Alcohol Withdrawal

Primer

Alcohol Withdrawal is a withdrawal syndrome that occurs within several hours to a few days of stopping heavy and prolonged alcohol use. The withdrawal syndrome includes autonomic hyperactivity, anxiety, and gastrointestinal symptoms.

Epidemiology

Around 50% of middle-class, high functioning individuals with alcohol use disorder will meet criteria for alcohol withdrawal at some point in their lives.
- In those who are homeless or hospitalized, this increases to 80%.^[1]

Prognosis

Acute alcohol withdrawal usually lasts between 4 to 5 days and only after long periods of heavy drinking.^[2]
During withdrawal, less than 10% will have severe autonomic hyperactivity, tremors, or alcohol withdrawal delirium.
- Tonic-clonic seizures occurs in less than 3% of individuals.^[3]

Comorbidity

Withdrawal is more likely in those with conduct disorder or antisocial personality disorder.

Risk Factors

Withdrawal is rare in those age 30 year and below, and the risk and severity of withdrawal increases with age.^[4]
Individuals on other depressant drugs (sedative-hypnotics) are at increased risk.
Alcohol withdrawal delirium can often occur alongside another unrelated medical event, when an individual is admitted to hospital. For example, for liver failure, pneumonia, gastrointestinal bleeding, head trauma, hypoglycemia, electrolyte imbalances, or postoperative care. Thus, it is always important to ask about alcohol during a hospital admission.

DSM-5 Diagnostic Criteria

Criterion A

Cessation of (or reduction in) alcohol use that has been heavy and prolonged.

Criterion B

At least 2 of the following, developing within several hours to a few days after the cessation of (or reduction in) alcohol use described in Criterion A:

Autonomic hyperactivity (e.g. - sweating or pulse rate greater than 100 beats per minute)
Increased hand tremor
Insomnia
Nausea or vomiting
Transient visual, tactile, or auditory hallucinations or illusions
Psychomotor agitation
Anxiety
Generalized tonic-clonic seizures

Criterion C

The signs or symptoms in Criterion B cause clinically significant distress or impairment in social, occupational, or other important areas of functioning.

Criterion 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.

Specifiers

Specifier

Specify if:

With perceptual disturbances: This specifier applies in the rare instance when hallucinations (usually visual or tactile) occur with intact reality testing, or auditory, visual, or tactile illusions occur in the absence of a delirium.

Signs and Symptoms

Nausea, vomiting, gastritis, hematemesis, dry mouth, puffy blotchy complexion, and mild peripheral edema can occur during withdrawal.^[5]
Withdrawal symptoms usually peak on the second day of abstinence and improve significantly by the fourth/fifth day.
However, symptoms of anxiety, insomnia, and autonomic dysfunction can remain for up to another 3 to 6 months.^[6]

Withdrawal Stages

It is important to know the stages of alcohol withdrawal so that symptoms are properly identified and also treated for the correct length of time.
Alcoholic hallucinosis is not the same as hallucinations in delirium tremens. Alcoholic hallucinosis is self-resolving, and the patient has insight into these hallucinations (which can be auditory, visual, or tactile - most commonly visual).
The vast majority of individuals going through alcohol withdrawal will not experience complicated withdrawal (i.e. - withdrawal seizures or delirium tremens).
- Generally speaking, between 10 to 30% of individuals with alcohol withdrawal will experience alcohol withdrawal seizures.^[7]

Alcohol Withdrawal Classification by Stages

	Stage 1	Stage 2	Stage 3	Stage 4	Stage 5
Time of last drink	6-8 hours	12-24 hours	12-48 hours	2-5 days	1-6 months
Definition	Mild withdrawal (in some cases can progress to DTs)	Alcoholic Hallucinosis (in some cases can progress to DTs)	Withdrawal Seizures	Delirium Tremens (DTs)^[8], 5% mortality	Chronic Alcohol Use
Symptoms	• Mild tremors • Anxiety • Nausea	• Stable Vitals • Tremors • Agitation • Insomnia • Hallucination (auditory, visual, tactile), but insight is maintained	• Same as Stage 2, but more severe • Seizures	• Unstable Vitals • Confusion • Agitation • Fever • Tachycardia • Hypertension • Diaphoresis	• Autonomic hyperactivity • Anxiety • Sleep disturbance

Screening and Rating Scales

Alcohol Withdrawal Tools and Scales

Name	Rater	Description	Download
CIWA-Ar	Clinician	The CIWA–Ar (revised) measures 10 symptoms. Scores of less than 8 to 10 indicate minimal to mild withdrawal. Scores of 8 to 15 indicate moderate withdrawal (marked autonomic arousal); and scores of 15 or more indicate severe withdrawal. It takes approximately 2 minutes to perform.	Download
PAWSS	Clinician	The PAWSS is the first validated tool for the prediction of severe alcohol withdrawal syndrome in the medically ill and its use may aid in the early identification of patients at risk for complicated withdrawal, allowing for prophylaxis before severe alcohol withdrawal syndromes occur.	Download

CIWA

The Clinical Institute Withdrawal Assessment (CIWA) was developed in Toronto, Canada in the 1980s.^[9] It is considered the gold-standard for measurement of alcohol withdrawal symptoms, and is used in the treatment of alcohol withdrawal in an inpatient setting. Whenever a patient scores > 10 on the CIWA, they should be given either lorazepam or diazepam.

PAWSS

The Prediction of Alcohol Withdrawal Severity Scale (PAWSS) is a validated screening tool that uses a combination of symptoms and signs to identifying patients at risk of developing severe alcohol withdrawal syndrome (i.e., withdrawal hallucinosis, withdrawal-related seizures, and delirium tremens).^[10]^[11]
The use of this tool is particularly important, as the CIWA does not indicate the probability that the patient will develop severe withdrawal syndrome, and only indicates whether the patient is experiencing withdrawal symptoms. This is particularly important for identifying high risk patients who may need more intensive medical management or prophylaxis.

Pathophysiology

Chronic exposure to alcohol is thought to cause an imbalance between GABA neurotransmission (decreased) and glutamate neurotransmission (increased).^[12]
- This is thought to cause a hyper-excitable brain state that can lead to seizures (if not adequately treated with benzodiazepines)
- Overall, glutamate is thought to play a more important role than GABA.^[13]
Additionally, there is also desensitization of the sympathetic nervous system, which results in autonomic disturbance including tachycardia, hypertension, diaphoresis, and orthostatic changes. In severe cases, this progresses to delirium tremens.

Withdrawal Seizures

During alcohol withdrawal, the loss of GABA-A receptor stimulation from alcohol causes a reduction in chloride flux and is associated with tremors, diaphoresis, tachycardia, anxiety, and seizures.^[14]

Differential Diagnosis

Other medical conditions
- The symptoms of alcohol withdrawal can resemble other medical conditions (e.g. - hypoglycemia, diabetic ketoacidosis). Essential tremor may be mistaken for tremulousness associated with alcohol withdrawal.
Sedative, hypnotic, or anxiolytic withdrawal
- Sedative, hypnotic, or anxiolytic withdrawal produces a syndrome similar to alcohol withdrawal.

Investigations

See main article: Alcohol Intoxication: Investigations

If there is a clinical suspicion for other medical disease or conditions (e.g. - delirium, head injury), other relevant lab tests and investigations should be ordered.

Physical Exam

Individuals may have tremors, difficulty with gait
Exam for stigmata of liver disease including hepatomegaly, spider angiomas
Esophageal varices and hemorrhoids may be present
Examine for asterixis if concerned about hepatic encephalopathy
Males with chronic alcohol use disorder may have decreased testicular size due to the feminizing effects associated with reduced testosterone levels.^[15]

Treatment

Alcohol and benzodiazepine withdrawal are treated the same way. Alcohol and benzodiazepine withdrawal are the two substance withdrawals that can be fatal!
Withdrawal seizures can be the initial clinical presentation; to prevent progression to more severe withdrawal symptoms.
Benzodiazepines must be used and are the first-line treatment; anti-epileptics do not work to prevent alcohol-related seizures.
- Antipsychotics can lower the seizure threshold, and thus should only be used if there are severe psychotic symptoms that place the patient at risk for serious harms to self or others (e.g. - aggression/violence).

Should withdrawal be managed as an outpatient or inpatient?

In most cases, alcohol withdrawal can be managed in an outpatient setting. However, there are several contraindications to this, including:

Severe psychiatric/medical comorbidity, or coexisting illness that requires inpatient treatment
Electrolyte disturbances/dehydration
Current severe alcohol withdrawal, especially with delirium
No possibility for follow-up
No reliable contact person to monitor the patient
Pregnancy
Seizure disorder or history of alcohol withdrawal seizures
Suicide risk
History of delirium tremens or seizures

Inpatient

Inpatient Alcohol Withdrawal Management

	Uncomplicated withdrawal	Complicated withdrawal
Definition	No history of siezures or delirium tremens	A history of withdrawal seizures, delirium tremens, pregnancy or geriatric
Management	• Diazepam 20mg PO q1-2h until CIWA < 10 OR • Lorazepam 2mg q1-2h until CIWA < 10	• Load with diazepam 20mg q1h x 3 = 60mg • Lorazepam 2mg q1h x 3 = 60mg total to start • Then administer CIWA based on symptoms

Think about the specific symptoms scored on the CIWA!

Think about the patient's scores: are they showing objective signs of autonomic instability in the score? A delirious person might score on AH/VH/agitation and have a “positive” CIWA!

Outpatient

Outpatient Alcohol Withdrawal Management

Sample Taper:
Diazepam 10mg QID x 3 days (total 40mg daily)
Diazepam 10mg BID x 3 days (total 20mg daily)
Diazepam 10mg qHS x 3 days (total 10mg daily)
Thiamine 300mg PO daily x 1 month

Liver Function

See also article: Introduction to Benzodiazepines

One may want to switch patients to lorazepam instead if blood work shows significantly elevated liver enzymes or if there are signs of acute liver failure (e.g. - jaundice).

Diazepam or Lorazepam?

The LOT benzodiazpines (Lorazepam, Oxazepam, and Tamazepam are metabolized via glucuronidation (Phase II metabolism), which is less dependent on global liver function. Thus, these benzodiazepines can be used in individuals with severe liver impairment.

Diazepam has a long half-life, multiple active metabolites, and should only be used in healthy patients with no signs of liver disease.
Lorazepam can be used in patients with hepatic impairment. It has an intermediate length half-life, and no metabolites. This makes it more suitable for use in the elderly, those with severe liver disease, respiratory distress, or if they already on existing opioids (to reduce the risk of respiratory depression). It can also be given in IM form reliably.

Thiamine

See main article: Wernicke Encephalopathy and Korsakoff Syndrome

Thiamine deficiency (vitamin B1) is common in patients with alcohol dependence. Cognitive impairments may be an early consequence of thiamine deficiency and Wernicke's encephalopathy is under-diagnosed and under-treated.^[16]
It is important to supplement patients with PO or IV thiamine.
Thiamine 100mg TID should be prescribed as ongoing supplementary therapy in alcohol use disorder patients identified as at risk for thiamine deficiency. ^[17]
For more severe cases, 200mg IV thiamine x 3 days, followed by oral supplementation is appropriate. Those with suspected Wernicke’s encephalopathy should receive thiamine 100mg IM/IV x 3 days, then 300mg PO x 3-12 months. Don’t forget to give fluids as well!

Drug-Drug Interactions

When managing alcohol withdrawal, drug-drug interactions should be considered.
If patients are on mood stabilizer like lithium or valproic acid, ensure that appropriate levels are drawn to make sure they are not suffering from medication-related toxicity.
- Lithium levels may increase due to increased diuresis from alcohol, and lithium toxicity can cause tremulousness and nausea (mimicking alcohol withdrawal)
- Valproic acid combined with with alcohol use increases risk of liver damage, and this can increase valproic acid levels due to decreased metabolism from the liver.

Folate

Folate deficiency is also common in chronic alcohol use.^[18]

Guidelines

Alcohol Use Disorder Guidelines

Guideline	Location	Year	PDF	Website
Canadian Guideline for the Clinical Management of High-Risk Drinking and Alcohol Use Disorder	Canada	2023	Link (see also: comment on sertraline use in AUD)	Link
Canadian Guidelines on Alcohol Use Disorder Among Older Adults	Canada	2020	-	Link
British Columbia Centre on Substance Use (BCCSU)	Canada	2019	Link	Link
National Institute for Health and Care Excellence (NICE)	UK	2011	-	Link
American Psychiatric Association (APA)	USA	2018	-	Link
European Federation of Neurological Societies (EFNS) - Wernicke Encephalopathy	Europe	2010	-	Link

Resources

For Patients

For Providers

Articles

Research

¹⁾ American Psychiatric Association. (2013). Diagnostic and Statistical Manual of Mental Disorders (5th ed.). Arlington, VA.

²⁾ American Psychiatric Association. (2013). Diagnostic and Statistical Manual of Mental Disorders (5th ed.). Arlington, VA.

³⁾ American Psychiatric Association. (2013). Diagnostic and Statistical Manual of Mental Disorders (5th ed.). Arlington, VA.

⁴⁾ American Psychiatric Association. (2013). Diagnostic and Statistical Manual of Mental Disorders (5th ed.). Arlington, VA.

⁵⁾ American Psychiatric Association. (2013). Diagnostic and Statistical Manual of Mental Disorders (5th ed.). Arlington, VA.

⁶⁾ American Psychiatric Association. (2013). Diagnostic and Statistical Manual of Mental Disorders (5th ed.). Arlington, VA.

⁷⁾ American Psychiatric Association. (2013). Diagnostic and Statistical Manual of Mental Disorders (5th ed.). Arlington, VA.

⁸⁾ Schuckit, Marc A. "Recognition and management of withdrawal delirium (delirium tremens)." New England Journal of Medicine 371.22 (2014): 2109-2113.

⁹⁾ Sullivan, J. T., Sykora, K., Schneiderman, J., Naranjo, C. A., & Sellers, E. M. (1989). Assessment of alcohol withdrawal: the revised clinical institute withdrawal assessment for alcohol scale (CIWA‐Ar). Addiction, 84(11), 1353-1357.

¹⁰⁾ Goodson, C. M., Clark, B. J., & Douglas, I. S. (2014). Predictors of severe alcohol withdrawal syndrome: a systematic review and meta‐analysis. Alcoholism: Clinical and Experimental Research, 38(10), 2664-2677.

¹¹⁾ Wood, E., Albarqouni, L., Tkachuk, S., Green, C. J., Ahamad, K., Nolan, S., ... & Klimas, J. (2018). Will This Hospitalized Patient Develop Severe Alcohol Withdrawal Syndrome?: The Rational Clinical Examination Systematic Review. JAMA, 320(8), 825-833.

¹²⁾ Brousse, G., Arnaud, B., Vorspan, F., Richard, D., Dissard, A., Dubois, M., ... & Sapin, V. (2012). Alteration of glutamate/GABA balance during acute alcohol withdrawal in emergency department: a prospective analysis. Alcohol and alcoholism, 47(5), 501-508.

¹³⁾ Pulvirenti, L., & Diana, M. (2001). Drug dependence as a disorder of neural plasticity: focus on dopamine and glutamate. Reviews in the Neurosciences, 12(2), 141-158.

¹⁴⁾ Hughes, J. R. (2009). Alcohol withdrawal seizures. Epilepsy & Behavior, 15(2), 92-97.

¹⁵⁾ American Psychiatric Association. (2013). Diagnostic and Statistical Manual of Mental Disorders (5th ed.). Arlington, VA.

¹⁶⁾ Dervaux, A., & Laqueille, X. (2017). Thiamine (vitamin B1) treatment in patients with alcohol dependence. Presse medicale (Paris, France: 1983), 46(2 Pt 1), 165-171.

¹⁷⁾ RebelEM:Should You Prescribe Oral Thiamine for Chronic Alcoholics?

¹⁸⁾ Medici, V., & Halsted, C. H. (2013). Folate, alcohol, and liver disease. Molecular nutrition & food research, 57(4), 596–606.

Table of Contents