Alcohol Withdrawal - Epidemiology, Clinical Manifestations, Course, Assessment, and Diagnosis - UpToDate

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Alcohol withdrawal: Epidemiology, clinical manifestations, course, assessment, and diagnosis
Author: Christine Pace, MD, MSc

Section Editor: Richard Saitz, MD, MPH, FACP, DFASAM
Deputy Editor: Richard Hermann, MD
All topics are updated as new evidence becomes available and our peer review process is complete.
Literature review current through: Oct 2017. | This topic last updated: Jul 20, 2017.
INTRODUCTION — Minor manifestations of alcohol withdrawal include anxiety, agitation, restlessness,

insomnia, tremor, diaphoresis, palpitations, headache, and alcohol craving, and often loss of appetite, nausea,
and vomiting. Moderate and severe withdrawal syndromes can include hallucinations, seizures, or delirium
tremens; the latter two can be life-threatening.
Most people with alcohol use disorder do not experience significant withdrawal when they stop or reduce
drinking, but withdrawal is common among medical and surgical inpatients and in emergency departments.
This topic reviews the clinical manifestations, course, assessment and diagnosis of alcohol withdrawal.
Ambulatory and inpatient management of alcohol withdrawal syndromes are reviewed separately. (See
"Medically supervised alcohol withdrawal in the ambulatory setting" and "Management of moderate and severe
alcohol withdrawal syndromes".)
The epidemiology, pathogenesis, clinical manifestations, course, screening, assessment, diagnosis, and
treatment of risky drinking and alcohol use disorder are also reviewed separately. (See "Risky drinking and
alcohol use disorder: Epidemiology, pathogenesis, clinical manifestations, course, assessment, and diagnosis"
and "Psychosocial treatment of alcohol use disorder" and "Pharmacotherapy for alcohol use disorder".)
EPIDEMIOLOGY — The prevalence of alcohol use disorder (alcohol abuse and dependence in DSM-IV) is
estimated to be 14 percent in community based samples in the United States [1] and as high as 40 percent
among hospitalized patients [2]. Approximately half of patients with alcohol use disorder experience alcohol
withdrawal when they reduce or stop drinking [3,4].
Predictors for the development of withdrawal in patients with alcohol use disorder include consumption of more
drinks per occasion and the presence of more alcohol-related problems [3,5,6] and is likely to be related to
greater physiologic dependence. Tools to assess for alcohol use disorder such as the Alcohol Use Disorders
Identification Test and Alcohol Use Disorders Identification Test – (Piccinelli) Consumption (AUDIT-PC) can be
used to identify these risk factors in a standardized fashion; for example, one study showed that an AUDIT-PC
score of four or more was 91 percent sensitive and 89.7 percent specific for the development of alcohol
withdrawal [5]. Patients who have not had any withdrawal symptoms more than 24 hours after cessation are
unlikely to develop such symptoms.
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Though alcohol withdrawal is usually mild, an estimated 20 percent of patients experience more advanced
manifestations such as hallucinosis, seizures, and delirium tremens [7]. Seizures and delirium tremens, which
are sometimes grouped as “severe alcohol withdrawal syndrome,” are a frequent reason for both general
inpatient and intensive care unit admissions; for example, alcohol withdrawal syndrome was found to account for
more than 10 percent of intensive care unit admissions to a Detroit hospital [8]. The development of alcohol
withdrawal contributes to the morbidity, mortality, and length of stay of patients admitted to the hospital for other
primary medical or surgical indications [4,9,10].
Genetic polymorphisms predictive of alcohol withdrawal among patients with alcohol use disorder are under
investigation [11].
PATHOPHYSIOLOGY — The pathophysiology of alcohol withdrawal syndrome is reviewed separately. (See

"Management of moderate and severe alcohol withdrawal syndromes", section on 'Pathophysiology'.)
CLINICAL PRESENTATION AND COURSE — Without treatment, symptoms of alcohol withdrawal generally
begin within 6 to 24 hours of the last drink or a sudden reduction in chronic alcohol drinking [12]. The onset and
duration of withdrawal symptoms vary based on the severity of the syndrome (table 1). Symptoms may emerge
before the blood alcohol level has returned to zero.
Mild withdrawal — Symptoms of early or mild alcohol withdrawal include anxiety, minor agitation, restlessness,
insomnia, tremor, diaphoresis, palpitations, headache, and alcohol craving. Patients often experience loss of
appetite, nausea, and vomiting. Physical signs include sinus tachycardia (heart rates may exceed 120
beats/min), systolic hypertension, hyperactive reflexes, and tremor [7,12]. Symptoms of mild withdrawal resolve
within one to two days.
Some patients with mild withdrawal will go on to develop additional manifestations of withdrawal, such as alcohol
hallucinosis, withdrawal seizures, or withdrawal delirium (delirium tremens). The latter are sometimes considered
together as “severe alcohol withdrawal syndrome.” Patients can have withdrawal seizures or hallucinosis without
manifesting symptoms of mild withdrawal.
Alcohol hallucinosis — Alcohol hallucinosis typically begins within 12 to 24 hours after the last drink and
resolves in another 24 to 48 hours. The risk for alcohol hallucinosis may be related to genetic factors [13] and/or
decreased thiamine absorption [14].
Alcoholic hallucinosis refers to hallucinations that are usually visual and commonly involve seeing insects or
animals in the room; auditory and tactile phenomena may also occur. In contrast to withdrawal delirium, alcoholic
hallucinosis is not associated with altered cognition such as disorientation, and vital signs are usually normal.
Withdrawal seizures — Alcohol withdrawal-related seizures occur within 6 to 48 hours after drinking either
stops or is significantly reduced. Such seizures occur in 10 to 30 percent of patients in alcohol withdrawal [15-
17]. Risk factors may include concurrent withdrawal from benzodiazepines or other sedative-hypnotic drugs;
other risk factors include relatively low potassium and platelet levels [4]. It has been observed that the risk of
seizures increases as patients undergo repeated withdrawals, which has been described as the “kindling effect.”
Genetic determinants are under investigation [18].
Seizures are typically generalized tonic-clonic convulsions, occurring singly or in clusters of two or three. In a
study, 60 percent of patients with seizures related to alcohol cessation had multiple seizures, and in 85 percent
of these patients, the recurrence took place within the first six hours [19]. Though it is rare for alcohol withdrawal
seizures to develop into status epilepticus, alcohol withdrawal is implicated in a sizable minority of status
epilepticus cases [12,20]. The presentation and treatment of convulsive status epilepticus are reviewed
separately. (See "Convulsive status epilepticus in adults: Classification, clinical features, and diagnosis" and
"Convulsive status epilepticus in adults: Treatment and prognosis".)
Withdrawal delirium — Withdrawal delirium (also known as delirium tremens or “DTs”) is a rapid-onset,
fluctuating disturbance of attention and cognition, sometimes with hallucinations, in the presence of alcohol
withdrawal [21]. In its most severe manifestation, withdrawal delirium is accompanied by agitation and signs of
extreme autonomic hyperactivity, including fever, severe tachycardia, hypertension, and drenching sweats.
Withdrawal delirium typically begins between 72 and 96 hours after the patient’s last drink and has been reported
to occur in 1 to 4 percent of patients hospitalized for alcohol withdrawal [22].
Genetic risk factors for delirium are under evaluation [23]. Retrospective studies have suggested the following
clinical risk factors though not all are borne out consistently across data [2,4,22,24-27]:
● Prior withdrawal delirium.
● Specific signs of chronic alcohol intake, chronic illness including cirrhosis and/or malnutrition, including low
or low-normal platelet, potassium, and magnesium levels.
● Development of alcohol withdrawal with a positive blood alcohol level.
● Clinical Institute Withdrawal Assessment Scale for Alcohol – Revised scores above 15 (especially in
association with a systolic blood pressure >150 mm Hg or a heart rate >100 beats per minute).
● Increasing age.
● Recent misuse of other agents which depress the central nervous system, such as benzodiazepines.
● Concurrent illness, such as respiratory, cardiac, or gastrointestinal disease.
Mortality rates from withdrawal delirium were historically as high as 20 percent. With appropriate medical
management, the mortality rate is between 1 and 4 percent, depending on the setting [12,22]. Death has been
attributed to cardiovascular complications, hyperthermia, aspiration, and severe fluid and electrolyte disorders.
Severe alcohol withdrawal syndrome — Although definitions vary, withdrawal seizures and withdrawal delirium
are often grouped together as severe alcohol withdrawal syndrome. A meta-analysis of studies examining
predictors of seizures, withdrawal delirium, or either found that a prior episode of seizure or delirium tremens was
predictive of the same complication developing later, a prior seizure did not consistently predict the occurrence of
withdrawal delirium, and vice-versa. Other than these factors, only low or low-normal potassium and platelet
levels were consistently predictive of the development of a manifestation of severe withdrawal across patient
populations studied.
Evidence for other predictors was not borne out in the meta-analysis [4], though some predictors were studied in
small samples only and the heterogeneity of studies limited conclusions. Similarly, although models to predict
risk of severe withdrawal have been proposed, no tools for clinicians to predict risk have been validated across
multiple populations or are in widespread use [2,25].
ASSESSMENT — Key goals in the assessment of a patient experiencing possible alcohol withdrawal are to:
● Evaluate for acute medical problems (eg, gastritis, pancreatitis, hepatitis, pneumonia) that could account
entirely for his or her presentation, exacerbate symptoms of alcohol withdrawal, and/or explain why the
patient ceased or reduced alcohol use.
● Determine the level of care needed for appropriate withdrawal management. Options include:
• Outpatient management, with ambulatory visits as needed.
• Inpatient management in an addiction treatment setting:
- Nonmedically managed (described by the addiction treatment system as level III.2). Support is
primarily social, by counselors or peers.
- Medically managed (described as level III.7). Nurses are on site 24 hours per day to monitor
patients. Clinicians provide consultation services, but are not on site 24 hours per day.
• Inpatient management in a medical (hospital) setting, where more intensive medical monitoring and
clinician assessment are available, including:
- General inpatient unit

- Intensive care unit (ICU)
• Steps to determine the level of care are as follows:
- Determine the likelihood of severe withdrawal, including seizures and delirium tremens; patients
likely to experience these complications require withdrawal management in a hospital setting, either
in a standard inpatient ward or the ICU depending on the clinical presentation and history (table 2).
Hospital policies regarding ICU admissions for this patient population may vary based on the
hospital setting, staffing model, and addiction expertise.
- Evaluate for acute or chronic medical comorbidities that could increase the morbidity and mortality
of alcohol withdrawal. Patients with complex chronic conditions, such as insulin-dependent
diabetes or hypertension on multiple medications, require at the very least management in a
medically-managed detoxification program. Patients with unstable chronic conditions or acute
conditions (such as pneumonia or pancreatitis) require additional medical monitoring in an inpatient
hospital setting. ICU monitoring may be required (table 2).
- Determine the likelihood of withdrawal from two or more substances. These patients require
management in an inpatient medically managed setting, rather than an outpatient setting; however,
if the two previous criteria do not apply, an acute treatment setting such as a level III.7
detoxification program may suffice, rather than a hospital setting.
- Determine the degree of social support in the home. Patients with limited social support who do not
need monitoring by a nurse or physician may benefit from inpatient withdrawal management in a
nonmedically managed detoxification program.
Patient history — Key features of the history include:
● History of alcohol and other drug use, including substances used, the time of last use, the duration of use,
the quantity and frequency of use, and the method of use (eg, oral, intravenous, inhaled, intranasal).
● For alcohol in particular, a detailed history of prior withdrawal experiences is important. A detailed alcohol
history helps determine the expected timeframe for emergence of withdrawal symptoms and the potential for
severe withdrawal syndromes.
● Substance use treatment history, including which treatments (such as inpatient or outpatient programs, 12-
step programs such as Alcoholics Anonymous, or medications such as naltrexone or acamprosate) have
been helpful or not helpful in the past.
● Mental health history. Comorbid mental illness may impact the patient’s withdrawal presentation.
Additionally, patients with mental illness may benefit from integrated treatment post-withdrawal care that is
focused on the dual diagnosis population. (See "Pharmacotherapy for co-occurring schizophrenia and
substance use disorder", section on 'Integrated treatment'.)
● Social history. Identification of social supports (such as a supportive family member who can encourage
abstinence and potentially dispense withdrawal medication) and barriers (such as homelessness) in the
patient’s life can also help determine the most appropriate further treatment (for example, inform a decision
between residential versus outpatient programs).
● Recent physical symptoms. A careful review of systems is important to identify medical problems that could
contribute to the patient’s presentation or worsen the morbidity of withdrawal. Once patients are preoccupied
by uncomfortable withdrawal symptoms or develop altered mental status related to their withdrawal, they
may not readily volunteer these symptoms.
Physical examination — The patient should receive a comprehensive physical examination to evaluate for
concurrent or alternative medical diagnoses that contribute to his or her clinical presentation, assess for any
chronic complications of alcohol use disorder, and determine the severity of the withdrawal. It should include a
thorough exam of the cardiovascular, pulmonary, and gastrointestinal systems, with additional attention to any
signs of cirrhosis; it should also include as a mental status exam and complete neurologic examination. The
neurologic exam must include assessment of gait and oculomotor function to rule out concurrent Wernicke
encephalopathy, which requires specific treatment. (See "Wernicke encephalopathy".)
Laboratory and other testing — Laboratory testing typically includes:
● A complete blood count.
● Serum electrolytes, including potassium, magnesium, and phosphate.
● Glucose.
● Creatinine.
● Liver function tests.
● Amylase and lipase.
● Blood alcohol level.
● Urine drug testing, which should include testing for benzodiazepines, cocaine, and opioids. The opioid test
should include not only opiates, which include heroin, codeine and morphine, but also buprenorphine,
oxycodone, methadone, and fentanyl, all of which are of increasing importance in the current opioid
epidemic.
● Urine human chorionic gonadotropin test for premenopausal women.
An electrocardiogram is suggested for patients over 50 years or if there is a history of cardiac problems.
Imaging — A head computerized tomography scan to rule out contributing or alternative pathology is indicated
for patients who present with a first seizure or for a presentation that is different from prior presentations or from
a typical withdrawal seizure. Mental status changes in patients with suspected alcohol withdrawal may or may
not require head imaging; imaging is important if the mental status changes are not typical for those associated
with alcohol withdrawal (for example, if the patient is sedated) and/or if there is any suspicion for head trauma.
A chest radiograph may be indicated for patients with chronic respiratory problems, respiratory symptoms, an
abnormal lung exam, or sedated mental status. An abdominal ultrasound or computerized tomography scan may
be indicated in patients reporting abdominal pain or with abnormal pancreatic or liver function tests.
CIWA-Ar scale — Although several symptom severity scales exist for alcohol withdrawal, the Clinical Institutes
Withdrawal Assessment Scale for Alcohol (CIWA-Ar) has been the most studied and is the most widely used
(table 3).
The CIWA scale can help determine the need for medically supervised withdrawal management. Patients with an
alcohol use disorder who have not had a drink for five days or more and have a CIWA score of less than 10 will
in most cases not need management.
For patients with a history of recent alcohol use who are able to communicate symptoms to their medical
providers, the CIWA scale can be used to guide symptom-triggered treatment. Randomized clinical trials have
shown that use of the scale in the treatment of withdrawal reduced the total amount of benzodiazepines needed
and shortened duration of treatment [28,29]. (See "Management of moderate and severe alcohol withdrawal
syndromes".)
The CIWA should not be used to diagnose alcohol withdrawal; the scale does not include the prerequisite of
heavy or prolonged alcohol use and the constellation of symptoms it tracks are nonspecific. CIWA should not be
used to guide treatment when an alcohol history has not been obtained and/or the patient cannot communicate
symptoms; this could lead to inappropriate and potentially risky use of benzodiazepines to treat manifestations of
illnesses other than withdrawal [30].
DIAGNOSIS
DSM-5 diagnostic criteria — DSM-5 diagnostic criteria for alcohol withdrawal are as follows [21]:
● A. Cessation of (or reduction in) alcohol use that has been heavy and prolonged.
● B. Two (or more) of the following, developing within several hours to a few days after the cessation of (or
reduction in) alcohol use described in criterion A:
• 1. Autonomic hyperactivity
• 2. Increased hand tremor
• 3. Insomnia
• 4. Nausea or vomiting
• 5. Transient visual, tactile, or auditory hallucinations or illusions
• 6. Psychomotor agitation
• 7. Anxiety
• 8. Generalized tonic-clonic seizures
● C. The signs or symptoms in criterion B cause clinically significant distress or impairment in social,
occupational, or other important areas of functioning.
● D. The signs or symptoms are not attributable to another medical condition and are not better explained by
another mental disorder, including intoxication or withdrawal from another substance.
Differential diagnosis — Alcohol withdrawal has a broad differential diagnosis depending on the clinical
presentation.
Early withdrawal symptoms — The differential diagnosis for symptoms associated with mild withdrawal
includes a wide range of conditions associated with central nervous system and/or autonomic hyperactivity. In a
patient with a history of recent heavy alcohol use, alcohol withdrawal is a leading diagnosis, but a broad
differential is important both in cases when patients are not able to give a reliable history and in cases were
comorbid medical conditions exacerbate the presentation of withdrawal. The differential should include:
● Infection, such as pneumonia, meningitis, encephalitis, or spontaneous bacterial peritonitis – The presence
of a fever should prompt the clinician to assume that an infection is present until proven otherwise. A history
of focal symptoms such as a cough, sweats, rigors, or abdominal pain, a physical examination with signs of
possible infection, such as abnormal breath sounds, and the presence of leukocytosis on a complete blood
count are clues that an infection may be the cause of a patient’s symptoms. When suspected, imaging,
blood cultures, and other testing can help identify an infectious source. (See "Evaluation of infection in the
older adult".)
● Acute coronary syndrome – The patient’s history and cardiac risk factors are clues to the presence of acute
coronary syndrome. An electrocardiogram and testing for cardiac biomarkers are important initial testing
when acute coronary syndrome is suspected. (See "Overview of the acute management of non-ST elevation
acute coronary syndromes".)
● Pulmonary embolus – Pulmonary embolus is an important consideration in hospitalized or postoperative

patients who develop unexplained tachycardia. History should probe for dyspnea, pleuritic pain, cough, or
symptoms of a deep venous thrombosis. A physical exam should look for dyspnea, abnormal lung sounds,
jugular venous distention, or limb swelling. Oxygen saturation and electrocardiogram testing should be
performed; further testing is based on the pretest likelihood of pulmonary embolus. (See "Clinical
presentation, evaluation, and diagnosis of the nonpregnant adult with suspected acute pulmonary
embolism".)
● Hyperthyroidism – The history may give clues as to the likelihood of hyperthyroidism, rather than alcohol
withdrawal; symptoms of hyperthyroidism will usually have a more prolonged time course than alcohol
withdrawal (ie, weeks to months) and may be associated with other symptoms such as menstrual
abnormalities or weight loss. The exam may show typical features of hyperthyroidism such as lid lag. A low
thyroid-stimulating hormone level is diagnostic of hyperthyroidism. (See "Overview of the clinical
manifestations of hyperthyroidism in adults".)
● Anxiety and/or panic disorder – Anxiety and/or panic disorder can be difficult to distinguish from alcohol
withdrawal in patients with a history of heavy alcohol use. Anxiety about withdrawal symptoms can intensify
the presentation of alcohol withdrawal. The patient’s history and course are the most helpful in distinguishing
the conditions when they are not comorbid; in particular, panic attacks are of shorter duration than
symptoms of alcohol withdrawal, typically lasting up to an hour rather than days, and gastrointestinal
symptoms may be less dominant.
● Intoxication – Intoxication with stimulants such as cocaine, methamphetamine, amphetamines, or synthetic

cathinones (such as “bath salts”) can resemble aspects of alcohol withdrawal, including the agitation,
tachycardia, hypertension, and in some cases, hallucinations. Physical examination of patients with
stimulant intoxication may reveal mydriasis and stereotyped behaviors such as picking, which are less
common in early alcohol withdrawal. The patient’s substance use history and urine drug testing can
distinguish the conditions, though notably many synthetic cathinones are not detectable in standard drug
testing.
● Withdrawal from other sedating substances – Withdrawal from benzodiazepines, opioids, and other sedating
substances may resemble mild alcohol withdrawal. Benzodiazepine withdrawal in particular can be virtually
indistinguishable from alcohol withdrawal, although tachycardia and hypertension are typically more
pronounced in the latter.
Opioid withdrawal may be associated with mild hypertension, tachycardia, tremor, diaphoresis, nausea, and
vomiting, but on exam, patients have pronounced mydriasis, piloerection, and rhinorrhea, which are absent
in alcohol withdrawal. Most patients with opioid withdrawal are also particularly troubled by muscle and
abdominal cramps, which are less pronounced in alcohol withdrawal. (See "Opioid withdrawal: Clinical
manifestations, course, assessment, and diagnosis" and "Medically supervised opioid withdrawal during
treatment for addiction".)
To rule out withdrawal from another substance, the patient’s history, urine drug testing, and sometimes
adjunctive information such as a review of a state controlled substance database for benzodiazepine
prescriptions, are essential. The clinician should be aware that the patient may have several different
withdrawal syndromes concurrently, each necessitating a different treatment strategy.
Alcohol withdrawal seizures — The differential diagnosis for an alcohol withdrawal seizure includes
epilepsy and seizures provoked by conditions such as hypoglycemia, hyponatremia, medication, substance
intoxication, or substance withdrawal (particularly benzodiazepines); following a patient’s first seizure, a thorough
evaluation including the patient’s history, laboratory testing, and imaging are required to distinguish between
possible etiologies (table 4 and table 5). Subsequent seizures that follow the reduction or cessation of alcohol
use, and do not have new features such as head trauma or fever, do not require the same degree of evaluation.
(See "Evaluation and management of the first seizure in adults".)
Alcohol hallucinosis — Visual hallucinations are present in a variety of conditions including retinal
pathology, visual loss, psychiatric disease such as schizophrenia, and delirium. The visual hallucinations in
alcohol withdrawal are usually (though not always) distinctive because they are associated with other signs and
symptoms of withdrawal such as tremor, tachycardia, hypertension, and diaphoresis. In contrast to hallucinations
associated with delirium (whether related to alcohol withdrawal or other medical conditions), the patient generally
has normal attention and orientation. (See "Approach to the patient with visual hallucinations".)
Withdrawal delirium — In contrast to alcohol withdrawal-associated hallucinosis or seizures, withdrawal

delirium always follows earlier manifestations of withdrawal. Thus, in many patients with withdrawal delirium, the
etiology is quite clear. Notable exceptions are the postoperative setting, or following a period of intubation and
sedation for a medical condition in the ICU; in these contexts, patients’ first evident symptom of withdrawal may
be delirium. Here, a broader array of etiologies must be considered. (See "Identification and management of
unhealthy alcohol use in the perioperative period", section on 'Alcohol withdrawal syndrome'.)
Patients with withdrawal delirium may or may not have autonomic instability. Particularly when this autonomic
instability is absent or minor, the differential diagnosis encompasses most causes of delirium (table 6). (See
"Diagnosis of delirium and confusional states".)
When autonomic instability accompanies withdrawal delirium, the differential is narrowed somewhat;
considerations include sepsis, encephalitis, meningitis, hyperthermia, or drug induced processes such as
neuroleptic malignant syndrome, anticholinergic toxicity, or intoxication with certain stimulants or dissociative
anesthetics. Drugs to consider include cocaine, methamphetamine, phencyclidine, ketamine, or synthetic
cathinones.
Obtaining history from family and/or close contacts familiar with the patient’s patterns of alcohol use is pivotal in
establishing alcohol withdrawal as a likely cause, particularly if the patient presents with delirium and other
features of withdrawal, such as seizures, were not witnessed; in many cases, comprehensive laboratory and
drug testing with or without imaging will be needed to rule out other possible etiologies. (See 'Laboratory and
other testing' above.)
INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, “The Basics” and
“Beyond the Basics.” The Basics patient education pieces are written in plain language, at the 5th to 6th grade
reading level, and they answer the four or five key questions a patient might have about a given condition. These
articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond
the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written
at the 10th to 12th grade reading level and are best for patients who want in-depth information and are
comfortable with some medical jargon.
Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these
topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on
“patient info” and the keyword(s) of interest.)
● Basics topic (see "Patient education: Alcohol withdrawal (The Basics)")
SUMMARY
● The one-year prevalence of DSM-5 alcohol use disorder (alcohol abuse and dependence in DSM-IV) is
estimated to be 14 percent among the general United States population. Approximately half of patients with
DSM-5 alcohol use disorder experience alcohol withdrawal. (See 'Epidemiology' above.)
● Without treatment, symptoms of alcohol withdrawal generally begin within 6 to 24 hours of the last drink or a
sudden reduction in chronic alcohol drinking (table 1). (See 'Clinical presentation and course' above.)
● Mild withdrawal symptoms include anxiety, agitation, restlessness, insomnia, tremor, diaphoresis,
palpitations, headache, and alcohol craving, and often loss of appetite, nausea, and vomiting. Physical signs
include tachycardia hypertension, hyperactive reflexes, and tremor. (See 'Mild withdrawal' above.)
● Additional severe manifestations of alcohol withdrawal occur in an estimated 20 percent of patients who
experience withdrawal symptoms, such as hallucinations, seizures and, delirium tremens. Withdrawal
seizures and delirium are sometimes grouped as part of severe alcohol withdrawal syndrome. (See 'Alcohol
hallucinosis' above and 'Withdrawal seizures' above and 'Withdrawal delirium' above.)
● Assessment of patients at risk for alcohol withdrawal should receive a comprehensive substance use
evaluation, including recent use, last use, and previous treatment history, physical examination, laboratory
tests, and serial monitoring of the withdrawal severity rating score, usually using the Clinical Institutes
Withdrawal Assessment Scale for Alcohol (table 3). (See 'Assessment' above and "Clinical assessment of
substance use disorders".)
● Diagnosis of alcohol withdrawal can be made using DSM-5 diagnostic criteria. Alcohol withdrawal has a
broad differential diagnosis depending on the clinical presentations of early withdrawal symptoms,
withdrawal seizures, hallucinations, and/or delirium, so clinicians should be alert for coexisting serious acute
medical conditions. (See 'DSM-5 diagnostic criteria' above and 'Diagnosis' above.)
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27. Wright T, Myrick H, Henderson S, et al. Risk factors for delirium tremens: a retrospective chart review. Am J
Addict 2006; 15:213.
28. Daeppen JB, Gache P, Landry U, et al. Symptom-triggered vs fixed-schedule doses of benzodiazepine for
alcohol withdrawal: a randomized treatment trial. Arch Intern Med 2002; 162:1117.
29. Saitz R, Mayo-Smith MF, Roberts MS, et al. Individualized treatment for alcohol withdrawal. A randomized
double-blind controlled trial. JAMA 1994; 272:519.
30. Hecksel KA, Bostwick JM, Jaeger TM, Cha SS. Inappropriate use of symptom-triggered therapy for alcohol
withdrawal in the general hospital. Mayo Clin Proc 2008; 83:274.
Topic 108527 Version 1.0
GRAPHICS
Timing of alcohol withdrawal syndromes
Onset after last

Syndrome Clinical findings
drink
Minor Tremulousness, mild anxiety, headache, diaphoresis, palpitations, anorexia, GI 6 to 36 hours

withdrawal upset; Normal mental status
Seizures Single or brief flurry of generalized, tonic-clonic seizures, short post-ictal 6 to 48 hours
period; Status epilepticus rare
Alcoholic Visual, auditory, and/or tactile hallucinations with intact orientation and normal 12 to 48 hours
hallucinosis vital signs
Delirium Delirium, agitation, tachycardia, hypertension, fever, diaphoresis 48 to 96 hours

tremens
Graphic 75499 Version 1.0
Suggested criteria for ICU admission of patients with alcohol withdrawal
Age >40
Cardiac disease (heart failure, arrhythmia, angina, myocardial ischemia, recent myocardial infarction)
Hemodynamic instability
Marked acid-base disturbances
Severe electrolyte abnormalities (hypokalemia, hypophosphatemia, hypomagnesemia, hypocalcemia)
Respiratory insufficiency (hypoxemia, hypercapnia, severe hypocapnia, pneumonia, asthma, COPD)
Potentially serious infections (wounds, pneumonia, trauma, urinary tract infection)
Signs of gastrointestinal pathology (pancreatitis, GI bleeding, hepatic insufficiency, suspected peritonitis)
Persistent hyperthermia (T >39°C [103°F])
Evidence of rhabdomyolysis
Renal insufficiency or increased fluid requirements
History of prior alcohol withdrawal complications (eg, delirium tremens, alcohol withdrawal seizures)
Need for frequent or high doses of sedatives or an intravenous infusion to control symptoms
Withdrawal despite an elevated ethanol concentration
COPD: Chronic obstructive pulmonary disease; GI: Gastrointestinal; ICU: Intensive care unit
Adapted from Carlson, RW, Keske, B, Cortez, D, J Crit Illness 1998; 13:311.
Clinical Institute Withdrawal Assessment Scale for Alcohol, revised (CIWA-Ar)
Nausea and vomiting Headache

0 No nausea or vomiting 0 Not present
1 1 Very mild
2 2 Mild
3 3 Moderate
4 Intermittent nausea with dry heaves 4 Moderately severe
5 5 Severe
6 6 Very severe
7 Constant nausea, frequent dry heaves and vomiting 7 Extremely severe
Paroxysmal sweats Auditory disturbances

0 No sweats visible 0 Not present
1 Barely perceptible sweating, palms moist 1 Very mild harshness or ability to frighten
2 2 Mild harshness or ability to frighten
3 3 Moderate harshness or ability to frighten
4 Beads of sweat obvious on forehead 4 Moderately severe hallucinations
5 5 Severe hallucinations
6 6 Extremely severe hallucinations
7 Drenching sweats 7 Continuous hallucinations
Anxiety Visual disturbances

0 No anxiety, at ease 0 Not present
1 1 Very mild photosensitivity
2 2 Mild photosensitivity
3 3 Moderate photosensitivity
4 Moderately anxious, guarded 4 Moderately severe visual hallucinations
5 5 Severe visual hallucinations
6 6 Extremely severe visual hallucinations
7 Acute panic state, consistent with severe delirium or 7 Continuous visual hallucinations
acute schizophrenia
Tactile disturbances
Agitation
0 None
0 Normal activity
1 Very mild paresthesias
1 Somewhat more than normal activity
2 Mild paresthesias
2
3 Moderate paresthesias
3
4 Moderately severe hallucinations
4 Moderately fidgety and restless
5 Severe hallucinations
5
6 Extremely severe hallucinations
6
7 Continuous hallucinations
7 Paces back and forth during most of the interview or
constantly thrashes about Orientation and clouding of sensorium
0 Oriented and can do serial additions
Tremor
1 Cannot do serial additions
0 No tremor
1 Not visible, but can be felt at fingertips 2 Disoriented for date by no more than 2 calendar days
2 3 Disoriented for date by more than 2 calendar days
3 4 Disoriented for place and/or patient
4 Moderate when patient's hands extended Total score is a simple sum of each item score
(maximum score is 67).
5
Score:
6
<10: Very mild withdrawal
7 Severe, even with arms not extended
10-15: Mild withdrawal
16-20: Modest withdrawal
>20: Severe withdrawal
Adapted from Sullivan JT, Skyora K, Schneiderman J, et al. Br J Addict 1989; 84:1353.
Causes of provoked seizures
Alcohol & drug withdrawal
Drug intoxication
Hyponatremia, hypernatremia
Hypomagnesium
Hypocalcemia
Hypoglycemia
Nonketotic hyperglycemia
Uremia
Hypoxia
Hyperthyroidism
Dialysis disequilibrium syndrome
Porphyria
Medications associated with seizures
Category Examples
Analgesics NSAIDs
Opioids (eg, hydromorphone, meperidine, pentazocine, propoxyphene*, tramadol)
Triptans
Anesthetics Intravenous or inhalation anesthetics (eg, alfentanil, enflurane, ketamine, methohexital,

propofol, sevoflurane, sufentanil)
Local anesthetics (eg, bupivacaine, cocaine, lidocaine, procaine, ropivacaine)
Anticancer drugs ¶ Busulfan

Chlorambucil
Cytarabine
Doxorubicin
Etoposide
Fluorouracil
Interferon alfa
Methotrexate
Mitoxantrone
Nelarabine
Platinum-based drugs (eg, cisplatin)
Vinblastine
Vincristine
Anticholinergics Oxybutynin
Scopolamine
Antiemetics Dronabinol
Metoclopramide
Ondansetron
Phenothiazines (eg, prochlorperazine)
Scopolamine
Antihistamines Diphenhydramine
Hydroxyzine
Antimicrobials Δ Antimalarials (eg, hydroxychloroquine, mefloquine)

Antiretrovirals
Antivirals
Carbapenems (eg, imipenem)
Cephalosporins
Fluoroquinolones (eg, ciprofloxacin)
Isoniazid ◊
Ivermectin
Linezolid
Metronidazole
Penicillins
Anti-Parkinson agents Dopamine agonists (eg, amantadine)

Rasagiline
Selegiline
Cardiovascular agents Antiarrhythmics
Beta-blockers
Cholinesterase Donepezil
inhibitors Galantamine
Rivastigmine
Contrast agents, Iohexol

iodinated Iopamidol
Erectile dysfunction Phosphodiesterase-5 inhibitors (eg, sildenafil, tadalafil, others)
Hypoglycemic agents Potentially any antidiabetic agent that can cause hypoglycemia
Immunosuppressants Azathioprine
Cyclosporine
Glucocorticoids
Mycophenolate
Tacrolimus
Muscle relaxants Baclofen

Carisoprodol
Cyclobenzaprine
Dantrolene
Tizanidine
Psychiatric Antipsychotics §
medications Atomoxetine
Bupropion
Buspirone
Lithium
Monoamine oxidase inhibitors ¥
Selective serotonin reuptake inhibitors ‡
Serotonin norepinephrine reuptake inhibitors ‡
Serotonin modulators
Tricyclic antidepressants (eg, amoxapine, clomipramine, maprotiline)
Pulmonary drugs Albuterol (salbutamol)

Aminophylline
Montelukast
Terbutaline
Theophylline
Stimulants Amphetamines
Methylphenidate
Sympathomimetics Anorexiants (eg, diethylpropion, phentermine, nonprescription diet aids)

and decongestants Caffeine
Phenylephrine
Pseudoephedrine
Others Epoetin
Flumazenil
Isotretinoin
Memantine
Nicotine
Sodium oxybate
Ticlopidine
The magnitude of risk of seizure for various categories and individual agents is not well established. Factors that may
contribute to the risk of seizure with medications include overdose, alcohol abuse, organ dysfunction, drug
interactions, older age, and a history of seizures. Illicit drugs use, herbs/natural remedies (eg, guarana),
nonprescription supplements, and abrupt withdrawal from chronic alcohol use and certain prescription medicines (eg,
antiepileptic drugs, baclofen, benzodiazepines) are also associated with seizure.
This table is not all-inclusive. For detailed prescribing information, including reported adverse effects, readers should
refer to the individual drug information topics within UpToDate. Comprehensive information on drug interactions can
be determined using the Lexi-Interact tool included within UpToDate.
NSAIDs: nonsteroidal anti-inflammatory drugs.

* Removed from market in most countries.
¶ For more details and additional anti-cancer drugs that have been associated with seizures, refer to UpToDate topic reviews
on the neurologic complications of anticancer therapies.
Δ Among antibiotics, evidence for an association is strongest for unsubstituted penicillins, fourth-generation cephalosporins,
imipenem, and ciprofloxacin in combination with renal dysfunction, brain lesions, and epilepsy [1].
◊ Seizures are a manifestation of pyridoxal-5-phosphate deficiency; they respond to pyridoxine and benzodiazepine
treatment. Refer to UpToDate topic review on isoniazid poisoning.
§ Clozapine has a higher risk of seizure than most other antipsychotics [2]; refer to UpToDate topic review on guidelines for
prescribing clozapine in schizophrenia for more information.
¥ Monoamine oxidase inhibitors include: furazolidone, isocarboxazid, linezolid, moclobemide, pargyline, phenelzine,
procarbazine, rasagiline, selegiline, tranylcypromine.
‡ Selective serotonin reuptake inhibitors and serotonin norepinephrine reuptake inhibitors do not increase seizure risk in
patients with epilepsy when used in therapeutic doses, but may be proconvulsant at toxic doses [3,4].
References:
1. Sutter S, Ruegg S, Tschudin-Sutter S, Seizures as adverse events of antibiotic drugs: A systematic review. Neurology
2015; 1332.
2. Hitchings AW, Drugs that lower the seizure threshold. Adverse Drug Reaction Bulletin 2016; 1151.
3. Kanner AM, Most antidepressant drugs are safe for patients with epilepsy at therapeutic doses: A review of the
evidence. Epilepsy Behav 2016;282.
4. Landmark CJ, Henning O, Johannessen SI. Proconvulsant effects of antidepressants - What is the current evidence?
Epilepsy Behav 2016;287.
Common causes of delirium and confusional states
Drugs and toxins

Prescription medications (eg, opioids, sedative-hypnotics, antipsychotics, lithium, skeletal muscle relaxers,
polypharmacy)
Non-prescription medications (eg, antihistamines)
Drugs of abuse (eg, ethanol, heroin, hallucinogens, nonmedicinal use of prescription medications)
Withdrawal states (eg, ethanol, benzodiazepines)
Medication side effects (eg, hyperammonemia from valproic acid, confusion from quinolones, serotonin syndrome)
Poisons:
Atypical alcohols (ethylene glycol, methanol)
Inhaled toxins (carbon monoxide, cyanide, hydrogen sulfide)
Plant-derived (eg, Jimson weed, Salvia)
Infections
Sepsis
Systemic infections; fever-related delirium
Metabolic derangements
Electrolyte disturbance (elevated or depressed): sodium, calcium, magnesium, phosphate
Endocrine disturbance (depressed or increased): thyroid, parathyroid, pancreas, pituitary, adrenal
Hypercarbia
Hyperglycemia and hypoglycemia
Hyperosmolar and hypoosmolar states
Hypoxemia
Inborn errors of metabolism: porphyria, Wilson's disease, etc.
Nutritional: Wernicke's encephalopathy, vitamin B12 deficiency, possibly folate and niacin deficiencies
Brain disorders
CNS infections: encephalitis, meningitis, brain or epidural abscess
Epileptic seizures, especially nonconvulsive status epilepticus*
Head injury*
Hypertensive encephalopathy
Psychiatric disorders*
Systemic organ failure

Cardiac failure
Hematologic: thrombocytosis, hypereosinophilia, leukemic blast cell crisis, polycythemia
Liver failure: acute, chronic
Pulmonary disease, including hypercarbia and hypoxemia
Renal failure: acute, chronic
Physical disorders
Burns
Electrocution
Hyperthermia
Hypothermia
Trauma: with systemic inflammatory response syndrome, *head injury, fat embolism
* Disorders that, while not truly systemic or "medical", may produce the clinical picture of delirium or confusional state in all
other aspects.
Contributor Disclosures
Christine Pace, MD, MSc Nothing to disclose Richard Saitz, MD, MPH, FACP,
DFASAM Grant/Research/Clinical Trial Support: Alkermes [Alkermes provides study medication for a clinical trial
supported by NIH on Alcohol user disorder (injectable naltrexone)]. Richard Hermann, MD Nothing to disclose
Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are
addressed by vetting through a multi-level review process, and through requirements for references to be
provided to support the content. Appropriately referenced content is required of all authors and must conform to
UpToDate standards of evidence.
Conflict of interest policy

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Alcohol withdrawal: Epidemiology, clinical manifestations, course, assessment, and diagnosis

Author: Christine Pace, MD, MSc

INTRODUCTION — Minor manifestations of alcohol withdrawal include anxiety, agitation, restlessness,

PATHOPHYSIOLOGY — The pathophysiology of alcohol withdrawal syndrome is reviewed separately. (See

● Prior withdrawal delirium.

● Development of alcohol withdrawal with a positive blood alcohol level.

● Concurrent illness, such as respiratory, cardiac, or gastrointestinal disease.

• Outpatient management, with ambulatory visits as needed.

• Inpatient management in an addiction treatment setting:

- General inpatient unit

• Steps to determine the level of care are as follows:

Patient history — Key features of the history include:

Laboratory and other testing — Laboratory testing typically includes:

● A complete blood count.

● Serum electrolytes, including potassium, magnesium, and phosphate.

● Liver function tests.

● Amylase and lipase.

● Blood alcohol level.

● Urine human chorionic gonadotropin test for premenopausal women.

● Pulmonary embolus – Pulmonary embolus is an important consideration in hospitalized or postoperative

● Intoxication – Intoxication with stimulants such as cocaine, methamphetamine, amphetamines, or synthetic

Withdrawal delirium — In contrast to alcohol withdrawal-associated hallucinosis or seizures, withdrawal

● Basics topic (see "Patient education: Alcohol withdrawal (The Basics)")

Use of UpToDate is subject to the Subscription and License Agreement.

withdrawal syndrome. Alcohol 2014; 48:375.

Topic 108527 Version 1.0

Timing of alcohol withdrawal syndromes

Onset after last

Minor Tremulousness, mild anxiety, headache, diaphoresis, palpitations, anorexia, GI 6 to 36 hours

Delirium Delirium, agitation, tachycardia, hypertension, fever, diaphoresis 48 to 96 hours

Graphic 75499 Version 1.0

Suggested criteria for ICU admission of patients with alcohol withdrawal

Marked acid-base disturbances

Severe electrolyte abnormalities (hypokalemia, hypophosphatemia, hypomagnesemia, hypocalcemia)

Respiratory insufficiency (hypoxemia, hypercapnia, severe hypocapnia, pneumonia, asthma, COPD)

Potentially serious infections (wounds, pneumonia, trauma, urinary tract infection)

Signs of gastrointestinal pathology (pancreatitis, GI bleeding, hepatic insufficiency, suspected peritonitis)

Persistent hyperthermia (T >39°C [103°F])

Renal insufficiency or increased fluid requirements

Withdrawal despite an elevated ethanol concentration

Graphic 73377 Version 2.0

Clinical Institute Withdrawal Assessment Scale for Alcohol, revised (CIWA-Ar)

Nausea and vomiting Headache

4 Intermittent nausea with dry heaves 4 Moderately severe

7 Constant nausea, frequent dry heaves and vomiting 7 Extremely severe

Paroxysmal sweats Auditory disturbances

2 2 Mild harshness or ability to frighten

3 3 Moderate harshness or ability to frighten

4 Beads of sweat obvious on forehead 4 Moderately severe hallucinations

6 6 Extremely severe hallucinations

7 Drenching sweats 7 Continuous hallucinations

Anxiety Visual disturbances

1 1 Very mild photosensitivity

4 Moderately anxious, guarded 4 Moderately severe visual hallucinations

5 5 Severe visual hallucinations

6 6 Extremely severe visual hallucinations

2 3 Disoriented for date by more than 2 calendar days

3 4 Disoriented for place and/or patient

16-20: Modest withdrawal

>20: Severe withdrawal

Graphic 64835 Version 2.0