Alcohol Use Disorder (AUD)

Risk factors

• Family history (heritability ~50%)
• Early-onset drinking (<14 years)
• Comorbid psychiatric illness — mood, anxiety, PTSD, ASPD, ADHD
• Trauma history
• Male sex, certain occupations, social environment
• Other SUDs

Pathophysiology

Chronic alcohol use produces neuroadaptation: upregulated glutamatergic (NMDA) and downregulated GABAergic tone, accounting for tolerance and withdrawal phenomena. Mesolimbic dopaminergic reinforcement drives compulsive use.

Clinical presentation

Differential diagnosis

• Mood/anxiety disorder — May drive self-medication; reassess after sustained abstinence
• PTSD — Frequent comorbidity; address trauma in treatment plan
• Withdrawal mimics: hyperthyroidism, sepsis, sympathomimetic intoxication — Vital signs, TSH, infectious workup
• Delirium from other causes — Especially in hospitalized; consider Wernicke encephalopathy

Diagnostic workup

Diagnostic algorithm

flowchart TD
  A[Last drink] --> B["6-12 h: Tremor, anxiety,<br/>insomnia, GI upset"]
  B --> C["12-48 h: Withdrawal seizures<br/>peak ~24 h"]
  B --> D["12-24 h: Alcoholic hallucinosis<br/>intact sensorium"]
  C --> E["48-96 h: Delirium tremens<br/>autonomic instability, confusion"]
  D --> E
  E --> F["Mortality ~5% treated,<br/>up to 35% untreated"]
  A -.-> G["Any stage: symptom-triggered<br/>benzodiazepine + thiamine"]

Treatment

Complications

• Withdrawal seizures (peak 12-48 h), delirium tremens (48-96 h, mortality ~5% treated, ~35% untreated)
• Wernicke encephalopathy (ophthalmoplegia, ataxia, confusion) and Korsakoff syndrome (anterograde amnesia, confabulation)
• Cirrhosis, hepatocellular carcinoma, pancreatitis
• Cardiomyopathy, hypertension, atrial fibrillation ('holiday heart')
• Cancer (oropharyngeal, esophageal, breast, colorectal)
• Fetal alcohol spectrum disorders
• Trauma, motor vehicle crashes, suicide

PANCE pearls

• Give IV thiamine 500 mg TID x 3 days for suspected Wernicke (not 100 mg PO which underdoses) — BEFORE glucose to prevent precipitating encephalopathy.
• DT typically begins 48-96 hours after last drink — risk factors include prior DT, prior withdrawal seizures, autonomic hyperactivity, electrolyte derangements.
• Naltrexone is contraindicated with opioid use (precipitates withdrawal); confirm opioid-free x 7-10 days before starting.
• AUDIT-C is a 3-question rapid screen; positive prompts brief intervention and consideration of pharmacotherapy.
• Pharmacotherapy is markedly underutilized — offer to every patient with AUD.
• Wernicke encephalopathy is a clinical diagnosis: thiamine is a cofactor for pyruvate dehydrogenase, alpha-ketoglutarate dehydrogenase, and transketolase, and deficiency damages the mammillary bodies, medial thalamus, and periaqueductal gray; the full triad is present in only a minority, so give empiric IV thiamine on suspicion without waiting for thiamine levels or MRI, and never withhold glucose from a hypoglycemic patient (give thiamine first or concurrently).

References

• USPSTF 2018 — Screening and Behavioral Counseling Interventions to Reduce Unhealthy Alcohol Use in Adolescents and Adults: USPSTF Recommendation. JAMA 2018
• VA/DoD 2021 — VA/DoD Clinical Practice Guideline for the Management of Substance Use Disorders (2021)
• NIAAA / SAMHSA — NIAAA Clinician's Guide; SAMHSA TIP 49: Incorporating Alcohol Pharmacotherapies
• DSM-5-TR — American Psychiatric Association. DSM-5-TR (2022)
• APA 2018 — Reus VI, Fochtmann LJ, Bukstein O, et al. The American Psychiatric Association Practice Guideline for the Pharmacological Treatment of Patients With Alcohol Use Disorder. Am J Psychiatry. 2018;175(1):86-90
• ASAM 2020 — The ASAM Clinical Practice Guideline on Alcohol Withdrawal Management. J Addict Med. 2020;14(3S Suppl 1):1-72
• EFNS 2010 — Galvin R, Bråthen G, Ivashynka A, Hillbom M, Tanasescu R, Leone MA. EFNS guidelines for diagnosis, therapy and prevention of Wernicke encephalopathy. Eur J Neurol. 2010;17(12):1408-1418