Today we will continue our current theme of substance use disorders as we discuss alcohol use disorder (AUD). Today's post includes an introduction, diagnostic criteria of AUD, epidemiology, pathogenesis, clinical pearls, management of intoxication and withdrawal, and treatment of AUD.
Today's Content Level: Intermediate
Alcohol primarily acts as a central nervous system (CNS) depressant. It does this by enhancing GABA_A receptors (inhibitory neurotransmitter) and inhibiting NMDA glutamate receptors (excitatory neurotransmitter).
Alcohol is reinforcing because it increases dopamine release in the brain's reward system, particularly in the mesolimbic pathway, leading to feelings of pleasure, relaxation, and euphoria. Its anxiolytic and disinhibitory effects further enhance socialization and stress relief, making repeated use more likely, which can contribute to addiction over time.
Alcohol use disorder (AUD) is the most common substance use disorder, affecting millions worldwide.
Diagnostic Criteria 3
Diagnostic criteria for all substance use disorders are the same, characterized by a ≥ 12-month period of problematic substance use that leads to impairment or distress and requires ≥2 additional criteria. See Day #160: Introduction to Substance Use Disorders for complete diagnostic criteria and severity specifiers.
Genetics, environmental influences, and mental health comorbidities contribute to vulnerability.
Prevalence: Data from the 2023 United States National Survey on Drug Use and Health (NSDUH) → 10.2% of Americans had an Alcohol Use Disorder (AUD) in the past year.
Gender and Age: Men have higher rates than women. Highest rates in ages 18–29.
Genetics and Biology: Genetics, including the impact of one’s environment on gene expression, account for about 50% of a person’s risk. Genes related to alcohol metabolism (e.g., ADH1B, ALDH2) play a role. Chronic alcohol use affects the mesolimbic dopamine system, leading to reinforcement and dependence. GABAergic and glutamatergic dysregulation contribute to withdrawal symptoms.
Environmental Influences: Early exposure to alcohol, traumatic experiences, and peer/social influences increase risk.
History
Always ask about alcohol use in routine psychiatric evaluations—many patients underreport consumption.
Social and occupational impairments often precede physical complications—look for subtle signs early.
Screening Questionnaires: AUDIT (Alcohol Use Disorders Identification Test); CAGE questionnaire.
At-risk drinking = ≥ 14 drinks/week in men (max 4/day), ≥ 7 drinks/week in women (max 3/day).
Binge drinking = ≥ 5 drinks for men or ≥ 4 for women in ≤ 2 hours. This is a red flag even in those who don’t meet full AUD criteria.
If positive screening, obtain a detailed alcohol history (onset, frequency, quantity, last use, history of blackouts), prior treatment attempts, periods of sobriety, withdrawal symptoms (particularly any history of withdrawal seizures or delirium tremens), impact on daily functioning, legal obligations, and co-occurring psychiatric or medical conditions.
AUD is a chronic relapsing disorder; long-term follow-up is key.
Keep in mind that it is common for people to abuse several substances at once. Always be on the lookout for multiple substance use.
Physical Exam
Assess for signs of intoxication, withdrawal, and long-term complications.
General: may appear disheveled, malnourished, or intoxicated (e.g., slurred speech, unsteady gait).
Vital signs: hypertension (chronic alcohol use), hypotension & tachycardia (suggest withdrawal or dehydration), hypothermia (if intoxicated or malnourished).
Neurological: confusion & memory impairments +/- nystagmus (suggestive of Wernicke-Korsakoff syndrome), tremors (withdrawal-related), gait instability (cerebellar dysfunction from chronic alcohol use), peripheral neuropathy (distal paresthesias due to B-vitamin deficiencies), seizures (withdrawal-related or due to structural brain changes).
Skin / HEENT: liver dysfunction → jaundice, scleral icterus, spider angiomata, palmar erythema, bruising (coagulopathy from liver disease), and gynecomastia.
Cardiovascular: tachycardia (withdrawal, dehydration), signs of heart failure from alcoholic cardiomyopathy (edema, JVD).
Abdominal: hepatomegaly (fatty liver, hepatitis, cirrhosis) and splenomegaly (portal hypertension), ascites/edema (advanced liver disease) and caput medusae (sign of portal hypertension).
MSK: muscle wasting (protein-calorie malnutrition).
Labs
Several lab tests are useful for screening, assessing severity, monitoring complications, and tracking treatment progress by providing evidence of alcohol use, assessing organ damage, and ruling out other conditions.
Biomarkers for Alcohol Use: these biomarkers can indicate recent or chronic alcohol consumption. Arranged in order from smallest to largest detection window.
Blood Alcohol Level (BAL) and Breathalyzer (breath alcohol test, BrAC): Reflects acute intoxication (up to ~12 hours depending on amount ingested), but does not indicate chronic use.
Ethyl Glucuronide (EtG) & Ethyl Sulfate (EtS): Urine test detects recent alcohol use (EtG up to 80 hours (3-4 days); EtS up to 24 hours). Good for relapse monitoring, but can be falsely positive with incidental alcohol exposure (e.g., mouthwash). Can be detected in hair up to 90 days, but rarely used.
Carbohydrate-Deficient Transferrin (CDT): Best for detecting chronic heavy alcohol use (4-5 drinks/day for 2 weeks). Indicates heavy drinking within the past ~2-3 weeks. Can be used to monitor abstinence or relapse, and is ideal for long-term alcohol use trends. May be unreliable in patients with liver disease.
Phosphatidylethanol (PEth): Highly specific for alcohol consumption, detecting use up to 3-4 weeks. Not affected by incidental exposure like EtG/EtS. Very sensitive to any alcohol use (as little as 1-2 drinks), thus is excellent for relapse detection.
Gamma-Glutamyl Transferase (GGT): Elevated in chronic alcohol use and liver disease. Can normalize within a few weeks of abstinence (~2-6 weeks). GGT is not specific to alcohol use. It can also be increased due to other liver diseases, medications, and metabolic conditions.
Aspartate Aminotransferase (AST) & Alanine Aminotransferase (ALT): AST:ALT ratio >2:1 is suggestive of alcohol-related liver disease. ALT is usually lower compared to AST in AUD. Can remain elevated for weeks to months depending on liver damage.
Mean Corpuscular Volume (MCV): Increased in chronic alcohol use due to alcohol’s effects on bone marrow. Can take months to normalize after stopping alcohol.
Alcohol-Related Organ Damage and Nutritional Deficiencies: chronic alcohol use can lead to liver, pancreas, and nutritional deficiencies.
Liver Function Tests (LFTs): Bilirubin, albumin, and INR can assess liver function and damage. Low albumin and elevated INR suggest advanced liver disease.
Complete Blood Count (CBC): Macrocytosis (↑MCV) due to direct alcohol toxicity on bone marrow. Thrombocytopenia (low platelets) in liver disease or bone marrow suppression.
Electrolytes & Metabolic Panel: Hyponatremia (especially in SIADH due to alcohol). Hypokalemia, hypomagnesemia, hypophosphatemia (seen in malnutrition and refeeding syndrome). Elevated BUN/Creatinine suggests dehydration or kidney dysfunction such as an acute kidney injury. Creatine kinase (CK) if any suspicion of rhabdomyolysis.
Lipid Panel: Chronic alcohol use can lead to hypertriglyceridemia.
Amylase & Lipase: Elevated in alcohol-induced pancreatitis.
Thiamine (Vitamin B1): Deficiency can lead to Wernicke-Korsakoff syndrome (encephalopathy, ataxia, ophthalmoplegia), which can be fatal or lead to irreversible memory impairment. Checking thiamine levels can aid in the diagnosis, but clinical presentation is more important. Prompt thiamine replacement therapy is crucial if the syndrome is suspected regardless of lab results, as normal blood thiamine levels may not reflect brain deficiency.
Folate & Vitamin B12: Alcohol interferes with absorption, leading to macrocytic anemia.
Vitamin D, Zinc, and Other Micronutrients: Often deficient in chronic malnutrition associated with AUD.
Alcohol Intoxication
Symptoms:
Slurred speech, incoordination, disinhibition, nystagmus, impaired attention, depressed level of consciousness (e.g., stupor, or coma in severe cases).
Exclude other causes of altered mental status (e.g., head trauma, hypoxia, hypoglycemia, hypothermia, electrolyte abnormalities, encephalopathy, other intoxications).
Treatment:
Supportive care (+ airway protection if needed for severely depressed consciousness)
IV fluids
Thiamine to prevent Wernicke’s encephalopathy (more details in withdrawal section).
Glucose (only after thiamine to prevent precipitating Korsakoff syndrome).
Alcohol Withdrawal 9, 10
Remember that withdrawal symptoms of a drug are usually opposite of its intoxication effects. For example, alcohol is sedating, but alcohol withdrawal can → brain excitation, anxiety, and seizures. Severe withdrawal from alcohol can be life-threatening.
Chronic alcohol use →
↑ GABA activity (enhanced inhibition, relaxation)
↓ Glutamate activity (suppressed excitation)
Brain adapts: ↓ GABA receptor sensitivity & ↑ glutamate receptor activity to compensate.
Abrupt alcohol cessation →
↓ GABA activity (reduced inhibition)
↑ Glutamate activity (excess excitation)
CNS overreactivity → withdrawal symptoms.
Symptoms:
Starts within 6–24 hours of last drink, peaks at 48–72 hours, and some symptoms can last up to a week.
Uncomplicated withdrawal: anxiety, agitation, tremors, headache, insomnia, nausea, tachycardia, sweating, hyperreflexia.
Complicated withdrawal:
Hallucinations (aka alcoholic hallucinosis): 12-24 hours after last drink. Most commonly visual and/or tactile hallucinations with preserved attention and orientation. Typically resolves within 24-48 hours.
Seizures: 12-48 hours after last drink.
Delirium tremens (DTs): 48-96 hours after last drink. Confusion/disorientation, agitation, autonomic instability, +/- hallucinations. Potentially life-threatening condition. Can last 3-5 days, sometimes longer.
Use the Prediction of Alcohol Withdrawal Severity Scale (PAWSS) to predict risk of severe/complicated alcohol withdrawal in hospitalized patients.
Use the Clinical Institute Withdrawal Assessment Scale for Alcohol (CIWA-Ar) to help assign a severity score to current withdrawal symptoms and help guide treatment. >8 none to minimal; 8-15 mild; 16-20 moderate; >20 severe.
Treatment:
Benzodiazepines (BZDs): Agonists at GABA-A receptors, so BZDs help compensate for the sudden loss of alcohol's GABAergic effects during withdrawal. This results in stabilization of neuronal excitability, reduction of autonomic hyperactivity, and provides anxiolytic and sedative effects that ease discomfort.
First-line BZDs for alcohol withdrawal typically include lorazepam, diazepam, or chlordiazepoxide. Lorazepam is typically chosen if there is liver dysfunction, because it is not substantially metabolized by the liver.
Symptom-triggered treatment (based on CIWA-Ar scores) is often adequate.
In cases of severe withdrawal or history of complicated withdrawals, loading doses with a gradual taper can be used. Tapers generally take between 3-7 days, but can extend beyond that in severe cases.
Alternatives: Institution-specific protocols may use other phenobarbital), anticonvulsants (e.g., carbamazepine, gabapentin), or α-2 agonists (e.g., clonidine, dexmedetomidine) although evidence is variable.
Thiamine: If Wernicke Encephalopathy is on the differential, high-dose IV or IM thiamine is indicated (e.g., 500mg IV Q8h for 3-5 days). Otherwise, prophylactic thiamine PO 100mg daily is typically given.
IV fluids, electrolyte corrections, vitamins: Hypokalemia and hypomagnesemia are common. Folate and multivitamins can be given.
ICU admission: If DTs or severe autonomic instability.
•Effective treatment requires a combination of medical, psychological, and social interventions. A multi-disciplinary team—often including psychiatrists, primary care providers, therapists, social workers, and peer support specialists collaborates to address all aspects of the AUD.
Determine the Appropriate Treatment Setting: Choosing the right level of care depends on substance use severity, comorbid conditions, and prior treatment history. See Day 60: Intro to SUD for a description of each level of care.
Severe cases (DTs, history of complicated withdrawal) → inpatient detox, ideally followed by a residential treatment program, aka "rehab."
Mild/moderate cases → outpatient management with close follow-up. If outpatient treatment has failed, consider IOP or PHP.
Regardless of treatment setting, best practice may include random monitoring (e.g., breathalyzer, urine ethanol, urine EtG, PEth, etc.) + other drug screening.
Psychosocial Interventions: Individual and/or group therapy should be part of every SUD treatment approach. See Day 60: Intro to SUD for a discussion of interventions that include behavioral therapies, peer support & 12-step programs, and family support resources.
Medication-Assisted Treatment (MAT): MAT is an important component for treatment of AUD, improving retention in treatment and reducing relapse rates. MAT should be considered if patients prefer trying medications or if they fail other treatments without MAT. Naltrexone, acamprosate, and disulfiram are all FDA-approved for AUD, but Naltrexone is most commonly used.
Naltrexone
First-line option.
MOA: Mu-opioid receptor antagonist.
Reduces cravings and the pleasurable effects of drinking. Can be used while drinking. There is a long-acting injectable version, which can help adherence.
Limitations: Can cause hepatotoxicity; should generally be avoided if liver enzymes (AST/ALT) are more than 3–5 times the upper limit of normal. Also, naltrexone is contraindicated in opioid users since it induces withdrawal.
Acamprosate
Alternative first-line option, but three times a day (TID) dosing limits practicality.
MOA: Modulates glutamate (NMDA antagonist, GABA agonist).
Reduces cravings and withdrawal-related discomfort. It is safe in liver disease.
Limitations: Avoid in renal impairment.
Disulfiram
Second-line option.
MOA: Inhibits aldehyde dehydrogenase, causing acetaldehyde buildup when alcohol is consumed. This leads to flushing, nausea, tachycardia, and other uncomfortable hangover-like effects.
Limitations: It is an aversion therapy, so it requires high motivation and adherence. It also has the potential to cause hepatotoxicity.
Off-label options
Gabapentin and topiramate have also been successfully used, however they are not FDA-approved. Gabapentin can help reduce cravings and withdrawal symptoms and may improve abstinence rates, particularly in those with co-occurring insomnia or anxiety. Topiramate can decrease cravings and binge drinking and may reduce reinforcing effects of alcohol.
Conclusion
•Alcohol use disorder is a prevalent but treatable condition. Early recognition and intervention can significantly improve outcomes. Clinicians should incorporate routine screening, evidence-based treatments, and long-term follow-up into practice. With a combination of pharmacologic and psychosocial approaches, patients can achieve recovery.
•In our next post we will discuss sedative-hypnotics, focusing on benzodiazepines, but also discussing barbiturates and Z-drugs.
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