Alcohol use disorder

• Alcohol use disorder (AUD) is a chronic condition in which drinking persists despite harm, with impaired control, craving, tolerance, or withdrawal.
• It is common: in 2019 about 400 million people aged 15 years or older lived with an alcohol use disorder, of whom 209 million had alcohol dependence.^[4]
• Most people with AUD are never treated; screening and a brief conversation in any clinical setting change more lives than any later intervention.
• Withdrawal can kill. Delirium tremens appears in 3-5% of patients about 72 hours after the last drink and carries up to 50% mortality when missed.^[5]
• After withdrawal is safely completed, naltrexone 50 mg daily, acamprosate up to 1998 mg daily, or disulfiram 200 mg daily, combined with psychological support, reduce relapse.^[1]

By the end of this page you should be able to:

1. Define AUD and place it on the spectrum from low-risk drinking through hazardous and harmful drinking.
2. Screen a patient with AUDIT, AUDIT-C, CAGE and the NIAAA single question, using the stated cut-offs.
3. Recognise and time-limit the features of alcohol withdrawal, and score it with the CIWA-Ar scale.
4. Prescribe a benzodiazepine regimen for withdrawal and state when inpatient supervision is required.
5. Recognise delirium tremens and treat it with the first-line agents named in NICE CG100.
6. Give parenteral thiamine correctly, including the relation to glucose.
7. Compare naltrexone, acamprosate and disulfiram by dose, timing, monitoring and warnings.
8. Adapt assessment and management for pregnancy, adolescents and older adults.

Alcohol use exists on a spectrum.^[7] At one end is low-risk use. In the middle is risky or hazardous drinking: in the UK NICE definitions, drinking more than 14 units a week but fewer than the harmful amounts.^[2] Harmful drinking (high-risk drinking) is a pattern that is already causing mental or physical damage.^[2] At the severe end is alcohol dependence, the central form of AUD.

Helpful quantitative thresholds from NICE CG100 are:^[2]

• Harmful drinking: 35 units or more a week for women, 50 units or more for men. ^[2]
• Hazardous drinking: more than 14 units a week but less than those amounts.

For a patient, a standard drink is a more practical measure (one small glass of wine, half a pint of beer, or a single measure of spirits), and the USPSTF gives the US definitions: 12 oz of 5% beer, 5 oz of 12% wine, or 1.5 oz of 40% liquor.^[3] Risky use in the NIAAA definition is exceeding 4 standard drinks per day or 14 per week for healthy men aged 21 to 64, and 3 per day or 7 per week for women of any age and men 65 or older.^[3]

The diagnosis is clinical. Two commonly used official systems are DSM-5-TR and ICD-11; DSM-5-TR treats AUD as a single diagnosis with severity graded by the number of criteria met. NICE CG115 adds that abstinence is the appropriate goal for most people with alcohol dependence, and for those who misuse alcohol and have significant psychiatric or physical comorbidity such as depression or alcohol-related liver disease.^[1]

Alcohol is the most commonly used psychoactive substance worldwide, and ethanol is both psychoactive and toxic, with the potential to cause dependence.^[4]

• Deaths: in 2019 about 2.6 million deaths were caused by alcohol consumption worldwide; 1.6 million were from noncommunicable diseases, 700 000 from injuries and 300 000 from communicable diseases.^[4] Alcohol caused 6.7% of all deaths among men and 2.4% among women.^[4]
• Burden: an estimated 400 million people, or 7% of the world population aged 15 years or older, lived with alcohol use disorders in 2019; 209 million (3.7% of the adult world population) lived with alcohol dependence.^[4]
• Sex: 52% of men and 35% of women were current drinkers in 2019; men consumed 8.2 litres of pure alcohol per person per year against 2.2 litres for women.^[4]
• Age: people aged 20 to 39 were disproportionately affected, carrying 13% of alcohol-attributable deaths in 2019.^[4]
• United States: alcohol is the most commonly used substance; about 84% of adults reported lifetime use in 2022; 29.5 million people aged 12 or over have AUD, yet only 7.6% receive treatment.^[7] AUD contributes to over 200 000 US hospitalisations annually and 7.4% of emergency department visits.^[7] In NIAAA survey data quoted by USPSTF, an estimated 7.8% of men and 4.2% of women met criteria for AUD.^[3] About 1 in 10 deaths in US adults aged 20 to 64 is attributable to excessive alcohol use.^[3]
• Treatment access: screening, brief intervention and treatment remain patchy globally, and fewer than 1% to no more than 14% of people with an alcohol use disorder are in contact with treatment where data exist.^[4]

No single cause explains AUD; susceptibility builds from repeated exposure and interaction between host, drink and setting.

• Dose and duration of use. Heavier and longer drinking raises the risk of dependence; alcohol withdrawal symptoms manifest in about 50% of people who misuse alcohol.^[5]
• Genes and family history. AUD clusters in families through both shared environment and heritability; familial risk is the clearest non-modifiable factor a student should look for in the history.
• Sex, ethnicity and social factors. In US data cited in one teaching review, rates of use are higher among white males, Native Americans and people of lower socioeconomic status.^[5]
• Comorbidity. Depression, anxiety, post-traumatic stress, other substance use, chronic pain and liver disease all increase risk and complicate treatment.^[1]
• Early onset and trauma. Starting to drink young and childhood adversity are both associated with later AUD.
• Physical route. Chronic use leads to GABA-A receptor downregulation and NMDA receptor upregulation, so the nervous system is left hyperexcitable when drinking stops; this is the mechanism of withdrawal, described below.^[5]

Ethanol is a central nervous system depressant that acts mainly by enhancing GABA-A receptor signalling and, with chronic use, by increasing glutamate (NMDA) signalling to compensate. The result is neuroadaptation: with continued heavy use the brain expects alcohol to be present, and sudden removal produces hyperexcitability. That is the mechanism of tremor, sweating, tachycardia, seizures and delirium tremens.^[5]

Ethanol is metabolised in the liver to acetaldehyde and then acetate. Chronic misuse produces nutritional deficits (thiamine, folate, magnesium, phosphate) and toxicity to the liver, pancreas, heart, nerves and brain. Malnutrition matters because thiamine (vitamin B1) stores are low; glucose loads can precipitate or worsen Wernicke encephalopathy by consuming residual thiamine.^[5]

AUD is also a reward-circuit disorder: repeated drinking sensitises dopaminergic pathways, which drives craving and loss of control even when drinking is no longer pleasurable.

Patients rarely say "I have AUD". They say they drink more than they plan, need a drink in the morning, or that others have complained. Ask quantity and frequency in standard drinks, the largest amount in one day, tolerance, blackouts, injuries, and withdrawal symptoms on days without drinking. Ask about psychiatric symptoms, sleep, pain, and family history.

Symptoms that suggest established dependence include craving, drinking to avoid or relieve withdrawal, failed attempts to cut down, and neglect of role obligations.^[2]

Look for stigmata of chronic alcohol use and its complications:

• Autonomic overactivity during withdrawal: coarse tremor of the hands and tongue, sweating, tachycardia, hypertension.
• Chronic liver disease: spider naevi, palmar erythema, gynecomastia, testicular atrophy, jaundice, ascites.
• Nutritional deficiency: angular stomatitis, glossitis, peripheral neuropathy, proximal myopathy.
• Neurology: nystagmus, ophthalmoplegia, ataxia, confusion (triad of Wernicke encephalopathy), memory gaps.
• Mental state: depression, anxiety, insomnia, hallucinations; risk of self-harm.

A quick screen of cognition and the presence or absence of the Wernicke triad guide urgent thiamine use.

Alcohol withdrawal is the clinical syndrome that follows reduction or cessation in a person who is dependent. Pearls from one emergency medicine teaching review:^[5]

• Symptoms typically begin a few hours after reduction or cessation, peak at one to three days, and can last up to 14 days.
• Mild features: anxiety, tremor, sweating, nausea and vomiting, insomnia.
• Hallucinations occur in 2-8% of patients, typically 12-24 hours after the last drink. ^[5]
• Seizures (generalised tonic-clonic) occur in 6-15% of patients, typically 12-48 hours after the last drink. ^[5]
• Delirium tremens occurs in 3-5% of patients, about 72 hours after the last drink. ^[5]

The Clinical Institute Withdrawal Assessment for Alcohol, revised (CIWA-Ar) is a validated 10-item tool that quantifies the severity of withdrawal and guides treatment throughout withdrawal.^[2][5] Total scores range from 0 to 67.^[5] Symptom-triggered treatment guided by the CIWA-Ar is preferred over fixed dosing, with the goal of a lightly dozing but arousable patient.^[5]

Wernicke encephalopathy is an acute, reversible brain syndrome from thiamine deficiency, presenting fully or partly with confusion, ataxia and ophthalmoplegia. It is not the same as withdrawal: a patient can have both, and thiamine is given before or with glucose in suspected cases.^[5][2]

Screening should be universal in primary care and inpatient practice; the NICE and USPSTF recommendations agree on validated tools.^[1][3]

US criteria for risky limits from NIAAA, quoted by USPSTF, are: more than 4 drinks a day or 14 a week for men aged 21 to 64; more than 3 a day or 7 a week for women of any age and men 65 or older.^[3]

A full assessment is indicated when AUDIT exceeds 15 or the clinical picture suggests dependence.^[1] NICE recommends adjusting the criteria for women, older people, children and young people, and people with established liver disease, who may metabolise alcohol differently.^[1]

Investigations serve three purposes: confirming the pattern of use, identifying complications, and planning withdrawal safely.

• Laboratory: full blood count, mean corpuscular volume, electrolytes, magnesium, phosphate, glucose, liver function tests, pancreatic enzymes, renal function, coagulation, and thiamine status in context.
• Cardiac: ECG (alcohol can be pro-arrhythmic), particularly in older patients or those with symptoms.
• Imaging: chest radiograph if infection suspected; brain imaging only when trauma, seizure, focal signs, or delirium beyond expected withdrawal.
• Scales: CIWA-Ar during acute withdrawal; SADQ or LDQ at baseline; AUDIT as a routine outcome measure.^[1]
• Comorbidity screen: depression, anxiety, post-traumatic stress, other substances, and risk of self-harm.

Wernicke encephalopathy is a clinical diagnosis; do not delay thiamine for imaging.

For most people with alcohol dependence the appropriate goal is abstinence.^[1] For others, harm reduction may be realistic. Never promise a cure: AUD behaves like other chronic relapsing conditions, and engagement plus medication plus psychology improves outcomes.

The overall approach is to screen, assess severity, decide the setting for withdrawal, complete withdrawal safely, start relapse-prevention medication and psychological support, and follow up.

The first question is where withdrawal should happen.

Community-based assisted withdrawal is suitable for many patients who drink under 15 units a day, or who do not have high-risk features. NICE CG115 suggests considering community-based assisted withdrawal or specialist assessment for adults who typically drink over 15 units daily and or who score 20 or more on AUDIT, and lists inpatient or specialist management when there are safety concerns.^[1]

Inpatient or specialist assisted withdrawal is more appropriate when a person:^[1]

• typically drinks over 30 units a day;
• has a SADQ score over 30;
• has a history of epilepsy, withdrawal-related seizures or delirium tremens during previous withdrawals;
• needs concurrent withdrawal from alcohol and benzodiazepines;
• drinks 15 to 30 units daily with significant psychiatric or physical comorbidity or significant learning disability or cognitive impairment.

NICE CG100 adds that people in acute withdrawal who have, or are at high risk of, alcohol withdrawal seizures or delirium tremens should be offered admission for medically assisted withdrawal.^[2]

Medication. The preferred medication for assisted withdrawal is a benzodiazepine: chlordiazepoxide or diazepam.^[1] Carbamazepine may be considered, and clomethiazole may be offered as an alternative in inpatient settings only, with caution and according to its product information.^[2] NICE CG100: offer pharmacotherapy for acute withdrawal as benzodiazepine or carbamazepine, with clomethiazole in inpatient settings only.^[2]

• Fixed-dose regimen (community): start with a standard dose and reduce to zero over 7 to 10 days according to a standard protocol.^[1]
• Initial dose is titrated to severity of dependence and daily drinking, with higher doses for severe dependence, within product information limits.^[1]
• In a hospital or any setting with 24-hour assessment and monitoring, follow a symptom-triggered regimen instead.^[2]

One emergency medicine review gives practical intravenous doses for the acutely ill patient:^[5]

• Diazepam: typical loading dose 10-20 mg IV; rapid onset, active metabolites, metabolised by the liver, so use cautiously with impaired liver function. ^[5]
• Lorazepam: typical dose 2-4 mg IV; rapid onset, no active metabolites, metabolised by the kidneys. ^[5]
• Phenobarbital: typical dose 10-15 mg/kg IV, with bolus doses of 65 mg, 130 mg and 260 mg IV. ^[5]
• Propofol: 0.3-1.25 mg/kg/h infusion, usually as an adjunct for intubated patients. ^[5]
• Ketamine: 0.2 mg/kg/h infusion, as a second-line agent with other agents. ^[5]

Monitoring includes pulse, blood pressure, temperature, CIWA-Ar where it helps, and good supportive care: thiamine, fluids, electrolyte correction, glucose control and a calm, well-lit environment.^[2][5]

In delirium tremens, oral lorazepam is first-line treatment. If symptoms persist or oral medication is declined, offer parenteral lorazepam or haloperidol.^[2] Both uses were off-label as of the 2017 update of CG100, so follow local product information.^[2] If delirium tremens develops during treatment for acute withdrawal, review the withdrawal drug regimen.^[2]

For alcohol withdrawal seizures, offer a quick-acting benzodiazepine such as lorazepam to reduce the chance of further seizures, and do not offer phenytoin.^[2]

People at risk of Wernicke encephalopathy need thiamine, and the dose depends on risk and setting.^[2]

• Offer prophylactic oral thiamine to harmful or dependent drinkers who are malnourished or at risk of malnourishment, or who have decompensated liver disease, and before and during a planned medically assisted withdrawal.^[2]
• Offer prophylactic parenteral thiamine followed by oral thiamine to those same patients when they attend an emergency department or are admitted with an acute illness or injury.^[2]
• Offer parenteral thiamine to people with suspected Wernicke encephalopathy, maintaining a high index of suspicion, particularly if the person is intoxicated. Parenteral treatment continues for a minimum of 5 days unless Wernicke encephalopathy is excluded; oral thiamine follows.^[2]
• Doses should be toward the upper end of the BNF range, by the oral or parenteral route as recommended.^[2]
• In acute practice, give intravenous thiamine 500 mg with glucose, concurrently and not after, to prevent or treat Wernicke encephalopathy.^[5]
• Give thiamine before or with glucose: glucose metabolism consumes thiamine and can worsen Wernicke encephalopathy.^[5]

NICE CG115 adds that people entering planned assisted withdrawal in specialist inpatient alcohol services or prison settings who are malnourished or at risk of malnourishment, or who have decompensated liver disease, should receive parenteral thiamine followed by oral thiamine.^{[1] [2]}

Withdrawal alone does not treat AUD. The ASAM Clinical Practice Guideline on Alcohol Withdrawal Management (2020 edition) states that withdrawal management alone is not effective treatment for AUD and should be a component of engaging the patient in ongoing treatment.^[6]

After withdrawal, combine any pharmacotherapy with an individual psychological intervention such as cognitive behavioural therapy, motivational enhancement, or contingency management.^[1] Mutual-aid groups and follow-up with the same team help sustain change. Involve family where the patient consents.

NICE CG115 recommends offering relapse-prevention medication after successful withdrawal for people with moderate and severe alcohol dependence.^[1]

Acamprosate. Usually prescribed at 1998 mg per day (666 mg three times a day), with a maximum of 1332 mg per day if the person weighs less than 60 kg.^[1] It is usually prescribed for up to 6 months, or longer for those who benefit and wish to continue, and stopped if drinking persists for 4 to 6 weeks after starting.^[1]

Naltrexone (oral). Start at 25 mg per day and aim for a maintenance dose of 50 mg per day, with the same usual 6-month duration and stopping rule.^[1]

Disulfiram. Usually 200 mg per day, starting at least 24 hours after the last alcoholic drink.^[1] If a 200 mg dose, taken regularly for at least 1 week, does not produce a sufficiently unpleasant reaction to deter drinking, consider increasing the dose in consultation with the patient.^[1]

Before starting disulfiram, test liver function, urea and electrolytes to assess for liver or renal impairment, and check the product information for warnings and contraindications, including a history of severe mental illness, stroke, heart disease or hypertension and pregnancy.^[1] Patients should stay under supervision at least every 2 weeks for the first 2 months and monthly for the following 4 months, and be medically monitored at least every 6 months after the initial 6 months; if possible, a family member or carer who understands the drug oversees administration.^[1] Warn that the disulfiram-alcohol reaction can be triggered by alcohol in food, perfume and aerosols, with flushing, nausea, palpitations and, more seriously, arrhythmias, hypotension and collapse, and that the rare complication of hepatotoxicity requires stopping the drug and urgent medical attention for unwellness, fever or jaundice.^[1]

Naltrexone too should be considered in relation to opioid use and pregnancy; follow local product information.

• Refer to specialist alcohol services for comprehensive assessment in adults scoring more than 15 on AUDIT.^[1]
• Refer urgently for withdrawal with high-risk features, pregnancy, adolescents, significant comorbidity, or suspected Wernicke encephalopathy.
• Reassess drinking, AUDIT and goals at each visit; support harm reduction if abstinence is not immediately achievable.

Alcohol is associated with damage in nearly every system:

• During and immediately after withdrawal: seizures, delirium tremens, electrolyte disturbance, aspiration, pneumonia, death.^[2][5]
• Liver: alcoholic hepatitis, cirrhosis, hepatocellular carcinoma.
• Gastrointestinal: gastritis, Mallory-Weiss tears, pancreatitis.
• Cardiovascular: hypertension, cardiomyopathy, arrhythmias.
• Neurological: peripheral neuropathy, cerebellar degeneration, Wernicke and Korsakoff syndromes, alcoholic dementia.
• Psychiatric: depression, anxiety, suicide, other substance use.
• Pregnancy and child health: fetal alcohol spectrum disorders, preterm birth, miscarriage, stillbirth.^[4]
• Social and legal: injury, violence, loss of employment, homelessness.

The natural history is relapsing. Many people cut down or stop drinking after brief interventions, but established dependence usually needs repeated engagement over years. About 7.6% of people with AUD in the United States receive treatment, so improving access and follow-up is as important as drug choice.^[7] Treatment with medication and psychosocial support improves abstinence and reduces heavy-drinking days. All three drugs discussed are recommended in NICE CG115 for post-withdrawal patients who are appropriately selected and monitored.^[1]

• Prevention includes price and availability policies, limits on marketing, early education, and screening in primary care and hospitals, areas where WHO notes large gaps in access.^[4]
• Screen all adults for unhealthy alcohol use and provide brief interventions; ASAM recommends routine screening of adults and appropriate interventions where needed.^[3]
• NICE CG115: use AUDIT for identification and outcome monitoring; comprehensive assessment for adults scoring more than 15.^[1]
• Pregnancy: WHO recommends screening all women before pregnancy and in the first trimester with a validated tool, and offering a brief intervention to every pregnant woman who uses alcohol.^[3][4] ACOG agrees with routine screening. Alcohol in pregnancy is a leading preventable cause of birth defects and developmental disability.^[3][4]

Pregnancy and breastfeeding. Avoid alcohol in pregnancy; there is no known safe threshold, and alcohol causes fetal alcohol spectrum disorders and increases the risk of preterm birth, miscarriage and stillbirth.^[4] Screening and brief intervention for all women before pregnancy and in the first trimester is recommended by WHO.^[3] Disulfiram and other relapse-prevention drugs generally require specialist review in pregnancy and breastfeeding.

Children and adolescents aged 10 to 17 years. NICE CG115 recommends an initial brief assessment rather than the adult pattern, with lower AUDIT thresholds for younger adolescents because of the more harmful effects of a given level of drinking, and inpatient care if assisted withdrawal is required.^[1] USPSTF recommends screening adolescents as part of unhealthy alcohol use screening.^[3]

Older adults. NICE CG115 specifically says to adjust assessment criteria for older people, who may metabolise alcohol differently and who are more vulnerable to falls, drug interactions, cognitive impairment and liver disease.^[1] Lower-risk thresholds and a higher index of suspicion are appropriate.

Low-resource settings. Many countries lack specialist alcohol services.^[4] In such settings:

• Use AUDIT and the SASQ, which cost nothing and take minutes.
• Give brief advice based on the result.
• Use fixed-dose chlordiazepoxide or diazepam for withdrawal where safe monitoring allows; admit anyone with high-risk features.
• Give parenteral thiamine and glucose to suspected Wernicke cases; thiamine is inexpensive and often stocked.
• Refer to the next level of care and support mutual-aid groups.

Alcohol use disorder connects to the pages on Wernicke-Korsakoff syndrome, alcohol withdrawal and intoxication, liver disease and cirrhosis, pancreatitis, and substance misuse. These are listed here as plain text because they are planned MedGrasp topics; cross-links can be added once they are verified.

• AUD is a chronic, relapsing disorder spanning hazardous drinking through severe dependence; abstinence is the goal for most dependent patients.
• In 2019, 400 million people aged 15 or older (7%) had an alcohol use disorder, 209 million of them with dependence.
• Screen universally with AUDIT, AUDIT-C, CAGE or the single question; comprehensive assessment is indicated above 15 on AUDIT.
• Dependence is diagnosed by clinical criteria and quantified with SADQ or LDQ; adjust cut-offs for women, older adults, young people and people with liver disease.
• Withdrawal begins within hours, peaks at one to three days, and can last up to 14 days; seizures occur in 6-15% of patients and delirium tremens in 3-5% at about 72 hours.
• Delirium tremens has up to 50% mortality if missed; treat with oral lorazepam first, then parenteral lorazepam or haloperidol.
• Benzodiazepines (chlordiazepoxide or diazepam) are the preferred withdrawal drugs; use fixed dosing over 7 to 10 days in the community and symptom-triggered dosing with 24-hour monitoring.
• Give thiamine toward the upper BNF range, parenterally and for at least 5 days in suspected Wernicke encephalopathy, and always before or with glucose. ^[2]
• After withdrawal, offer acamprosate (1998 mg daily, 1332 mg if under 60 kg), naltrexone (start 25 mg, maintain 50 mg), or disulfiram (200 mg daily from 24 hours after the last drink).
• Withdrawal management alone is not treatment for AUD; combine medication with psychological intervention and follow-up.
• Screen all women before pregnancy and in the first trimester; alcohol in pregnancy causes fetal alcohol spectrum disorders and other complications.