November 2021
◆
Volume 104, Number 5 www.aafp.org/afp American Family Physician 461
Altered mental status (AMS) can present as
changes in consciousness, appearance, behavior,
mood, aect, motor activity, or cognitive func-
tion.
1-3
Recent changes are the focus of this arti-
cle and are approached dierently than chronic
changes. Recent changes occur within seconds to
days and usually pose a more immediate threat
to a patient’s well-being than chronic changes.
2-4
AMS is common and is estimated to account
for 5% of adult emergency department encoun-
ters.
5
Older people are especially susceptible,
as evidenced by their high rates of delirium
(Table 1).
6
Additionally, AMS is associated with
poor patient outcomes, especially when recogni-
tion is delayed.
7,8
e dierential diagnosis for AMS is broad. A
history and physical examination are the corner-
stones of diagnosis, and their ndings guide diag-
nostic testing. Preventive measures can decrease
incidence and are important to use in patients at
high risk. e goal of treatment is to correct the
precipitating cause of the AMS.
2,3,9-11
Causes of Recent AMS
Causes of recent AMS include primary central
nervous system insults, systemic infections, met-
abolic disturbances, toxin exposure, medications,
chronic systemic diseases, and psychiatric condi-
tions (Table 2).
2-4,9,10
Although a single abnormal-
ity may cause the alteration in mental status (e.g.,
opiate overdose), oen the cause is multifactorial
(e.g., dehydration, constipation, high-risk medi-
cation use).
2-4,9,10
Among the most common and important pre-
sentations of AMS is delirium, especially in older
adults who are hospitalized.
6,9
e hallmarks
of delirium are acute, uctuating changes in
Recent-Onset Altered Mental Status:
Evaluation and Management
Brian Veauthier, MD; Jaime R. Hornecker, PharmD; and Tabitha Thrasher, DO
University of Wyoming Family Medicine Residency Program, Casper, Wyoming
Additional content at https:// www.aafp.org/afp/2021/1100/
p461.html.
CME
This clinical content conforms to AAFP criteria for
CME. See CME Quiz on page 449.
Author disclosure: No relevant financial aliations.
Potential precipitating factors for the recent onset of altered mental status (AMS) include primary central nervous system
insults, systemic infections, metabolic disturbances, toxin exposure, medications, chronic systemic diseases, and psychiat-
ric conditions. Delirium is also an important manifestation of AMS, especially in
older people who are hospitalized. Clinicians should identify and treat revers-
ible causes of the AMS, some of which require urgent intervention to minimize
morbidity and mortality. A history and physical examination guide diagnostic
testing. Laboratory testing, chest radiography, and electrocardiography help
diagnose infections, metabolic disturbances, toxins, and systemic conditions.
Neuroimaging with computed tomography or magnetic resonance imaging
should be performed when the initial evaluation does not identify a cause or
raises concern for intracranial pathology. Lumbar puncture and electroenceph-
alography are also important diagnostic tests in the evaluation of AMS. Patients
at increased risk of AMS benefit from preventive measures. The underlying
etiology determines the definitive treatment. When intervention is needed to
control patient behaviors that threaten themselves or others, nonpharmacologic interventions are preferred to medica-
tions. Physical restraints should rarely be used and only for the shortest time possible. Medications should be used only
when nonpharmacologic treatments are ineective. (Am Fam Physician. 2021; 104(5):461-470. Copyright © 2021 American
Academy of Family Physicians.)
Illustration by Todd Buck
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462 American Family Physician www.aafp.org/afp Volume 104, Number 5
◆
November 2021
ALTERED MENTAL STATUS
attention, awareness, and cognition that are not attribut-
able to a neurocognitive disorder. Evidence of a secondary
cause of AMS is oen also present.
6,9
Other features include
sleep disturbances, hallucinations, delusions, inappro-
priate behavior, and emotional instability.
11
Delirium was
reviewed in a previous American Family Physician article.
6
Evaluation
Changes in consciousness, appearance, behavior, mood,
aect, or motor activity are usually apparent by general
observation and interaction with the patient.
URGENT INTERVENTION
AMS can be caused by a life-threatening condition. ere-
fore, the rst step in evaluating the patient is addressing
abnormalities in the airway, breathing, and circulation
(ABCs; Figure 1).
2,3,10,12-18
Once the ABCs have been stabilized, clinicians should
evaluate for other conditions for which rapid intervention
is needed to decrease the risk of morbidity and mortality.
Abnormal vital signs may identify an obvious cause such
as hypothermia, hypoxemia, or a hypertensive emergency,
and such abnormalities should be addressed urgently.
2,3,10
A point-of-care glucose level should be obtained, and
if hypoglycemia is present, glucose should be adminis-
tered immediately unless the patient is at risk of thia-
mine deciency (e.g., alcoholism, gastric bypass surgery).
en thiamine must be administered before glucose to
avoid Wernicke encephalopathy (i.e., AMS, oculomotor
dysfunction, and ataxia due to thia-
mine deciency).
2,3,10
If concern exists for intracranial
hemorrhage (e.g., anticoagulated state,
head trauma) or ischemic stroke (e.g.,
focal abnormalities found during a
neurologic examination), neuroim-
aging should be performed immedi-
ately to determine the next steps for
care. Patients with a hemorrhage may
require urgent surgery, and those with
ischemic stroke can be triaged for
reperfusion.
2,3,10
Patients with status epilepticus
need urgent anticonvulsive therapy
and serum sodium testing. Patients
with suspected sepsis require uid
resuscitation, urgent broad-spectrum
antibiotics aer cultures are obtained,
and source control. Similarly, if
meningitis is suspected, antibiot-
ics at appropriate doses are urgently
required following neuroimaging and lumbar puncture.
If clinical suspicion is high and lumbar puncture will be
delayed, antibiotics should be given empirically. When an
opiate overdose is suspected, naloxone should be adminis-
tered immediately.
2,3,10
TABLE 1
Incidence and Prevalence of Delirium
in Older People
Setting Rate
Incidence during hospital admission
After hip fracture 28% to 61%
After surgery 15% to 53%
During hospitalization (medical inpatients) 3% to 29%
Prevalence
Intensive care unit
With mechanical ventilation 60% to 80%
Without mechanical ventilation 20% to 50%
Hospice 29%
Community (people 85 years or older) 14%
At hospital admission 10% to 31%
Long-term care facility and postacute care 1% to 60%
Adapted with permission from Kalish VB, Gillham JE, Unwin BK.
Delirium in older persons: evaluation and management [published
corrections appear in Am Fam Physician. 2015; 92(6): 430, and Am
Fam Physician. 2014; 90(12): 819]. Am Fam Physician. 2014; 90(3): 152.
BEST PRACTICES IN NEUROLOGY
Recommendations from the Choosing Wisely Campaign
Recommendation
Sponsoring
organization
Do not assume a diagnosis of dementia in an older adult who
presents with an altered mental status and/or symptoms of con-
fusion without assessing for delirium or delirium superimposed
on dementia using a brief, sensitive, validated assessment tool.
American Acad-
emy of Nursing
Do not use antipsychotics as the first choice to treat behavioral
and psychological symptoms of dementia.
American Geriat-
rics Society
Do not use physical or chemical restraints, outside of emer-
gency situations, when caring for long-term care residents with
dementia who display behavioral and psychological symptoms
of distress; instead, assess for unmet needs or environmental
triggers and intervene using nonpharmacologic approaches
initially whenever possible.
American Acad-
emy of Nursing
Source: For more information on the Choosing Wisely Campaign, see https:// www.choosing
wisely.org. For supporting citations and to search Choosing Wisely recommendations relevant
to primary care, see https:// www.aafp.org/afp/recommendations/search.htm.
November 2021
◆
Volume 104, Number 5 www.aafp.org/afp American Family Physician 463
TABLE 2
Selected Causes of Recent Changes
in Mental Status
Central nervous system insults
Demyelinating conditions
Direct brain trauma
(concussion)
Epidural hematoma
Intraparenchymal hemorrhage
Ischemic stroke
Meningoencephalitis
Neoplasm (primary or
metastatic)
Seizure (status epilepticus,
nonconvulsive status epi-
lepticus, or postictal state)
Subarachnoid hemorrhage
Subdural hematoma
Commonly used medications
Antibiotics (fluoroquinolones,
cephalosporins)
Antidepressants (tertiary amine
tricyclics, monoamine oxidase
inhibitors)
Antipsychotics
Benzodiazepines
Beta blockers
Bladder antispasmodics
Dopamine agonists
General anesthetics
Opioid analgesics
Sedatives or hypnotics
Skeletal muscle relaxants
Sympathomimetics
Metabolic disturbances
Hepatic failure
Hypercalcemia
Hypermagnesemia
Hypoadrenalism/
hyperadrenalism
Hypoglycemia/
hyperglycemia
Hyponatremia/
hypernatremia
Hypophosphatemia
Hypothyroidism/
hyperthyroidism
Renal failure
Thiamine deficiency
Systemic diseases or conditions
Arrhythmia
Autoimmune conditions
Constipation
Dehydration
Heart failure
Hypercapnia
Hypertensive emergency
Hypothermia
Hypoxia
Myocardial infarction
Pain
Pancreatitis
Primary psychiatric
conditions
Sleep deprivation
Urinary retention
Systemic infections
Acute viral (influenza,
COVID-19, and others)
Intra-abdominal
Pneumonia
Sepsis
Urinary tract
Toxins
Alcohol (withdrawal or
intoxication)
Illicit substances (with-
drawal or intoxication)
Note: A single etiology may cause the altered mental status, but often
the change results from the additive eect of coexisting conditions.
The conditions in this table are also the secondary causes of delirium,
and often more than one abnormality is causing the delirium.
Information from references 2-4, 9, and 10.
FIGURE 1
Algorithm for the initial evaluation and management
of patients with recent altered mental status.
Information from references 2, 3, 10, and 12-18.
Diagnosis unclear
Neuroimaging if not
already completed;
additional testing†
Magnetic resonance
imaging of the brain if
not already completed
Consider electroen-
cephalography and
lumbar puncture
Diagnosis
unclear
Specialty
consultation
Diagnosis
unclear
Specialty
consultation
Diagnosis
identified
Treat
Diagnosis
identified
Treat
Diagnosis unclearDiagnosis
identified
Treat
Diagnosis
identified
Treat
accordingly
Complete comprehensive history
and physical examination; diag-
nostic studies as indicated per
history and physical examination†
No
Intervene according to the
diagnosis‡ (e.g., bacterial
meningitis, hypoglycemia,
intracranial bleeding,
opiate overdose, sepsis,
status epilepticus, stroke)
Yes
Address, specialty
consultation
Yes
Check vitals, glucose level, and
complete a history and physical exam-
ination; urgent testing as indicated by
history and physical examination*
Time-sensitive diagnosis identified?
No
Evaluate ABCs
Abnormalities with ABCs?
ABCs = airway, breathing, circulation.
*—Examples of urgent testing are neuroimaging to identify or rule out
intracranial hemorrhage, sodium level for acute seizure, blood cultures
for sepsis, and lumbar puncture for meningitis. See text for details.
†—See text for discussion on diagnostic testing options.
‡—See text for details on interventions.
464 American Family Physician www.aafp.org/afp Volume 104, Number 5
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November 2021
TABLE 3
Components of the Mental Status Examination for Identifying Causes of Recent-Onset Altered
Mental Status
Component Definition/content What to assess Sample questions/tests Potential diagnoses if abnormal
General observations
Appearance
and behavior
Body habitus, eye contact,
interpersonal style, style
of dress
Appearance: attention to detail, attire,
distinguishing features (e.g., scars, tattoos),
grooming, hygiene
Behavior: candid, congenial, cooperative,
defensive, engaging, guarded, hostile, irrita-
ble, open, relaxed, resistant, shy, withdrawn
Eye contact: fleeting, good, none, sporadic
NA Disheveled: depression, schizophrenia/psychotic disorder, sub-
stance use
Irritable: anxiety
Paranoid: psychotic disorder
Poor eye contact: depression, psychotic disorder
Provocative: personality disorder or trait
Mood and
aect
Mood: subjective report of
emotional state by patient
Aect: objective observa-
tion of patient’s emotional
state by physician
Body movements/making contact with oth-
ers, facial expressions (tearfulness, smiles,
frowns)
How is your mood?
Have you felt sad/discouraged lately?
Have you felt energized/out of control
lately?
Mood disorder, schizophrenia, substance use
Motor
activity
Facial expressions, move-
ments, posture
Akathisia: excessive motor activity (e.g., pac-
ing, wringing of hands, inability to sit still)
Bradykinesia: psychomotor retardation
(e.g., slowing of physical and emotional
reactions)
Catatonia: immobility with muscular rigidity
or inflexibility
NA Akathisia: anxiety, drug overdose or withdrawal, medica-
tion eect, mood disorder, posttraumatic stress disorder,
schizophrenia
Bradykinesia: depression, medication eect, schizophrenia
Catatonia: schizophrenia/psychotic disorder, severe depression
Cognitive functioning
Attention Ability to focus based on
internal or external priorities
— Count by sevens or fives
Spell a word backward
Attention-deficit/hyperactivity disorder, delirium, mood disorder,
psychotic disorder
Executive
functioning
Ordering and implementa-
tion of cognitive functions
necessary to engage in
appropriate behaviors
Testing each cognitive function involved in
completing a task
Oral Trail-Making Test: ask patient to alter-
nate numbers with letters in ascending order
(e.g., A1, B2, C3)
Delirium, mood disorder, psychotic disorder, stroke
Gnosia Ability to name objects and
their function
— Show patient a common object (e.g., pen,
watch, mobile phone) and ask if they can
identify it and describe how it is used
Stroke
Language Verbal or written
communication
Appropriateness of conversation, rate of
speech (> 100 words per minute is normal;
< 50 words per minute is abnormal), reading
and writing appropriate to education level
NA Rapid or pressured speech: mania
Slow or impoverished speech: delirium, depression, schizophrenia
Inappropriate conversation: personality disorder, schizophrenia
Limited literacy skills: depression
Memory Recall of past events Declarative: recall of recent and past events
Procedural: ability to complete learned
tasks without conscious thought
When is your birthday?
What are your parents’ names?
Where were you born?
Where were you on September 11, 2001?
Ask patient to repeat three words immedi-
ately and again in five minutes
Ask patient to sign their name while answer-
ing unrelated questions (each test must be
tailored to the individual patient)
Short-term deficit: amotivation, attention-deficit/hyperactivity
disorder, inattention, substance use
Long-term deficit: amnesia, dissociative disorder
Orientation Ability of patient to recog-
nize their place in time and
space
Time, space, person What year/month/day/time is it?
What city/building/floor/room are you in?
What is your name? When were you born?
Amnesia, delirium, mania, severe depression
Note: Each of these items may be suggestive of diagnoses, but none is sucient to make a diagnosis without a comprehensive clinical evaluation.
NA = not applicable.
continues
November 2021
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Volume 104, Number 5 www.aafp.org/afp American Family Physician 465
IDENTIFYING THE CAUSE OF AMS
Aer addressing the need for immediate interventions, a
complete history should be obtained to identify the cause of
a patient’s AMS. A surrogate historian is oen needed.
2,3,9,10
Baseline cognitive function should be claried. e tim-
ing of the onset of mental status changes is also import-
ant because abrupt and severe changes indicate a more
serious pathology. e results of numerous observational
assessments and answers to questions asked directly to
the patient (when possible) can oen suggest a cause
1-3,10
(Table 3
1
).
Delirium is common but frequently overlooked, and
is associated with serious medical conditions; therefore,
assessment for delirium should always be considered in
patients with acute AMS, especially in those at high risk
(Table 4).
6,9,11
e Confusion Assessment Method is a widely
used, validated tool to identify delirium with a high sensi-
tivity (94% to 100%) and specicity (90% to 95%)
11
(Table 5
6
).
e 4 A’s test is also a reliable screening tool (sensitivity of
89.7% and specicity of 84.1%) and is available at https://
www.mdcalc.com/4-test-delirium-screening.
11
e ultra-
brief test requires only two questions—What is the day of
the week? and Name the months of the year backwards—and
has a sensitivity of 93% and specicity of 64%. e high
sensitivity makes it useful to rule out delirium when both
questions are answered correctly, but a positive test (i.e.,
incorrect answers) requires conrmation with a tool such as
the Confusion Assessment Method.
11,19
A thorough medication history, including new or recent
changes in prescription medications, over-the-counter
medications, herbal products, and nutritional supplements,
is essential. Consulting the patient’s pharmacy may help
with this task. Comorbid medical conditions, recent surger-
ies or procedures, and the use of alcohol and recreational
drugs can increase the risk of or cause AMS and should be
identied.
2,3,9,10
Other aspects of the history should focus on associ-
ated symptoms or events of infection, trauma, neurologic
changes, and headaches, any of which might identify a pre-
cipitating cause. A complete review of systems may uncover
additional factors (e.g., constipation, urinary retention)
contributing to AMS.
2,3,9,10
PHYSICAL EXAMINATION
e neurologic examination is important to identify AMS
and determine the cause. In addition to the mental status
examination, cranial nerves, motor function, reexes, sen-
sation, and coordination should be evaluated. Focal abnor-
malities can suggest intracranial pathology such as stroke,
neoplasm, or demyelinating conditions. If a patient is exhib-
iting asterixis, it suggests metabolic encephalopathy.
1-3,10,12
TABLE 3
Components of the Mental Status Examination for Identifying Causes of Recent-Onset Altered
Mental Status
Component Definition/content What to assess Sample questions/tests Potential diagnoses if abnormal
General observations
Appearance
and behavior
Body habitus, eye contact,
interpersonal style, style
of dress
Appearance: attention to detail, attire,
distinguishing features (e.g., scars, tattoos),
grooming, hygiene
Behavior: candid, congenial, cooperative,
defensive, engaging, guarded, hostile, irrita-
ble, open, relaxed, resistant, shy, withdrawn
Eye contact: fleeting, good, none, sporadic
NA Disheveled: depression, schizophrenia/psychotic disorder, sub-
stance use
Irritable: anxiety
Paranoid: psychotic disorder
Poor eye contact: depression, psychotic disorder
Provocative: personality disorder or trait
Mood and
aect
Mood: subjective report of
emotional state by patient
Aect: objective observa-
tion of patient’s emotional
state by physician
Body movements/making contact with oth-
ers, facial expressions (tearfulness, smiles,
frowns)
How is your mood?
Have you felt sad/discouraged lately?
Have you felt energized/out of control
lately?
Mood disorder, schizophrenia, substance use
Motor
activity
Facial expressions, move-
ments, posture
Akathisia: excessive motor activity (e.g., pac-
ing, wringing of hands, inability to sit still)
Bradykinesia: psychomotor retardation
(e.g., slowing of physical and emotional
reactions)
Catatonia: immobility with muscular rigidity
or inflexibility
NA Akathisia: anxiety, drug overdose or withdrawal, medica-
tion eect, mood disorder, posttraumatic stress disorder,
schizophrenia
Bradykinesia: depression, medication eect, schizophrenia
Catatonia: schizophrenia/psychotic disorder, severe depression
Cognitive functioning
Attention Ability to focus based on
internal or external priorities
— Count by sevens or fives
Spell a word backward
Attention-deficit/hyperactivity disorder, delirium, mood disorder,
psychotic disorder
Executive
functioning
Ordering and implementa-
tion of cognitive functions
necessary to engage in
appropriate behaviors
Testing each cognitive function involved in
completing a task
Oral Trail-Making Test: ask patient to alter-
nate numbers with letters in ascending order
(e.g., A1, B2, C3)
Delirium, mood disorder, psychotic disorder, stroke
Gnosia Ability to name objects and
their function
— Show patient a common object (e.g., pen,
watch, mobile phone) and ask if they can
identify it and describe how it is used
Stroke
Language Verbal or written
communication
Appropriateness of conversation, rate of
speech (> 100 words per minute is normal;
< 50 words per minute is abnormal), reading
and writing appropriate to education level
NA Rapid or pressured speech: mania
Slow or impoverished speech: delirium, depression, schizophrenia
Inappropriate conversation: personality disorder, schizophrenia
Limited literacy skills: depression
Memory Recall of past events Declarative: recall of recent and past events
Procedural: ability to complete learned
tasks without conscious thought
When is your birthday?
What are your parents’ names?
Where were you born?
Where were you on September 11, 2001?
Ask patient to repeat three words immedi-
ately and again in five minutes
Ask patient to sign their name while answer-
ing unrelated questions (each test must be
tailored to the individual patient)
Short-term deficit: amotivation, attention-deficit/hyperactivity
disorder, inattention, substance use
Long-term deficit: amnesia, dissociative disorder
Orientation Ability of patient to recog-
nize their place in time and
space
Time, space, person What year/month/day/time is it?
What city/building/floor/room are you in?
What is your name? When were you born?
Amnesia, delirium, mania, severe depression
Note: Each of these items may be suggestive of diagnoses, but none is sucient to make a diagnosis without a comprehensive clinical evaluation.
NA = not applicable.
continues
466 American Family Physician www.aafp.org/afp Volume 104, Number 5
◆
November 2021
ALTERED MENTAL STATUS
TABLE 3 (continued)
Components of the Mental Status Examination for Identifying Causes of Recent-Onset Altered
Mental Status
Component Definition/content What to assess Sample questions/tests Potential diagnoses if abnormal
Cognitive functioning (continued)
Praxis Ability to carry out inten-
tional motor acts
Apraxia: inability to carry out motor acts;
deficits may exist in motor or sensory sys-
tems, comprehension, or cooperation
Could you show me how to use this
hairbrush/hammer/pencil?
Delirium, intoxication, stroke
Prosody Ability to recognize the
emotional aspects of
language
— Repeat “Why are you here?” with multiple
inflections (e.g., happy, surprised, excited,
angry, sad) and ask patient to identify the
emotion
Ask the patient to say the same sentence
with each of the above emotional inflections
Mood disorder, schizophrenia
Thought
content
What the patient is thinking Delusions, hallucinations, homicidality,
obsessions, phobias, suicidality
Do you have thoughts or images in your
head that you cannot get out?
Do you have any irrational or excessive fears?
Do you think people are trying to hurt you in
some way?
Are people talking behind your back?
Do you think people are stealing from you?
Do you feel life is not worth living?
Do you see things that upset you?
Do you ever see/hear/smell/taste/feel things
that are not really there?
Have you ever heard or seen something
other people have not?
Have you ever thought about hurting others
or getting even with someone who wronged
you?
Have you ever thought about hurting your-
self? If so, how would you do it?
Have you ever thought the world would be
better o without you?
Delusions: fixed delusions, mania, psychotic disorder/
psychotic depression
Hallucinations: delirium, mania, schizophrenia, severe
depression, substance use
Homicidality: mood disorder, personality disorder, psychotic
disorder
Obsessions: obsessive-compulsive disorder, posttraumatic
stress disorder, psychotic disorder
Phobias: anxiety disorder, posttraumatic stress disorder
Suicidality: depression, posttraumatic stress disorder, sub-
stance use
Thought
processes
Organization of thoughts in
a goal-oriented pattern
Circumferential: patient goes through mul-
tiple related thoughts before arriving at the
answer to a question
Disorganized thoughts: patient moves from
one topic to another without organization
or coherence
Tangential: patient listens to question and
begins discussing related thoughts, but
never arrives at the answer
Generally apparent throughout the
encounter
Anxiety, delirium, depression, schizophrenia, substance use
Visuospatial
proficiency
Ability to perceive and
manipulate objects and
shapes in space
— Ask patient to copy intersecting pentagons
or a three-dimensional cube on paper
Draw a triangle and ask patient to draw the
same shape upside down
Delirium, stroke
Note: Each of these items may be suggestive of diagnoses, but none is sucient to make a diagnosis without a comprehensive clinical evaluation.
NA = not applicable.
Adapted with permission from Norris D, Clark MS, Shipley S. The mental status examination. Am Fam Physician. 2016; 94(8): 636.
November 2021
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Volume 104, Number 5 www.aafp.org/afp American Family Physician 467
ALTERED MENTAL STATUS
Attention to eye and vision abnormalities can also pro-
vide important diagnostic clues. Visual eld defects can
indicate a stroke. Pupillary abnormalities may be present
with substance abuse, stroke, or pending cerebral hernia-
tion. e ability to perform extraocular movements may
dierentiate a suspected comatose patient from one with
a locked-in syndrome. Ophthalmoplegia is an important
nding of Wernicke encephalopathy, and nystagmus can
identify drug intoxication or stroke. Papilledema suggests
increased intracranial pressure.
2,3,10
Examination of the head, ears, nose, and throat should
focus on signs of trauma and infection. When examin-
ing the neck, thyroid abnormalities and meningismus are
important ndings that suggest thyroid disorders and ner-
vous system infections, respectively. Examination of the
heart, lungs, and abdomen can indicate important sys-
temic causes of AMS, such as heart failure, pneumonia, and
decompensated hepatic disease.
2,3,10
Examination of the skin can show signs of chronic sys-
temic disease (e.g., jaundice), systemic infection (e.g., pete-
chiae), or local infection with cellulitis or abscess, or locate
medication patches. A musculoskeletal examination may
identify inamed joints indicating infection or an autoim-
mune condition.
2,3,10
A genitourinary and rectal examination can identify
infection. e rectal examination can show gastrointes-
tinal bleeding or neurologic compromise when tone is
reduced.
2,3,10
TESTING
e history and physical examination guide diagnostic test-
ing; however, the following initial tests can be considered
for all patients with AMS when the diagnosis is not clear:
complete blood count, electrolytes, liver function tests,
serum ammonia, blood urea nitrogen, creatinine, phospho-
rus, magnesium, blood gas analysis, thyroid testing, blood
culture, urinalysis, viral antigen or polymerase chain reac-
tion tests when community prevalence is high, toxicology
screening, chest radiography, and electrocardiography.
2,3,10
Considering that the above tests are noninvasive and rel-
atively inexpensive, they should be used liberally, especially
when the etiology is not clear from the history and physi-
cal examination. Additional tests to consider when initial
evaluation is not diagnostic are adrenal function, erythro-
cyte sedimentation rate, C-reactive protein, extended tox-
icology screening, and serologic testing for autoimmune
disorders.
2,3,10
NEUROIMAGING
Unless the etiology is clear and the risk of intracranial
pathology is low, neuroimaging should be included in the
TABLE 3 (continued)
Components of the Mental Status Examination for Identifying Causes of Recent-Onset Altered
Mental Status
Component Definition/content What to assess Sample questions/tests Potential diagnoses if abnormal
Cognitive functioning (continued)
Praxis Ability to carry out inten-
tional motor acts
Apraxia: inability to carry out motor acts;
deficits may exist in motor or sensory sys-
tems, comprehension, or cooperation
Could you show me how to use this
hairbrush/hammer/pencil?
Delirium, intoxication, stroke
Prosody Ability to recognize the
emotional aspects of
language
— Repeat “Why are you here?” with multiple
inflections (e.g., happy, surprised, excited,
angry, sad) and ask patient to identify the
emotion
Ask the patient to say the same sentence
with each of the above emotional inflections
Mood disorder, schizophrenia
Thought
content
What the patient is thinking Delusions, hallucinations, homicidality,
obsessions, phobias, suicidality
Do you have thoughts or images in your
head that you cannot get out?
Do you have any irrational or excessive fears?
Do you think people are trying to hurt you in
some way?
Are people talking behind your back?
Do you think people are stealing from you?
Do you feel life is not worth living?
Do you see things that upset you?
Do you ever see/hear/smell/taste/feel things
that are not really there?
Have you ever heard or seen something
other people have not?
Have you ever thought about hurting others
or getting even with someone who wronged
you?
Have you ever thought about hurting your-
self? If so, how would you do it?
Have you ever thought the world would be
better o without you?
Delusions: fixed delusions, mania, psychotic disorder/
psychotic depression
Hallucinations: delirium, mania, schizophrenia, severe
depression, substance use
Homicidality: mood disorder, personality disorder, psychotic
disorder
Obsessions: obsessive-compulsive disorder, posttraumatic
stress disorder, psychotic disorder
Phobias: anxiety disorder, posttraumatic stress disorder
Suicidality: depression, posttraumatic stress disorder, sub-
stance use
Thought
processes
Organization of thoughts in
a goal-oriented pattern
Circumferential: patient goes through mul-
tiple related thoughts before arriving at the
answer to a question
Disorganized thoughts: patient moves from
one topic to another without organization
or coherence
Tangential: patient listens to question and
begins discussing related thoughts, but
never arrives at the answer
Generally apparent throughout the
encounter
Anxiety, delirium, depression, schizophrenia, substance use
Visuospatial
proficiency
Ability to perceive and
manipulate objects and
shapes in space
— Ask patient to copy intersecting pentagons
or a three-dimensional cube on paper
Draw a triangle and ask patient to draw the
same shape upside down
Delirium, stroke
Note: Each of these items may be suggestive of diagnoses, but none is sucient to make a diagnosis without a comprehensive clinical evaluation.
NA = not applicable.
Adapted with permission from Norris D, Clark MS, Shipley S. The mental status examination. Am Fam Physician. 2016; 94(8): 636.
468 American Family Physician www.aafp.org/afp Volume 104, Number 5
◆
November 2021
initial assessment of recent AMS.
12-14
Patients with trauma,
anticoagulation, hypertension, hypertensive emergency,
headache, nausea or vomiting, clinical concern for infec-
tion, new-onset seizure, neurologic ndings on examina-
tion, history of cancer, older age, and a known intracranial
process all require imaging. Neuroimaging should be per-
formed in patients who did not previously receive imaging
and in whom initial therapy has failed. In patients with
new-onset delirium, imaging should be considered if there
is no other obvious precipitating cause.
13
Noncontrast computed tomography (CT) of the head is
the initial study for most patients. Noncontrast CT is widely
available, can be completed quickly, identies most pathol-
ogy requiring urgent intervention, and is better tolerated by
patients than magnetic resonance imaging (MRI). If MRI
is available and tolerated by the patient, it can also be the
initial imaging study and is preferred to CT if the progres-
sion of an inammatory process (e.g., multiple sclerosis)
is suspected. Contrast is helpful when infection, tumor,
inammatory pathology, or vascular abnormalities are
suspected.
13-15
MRI should be considered when CT was the initial study
but was not diagnostic; it can detect pathology not evident
on CT such as acute, minor, or posterior circulation isch-
emia, encephalitis, subtle subarachnoid hemorrhages, and
inammatory conditions. MRI may also be indicated to
better dene pathology found on CT.
13-15
LUMBAR PUNCTURE
Lumbar puncture can help identify several causes of AMS,
including meningitis, encephalitis, subarachnoid hem-
orrhage, autoimmune conditions, and metastases to the
subarachnoid space. When there is clinical suspicion for
meningitis, a lumbar puncture is mandatory. Standard
testing of cerebrospinal uid includes a cell count with
dierential, protein, glucose, and culture. Obtaining addi-
tional uid for freezing is prudent because other testing may
be needed.
2,3,20
For patients with immunosuppression, the threshold for
lumbar puncture should be low, and testing for infectious
agents will need to be broadened beyond standard testing.
Consulting an infectious disease specialist should be con-
sidered for these patients.
2,3
Patients with AMS have an increased risk of intracranial
pathology that could result in cerebral herniation from a
lumbar puncture. erefore, neuroimaging should be done
before performing a lumbar puncture.
2,3,21
ELECTROENCEPHALOGRAPHY
Electroencephalography is an important study to rule out
nonconvulsive seizures, which may occur in 8% to 30% of
patients with AMS without an obvious cause.
16
It can also
help diagnose metabolic encephalopathy and infectious
encephalitis.
17,18
A normal electroencephalogram may help
exclude a suspected seizure disorder and support a primary
psychiatric cause of AMS.
PATIENTS WITH UNDERLYING DEMENTIA
Patients with dementia have an increased risk of AMS.
6,9,11
Clinicians are oen challenged to determine if decits are
chronic or new, and substantial eorts should be made to
identify the patient’s baseline status. Clinicians should bal-
ance the risk of unnecessary testing and intervention for
TABLE 5
Confusion Assessment Method
for the Diagnosis of Delirium
(1) Acute onset and fluctuating course
Is there evidence of an acute change in mental status from
the patient’s baseline? Did this behavior fluctuate during the
past day (that is, did it tend to come and go or increase and
decrease in severity)?
(2) Inattention
Does the patient have diculty focusing attention; for exam-
ple, being easily distracted or having diculty keeping track
of what was being said?
(3) Disorganized thinking
Is the patient’s speech disorganized or incoherent; for example,
rambling or irrelevant conversation, unclear or illogical flow of
ideas, or unpredictable switching from subject to subject?
(4) Altered level of consciousness
Overall, how would you rate this patient’s level of conscious-
ness: alert (normal); vigilant (hyperalert); lethargic (drowsy,
easily aroused); stupor (dicult to arouse); coma (unarousable)?
Note: The diagnosis of delirium requires a present/abnormal rating
for criteria 1 and 2, and either 3 or 4.
Adapted with permission from Kalish VB, Gillham JE, Unwin BK.
Delirium in older persons: evaluation and management [published
corrections appear in Am Fam Physician. 2015; 92(6): 430, and Am
Fam Physician. 2014; 90(12): 819]. Am Fam Physician. 2014; 90(3): 155.
TABLE 4
Common Risk Factors for Altered Mental
Status or Delirium
Age older than 65 years
Anesthesia
Baseline cognitive impairment
Baseline poor functional status
Change in environment
Constipation and/or urinary
retention
Dehydration
Depression
History of alcohol misuse
History of delirium
Intensive care unit stay
Malnutrition
Medical illnesses
(e.g., heart, lung, liver,
kidney)
Polypharmacy
Sleep deprivation
Social isolation
Surgery
Tethers (e.g., urinary
catheter, intravenous
tubing)
Visual or hearing
impairment
Information from references 6, 9, and 11.
November 2021
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Volume 104, Number 5 www.aafp.org/afp American Family Physician 469
ALTERED MENTAL STATUS
chronic situations the clinician may be unaware of vs. miss-
ing a new treatable condition causing AMS. Advance direc-
tives and input from the family can help guide evaluation
and treatment decisions.
A common pitfall for patients with dementia who are in a
care facility is inappropriately attributing AMS to a urinary
tract infection. Many patients who are institutionalized
have asymptomatic bacteriuria, and treatment is not indi-
cated unless a urinary infection with symptoms is present.
22
Management should focus on identifying other causes for
the patient’s AMS.
Prevention
When patients are at risk of AMS, particularly
for delirium, nonpharmacologic preventive mea-
sures can decrease incidence, especially in those
who are hospitalized.
6,9,11
e use of multiple mea-
sures through a multidisciplinary team approach
is most eective. ere is no convincing evidence
to support the use of medications to prevent AMS
or delirium.
6,9,11
Treatment
Denitive therapy for AMS is treatment of the
underlying causes or the removal of precipitat-
ing agents. However, when patients’ behaviors
threaten themselves or others before a reversible
cause can be identied or fully treated, interven-
tion is needed to avoid harm. In these situations,
nonpharmacologic interventions are the treat-
ment of choice.
2,3,6,10,11
NONPHARMACOLOGIC TREATMENTS
Reassurance and use of de-escalation techniques by sta,
family, or friends can be eective. Reducing articial light-
ing and other environmental stimuli such as monitoring
alarms can also help calm patients. A family member or
assigned sta can stay at the patient’s bedside to ensure
that patients do not harm themselves. Additional mea-
sures include those used for AMS or delirium prevention
(Table 6
6,9,11
).
Physical restraints are not considered standard inter-
ventions and should rarely be used, and then only as a last
resort and for the shortest time possible.
2,6,9-11
SORT: KEY RECOMMENDATIONS FOR PRACTICE
Clinical recommendation
Evidence
rating Comments
Delirium is common but frequently overlooked, and it is associated with serious medical
conditions; therefore, screening should always be considered in patients with acute AMS,
especially in those at high risk.
6,9,11
C Systematic review, nar-
rative review, and expert
consensus
Unless the etiology is clear and the risk of intracranial pathology is low, neuroimaging
should be part of the initial assessment of recent changes in mental status. Noncontrast
computed tomography of the head is the initial study for most patients.
12-14
C Expert consensus
Electroencephalography is an important study to rule out nonconvulsive seizures, which
may occur in 8% to 30% of patients with AMS without an obvious cause.
16
C Evidence-based review
When patients are at risk of AMS or delirium, nonpharmacologic preventive measures
decrease incidence, especially in those who are hospitalized. The use of multiple measures
through a multidisciplinary team approach is most eective.
6,9,11
B Systematic review, narra-
tive reviews, and expert
consensus
Medication to manage behaviors associated with AMS should be used only when nonphar-
macologic measures are ineective, and then only when it is essential to control behavior.
Studies evaluating the eectiveness of medications used for their sedative eects yield
conflicting results, and these medications may cause harm due to adverse eects.
11,23,24
C Systematic reviews,
cohort study, and expert
consensus
AMS = altered mental status.
A = consistent, good-quality patient-oriented evidence; B = inconsistent or limited-quality patient-oriented evidence; C = consensus, disease-oriented
evidence, usual practice, expert opinion, or case series. For information about the SORT evidence rating system, go to https:// www.aafp.org/afpsort.
TABLE 6
Measures to Prevent Delirium
Adequate hydration
Adequate nutrition
Adequate oxygenation
Avoid constipation
Avoid tethering (intravenous
lines, monitors, Foley catheter)
Cognitively stimulating activities
Early mobilization
Ensure patient has assistive
devices (eyeglasses, hearing
aids, mobility devices)
Geriatric specialty consultation
Infection prevention
Limit psychoactive medications
Pain management
Presence of family and caretakers
Orientation (accurate calendars
and clocks, and appropriate
lighting; reorientation by sta and
family)
Sleep enhancement measures
(avoid nighttime disturbances, use
appropriate lighting, reduce noise
at night)
Information from references 6, 9, and 11.
470 American Family Physician www.aafp.org/afp Volume 104, Number 5
◆
November 2021
ALTERED MENTAL STATUS
MEDICATION
Medication to manage behaviors associated with AMS
should be used only when nonpharmacologic measures are
not eective, and then only when it is essential to control
behavior. Studies evaluating the eectiveness of medications
used for their sedative eects yield conicting results and
may cause harm due to adverse eects.
11,23,24
Antipsychotics
have historically been used o-label to treat delirium; how-
ever, a recent systematic review does not support the use of
these agents in hospitalized adults with delirium.
24
Anti-
psychotics also carry a U.S. Food and Drug Administration
boxed warning about an increased risk of death when used
in older adults with dementia-related psychosis.
Benzodiazepines should generally be avoided unless
they are being used to treat alcohol withdrawal or seizures
because they may worsen delirium. For any agent, the low-
est eective dose for the minimum time necessary should
be used. Medications used when nonpharmacologic modal-
ities fail are listed in eTable A.
Data Sources: PubMed (including use of the Clinical Queries
feature), the Cochrane Database of Systematic Reviews, Essential
Evidence Plus, and UpToDate were searched using the key terms
altered mental status and encephalopathy. Also searched were
specific etiologies of altered mental status. Search dates: Janu-
ary 19 to February 22, 2021, and August 20, 2021.
The Authors
BRIAN VEAUTHIER, MD, is the program director of the Univer-
sity of Wyoming Family Medicine Residency Program, Casper.
JAIME R. HORNECKER, PharmD, BCPS, BCACP, CDCES,
DPLA, is a clinical professor at the University of Wyoming
School of Pharmacy and the Family Medicine Residency
Program.
TABITHA THRASHER, DO, is the program director of the
University of Wyoming Geriatric Fellowship and a clinical
assistant faculty member at the University of Wyoming Family
Medicine Residency Program.
Address correspondence to Brian Veauthier, MD, 1522 E. A St.,
Casper, WY 82601 (email: bveauthi@ uwyo.edu). Reprints are
not available from the authors.
References
1. Norris D, Clark MS, Shipley S. The mental status examination. Am Fam
Physician. 2016; 94(8): 635-641. Accessed July 14, 2021. https:// www.
aafp.org/afp/2016/1015/p635.html
2. Smith AT, Han JH. Altered mental status in the emergency department.
Semin Neurol. 2019; 39(1): 5-19.
3. Douglas VC, Josephson SA. Altered mental status. Continuum (Minneap
Minn). 2011; 17(5 Neurologic Consultation in the Hospital): 967-983.
4. Erkkinen MG, Berkowitz AL. A clinical approach to diagnosing enceph-
alopathy. Am J Med. 2019; 132(10): 1142-1147.
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etiology in the ED. Am J Emerg Med. 2002; 20(7): 613-617.
6. Kalish VB, Gillham JE, Unwin BK. Delirium in older persons: evaluation
and management [published corrections appear in Am Fam Physician.
2015; 92(6): 430, and Am Fam Physician. 2014; 90(12): 819]. Am Fam Phy-
sician. 2014; 90(3): 150-158. Accessed July 14, 2021. https:// www.aafp.
org/afp/2014/0801/p150.html
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patients and the risk of postdischarge mortality, institutionalization, and
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10. Wilber ST, Ondrejka JE. Altered mental status and delirium. Emerg Med
Clin North Am. 2016; 34(3): 649-665.
11. Oh ES, Fong TG, Hshieh TT, et al. Delirium in older persons: advances
in diagnosis and treatment. JAMA. 2017; 318(12): 1161-1174.
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13. Luttrull MD, Boulter DJ, Kirsch CFE, et al.; Expert Panel on Neurologi-
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14. Salmela MB, Mortazavi S, Jagadeesan BD, et al.; Expert Panel on Neu-
rologic Imaging. ACR Appropriateness Criteria cerebrovascular disease.
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16. Zehtabchi S, Abdel Baki SG, Malhotra S, et al. Nonconvulsive seizures
in patients presenting with altered mental status: an evidence-based
review. Epilepsy Behav. 2011; 22(2): 139-143.
17. Hemphill J III, Smith S, Josephson S, et al. Severe acute encephalop-
athies and critical weakness. In: Jameson JL, Kasper DL, Fauci AS, et
al., eds. Harrison’s Principles of Internal Medicine, 20e. McGraw-Hill;
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18. Young GB. Metabolic and inflammatory cerebral diseases: electrophys-
iological aspects. Can J Neurol Sci. 1998; 25(1): S16-S20.
19. Fick DM, Inouye SK, Guess J, et al. Preliminary development of an
ultrabrief two-item bedside test for delirium. J Hosp Med. 2015; 10(10):
645-650.
20. Shahan B, Choi EY, Nieves G. Cerebrospinal fluid analysis [published
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aafp.org/afp/2021/0401/p422.html
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head before lumbar puncture in adults with suspected meningitis.
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November 2021
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Volume 104, Number 5 www.aafp.org/afp American Family Physician 470A
ALTERED MENTAL STATUS
eTABLE A
Medications Used in the Management of Agitation or Delirium When Nonpharmacologic
Interventions Fail
Drug Dose* and route
Maximum
daily dosage Onset Treatment considerations
Antipsychotics
Droperidol 2.5 to 10 mg IV 20 mg 3 to 10 minutes FDA boxed warning: increased mortality
in older patients with dementia-related
psychosis
Adverse eects: extrapyramidal symptoms,
QTc prolongation, increased risk of falls,
aspiration
5 to 10 mg IM 20 mg 3 to 10 minutes
Haloperidol 0.5 to 1 mg orally every
four to six hours
30 mg 15 to 30 minutes
0.5 to 1 mg IM/IV every
30 to 60 minutes
30 mg 5 to 20 minutes
Olanzapine (Zyprexa) 5 to 10 mg IM 30 mg 15 minutes
2.5 to 5 mg orally 20 mg 30 to 60 minutes
Quetiapine (Seroquel) 12.5 to 25 mg orally 150 mg 15 to 45 minutes
Ziprasidone (Geodon) 5 to 10 mg IM 40 mg 15 minutes
Benzodiazepines
Lorazepam (Ativan) 0.5 to 2 mg IM/IV/orally 10 mg 3 to 5 minutes May worsen delirium
Generally reserved for alcohol withdrawal
and seizures
Midazolam 2 to 5 mg IM/IV 20 mg 1 to 10 minutes
Ketamine 0.5 to 1 mg per kg IV 200 mg 0.5 minutes Use caution in patients with cardio-
vascular disease; may increase blood
pressure and heart rate
4 to 5 mg per kg IM 500 mg 3 to 4 minutes
FDA = U.S. Food and Drug Administration; IM = intramuscularly; IV = intravenously.
*—Smaller initial doses repeated as needed are preferred over larger initial doses or dose escalation, especially in older adults.
Information from:
Douglas VC, Josephson SA. Altered mental status. Continuum (Minneap Minn). 2011; 17(5 Neurologic Consultation in the Hospital): 967-983.
Kalish VB, Gillham JE, Unwin BK. Delirium in older persons: evaluation and management [published corrections appear in Am Fam Physician.
2015; 92(6): 430, and Am Fam Physician. 2014; 90(12): 819]. Am Fam Physician. 2014; 90(3): 150-158. Accessed July 14, 2021. https:// www.aafp.org/
afp/2014/0801/p150.html
Lexicomp Online, Pediatric and Neonatal Lexi-Drugs Online. UpToDate, Inc.; 2021. Accessed August 23, 2021. https:// online.lexi.com
Linder LM, Ross CA, Weant KA. Ketamine for the acute management of excited delirium and agitation in the prehospital setting. Pharmacotherapy.
2018; 38(1): 139-151.
Mattison MLP. Delirium. Ann Intern Med. 2020; 173(7): ITC49-ITC64.
Oh ES, Fong TG, Hshieh TT, et al. Delirium in older persons: advances in diagnosis and treatment. JAMA. 2017; 318(12): 1161-1174.
Smith AT, Han JH. Altered mental status in the emergency department. Semin Neurol. 2019; 39(1): 5-19.
Wilber ST, Ondrejka JE. Altered mental status and delirium. Emerg Med Clin North Am. 2016; 34(3): 649-665.
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