Delirium in the medically ill is also associated with an increased
mortality rate (22, 23). Elderly patients who develop delirium during
a hospitalization have been estimated to have a 22%–76% chance
of dying during that hospitalization (22, 24). Patients who develop
delirium during a hospitalization also have a very high rate of
death during the months following discharge. Several studies suggest
that up to 25% of patients with delirium die within 6 months
and that their mortality rate in the 3 months after diagnosis
is 14 times as high as the mortality rate for patients with affective disorders
(25, 26).
The disorders included in the delirium section of DSM-IV have
a common symptom presentation but are differentiated according to
presumed etiology (see Table 1 for a list of common etiologies).
Central nervous system disorder
Head trauma
Postictal state
Vascular disease (e.g., hypertensive encephalopathy)
Degenerative disease
Metabolic disorder
Renal failure (e.g., uremia)
Hepatic failure
Thiamine deficiency
Fluid or electrolyte imbalance
Acid-base imbalance
Cardiopulmonary disorder
Myocardial infarction
Congestive heart failure
Cardiac arrhythmia
Respiratory failure
Systemic illness
Substance intoxication or withdrawal
Severe trauma
Sensory deprivation
Temperature dysregulation
Postoperative state
In determining that delirium is due to a general medical condition,
the clinician must first establish the presence of a general medical
condition and then establish that the delirium is etiologically
related. A careful and comprehensive assessment is necessary to
make this judgment. A temporal association between the onset, exacerbation,
or remission of the general medical condition and that of the delirium is
a helpful guide. Evidence from the literature that suggests the
condition in question can be directly associated with the development
of delirium is also useful. Delirium can be associated with many different
general medical conditions, each of which has characteristic physical
examination and laboratory findings. When these are present they
may help confirm the relationship between delirium and the general
medical condition. General medical conditions commonly causing delirium
are shown in Table 1.
Delirium is frequently due to substance use or withdrawal
(27). Substances with the potential to cause delirium include both
agents that are not usually regarded as having psychoactive properties and
those with established psychoactive properties. Delirium that occurs
during substance intoxication may arise within minutes to hours
after ingestion of high doses of drugs such as cocaine or hallucinogens;
other drugs, such as alcohol, barbiturates, or meperidine, may cause
delirium after intoxication is sustained for several days. During
substance intoxication, the potential for additional agents with
anticholinergic activity to cause delirium is increased. Usually
the delirium resolves as the intoxication ends or within hours to
days thereafter. Delirium associated with substance withdrawal develops
as fluid and tissue concentrations of the substance decrease after
reduction of sustained, high-dose use of certain substances. Substance-withdrawal
delirium can also occur after the reduction of lower doses in patients
having poor clearance, experiencing drug interactions, or taking combinations
of drugs. The duration of the delirium usually varies with the half-life
of the substance involved. Longer-acting substances usually are
associated with less severe but more protracted withdrawal and may
not have an onset of withdrawal symptoms for days or weeks after
use of the substance is discontinued. Substance-withdrawal delirium
may continue for only a few hours or may persist for as long as
2–4 weeks.
Table 2 lists substances associated with
delirium, including substances of abuse, prescription medications,
and toxins.
Drugs of abuse
Antiasthmatic agents
Antihypertensive and cardiovascular
Antiparkinsonian medications
Gastrointestinal medications
Muscle relaxants
Immunosuppressive agents
Lithium and psychotropic medications
with anticholinergic properties
Organophosphate insecticides
Carbon monoxide
Carbon dioxide
Volatile substances, such as fuel or
organic solvents
Delirium, particularly in the critically ill and in elderly
hospitalized patients, often has multiple etiologies (25). Francis
and Kapoor (28) found that while 56% of elderly patients
with delirium had a single definite or probable etiology for delirium,
the remaining 44% had an average of 2.8 etiologies per
Occasionally, no clear etiology is immediately apparent. Often,
unrecognized medication use or substance abuse is the cause of an
intoxication or withdrawal delirium, and sometimes a rare cause
of delirium, such as disseminated intravascular coagulation, is
eventually revealed. There has been some controversy as to whether
particular settings can themselves cause delirium (e.g., there has
been speculation that the intensive care environment can cause "intensive
care unit psychosis"). Koponen et al. (11) found a clear
organic etiology in 87% of patients with delirium, and
they found relatively little evidence that delirium was caused primarily
by environmental factors.
Although standard psychiatric, general medical, and neurological
histories and examinations are usually sufficient to diagnose and
evaluate the severity of delirium, they can be supplemented by assessments
using formal instruments. A large number of delirium assessment
methods have been designed, some intended for clinical evaluations
and others for research. Detailed reviews of the psychometric properties
of instruments, as well as suggestions for choosing among
instruments for particular clinical evaluations or research purposes,
are available (29–31). Four types of instruments are briefly
mentioned in the following sections: tests that screen for delirium
symptoms, delirium diagnostic instruments, delirium symptom severity
ratings, and some experimental laboratory tests.
Several tools have been developed to screen for delirium symptoms
among patients, and most have been designed to be administered by
nursing staff. These may aid in the recognition of delirium, especially
in nursing homes, where physician visits are less frequent. The
number of delirium symptoms covered, the specificity of items for delirium,
and the complexity of administration all vary. Screening instruments
include the Clinical Assessment of Confusion–A (CAC-A)
(32), the Confusion Rating Scale (CRS) (33), the MCV Nursing Delirium
Rating Scale (MCV-NDRS) (34), and the NEECHAM Confusion Scale (35).
Investigators have designed a variety of instruments to make
a formal diagnosis of delirium. These instruments consist of operationalized
delirium criteria from a variety of diagnostic systems, often in
the form of a checklist incorporating information from patient observation
and the medical record (e.g., DSM-III-R, DSM-IV, ICD-9, and ICD-10).
The rate of delirium diagnosis obtained by using these diagnostic
instruments varies according to both the diagnostic system that
was used and the particular way in which the authors chose to operationalize
the criteria. One structured diagnostic interview schedule, the
Delirium Symptom Interview (DSI), can be administered by lay interviewers and
used in epidemiological studies (36). Other delirium diagnostic
instruments include the Confusion Assessment Method (CAM) (37),
Delirium Scale (Dscale) (38), Global Accessibility Rating Scale
(GARS) (39), Organic Brain Syndrome Scale (OBS) (40), and Saskatoon
Delirium Checklist (SDC) (41).
Several instruments have been developed to rate the severity
of delirium symptoms. Ratings are generally based both on behavioral
symptoms and on confusion and cognitive impairment. Rating the severity
of delirium over time may be useful for monitoring the effect of
an intervention or plotting the course of a delirium over time.
These scales have also been used to make the diagnosis of delirium by
considering patients with scores above a specified cutoff to have
the diagnosis. Such rating scales include the Delirium Rating Scale
(DRS) (42) and the Memorial Delirium Assessment Scale (MDAS) (43).
Several laboratory evaluations have been investigated for
possible use in evaluating delirium. With the exception of the EEG,
these tests are experimental and currently appropriate only for
research purposes. For several decades, investigators have observed
EEG changes in patients with delirium (44). EEG changes consist
mainly of generalized slowing, although low-voltage fast activity
is seen in some types of delirium, such as delirium tremens (45).
The presence of EEG abnormalities has fairly good sensitivity for
delirium (in one study, the sensitivity was found to be 75%),
but their absence does not rule out the diagnosis; thus, the EEG
is no substitute for careful clinical observation. Among the experimental
laboratory tests that have been investigated for use in delirium,
those that appear to show some promise include brain imaging (46, 47) and measures of serum anticholinergic activity (48).
Several therapeutic modes are employed in the treatment of
delirium and are discussed in this section. First, the cornerstone
of treatment, psychiatric management, is defined and its components are
described. Treatment of the delirium itself involves a set of environmental
and supportive interventions and specific pharmacologic treatments.
Environmental manipulations are generally designed to help reorient
the patient and modulate the degree of stimulation. Supportive measures are
designed to provide patient, family, and friends with both reassurance
and education regarding the nature, temporal course, and sequelae
of delirium.
Psychiatric management involves an array of tasks that the
psychiatrist should seek to ensure are performed for all patients
with delirium. A psychologically informed understanding of the patient and
the family may facilitate these tasks. These tasks are designed
to facilitate the identification and treatment of the underlying
cause(s) of delirium, improve the patient's level of functioning,
and ensure the safety and comfort of patients and others. In many
cases, the psychiatrist will be part of, or a consultant to, a multidisciplinary
team and should encourage the administration of the full range of
needed treatments.
Delirium frequently heralds a medical emergency, and patients
are usually managed in an acute-care hospital setting. For some
patients with milder symptoms, once the etiology of delirium has been
identified and general medical management has begun, psychiatric
and general medical management can take place in an alternative
setting (e.g., skilled nursing facility, home, hospice). The psychiatrist
is commonly asked to consult when a patient develops delirium on
a general medical or surgical unit in the hospital; however, delirium
may also present as an emergency in either the psychiatric outpatient
or inpatient setting.
The appropriate treatment of delirium involves interventions
to search for and correct underlying causes, as well as relieve
current symptoms. Joint and coordinated management of the patient
with delirium by the psychiatrist and internist, neurologist, or
other primary care or specialty physicians will frequently help
ensure appropriate comprehensive evaluation and care.
An essential principle in the psychiatric management of delirium
is the identification and correction of the etiologic factors. Careful
review of the patient's medical history and interview of
family members or others close to the patient may provide some direction.
Appropriate laboratory and radiological investigations such as those
listed in Table 3 may be necessary to determine the underlying cause(s)
of delirium. The choice of specific tests to be undertaken will
depend on the results of the clinical evaluation.
Physical status
Physical and neurological examinations
Review of vital signs and anesthesia record if postoperative
Review of general medical records
Careful review of medications and correlation with
behavioral changes
Mental status
Cognitive tests (e.g., clock face, digit span, Trailmaking
Basic laboratory testsconsider
for all patients with delirium
Blood chemistries: electrolytes, glucose, calcium,
albumin, blood urea nitrogen (BUN), creatinine, SGOT, SGPT, bilirubin, alkaline
phosphatase, magnesium, PO4
Complete blood count (CBC)
Chest X-ray
Measurement of arterial blood gases or oxygen saturation
Additional laboratory
testsordered as indicated by
clinical condition
Urine culture and sensitivity (C&S)
Urine drug screen
Blood tests (e.g., venereal disease research laboratory [VDRL],
heavy metal screen, B12 and folate
levels, lupus erythematosus [LE] prep, antinuclear antibody [ANA],
urinary porphyrins, ammonia, human immunodeficiency virus [HIV])
Blood cultures
Measurement of serum levels of medications (e.g., digoxin, theophylline,
phenobarbital, cyclosporine)
Lumbar puncture
Brain computerized tomography (CT) or magnetic resonance imaging
Electroencephalogram (EEG)
Source. From guidelines
by Trzepacz and Wise (4949).
A patient with delirium may have life-threatening general
medical conditions that demand therapeutic intervention even before
a specific or definitive etiology is determined. In addition to ensuring
that diagnostic tests essential to identifying the cause of delirium
are ordered, when acting as a consultant, the psychiatrist should
raise the level of awareness of the general medical staff concerning
the potential morbidity and mortality associated with delirium.
Increased observation and monitoring of the patient's general
medical condition should include frequent monitoring of vital signs,
fluid intake and output, and levels of oxygenation. A patient's
medications should be carefully reviewed; nonessential medications
should be discontinued, and doses of needed medications should be
kept as low as possible.
The goal of diagnosis is to discover reversible causes of
delirium and prevent complications through prompt treatment of these
specific disorders. One must give a high priority to identifying and
treating such disorders as hypoglycemia, hypoxia or anoxia, hyperthermia,
hypertension, thiamine deficiency, withdrawal states, and anticholinergic-induced
or other substance-induced delirium. Examples of specific reversible
causes of delirium and treatments for these disorders appear in Table 4.
Hypoglycemia or delirium of unknown
etiology where hypoglycemia is suspected
Tests of blood and urine for diagnosis
Thiamine hydrochloride, 100 mg i.v. (before glucose)
50% glucose solution, 50 ml i.v.
Hypoxia or anoxia (e.g., due to pneumonia, obstructive
or restrictive pulmonary disease, cardiac disease, hypotension,
severe anemia, or carbon monoxide poisoning)
Immediate oxygen
Hyperthermia (e.g., temperature above 40.5'°C
or 105'°F)
Rapid cooling
Severe hypertension (e.g., blood pressure
of 260/150 mm Hg) with papilledema
Prompt antihypertensive treatment
Alcohol or sedative withdrawal
Appropriate pharmacologic intervention
Thiamine, intravenous glucose, magnesium, phosphate,
and other B vitamins, including folate
Wernicke's encephalopathy
Thiamine hydrochloride, 100 mg i.v., followed by thiamine
daily, either intravenously or orally
Anticholinergic delirium
Withdrawal of offending agent
In severe cases, physostigmine should be considered
unless contraindicated
Behavioral disturbances, cognitive deficits, and other manifestations
of delirium may endanger patients or others. Psychiatrists must
assess the suicidality and violence potential of patients and implement
or advocate interventions to minimize these risks (e.g., remove
dangerous items, increase surveillance and supervision,
and institute pharmacotherapy). Suicidal behaviors are often inadvertent
in delirium and occur in the context of cognitive impairment and/or
in response to hallucinations or delusions. Additional assessments
of a patient's risk for falls, wandering, inadvertent self-harm, etc.,
should also be made with appropriate measures taken to ensure safety.
Whenever possible, means other than restraints, such as sitters,
should be used to prevent the delirious patient from harming himself
or herself, others, or the physical environment. Restraints themselves
can increase agitation or carry risks for injuries and should be
considered only when other means of control are not effective or
appropriate (50). A patient who is restrained should be seen as frequently
as is necessary to monitor changes in the patient's condition
(51). The justification for initiating restraints and continuing
use of restraints should be documented in the patient's
medical record. Additional rules may apply in some jurisdictions,
and the psychiatrist should become familiar with applicable regulations
and institutional policies (52).
The psychiatrist must periodically assess the patient's
delirium symptoms, mental status, and other psychiatric symptoms.
The symptoms and behavioral manifestations of delirium can fluctuate rapidly,
and regular monitoring will allow for the adjustment of treatment
Important behavioral issues that must be addressed include
depression, suicidal ideation or behavior, hallucinations, delusions,
aggressive behavior, agitation, anxiety, disinhibition, affective lability,
cognitive deficits, and sleep disturbances. It is helpful to record
serial assessments of mental status and symptoms over time, as these
may indicate the effectiveness of interventions and new or worsening
medical conditions. A structured or semistructured instrument, such
as those described in Section II.F, may aid in the systematic completion
of this task.
Knowledge of the patient's and the family's
psychodynamic issues, personality variables, and sociocultural environment
may aid in dealing effectively with specific anxieties and reaction
patterns on the part of both the patient and the family. This understanding
may be based on prior acquaintance with the patient, current interviews
or interaction with the patient or family, and/or history
from the family.
It is important for the psychiatrist who is treating the patient
with delirium to establish and maintain a supportive therapeutic
stance. Understanding the underlying affect, concerns, and premorbid personality
of the patient is frequently helpful in maintaining a supportive
alliance. A solid alliance with the family is also desirable, as
family members are a critical source of potential support for patients
and information on patients who may be unable to give reliable histories.
Establishing strong alliances with the multiple clinicians and caregivers
frequently involved in the care of delirious medically ill patients
is also crucial.
Educating patients and families regarding delirium, its etiology,
and its course is an important role for psychiatrists involved in
the care of patients with delirium. Patients may vary in their ability
to appreciate their condition; however, providing reassurance that
delirium is usually temporary and that the symptoms are part of
a medical condition may be extremely beneficial to both patients
and their families. Specific educational and supportive interventions
are discussed in more detail in the following paragraphs.
Nursing staff make frequent observations of patients over
time, which places them in an excellent position to detect the onset
and monitor the course of delirium. Education of nursing staff on
each shift regarding the clinical features and course of delirium
can be an important task for psychiatrists.
Because of the behavioral problems accompanying delirium,
there may be a tendency for some general medical physicians to overlook
underlying general medical problems contributing to a patient's
delirium and to consider the problem to be entirely in the realm
of the psychiatrist. In such instances, providing education to other
physicians regarding the underlying physiological etiologies of
delirium may be an important task for the psychiatrist.
Following recovery, patients' memory for the experience
and events of the delirium is variable. Some patients gradually
or abruptly lose all apparent recall of the delirious experience,
while others have vivid, frightening recollections. Explanations
regarding delirium, its etiology, and its course should be reiterated.
Supportive interventions that are a standard part of psychiatric
management following a traumatic experience should be used for those
with distressing postdelirium symptoms. Following recovery, all
patients who have experienced delirium should be educated about
the apparent cause of their delirium (when this could be identified)
so that the patient, family, and subsequent physicians can be made
aware of risk factors that may lead to delirium in the future. Psychotherapy
focused on working through the experience of the delirium may, at
times, be necessary to resolve anxiety, guilt, anger, depression,
or other emotional states. These states may be compounded by the
patient's preexisting psychological, social, or cultural
Management of delirium includes a specific array of interventions
by nursing, psychological, general medical, and psychiatric staff
that can be broadly categorized as environmental interventions. The
general goals are to reduce environmental factors that exacerbate
delirium, confusion, and misperception while providing familiarity
and an optimal level of environmental stimulation. While there is
no empirical evidence that the environment by itself causes delirium,
certain environmental conditions may exacerbate delirium.
"Timelessness" in hospital intensive care
units (ICUs) (i.e., a similar environment regardless of the time
of day) appears to contribute to disorganization of sleep-wake cycles,
which in turn aggravates fatigue and confusion. Some ICUs have introduced
windows, while others change the lighting to cue night versus day.
The ICU can be a very noisy environment, with beeps, alarms, pumps,
respirators, overhead paging, resuscitation efforts, etc. The confused
patient with delirium may become overstimulated by too much noise,
and efforts should be made to reduce this whenever possible. On
the other hand, understimulation from the environment may leave
the patient with delirium undistracted from his or her own internal
disorganized perceptions and thoughts; too quiet an environment
may exacerbate delirium. It is important to provide a regular amount
of modest stimulation (vocal, visual, tactile) to the patient with
Delirium can also be aggravated by sensory impairments, including
visual impairment (53) and auditory impairment (54). By restoring
a patient's glasses or hearing aid, one may substantially
reduce the manifestations of delirium. Ensuring that there is an
analog clock and a calendar that the patient can see will further
facilitate orientation. Steps that render the environment more familiar
and less alien, such as bringing in family photographs or favorite
objects from home (e.g., stuffed animals) or actually having family
members there when possible, are also helpful. Especially in a room
that may be dark at night, night-lights can help reduce anxiety.
There is some empirical evidence that these environmental
interventions can reduce the severity of delirium and improve outcomes
(55–58). While there are no large, rigorous, randomized
controlled trials, these environmental interventions are widely
endorsed because of clinical experience and the lack of adverse
effects. Although the value of environmental interventions is widely
recognized, they remain substantially underutilized (59).
Nursing, psychological, general medical, and psychiatric staff
and family members can also provide cognitive-emotional support
designed to strengthen any retained adaptive cognitive functioning
that the patient possesses. The goal of these interventions is to
reduce anxiety and the unfamiliar while providing understanding
and support.
Central to providing cognitive and emotional support are efforts
to deal with disorientation. All who come in contact with the patient
should provide reorientation, which entails reminding the patient in
an unpressured manner of where he or she is, the date and time,
and what is happening to him or her.
The patient's emotional reaction to symptoms of delirium
can itself be a significant aggravating factor. The patient should
be told that the symptoms are temporary and reversible and do not
reflect a persistent psychiatric disorder. Similarly, the perception
of cognitive deficits may lead patients to conclude that they have
suffered brain damage. Unless the delirium is thought to be due
to a major stroke or injury or to another event that may cause permanent
brain injury, all who have contact with the patient should reassure
her or him that these deficits are common and reversible symptoms associated
with the particular illness, surgery, or other treatment.
There have been no large clinical trials examining the efficacy
of cognitive and emotional support in delirium. However, as with
environmental interventions, increased use of these currently underutilized
supportive measures has been encouraged on the basis of clinical
experience, common sense, and lack of adverse effects (59).
Educating patients' friends and family about delirium
is extremely helpful since they may have the same worries as the
patient (e.g., the patient has a permanent psychiatric illness or
is brain damaged) and become frightened and demoralized instead
of being hopeful and encouraging the patient (60).
It may be useful to recommend that family and friends spend
time in the patient's room and bring familiar objects from
home to help orient the patient and help him or her feel secure.
The primary treatment of the symptoms of delirium is largely
pharmacologic. The high-potency antipsychotic medication haloperidol
is most frequently employed, although other pharmacologic and somatic
interventions have been used in particular instances. Recently,
there has been increased use of risperidone (61, 62). The available
studies of the efficacy and other outcomes from use of these treatments
for patients with delirium are reviewed in this section.
Several important points should be considered when evaluating
the evidence for specific somatic interventions. While haloperidol
has been the most studied pharmacologic treatment, few studies have
used a standardized definition of delirium (e.g., based on DSM-IV
criteria). In addition, few investigations have used reliable and
valid delirium symptom rating measures to assess symptom severity
before and after intervention.
For somatic treatments other than haloperidol, there have
been no large, prospective trials or studies including a control
group. Information regarding the efficacy of these treatments comes mainly
from small case series or case reports; interpretation of the results
from many of these case presentations is also made difficult by
the use of nonstandardized definitions of delirium or informal measures
of delirium symptom severity.
Antipsychotics have been the medication of choice in the treatment
of delirium. Evidence for their efficacy has come from numerous
case reports and uncontrolled trials (63, 64). A series of controlled trials
also showed that antipsychotic medications can be used to treat
agitation and psychotic symptoms in medically ill and geriatric
patient populations (65–69). However, most of these trials were
not conducted with patients who had clearly or consistently defined
delirium; in some studies, agitation and disorientation were the
sole criteria and symptom assessments ranged from questionnaires
to simple identification without symptom descriptions.
A randomized, double-blind, comparison trial by Breitbart
et al. (70) identified delirium by using standardized clinical measures,
and it demonstrated the clinical superiority of antipsychotic medications
over benzodiazepines in delirium treatment. The Delirium Rating
Scale, Mini-Mental State examination, and DSM-III-R were used to
make the diagnosis in 244 hospitalized AIDS patients. The subjects
were randomly assigned to one of three medications: chlorpromazine,
haloperidol, and lorazepam. There were statistically significant
decreases in scores on the Delirium Rating Scale after 2 days in
the haloperidol and chlorpromazine groups but not in the lorazepam
group (the mean decreases in scores were 8.0, 8.5, and 1.0, respectively).
The improvement in delirium symptoms observed among those treated
with antipsychotic medications occurred quickly, usually before
the initiation of interventions directed at the medical etiologies
of the delirium.
Droperidol, a butyrophenone with a rapid onset of action and
relatively short half-life that is more sedating than haloperidol,
has also been found to be an effective treatment for hospitalized
patients with agitation, although not necessarily delirium (71).
Results of two double-blind clinical trials comparing droperidol
to haloperidol suggest that a more rapid response may be obtained
with droperidol. Resnick and Burton (72) reported that 30 minutes
after intramuscular injections, 81% of patients initially
treated with 5 mg of haloperidol required a second injection, compared
to only 36% of patients initially given 5 mg of droperidol.
Thomas and colleagues (69), comparing 5 mg i.m. of droperidol to
5 mg i.m. of haloperidol, found significantly decreased
combativeness among the droperidol treatment group after 10, 15,
and 30 minutes. There has been very little study of the
newer antipsychotic medications (risperidone, olanzapine,
and quetiapine) in the treatment of delirium. Although there have
been several case reports of use of risperidone for patients with
delirium (61, 62, 73, 74), there have been no published clinical
trials of any of the new antipsychotic medications for patients
with delirium.
Phenothiazines can be associated with sedation, anticholinergic
effects, and α‐adrenergic blocking effects
that can cause hypotension; each of these side effects may complicate
delirium. Butyrophenones, particularly haloperidol and droperidol,
are considered the safest and most effective antipsychotics for
delirium. Haloperidol, a high-potency dopamine-blocking agent with
few or no anticholinergic side effects, minimal cardiovascular side
effects, and no active metabolites, has generally been considered
the antipsychotic medication of first choice in the treatment of
delirium. High-potency antipsychotic medications also cause less
sedation than the phenothiazines and therefore are less likely to
exacerbate delirium. Although droperidol may have the advantages
of a more rapid onset of action and a shorter half-life than haloperidol,
droperidol is associated with greater sedation and hypotensive effects
The use of antipsychotic medications can be associated with
neurological side effects, including the development of extrapyramidal
side effects, tardive dyskinesia, and neuroleptic malignant syndrome.
However, there is some evidence to suggest that extrapyramidal side
effects may be less severe when antipsychotic medications are administered
intravenously (76). One case series involved 10 consecutive general
medical inpatients receiving doses of oral or intravenous haloperidol
at approximately 10 mg/day. Four patients were
given intravenous medication, and six were given oral doses. Although
delirium was not identified as the reason for treatment, five patients
met diagnostic criteria by description. There was no significant
difference in the incidence of akathisia, but the group receiving
intravenous medication experienced less severe extrapyramidal symptoms.
Neither method of administration resulted in acute dystonic reactions
or changes in blood pressure or pulse rate (76).
Haloperidol used in the treatment of delirium has been found
in some instances to lengthen the QT interval, which can lead to
torsades de pointes, a form of polymorphic ventricular tachycardia that
can degenerate to ventricular fibrillation and sudden death. Estimates
of the incidence of torsades de pointes among patients with delirium
treated with intravenous haloperidol have ranged from four out of
1,100 patients (77) to eight out of 223 patients (78). Although
development of this serious event has been associated with higher
intravenous doses (>35 mg/day) of haloperidol, it is important to
note that torsades de pointes has also been reported with low-dose
intravenous haloperidol and oral haloperidol as well (78, 79). Droperidol
has also been associated with lengthening of the QT interval, and
it may also be associated with torsades de pointes and sudden death.
Other side effects of antipsychotic medication use can rarely
include lowering of the seizure threshold, galactorrhea, elevations
in liver enzyme levels, inhibition of leukopoiesis, neuroleptic malignant
syndrome, and withdrawal movement disorders.
Although different antipsychotic medications can be given
orally, intramuscularly, or intravenously, in emergency situations
or when there is lack of oral access, intravenous administration
may be most effective. In addition, as described in the preceding
section on side effects, there is some evidence that antipsychotic
medications may cause less severe extrapyramidal side effects when administered
intravenously (76). Intravenous administration of haloperidol has
not yet received approval by the Food and Drug Administration (FDA).
There have been few studies to determine the optimal doses
of antipsychotic medications in the treatment of delirium. On the
basis of doses used in several studies, starting haloperidol in
the range of 1–2 mg every 2–4 hours as needed
has been suggested (80). Low doses, for example as low as 0.25–0.50
mg of haloperidol every 4 hours as needed, have been suggested
for elderly patients (81). On the other hand, severely agitated
patients may require titration to higher doses. Bolus intravenous haloperidol
doses exceeding 50 mg with total daily doses up to 500
mg have been reported, and they were associated with minimal effects
on heart rate, respiratory rate, blood pressure, and pulmonary artery
pressure and minimal extrapyramidal side effects (82, 83).
Several studies (75, 84) have examined the use of continuous
intravenous infusions of haloperidol or droperidol among agitated
medically ill patients who have required multiple bolus intravenous injections
of antipsychotic medications. The results indicate that this means
of administration can be safe and may help avoid some of the complications
associated with repeated bolus dosing (e.g., hypotension). The authors
of one study (84) recommended continuous infusion of haloperidol
for patients who required more than eight 10-mg haloperidol boluses
in 24 hours or more than 10 mg/hour for more than
5 consecutive hours. They suggested initiating haloperidol with
a bolus dose of 10 mg followed by continuous infusion at 5–10
Because antipsychotic medications used in the treatment of
delirium have occasionally been found to lengthen the QT interval,
possibly leading to torsades de pointes, ventricular fibrillation,
and sudden death, recommendations for medication management include
a baseline ECG with special attention paid to the length of the
QTc interval. A prolongation of the QTc interval to greater than 450
msec or to greater than 25% over that in previous ECGs
may warrant telemetry, a cardiology consultation, and dose reduction
or discontinuation (85, 86). It has also been recommended that serum levels
of magnesium and potassium be monitored in critically ill patients,
especially those whose baseline QTc interval is 440 msec or longer,
those who are receiving other drugs that increase the QT interval,
or those who have electrolyte disturbances (87).
Few controlled studies have evaluated the efficacy of benzodiazepines
as a monotherapy (i.e., not in combination with other pharmacotherapies)
for the treatment of delirium. The limited data that are available
suggest that benzodiazepine monotherapy may be ineffective as a
treatment for general cases of delirium caused by a variety of etiologies.
For example, the comparison by Breitbart et al. (70), described
in Section III.C.1, indicated that lorazepam, given alone, was less
effective as a treatment for delirium than either haloperidol or
Although there appears to be little evidence to support the
use of benzodiazepines alone for general cases of delirium, there
may be certain types of delirium for which benzodiazepines have
advantages and are preferable. For example, benzodiazepines are
the treatment of choice for delirium related to alcohol or benzodiazepine
withdrawal. Other specific clinical circumstances in which benzodiazepines
may be useful include instances when there is a need for a medication
that can raise the seizure threshold (unlike antipsychotics, which
lower the seizure threshold) or when anticholinergic side effects
or akathisia associated with antipsychotics would seriously exacerbate
a patient's condition.
There have been several reports of the combination of antipsychotics
and benzodiazepines for the treatment of delirium, and the results
indicate that this combination may decrease medication side effects
and potentially increase clinical effectiveness in special populations,
for example severely ill cancer patients or AIDS patients. Results
of several open studies using intravenous haloperidol along with
intravenous lorazepam suggest that the combined treatment is more
efficacious, with a shorter duration of the delirium and fewer extrapyramidal
symptoms, than intravenous haloperidol alone (16, 63, 88). Most
of these studies defined delirium according to DSM criteria but
did not use standardized assessment tools.
The adverse effects of benzodiazepines on mental status have
received some attention. Marcantonio et al. (89) demonstrated an
association between benzodiazepine use and postoperative delirium in
a prospective study of psychoactive medications given to patients
admitted for elective noncardiac procedures. Long-acting benzodiazepines
in particular posed problems. Benzodiazepines have been associated
with sedation, behavioral disinhibition, amnesia, ataxia, respiratory
depression, physical dependence, rebound insomnia, withdrawal reactions,
and delirium. Geriatric populations are at greater risk for the
development of these complications; children and adolescents may
also be at increased risk for disinhibition reactions, emotional
lability, increased anxiety, hallucinations, aggression, insomnia,
euphoria, and incoordination (16, 90, 91).
Benzodiazepines are generally contraindicated in delirium
from hepatic encephalopathy due to accumulation of glutamine, which
is related chemically to γ-aminobutyric acid (GABA). Benzodiazepines
should also be avoided, or used with caution, in patients with respiratory
insufficiency. For patients who have hepatic insufficiency or are
taking other medications metabolized by the cytochrome P450 system,
benzodiazepines that are predominantly metabolized by glucuronidation (lorazepam,
oxazepam, and temazepam) should be used when a benzodiazepine is
When benzodiazepines are used, relatively short-acting medications
with no active metabolites (e.g., lorazepam) should be selected.
Few studies have investigated the optimal dose of benzodiazepines
for the treatment of delirium. However, the dose must be carefully
considered, given the possibility that benzodiazepines may exacerbate
symptoms of delirium. In cases of delirium due specifically to alcohol
or sedative-hypnotic withdrawal, higher doses of benzodiazepines
and benzodiazepines with longer half-lives may be required.
In a report of a case series of 20 critically ill cancer patients
for which benzodiazepines and antipsychotics were administered together,
Adams et al. (63) suggested that treatment be started with 3 mg i.v.
of haloperidol followed immediately by 0.5–1.0 mg i.v.
of lorazepam. Additional doses and the frequency are then titrated
to the patient's degree of improvement. For example, Adams
et al. stated that if little or no improvement is observed within
20 minutes, an additional dose of 5 mg i.v. of haloperidol
and 0.5–2.0 mg i.v. of lorazepam can be given. In some
cases of severe agitation, the eventual doses of both medications
have been quite large (e.g., daily doses of lorazepam between 20
and 30 mg and of haloperidol between 100 and 150 mg).
Anticholinergic mechanisms have been implicated in the pathogenesis
of many medication-induced deliriums. In addition, anticholinergic
mechanisms may be involved in delirium from hypoxia, hypoglycemia,
thiamine deficiency, traumatic brain injury, and stroke (49). However, cholinergic
medications have been used in a very limited fashion to treat delirium,
almost exclusively in cases of delirium clearly caused by anticholinergic
medications. Physostigmine, a centrally active cholinesterase inhibitor,
has been used most often, with tacrine and donepezil receiving less
In one prospective study (92), physostigmine reversed delirium
among 30 patients in a postanesthesia recovery room, in whom either
atropine or scopolamine had caused the delirium. In four single case
reports of delirium diagnosed by clinical interviews, physostigmine
reversed the delirium resulting from ranitidine (93), homatropine
eyedrops (94), benztropine (95), and meperidine (96).
In a single case study (97), tacrine reversed delirium induced
by anticholinergic medication. Newer cholinesterase inhibitors with
fewer side effects than tacrine have not been studied for treatment
of delirium.
Many side effects of cholinesterase inhibitors are caused
by cholinergic excess; such effects include bradycardia, nausea,
vomiting, salivation, and increased gastrointestinal acid. Physostigmine can
cause seizures, particularly if intravenous administration is too
rapid (98). Tacrine has been associated with asymptomatic increases
in liver enzyme levels. A threefold increase has been observed in
approximately 30% of patients and is generally reversible
with discontinuation of treatment; 5%–10% of
patients develop more marked (e.g., tenfold) but still generally
reversible increases in liver enzyme levels that warrant discontinuation
of tacrine treatment (99).
Physostigmine is usually administered parenterally. Doses
that have been used in studies of delirium have included intravenous
or intramuscular injections ranging from 0.16 to 2.00 mg and continuous
intravenous infusions of 3 mg/hour (92–96).
In the single case study of tacrine used to reverse delirium
induced by anticholinergic medication, 30 mg i.v. was used (97).
Certain vitamin deficiencies are commonly described as causing
delirium. Consequently, one would expect such deliria to reverse
at least to some extent with repletion of the deficient vitamin. Although
this has not been subjected to rigorous trials, there are some case
reports and case series supporting this effect. A malnourished hemodialysis
patient with nicotinamide deficiency had a paranoid delirium that
responded to parenteral nicotinamide, 500 mg/day (100).
Bahr et al. (101) reported that of two chronic alcoholic patients
with B vitamin deficiency, malnutrition, and central pontine myelinolysis,
one improved quickly with intravenous vitamins. Thiamine deficiency
delirium (DSM-III-R) was treated with vitamin B complex in six of
13 elderly medically ill patients, but only one patient had a dramatic
response to treatment (102).
In one randomized controlled trial (103), 26 elderly patients
undergoing orthopedic surgery received treatment with intravenous
vitamins B and C preoperatively and postoperatively and were compared
to 32 age-matched surgical control subjects who did not receive
vitamins. There was no difference between the intervention and control
groups in the incidence of postoperative confusion (39% versus
38%) or in the preoperative thiamine status as determined
by serum assays.
In general, any patient with delirium who has a reason to
be B vitamin deficient (e.g., alcoholic or malnourished) should
be given multivitamin replacement.
Hypoxia, fatigue, and the metabolic consequences of overexertion
all exacerbate delirium. Such hypercatabolic conditions are likely
to accompany certain causes of agitated delirium (e.g., hyperdynamic
heart failure, adult respiratory distress syndrome, hyperthyroid
storm). For such patients and for any cases of agitated delirium
unresponsive to other pharmacologic interventions, the patient may
require a paralytic agent and mechanical ventilation. This improves
oxygenation and reduces skeletal muscle exertion. The patient is
usually heavily sedated. Morphine (or other opiate) is also an important
palliative treatment in cases of delirium where pain is an aggravating
factor (104). However, some opiates can exacerbate delirium, particularly
through their metabolites, which possess anticholinergic activity
(89). Among opiates, meperidine and fentanyl are particularly anticholinergic.
ECT has not been shown to be an effective treatment for general
cases of delirium. Earlier case reports and case series had significant
limitations: standardized diagnostic criteria and rating scales were
not used; patients with schizophrenia, mania, postpartum psychosis,
or psychotic depression were included and diagnosed with delirium
because they had disorganized thinking and cognition; and few details
concerning the manner in which ECT was performed were provided (105–111).
There is limited evidence for ECT as a treatment for particular
cases of delirium due to specific etiologies. MEDLINE literature
searches identified two case reports of ECT use for the delirium
that is a component of neuroleptic malignant syndrome. In one study
(112), the delirium symptoms improved in 24 of 29 patients with
neuroleptic malignant syndrome who were treated with ECT. In the
second study (113), 26 of 31 patients with neuroleptic malignant
syndrome who were treated with ECT and hydration were described
as having improved delirium symptoms. ECT has been studied in small
samples of patients with delirium tremens. In one older study (109),
10 patients receiving ECT and conventional treatment had
a shorter duration of delirium symptoms than 10 patients receiving
conventional treatment alone (mean, 0.85 versus 2.8 days, respectively).
In one case report (106), a patient with delirium tremens who had
not responded to high-dose benzodiazepine treatment was described
as recovering after ECT. In two case reports (114, 115), patients
with protracted courses of delirium after traumatic brain injuries
improved after receiving ECT. Because of the lack of compelling
evidence, as well as the availability of alternative means of management,
ECT is not presently used in the United States for treatment of
delirium tremens.
In addition to the very limited evidence that ECT is an effective
treatment for delirium, there may be considerable risks with ECT
in medically unstable patients. For these reasons, ECT should be considered
only rarely for patients with delirium due to specific etiologies
such as neuroleptic malignant syndrome and should not be considered
initially as a substitute for more conservative and conventional
treatments. ECT itself may carry a risk of both postictal delirium
(lasting minutes to hours) and interictal delirium (lasting
days) after the procedure (116–120). Beyond that time period, ECT
can also exacerbate cognitive deficits, such as memory impairment.
Certain patient populations at higher risk for these adverse effects
from ECT include patients with Parkinson's disease (particularly
those taking carbidopa), Huntington's disease, or caudate
or other basal ganglia strokes (119, 121–125).
After the diagnosis of delirium is made (see Section II) a
treatment plan is developed. The components of the treatment plan
and factors that go into a psychiatrist's choice of treatment
recommendations are discussed in this section. Although the treatment
of delirium involves multiple modalities, certain components are
essential and should be implemented with all patients. Other components
of treatment may involve a choice between specific therapies, and
this choice should be guided by a careful assessment of the patient's
clinical condition, etiology, and comorbid conditions.
Psychiatric management is the cornerstone of successful treatment
for delirium and should be implemented for all patients with delirium.
The goals of psychiatric management are similar for all patients
with delirium and involve facilitating the identification and treatment
of underlying etiologies, improving patient functioning and comfort,
and ensuring the safety of patients and others. The specific elements
(see Section III.A) include coordinating care with other clinicians;
ensuring that the etiology is identified; ensuring that interventions
for acute conditions are initiated; ensuring that disorder-specific
treatments are provided; monitoring and ensuring safety; assessing
and monitoring psychiatric status; establishing and maintaining
supportive therapeutic alliances with patients, families, and other
treaters; educating the patient and family regarding the illness;
and postdelirium management.
One aspect of the management of delirium involves environmental
interventions and cognitive-emotional support provided by nursing,
general medical, and psychiatric treaters. The general goals of
environmental interventions are to remove factors that exacerbate
delirium while providing familiarity and an optimal level of environmental
stimulation; the general goals of supportive management include
reorientation, reassurance, and education concerning delirium. Specific
examples of environmental and supportive interventions are given
in Section III.B. These interventions are recommended for all patients
with delirium, on the basis of some formal evidence but mainly because
of the value observed through clinical experience and the absence
of adverse effects.
The specific features of a patient's clinical condition,
the underlying cause(s) of the delirium, and associated conditions
may be used by the psychiatrist to determine the choice of specific
somatic therapy. Antipsychotic medications are the pharmacologic
treatment of choice in most cases of delirium because of their efficacy
in the treatment of psychotic symptoms. Haloperidol is most frequently
used because of its short half-life, few or no anticholinergic side
effects, no active metabolites, and lower likelihood of causing
sedation. Haloperidol may be administered orally or intramuscularly,
but it appears to cause fewer extrapyramidal side effects when administered intravenously.
An optimal dose range for patients with delirium has not been determined.
Initial doses of haloperidol in the range of 1–2 mg every
2–4 hours as needed have been used, and even lower starting
doses (e.g., 0.25–0.50 mg every 4 hours as needed) are
suggested for elderly patients. Titration to higher doses may be
required for patients who continue to be agitated. Although total daily
intravenous doses in the hundreds of milligrams have been given
under closely monitored conditions, much lower doses usually suffice.
Continuous intravenous infusions of antipsychotic medications can
be used for patients who have required multiple bolus doses of antipsychotic medications.
Initiating haloperidol with a bolus dose of 10 mg followed by continuous
intravenous infusion of 5–10 mg/hour has been
suggested. Droperidol, either alone or followed by haloperidol, can
be considered for patients with delirium and acute agitation for
whom a more rapid onset of action is required. The ECG should be
monitored in patients receiving antipsychotic medications for delirium,
and a QTc interval longer than 450 msec or more than 25% over
baseline may warrant a cardiology consultation and consideration
of discontinuation of the antipsychotic medication. The availability
of new antipsychotic medications (risperidone, olanzapine, and quetiapine)
with their different side effect profiles has led some physicians
to use these agents for the treatment of delirium.
Benzodiazepines can exacerbate symptoms of delirium and, when
used alone for general cases of delirium, have been shown to be
ineffective. For these reasons, benzodiazepines as monotherapies are
reserved for specific types of patients with delirium for which
these medications may have particular advantages. For example, benzodiazepines
are used most frequently to treat patients with delirium that has
been caused by withdrawal of alcohol or benzodiazepines. When a
benzodiazepine is used, medications such as lorazepam, which are
relatively short-acting and have no active metabolites, are preferable.
Combining a benzodiazepine with an antipsychotic medication can
be considered for patients with delirium who can only tolerate lower
doses of antipsychotic medications or who have prominent anxiety
or agitation. Combined treatment can be started with 3 mg
i.v. of haloperidol followed immediately by 0.5–1.0 mg
i.v. of lorazepam and then adjusted according to the patient's
degree of improvement.
Other somatic interventions have been suggested for patients
with delirium who have particular clinical conditions or specific
underlying etiologies; however, few data are available regarding
the efficacy of these interventions in treating delirium. There
is some suggestion that cholinergics such as physostigmine and tacrine
may be useful in delirium caused by anticholinergic medications. Agitated
patients with delirium with hypercatabolic conditions (e.g., hyperdynamic
heart failure, adult respiratory distress syndrome, hyperthyroid
storm) may require paralysis and mechanical ventilation. For patients
with delirium in whom pain is an aggravating factor, palliative
treatment with an opiate such as morphine is recommended. ECT may
be a treatment consideration in a few cases of delirium due to a
specific etiology such as neuroleptic malignant syndrome; any potential benefit
of ECT should be weighed against the risks of ECT for patients who
are often medically unstable. Any patient with delirium with a reason
to be deficient in B vitamins (e.g., alcoholic or malnourished)
should be given multivitamin replacement.
Decisions regarding the care of patients with delirium are
often complex because of risks associated with treatments, and these
decisions frequently have to be made quickly because of the seriousness
of the underlying general medical conditions. Unfortunately, delirium
intermittently affects consciousness, attention, and cognition and
can impair a patient's decisional capacity (i.e., the ability
to make decisions as determined by a clinician's evaluation)
or competence (i.e., the ability to make decisions as determined
by a court of law) (126, 127).
The presence or diagnosis of delirium does not in itself mean
that a patient is incompetent or lacks capacity to give informed
consent (128). Instead, a determination of decisional capacity or
competence to give informed consent involves formal assessment of
a patient's understanding about the proposed intervention
(including the intervention's risks, benefits, and alternatives)
and the consequences of the decisions to be made.
Decision-making guidelines have been suggested for patients
with delirium who lack decisional capacity or competence to give
informed consent (129). The urgency with which treatment is needed and
the risks and benefits of treatments can be used by the treating
physician to choose between several alternative courses of action.
In medical emergencies requiring prompt intervention, the first alternative
is to treat the patient with delirium without informed consent,
under the common-law doctrine of implied consent (i.e., that treatment
may be provided in medical emergencies without informed consent
if it is appropriate treatment that a reasonable person would want).
In nonemergency situations, the clinician should obtain input or
consent from surrogates. Involving interested family members can
be especially helpful for choosing among equally beneficial interventions
that involve low or moderate risks. The opinion of a second clinician
can be useful for making decisions involving more uncertainty or
interventions associated with greater risks. Obtaining the consultation
of a hospital's administrator, risk manager, or legal counsel
may also provide a means for reassuring family members and the treatment
team that reasonable decisions are being made. For decisions that involve
significant risks or substantial disagreements involving family
members, a court-appointed guardian can be sought if time permits.
In more emergent cases, an urgent hearing with a judge may be required.
All assessments of a patient's decisional capacity or competence
and the reasons for a particular course of action should be documented
in the patient's medical record.
Delirium is often misdiagnosed as depression or dementia.
These disorders can be diagnosed during a delirium only when the
patient's history reveals symptoms that clearly existed
before the delirium onset. When delirium is comorbid with other psychiatric
disorders, the delirium should be treated first and the treatments
for these other disorders, such as antidepressant or anxiolytic medications,
should be minimized or not begun until the delirium is resolved.
Medications for psychiatric disorders can both be the cause of delirium
and exacerbate or contribute to delirium from other causes.
Approximately 30%–40% of hospitalized
AIDS patients develop delirium (6, 16, 70). Early reports concerning
the increased sensitivity of AIDS patients to the extrapyramidal
side effects of dopamine-blocking antipsychotic drugs have made
clinicians cautious in using high doses of antipsychotics, such
as haloperidol (130, 131). At lower doses, antipsychotics such as
haloperidol and chlorpromazine have been demonstrated to be safe
and effective with minimal extrapyramidal side effects
The liver is the body's detoxifying organ for drugs
and other molecules. Hepatic insufficiency significantly affects
the metabolism of many medications. Most psychotropic medications
undergo hepatic transformation. In addition, the liver produces
albumin and other plasma proteins that transport bound medications
in the bloodstream. When these protein levels decrease because of
liver dysfunction, unbound medications can enter tissues at an accelerated
rateincluding crossing the blood-brain barrierand
can also be more available for catabolism or excretion. Thus, the
former effect may alter therapeutic effects or cause side effects,
while the latter may result in less therapeutic effect than expected
at a given dose.
Haloperidol undergoes metabolism by the P450 2D6 enzyme system,
which reduces it to reduced haloperidol. The latter is in equilibrium
with the parent drug. In addition, glucuronidation is an important
route of metabolism of haloperidol (132). This suggests that its
pharmacokinetics in patients with liver insufficiency would be similar
to those in other patients when used to treat delirium.
On the other hand, many benzodiazepines require oxidation
by the liver. The exceptions are lorazepam, temazepam, and oxazepam,
which require only glucuronidation.
It is therefore preferred that benzodiazepines requiring only glucuronidation
be used to treat delirium secondary to sedative-hypnotic or alcohol
withdrawal in patients who have liver insufficiency. Of these, lorazepam
is usually chosen because it is well absorbed when given orally,
intramuscularly, or intravenously.
The elderly are particularly vulnerable to delirium due to
changes in brain function, multiple general medical problems, polypharmacy,
reduced hepatic metabolism of medications, multisensory declines,
and brain disorders such as dementia. Conducting a careful medical
evaluation that includes particular attention to a patient's
level of oxygenation, possible occult infection (e.g., urinary tract infection),
and the possible role of medications is an essential initial approach
to the management of delirium in the elderly. Medications with anticholinergic
effects are often the culprit; however, even medications not generally
recognized as possessing anticholinergic effects (e.g., meperidine,
digoxin, and ranitidine) can be responsible (133–135).
Nursing home patients are at particular risk of delirium.
Low doses of antipsychotic medication usually suffice in treating
delirium in elderly patients, for example, beginning with
0.5 mg haloperidol once or twice a day. The benefits of restraints
may be greater for elderly patients than for younger patients because
of the greater risk of falls and hip fractures in older populations;
hip and other fractures often carry a grim prognosis for elderly
patients, who may never return to independent functioning. On the
other hand, the risks associated with restraints may be greater
among the elderly, and other means to prevent falls should be considered
if possible. When extrapyramidal side effects occur early in the
treatment of delirium, Lewy body dementia should be considered in
the differential diagnosis.
Larry Altstiel, M.D.
Varda Peller Backus, M.D.
William T. Beecroft, M.D.
Jeffrey L. Berlant, M.D.
D. Peter Birkett, M.D.
Charles H. Blackinton, M.D.
Mel Blaustein, M.D.
Barton J. Blinder, M.D.
Harold E. Bronheim, M.D.
Thomas Markham Brown, M.D.
Stephanie Cavanaugh, M.D.
Christopher C. Colenda, M.D.
Dave M. Davis, M.D.
Horace A. DeFord, M.D.
Prakash Desai, M.D.
Joel E. Dimsdale, M.D.
Ann Maxwell Eward, Ph.D.
Laura J. Fochtmann, M.D.
David G. Folks, M.D.
Gilles L. Fraser, Pharm.D.
Richard K. Fuller, M.D.
Dolores Gallagher-Thompson
Larry Goldman, M.D.
Sheila Hafter Gray, M.D.
Robert M. Greenberg, M.D.
Jon E. Gudeman, M.D.
Edward Hanin, M.D.
Carla T. Herrerias, M.P.H.
Daniel W. Hicks, M.D.
John Hughes, M.D.
Keith Isenberg, M.D.
Sue C. Jacobs, Ph.D.
Sandra Jacobson, M.D.
Leslie Dotson Jaggers, Pharm.D.
Charles Kaelber, M.D.
Barbara Kamholz, M.D.
Gary Kaplan, M.D.
Fred Karlin, M.D.
Roger G. Kathol, M.D.
Sherry Katz-Bearnot, M.D.
David J. Knesper, M.D.
Bob G. Knight, Ph.D.
Ronald R. Koegler, M.D.
Sharon Levine, M.D.
Glenn Lippman, M.D.
Rex S. Lott, Pharm.D.
Velandy Manohar, M.D.
Peter J. Manos, M.D., Ph.D.
James R. McCartney, M.D.
Dinesh Mittel, M.D.
Kevin O'Connor, M.D.
Joseph F. O'Neill, M.D.
Edmond H. Pi, M.D.
Michael K. Popkin, M.D.
Peter V. Rabins, M.D.
Stephen R. Rapp, M.D.
Vaughn I. Rickert, Psy.D.
Jonathan Ritro, M.D.
Laura Roberts, M.D.
Stephen M. Saravay, M.D.
Marc A. Schuckit, M.D.
Ben Seltzer, M.D.
Todd Semla, Pharm.D.
David Servan-Schreiber, M.D., Ph.D.
Elisabeth J. Shakin Kunkel, M.D.
Winston W. Shen, M.D.
Edward Silberman, M.D.
Theodore A. Stern, M.D.
Janice Zalen Stiers
John Tanquary, M.D.
William R. Tatomer, M.D.
Larry E. Tripp, M.D.
Vera Trzepacz, M.D.
Gary J. Tucker, M.D.
Peter VanDyck, M.D.
John Wattis, M.D.
William Weddington, M.D.
Richard D. Weiner, M.D.
Joseph Westermeyer, M.D., M.P.H., Ph.D.
Donald Wexler, M.D.
Thomas N. Wise, M.D.
Linda Worley, M.D.
William Zurhellen, M.D.
Alabama Department of
Mental Health and Mental Retardation
American Academy of Pediatrics
American College of Emergency Physicians
American Society of Health-System Pharmacists
Association for Academic Psychiatry
Association for the Advancement of Behavior Therapy
Association of Gay and Lesbian Psychiatrists
Group for the Advancement of Psychiatry
Michigan Psychiatric Society
National Institute on Alcohol Abuse and Alcoholism
Society of Adolescent Medicine
U.S. Department of Health and Human ServicesHIV/AIDS
The following coding system is used to indicate the nature
of the supporting evidence in the references:
[A] Randomized
clinical trial. A study of an intervention
in which subjects are prospectively followed over time; there are treatment
and control groups; subjects are randomly assigned to the two groups;
both the subjects and the investigators are blind to the assignments.
[B] Clinical trial. A
prospective study in which an intervention is made and the results
of that intervention are tracked longitudinally; study does not
meet standards for a randomized clinical trial.
[C] Cohort or longitudinal
study. A study in which subjects are prospectively
followed over time without any specific intervention.
[D] Case-control study. A
study in which a group of patients and a group of control subjects
are identified in the present and information about them is pursued
retrospectively or backward in time.
[E] Review with secondary
data analysis. A structured analytic review
of existing data (e.g., a meta-analysis or a decision analysis).
[F] Review. A
qualitative review and discussion of previously published literature
without a quantitative synthesis of the data.
[G] Other. Textbooks,
expert opinion, case reports, and other reports not included above.
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