Alcohol Use Disorder

AUTHOR: Fred F. Ferri, MD

Definition

“Moderate drinking”: Moderate drinking has been defined as two standard drinks (e.g., 12 oz of beer) per day for men and one drink per day for women and persons older than 65 yr.
“Hazardous” or “at-risk drinking”: For men, at-risk drinking or harmful alcohol use is defined as more than 14 drinks/wk or more than four drinks/occasion. For women, at-risk drinking is defined as four or more drinks on one occasion or eight or more drinks per week.
“Alcohol withdrawal”: The American Psychiatric Association defines diagnostic criteria for alcohol withdrawal as follows:
1. Cessation of (or reduction in) alcohol use that has been heavy and prolonged
2. Two (or more) of the following, developing within several hours to a few days:
  1. Autonomic hyperactivity (e.g., sweating or pulse rate >100 beats/min)
  2. Increased hand tremor
  3. Insomnia
  4. Nausea and vomiting
  5. Transient visual, tactile, or auditory hallucinations or illusions
  6. Psychomotor agitation
  7. Anxiety
  8. Grand mal seizures
3. The symptoms cause clinically significant distress or impairment in social, occupational, or other important areas of functioning
The symptoms are not attributable to a general medical condition and are not better accounted for by another mental disorder.

Synonyms

Alcohol dependence syndrome

Substance abuse

Alcohol withdrawal syndrome

Alcoholism

ICD-10CM CODES
F10		Mental and behavioral disorders due to use of alcohol
F10.1		Mental and behavioral disorders due to use of alcohol: Harmful use
F10.2		Mental and behavioral disorders due to use of alcohol: Dependence syndrome
F10.3		Mental and behavioral disorders due to use of alcohol: Withdrawal state
F10.4		Mental and behavioral disorders due to use of alcohol: Withdrawal state with delirium
F10.5		Mental and behavioral disorders due to use of alcohol: Psychotic disorder
F10.6		Mental and behavioral disorders due to use of alcohol: Amnesic syndrome

Epidemiology & Demographics

Incidence (In U.S.)

The clinical history suggests alcohol problems in 15% to 20% of patients in primary care and hospitalized patients. In the U.S., alcohol use disorder generates nearly $223 billion in annual economic costs. An estimated 14% of adults in the U.S. have alcohol dependence. Alcohol accounts for 6.8% of age-standardized deaths in men and 2.2% in women.
Data from the 2020 National Survey on Drug Use and Health indicate that 7% of adults reported heavy alcohol use in the previous month, and only 4.2% of adults with alcohol use disorder received treatment.^1a
Alcohol-associated liver disease (ALD) is among the most common liver diseases, and more than 2 million people in the U.S. in 2017 had alcohol-associated cirrhosis.¹
20% achieve abstinence without help; 70% achieve sobriety for 1 yr.

Prevalence (In U.S.)

7% of population ≥18 yr

Predominant Sex

Lifetime risk for males 8% to 10%
Lifetime risk for females 3% to 5%

Peak Incidence

20 to 40 yr. The most common age range for initial treatment of alcohol dependence is 35 to 45 yr. However, the peak period for meeting alcohol dependence criteria is ≥10 yr earlier.

Genetics

More common with a family history of alcoholism and in patients of Irish, Scandinavian, and Native American descent

Physical Findings & Clinical Presentation

Recurring minor trauma
Gastrointestinal bleeding from gastritis and/or varices
Pancreatitis (acute and chronic)
Liver disease
Odor of alcohol on breath
Tremulousness
Tachycardia
Peripheral neuropathy
Recent memory loss

Etiology

Social and genetic factors important
Risk factors:
1. Broken homes
2. Unemployment
3. Divorce
4. Recurrent depression
5. Addiction to another substance, including tobacco
6. Working long hours (≥55 hours/wk)

Diagnosis ⬆ ⬇

Workup

The United States Preventive Services Task Force (USPSTF) recommends that clinicians screen adults 18 yr and older for alcohol misuse and provide persons engaged in risky or hazardous drinking with brief behavioral counseling interventions to reduce alcohol misuse. Several screening tests (CAGE [Table 1], TWEAK, CRAFFT, Alcohol Use Disorders Identification Test-Concise [AUDIT-C; Table 2]) are available. The four-item CAGE (feeling need to Cut down, Annoyed by criticism, Guilty about drinking, and need for an Eye-opener in the morning) is the most popular screening test in primary care. A positive response should lead to further questioning. The sensitivity of the CAGE ranges from 43% to 94% and its specificity ranges from 70% to 97%. The five-item TWEAK scale (Tolerance, Worry, Eye-openers, Amnesia, [K] cut down) and the TACE questionnaire (Tolerance, Annoyance, Cut down, Eye-opener) are designed to screen pregnant women for alcohol misuse. They detect lower levels of alcohol consumption that may pose risks during pregnancy. The CRAFFT questionnaire (riding in Car with someone who was drinking, using alcohol to Relax, using alcohol while Alone, Forgetfulness, criticism from Friends and Family, Trouble) is useful as a screening tool for adolescents. Its sensitivity is 92% and specificity 64% for alcohol use disorder. Single-question screening about alcohol consumption in a day (“When was the last time you had more than X drinks in a day?” [where X is five for men and four for women]) with the threshold set at “in the past 3 mo” is 85% sensitive and 70% specific in men and 82% and 70% in women for unhealthy alcohol use. The three-question AUDIT-C is a shorter form of the 10-item AUDIT, and the questions center on the quantity and frequency of alcohol use. It asks how often someone has had a drink containing alcohol, how many standard drinks containing alcohol one consumes on a typical day when one is drinking, and how often one has six or more drinks on one occasion. Scoring ranges from 0 to 4 on each question with a total score range of 0 to 12. A total score of 3 or higher for women and 4 or higher for men indicates alcohol use disorder and need for further assessment. Its sensitivity ranges from 85% in Hispanic women to 95% in white men.
Laboratory evaluation (see below).

TABLE 1 CAGE Questionnaire for Alcohol Problems Screening

C		Have you felt the need to Cut down on your drinking?
A		Have people Annoyed you by criticizing your drinking?
G		Have you ever felt bad or Guilty about your drinking?
E		Have you had a drink first thing in the morning to steady your nerves or to get rid of a hangover (i.e., an “Eye opener”)?

From Stern TA et al: Massachusetts General Hospital handbook of general hospital psychiatry, ed 7, Philadelphia, 2018, Elsevier.

TABLE 2 AUDIT-C Questionnaire for Alcohol Problems Screening ^a

Question		Score
How often did you have a drink containing alcohol in the past year?		Never (0 points) Monthly or less (1 point) 2-4 times per month (2 points) 2-3 times per week (3 points) >4 times per week (4 points)

AUDIT-C, Alcohol Use Disorders Identification Test-Concise.

^aAUDIT-C is scored 0-12, with score >4 (men) and >3 (women) considered positive for problematic drinking.

From Stern TA et al: Massachusetts General Hospital handbook of general hospital psychiatry, ed 7, Philadelphia, 2018, Elsevier.

Laboratory Tests

Lab tests alone do not accurately detect alcohol problems but can help identify medical complications related to alcohol use, such as pancreatitis or cirrhosis.

Gamma-glutamyltransferase (GGTP), generally elevated
Liver transaminases (alanine aminotransferase [ALT], aspartate aminotransferase [AST]), often elevated, may be normal or low in advanced liver disease
Low albumin level, hypophosphatemia, hypomagnesemia from malnutrition
Complete blood count (CBC) reveals elevated mean corpuscular volume from toxic effect of alcohol on erythrocyte development in nutritional deficiencies
Stool for occult blood may be positive as a result of gastritis or variceal bleeding
Red blood cell (RBC) folate, vitamin B₁₂ level, vitamin B₆, vitamin B₁ level

Imaging Studies

Indicated only with a history of trauma. CT or ultrasound of abdomen may reveal fatty liver or cirrhosis in advanced stages.

Treatment ⬆ ⬇

Nonpharmacologic Therapy

Twelve-step facilitation, cognitive behavioral therapy, and motivational enhancement therapy improve the chances of recovery in patients with alcohol use disorder and dependence.
Depression, if present, should be treated at same time alcohol is withdrawn.

Acute General Rx

Alcohol withdrawal syndrome (AWS) occurs when a person stops ingesting alcohol after prolonged consumption. It can result in four possible clinical patterns depending on the severity of the patient’s alcohol use and the time from the patient’s previous alcohol ingestion. Blood ethanol level decreases by ∼20 mg/dl/h in a normal person. Although discussed separately, these withdrawal states blend together in real life. Table 3 summarizes medications for the treatment of alcohol dependence. The cornerstone of treatment for alcohol withdrawal syndrome is the use of benzodiazepines.

Tremulous state (early alcohol withdrawal, “impending delirium tremens [DTs],” “shakes,” “jitters”)
1. Time interval: Usually occurs 6 to 8 h after the last drink or 12 to 48 h after reduction of alcohol intake; becomes most pronounced at 24 to 36 h
2. Manifestation: Tremors, mild agitation, insomnia, tachycardia; symptoms are relieved by alcohol
3. Detoxification can be in the outpatient (ambulatory) or inpatient setting. Candidates for outpatient detoxification should have a reasonable support system (e.g., reliable contact person) who can monitor progress and lack of any significant comorbid conditions (e.g., suicide risk, seizure disorder, coexisting benzodiazepine dependence, prior unsuccessful outpatient detoxification, pregnancy, cirrhosis) or risk factors for severe withdrawal (age >40 yr, drinking >100 g of ethanol daily [e.g., 1 pint of liquor or eight 12-oz cans of beer, random blood alcohol concentration >200 mg/dl])
4. Inpatient treatment:
  1. The management of alcohol withdrawal is facilitated by the use of ethanol withdrawal charts. An example of such a chart is shown in Fig. 1
  2. Admit to medical floor (private room); monitor vital signs q4h; institute seizure precautions; maintain adequate sedation
  3. Administer lorazepam as follows:
    1. Day 1: 2 mg PO q4h while awake and not lethargic
    2. Day 2: 1 mg PO q4h while awake and not lethargic
    3. Day 3: 0.5 mg PO q4h while awake and not lethargic
    4. NOTE: Hold sedation for lethargy or abnormal vital or neurologic signs. The preceding doses are only guidelines; it is best to titrate the dose case by case
  4. In patients with mild to moderate withdrawal and without history of seizures, individualized benzodiazepine administration (rather than a fixed-dose regimen) results in lower benzodiazepine administration and avoids unnecessary sedation. The Clinical Institute Withdrawal Assessment Scale for Alcohol, Revised (CIWA-Ar) scale (Box 1) can be used to measure the severity of alcohol withdrawal. It consists of 10 items: Nausea; tremor; autonomic hyperactivity; anxiety; agitation; tactile, visual, and auditory disturbances; headache; and disorientation. Each item is assigned a score from 0 to 7. For example, in the “agitation” category 0 indicates normal activity, and 7 indicates that the patient constantly thrashes about. For the category of “tremor,” 0 indicates that tremor is not present and 7 that tremor is severe, even with arms not extended. The maximum total score is 67. Patients with mild AWS symptoms (CIWA-Ar score <8) can be monitored on an outpatient basis. Benzodiazepines are beneficial for most patients with a CIWA-AR score ≥8 and are strongly recommended in patients with substantial withdrawal symptoms (CIWA-Ar score >12). Patients with CIWA-Ar score of ≥15 should be admitted to detox unit. In-patient treatment is also recommended for patients with history of withdrawal seizures and for those with suicidal ideation and significant comorbidities
  5. Beta-adrenergic blockers: Beta-blockers are useful for controlling blood pressure and tachyarrhythmias. However, they do not prevent progression to more serious symptoms of withdrawal and, if used, should not be administered alone but in conjunction with benzodiazepines. Beta-blockers should be avoided in patients with contraindications to their use (e.g., bronchospasm, bradycardia, or severe congestive heart failure). Centrally acting alpha-adrenergic agonists such as clonidine ameliorate symptoms in patients with mild to moderate withdrawal but do not reduce delirium or seizures
  6. Vitamin replacement: Thiamine 100 mg IV or IM for at least 5 days plus oral multivitamins. The IV administration of glucose can precipitate Wernicke encephalopathy in alcoholics with thiamine deficiency; therefore thiamine administration should precede IV dextrose
  7. Hydration PO or IV (high-caloric solution): If IV, glucose with Na⁺, K⁺, Mg²⁺, and phosphate replacement prn
  8. Laboratory studies:
    1. CBC, platelet count, international normalized ratio (INR)
    2. Electrolytes, glucose, blood urea nitrogen, creatinine
    3. GGTP, ALT, AST
    4. Phosphorus and magnesium
    5. Serum vitamin B₁₂ and folic acid (if megaloblastic features in blood smear)
  9. Diagnostic imaging: Generally not necessary; if subdural hematoma is suspected (evidence of trauma, persistent lethargy), a CT scan should be ordered
  10. Social rehabilitation: Group therapy such as Alcoholics Anonymous; identification and treatment of social and family problems should be initiated during the patient’s hospital stay
Alcoholic hallucinosis:
1. Manifestations: Hallucinations usually are auditory, but hallucinations occasionally are visual, tactile, or olfactory; usually there is no clouding of sensorium as in delirium (clinical presentation may be mistaken for an acute schizophrenic episode). Disordered perceptions become most pronounced after 24 to 36 h of abstinence.
2. Treatment: Same as for DTs (see “Withdrawal seizures”).
Withdrawal seizures (“rum fits”):
1. Time interval: Usually occurs 7 to 30 h after cessation of drinking, with a peak incidence between 13 and 24 h
2. Manifestations: Generalized convulsions with loss of consciousness; focal signs are usually absent; consider further investigation with CT scan of head and electroencephalography if clearly indicated (e.g., presence of focal neurologic deficits, prolonged postictal confusion state). In addition, in a febrile patient who is having a seizure or altered mental state, a lumbar puncture is necessary.
3. Treatment:
  1. Diazepam 2.5 mg/min IV until seizure is controlled (check for respiratory depression or hypotension) may be beneficial for prolonged seizure activity; IV lorazepam 1 to 2 mg q2h can be used in place of diazepam. Withdrawal seizures generally are self-limited and treatment is not required; the use of phenytoin or other anticonvulsants for short-term treatment of alcohol withdrawal seizures is not recommended
  2. Thiamine 100 mg IV, followed by IV dextrose, should also be administered.
  3. Electrolyte imbalances (increased Mg²⁺, decreased K⁺, increased or decreased Na⁺, decreased PO₄³-) that may exacerbate seizures should be corrected.
DTs:
1. Time interval: Variable; usually occurs within 1 wk after reduction or cessation of heavy alcohol intake and persists for 1 to 3 days. Peak incidence is 72 h and 96 h after the cessation of alcohol consumption.
2. Manifestations: Profound confusion, tremors, vivid visual and tactile hallucinations, autonomic hyperactivity; this is the most serious clinical presentation of alcohol withdrawal (mortality rate is approximately 15% in untreated patients).
3. Treatment:
  1. Admission to a detoxification unit where patient can be observed closely
  2. Vital signs q30min (neurologic signs, if necessary)
  3. Use of lateral decubitus or prone position if restraints are necessary
  4. NPO: Nasogastric tube for abdominal distention may be necessary but should not be routinely used
  5. Laboratory studies: Same as for early alcohol withdrawal
  6. Vigorous hydration (4 to 6 L/day): IV with glucose (Na⁺, K⁺, PO₄³– and Mg²⁺ replacement [if patient has hypophosphatemia or hypomagnesemia])
  7. Vitamins: Thiamine 100 mg IV qd. The initial dose of thiamine should precede the administration of IV dextrose; multivitamins (may be added to the hydrating solution)
  8. Sedation: Control of agitation should be achieved with rapid-acting sedative-hypnotic agents in adequate doses to maintain light somnolence for the duration of delirium
    1. Initially: Lorazepam 2 to 5 mg IM/IV repeated prn
    2. Maintenance (individualized dosage): Chlordiazepoxide, 50 to 100 mg PO q4 to 6h, lorazepam 2 mg PO q4h, or diazepam 5 to 10 mg PO tid; withhold doses or decrease subsequent doses if signs of oversedation are apparent
    3. Midazolam is also effective for managing DTs. Its rapid onset (sedation within 2 to 4 min of IV injection) and short duration of action (approximately 30 min) make it an ideal agent for titration in continuous infusion
  9. Treatment of seizures (as previously described)
  10. Diagnosis and treatment of concomitant medical, surgical, or psychiatric conditions

BOX 1 Alcohol Withdrawal Assessment Scoring Guidelines (Revised Clinical Institute Withdrawal Assessment for Alcohol Scale)

Nausea and Vomiting (0-7)

0, none; 1, mild nausea with no vomiting; 4, intermittent nausea; 7, constant nausea, frequent dry heaves and vomiting

Tremor (0-7)

0, no tremor; 1, not visible, but can be felt fingertip to fingertip; 4, moderate, with patient’s arms extended; 7, severe, even with arms not extended

Paroxysmal Sweats (0-7)

0, no sweats; 1, barely perceptible sweating, palms moist; 4, beads of sweat obvious on forehead; 7, drenching sweats

Anxiety (0-7)

0, no anxiety, patient at ease; 1, mildly anxious; 4, moderately anxious or guarded, so anxiety is inferred; 7, equivalent to acute panic states seen in severe delirium or acute schizophrenic reactions

Agitation (0-7)

0, normal activity; 1, somewhat more than normal activity; 4, moderately fidgety and restless; 7, pacing back and forth during, or constantly thrashing about

Tactile Disturbances (0-7)

Ask, “Have you experienced any itching, pins and needles sensation, burning or numbness, or a feeling of bugs crawling on or under your skin?”

0, none; 1, very mild itching, pins and needles, burning, or numbness; 2, mild itching, pins and needles, burning, or numbness; 3, moderate itching, pins and needles, burning, or numbness; 4, moderately severe tactile hallucinations; 5, severe hallucinations; 6, extremely severe hallucinations; 7, continuous hallucinations

Auditory Disturbances (0-7)

Ask, “Are you more aware of sounds around you? Are they harsh? Do they startle you? Do you hear anything that disturbs you or that you know isn’t there?”

0, not present; 1, very mild harshness or ability to startle; 2, mild harshness or ability to startle; 3, moderate harshness or ability to startle; 4, moderate hallucinations; 5, severe hallucinations; 6, extremely severe hallucinations; 7, continuous hallucinations

Visual Disturbances (0-7)

Ask, “Does the light appear to be too bright? Is its color different than normal? Does it hurt your eyes? Are you seeing anything that disturbs you?”

0, not present; 1, very mild sensitivity to light; 2, mild sensitivity; 3, moderate sensitivity; 4, moderate hallucinations; 5, severe hallucinations; 6, extremely severe hallucinations; 7, continuous hallucinations

Headache (0-7)

0, not present; 1, very mild; 2, mild; 3, moderate; 4, moderately severe; 5, severe; 6, very severe; 7, extremely severe

Orientation and Clouding of Sensorium (0-4)

Ask, “What day is this? Where are you? Who am I?”

0, oriented; 1, cannot do serial additions or is uncertain about date; 2, disoriented to date by no more than 2 calendar days; 3, disoriented to date by more than 2 calendar days; 4, disoriented to place and/or person

Total Score

0-9: Absent or minimal withdrawal
10-19: Mild to moderate withdrawal
More than 20: Severe withdrawal

From Sullivan JT et al: Assessment of alcohol withdrawal: the revised Clinical Institute Withdrawal Assessment for Alcohol Scale (CIWA-Ar), Br J Addict 84:1353-1357, 1989.

TABLE 3 Medications for the Treatment of Alcohol Dependence ∗

Medication	Dose and Route	Frequency	Effects	Major Common Adverse Effects
Alcohol Withdrawal
Benzodiazepines^†
Chlordiazepoxide ∗	25-100 mg, PO/IV/IM ^†	Every 4-6 h	Decreased severity of withdrawal; stabilization of vital signs; prevention of seizures and delirium tremens	Confusion, oversedation, respiratory depression
Diazepam ^‡	5-10 mg, PO/IV/IM ^†	Every 6-8 h
Oxazepam ^‡	15-30 mg, PO ^†	Every 6-8 h
Lorazepam ^‡	1-4 mg, PO/IV/IM ^†	Every 4-8 h
β-Blockers
Atenolol	25-50 mg, PO	Once a day	Improvement in vital signs	Bradycardia, hypotension
Propranolol	10-40 mg, PO	Every 6-8 h	Reduction in craving
α-Agonists
Clonidine	0.1-0.2 mg, PO	Every 6 h	Decreased withdrawal symptoms	Hypotension, fatigue
Antiepileptics
Carbamazepine	200 mg, PO	Every 6-8 h	Decreased severity of withdrawal; prevention of seizures	Dizziness, fatigue, red blood cell abnormalities
Prevention of Relapse
Disulfiram ^‡	125-500 mg, PO	Daily	Decreased alcohol use among those who relapse	Disulfiram-alcohol reaction, rash, drowsiness, peripheral neuropathy
Naltrexone ^‡	50 mg, PO	Daily	Increased abstinence, decreased drinking days	Nausea, abdominal pain, myalgias-arthralgias
	380 mg, IM	Every 4 wk
Acamprosate ^‡	666 mg, PO	Three times a day	Increased abstinence	Diarrhea

IM, intramuscular; IV, intravenous; PO, by mouth.

^∗Most commonly used medications listed.

^†Currently approved by U.S. Food and Drug Administration for the indication noted.

^‡Dose and routes given for standard fixed-dose regimens, which include dose tapers over time.

From Goldman L, Schafer AI: Goldman’s Cecil medicine, ed 24, Philadelphia, 2012, Saunders.

Figure 1 An example of an alcohol withdrawal chart.

From Cameron P et al: Textbook of adult emergency medicine, ed 5, 2020, Elsevier.

Chronic Rx

See “Referral.”
Pharmacotherapies for alcoholism include:
1. Acamprosate is a synthetic compound with a chemical structure similar to the neurotransmitter gamma-aminobutyric acid and the amino acid neuromodulator taurine. Its mechanism of action is not completely understood. It is indicated for the maintenance of abstinence from alcohol in patients with alcohol dependence who are abstinent at treatment initiation. It should be used only as part of a comprehensive psychosocial treatment program. It does not cause a disulfiram-like reaction as a result of ethanol ingestion. Dose is two 333-mg tablets tid. Treatment should be initiated as soon as possible after the period of alcohol withdrawal, when the patient has achieved abstinence, and should be maintained if the patient relapses. Avoid acamprosate if severe renal impairment is present.
2. The long-acting opiate antagonist naltrexone inhibits the rewarding effects of alcohol. The starting dose is 25 mg/day, increased to 50 mg PO qd after 1 wk. An extended-release, once-monthly injection of naltrexone is also available and can be used along with psychosocial support to maintain alcohol abstinence. In patients with opioid dependence, naltrexone can precipitate acute withdrawal syndrome and should not be used at least 7 days from last opioid use. There are no established guidelines on the appropriate length of naltrexone treatment for alcohol dependence. One study recommends at least 3 mo of treatment. Avoid naltrexone if acute hepatitis, hepatic failure, or ongoing opioid use is present.
3. Disulfiram (Antabuse): Dosage is 500 mg max qd for 1 to 2 wk, then 125 to 500 mg qd. It interferes with the metabolism of alcohol by inhibiting aldehyde dehydrogenase, causing an accumulation of acetaldehyde. It produces unpleasant symptoms (nausea, flushing, elevated blood pressure, headache, weakness) when alcohol is ingested. It is an older drug that is now rarely used.
4. Topiramate, baclofen, or gabapentin can be offered as second line drugs; to patients with moderate to severe alcohol use disorder topiramate might be preferable.
5. Avoid pharmacological treatments in pregnant or breastfeeding women.

Disposition

See “Referral.”

Referral

To Alcoholics Anonymous or Adult Children of Alcoholics
Family members to Al-Anon or Al-A-Teen
Many cities have Salvation Army Adult Rehabilitation centers; all patients accepted, regardless of ability to pay

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Basic Information ⬇

Diagnosis ⬆ ⬇

Treatment ⬆ ⬇

Pearls & Considerations ⬆ ⬇

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