Alcohol-Related Disorders

J. Greg Hobelmann, M.D., M.P.H., Jeffrey Hsu, M.D.

DEFINITION

  • Alcohol use disorders are medical conditions that are diagnosed when a patient’s drinking causes significant concern or harm, and decrease in functioning. They were formerly classified as either alcohol dependence (alcoholism) or alcohol abuse.

EPIDEMIOLOGY

  • Lifetime prevalence: men 10%, women 5%
  • Groups at increased risk: Individuals with a family history of alcoholism, trauma victims, and persons with personality disorders (borderline and antisocial)
  • Earlier exposure to alcohol increases risk
  • Quick development of high tolerance is predictive of developing dependence.
  • Genes account for approximately 60% of variance in developing alcohol dependence.
  • Estimated cost of alcohol abuse in the U.S. was $249 billion in 2010 according to the CDC.

DIAGNOSIS

Clinical Presentation

  • No typical pattern describes the progression from heavy drinking to problematic drinking, but certain features appear to be dominant:
    • Binge drinking or drinking to the point of intoxication
    • Increased tolerance to alcohol
    • Cravings to drink
    • Consequences from drinking: taking sick days from work, breakdown of interpersonal relationships, driving under the influence, legal problems, traumatic events
    • Blackouts (amnestic events during drinking)
    • Worsening of hangovers
    • Feelings of guilt, remorse, regret, or disgust over drinking, yet difficulty reducing intake
    • Concealment of drinking
    • Withdrawal with cessation of drinking
  • Physical features:
    • Arcus senilis
    • Tremor
    • Hypertension
    • Rhinophyma
    • Telangiectasias
    • Impaired cognitive function
    • Signs of liver failure
    • Signs of physical trauma
  • Medical complications:
    • Respiratory suppression: can occur after acute consumption of large amounts of alcohol and can be fatal
    • Wernicke’s encephalopathy: triad of ophthalmoplegia, ataxia, and confusion due to thiamine deficiency, reversible
    • Korsakoff syndrome: also due to thiamine deficiency and associated with short-term memory impairment, often irreversible
    • Alcohol withdrawal syndrome
      • Mild to moderate withdrawal (6-24 hrs after last drink): tremor, anxiety, insomnia, tachycardia, hypertension, diaphoresis, nausea, paresthesia, perceptual disturbances
      • Alcohol-induced psychotic disorder or hallucinosis (12 hrs after last drink): visual hallucinations of animals; auditory hallucinations of unformed sounds or derogatory voices
      • Seizures (48 hrs after last drink): generalized tonic-clonic motor seizures, can present in clusters
      • Alcohol withdrawal delirium or delirium tremens (72-96 hrs after last drink): altered sensorium, severe agitation, hallucinations without insight, profound sympathetic hyperactivity
    • Esophageal varices
    • Gastritis
    • Pancreatitis
    • Alcoholic hepatitis
    • Cirrhosis or fatty liver
    • Cardiomyopathy
    • Macrocytic anemia
    • Peripheral neuropathy
    • Fetal alcohol syndrome
    • Impaired sexual functioning
    • Increased risk of throat, mouth, breast cancer
    • Increased risk of death from motor vehicle accidents, falls, accidental drowning, suicide

Tests and Procedures

  • Screening for at-risk alcohol consumption
    • Single question screen: How many times in the past year have you had >5(men)/>4(women) drinks in a day? If answer >1 time(s), then positive screen
      • 1 standard drink = 12 oz beer, 5 oz wine, or 1.5 oz 80-proof spirits
    • Alcohol Use Disorders Identification Test (AUDIT)
      • 10-item questionnaire, assesses alcohol consumption and consequences of use
      • Positive score >8 for men, >4 for women
    • Liver function tests: aspartate transferase (AST):alanine transferase (ALT) ratio = 2:1 is suggestive of excessive alcohol consumption
    • Elevated gamma-glutamyl transpeptidase (GGT): 70-80% sensitive and specific
    • Elevated percent carbohydrate deficient transferrin (CDT): 70-80% specific
    • Triglycerides, uric acid and bilirubin are typically elevated
    • Raised mean corpuscular volume (MCV)
    • Elevated amylase and lipase with alcoholic pancreatitis
    • Early Detection of Alcohol Consumption (EDAC) score: Score obtained from a panel of 25 hematology and chemistry tests that may predict heavy drinking
  • Testing for alcohol ingestion
    • Blood alcohol concentration (mg/dL)
    • Breathalyzers (g/210 L)
    • Serum phosphatidylethanol (PEth)- can detect heavy alcohol consumption up to a month after cessation of drinking
    • Urine testing: qualitative measures which can be used to monitor ongoing abstinence
      • Urine alcohol: detected during acute intoxication
      • Urine ethyl glucuronide (Etg): very sensitive and can detect alcohol in the urine 5-7 days after consumption. False positives can occur with use of alcohol-based mouthwashes or hand sanitizer.

Differential Diagnosis

  • Brain trauma
  • Electrolyte disturbances
  • Hypoglycemia
  • Ketoacidosis (diabetic)
  • Meningitis
  • Neurological conditions such as multiple sclerosis
  • Stroke
  • Pneumonia or sepsis

TREATMENT

General

  • Treatment of acute intoxication is usually not needed as effects subside with time, but flumazenil can be used to reverse respiratory suppression.
  • Treatment of the chronic sequelae of alcohol use disorders is directed at treating the complications listed above.

Pharmacotherapy

  • Alcohol withdrawal treatment
    • Mild-moderate withdrawal
      • Benzodiazepines are the treatment of choice, effective at preventing alcohol withdrawal seizures and delirium.
      • Symptom-triggered dosing is associated with less use of medication and shorter duration of treatment.
        • Use an alcohol withdrawal severity scale such as the Clinical Institute Withdrawal Assessment-Alcohol, Revised (CIWA-Ar) to guide treatment
        • Administer benzodiazepine every hour until CIWA-Ar < 8. Then continue to monitor with CIWA-Ar q4-8 hrs until score < 8 x 24 hrs.
        • Benzodiazepine dosages:
          • Chlordiazepoxide 50-100 mg PO
          • Diazepam 10-20 mg PO/IV
          • Oxazepam 30-60 mg PO
          • Lorazepam 2-4 mg PO/IV/IM
        • Use lorazepam or oxazepam in patients with impaired liver functioning.
      • Select anticonvulsants have demonstrated similar efficacy to benzodiazepines at managing withdrawal symptoms.
        • Anticonvulsants tend to cause less sedation than benzodiazepines.
        • Studies were generally underpowered to compare rates of seizures of DTs.
        • Carbamazepine 600-800 mg or gabapentin 1200-1800 mg total daily compared favorably to Lorazepam 6-8 mg total daily.
  • Alcohol withdrawal seizures
    • Give initial IV dose of rapid-acting benzodiazepine (diazepam, lorazepam).
    • Follow with PO loading doses of benzodiazepine to prevent seizure recurrence.
    • Rule out trauma, infectious causes.
    • Phenytoin is not useful in managing seizures due to alcohol withdrawal.
  • Delirium tremens
    • Give diazepam 5mg IV q5 min x 2 doses, increase as needed to 10 mg q5 min x 2 doses, then 20 mg x q5 min x 2 doses, until light sedation achieved.
    • Close respiratory monitoring is needed.
    • Correct fluid and electrolyte imbalances.
    • Evaluate and treat for other causes of delirium.
    • Refractory cases not responsive to typical dosages of benzodiazepines may need endotracheal intubation and ICU admission. Adjunctive treatment with phenobarbital, propofol or dexmedetomidine have reportedly been helpful.
    • High mortality rate if untreated. Death is typically caused by pneumonia, cardiovascular complications, and trauma.
  • Adjunctive medications used for withdrawal management
    • Haloperidol 2-5 mg PO/IV/IM for agitation/hallucinations not responding to benzodiazepines. Use cautiously, as neuroleptics can reduce seizure threshold.
    • Carbamazepine 200 mg PO qid tapered over 5-10 days. May help reduce severity of withdrawal symptoms and prevent seizures.
    • Valproic acid and gabapentin are anticonvulsants that have shown some positive results in mitigating withdrawal symptoms.
  • Wernicke-Korsakoff syndrome:
    • Prophylaxis: Thiamine 500 mg IV/IM daily x 3-5 days
    • Treatment: Thiamine 500 mg IV tid x 3 days followed by 250 mg IV daily x 5 days
    • Give IV thiamine as slow infusion over 30 min to minimize risk of anaphylaxis.
    • Oral thiamine is poorly absorbed and not as helpful as IV treatment.
    • Administer thiamine before giving glucose, which can precipitate the disorder.
    • Replace fluids and electrolytes, including magnesium as needed.
  • FDA-approved medications for treatment of alcohol dependence
    • Disulfram
      • Dosage: 250 mg-500 mg PO daily
      • Inhibits action of aldehyde dehydrogenase, which results in high concentrations of aldehyde after alcohol ingestion, causing an aversive reaction
      • More effective when taken under supervision
      • Aversive symptoms include headache, nausea, vomiting, skin flushing, shortness of breath, diaphoresis, dizziness, confusion, palpitations, and hypotension.
      • More severe reactions can occur, including cardiovascular collapse and seizures.
      • May cause hepatic impairment/hepatitis, so monitoring of LFTs is recommended.
    • Naltrexone
      • Dosage: 50-100 mg PO daily, extended-release injectable dosage 380 mg IM q4 weeks
      • μ-opioid receptor antagonist; blocks rewarding effect of alcohol on endogenous opioid system
      • Effect size is small, but naltrexone has consistently shown reduction in heavy drinking in randomized controlled trials, especially in combination with psychotherapy.
      • Side effects: nausea, headache, dizziness
      • May precipitate opioid withdrawal: Patients should have an opioid-free period of 7-10 days before starting.
      • Black box warning for hepatotoxicity. Consider LFT monitoring.
    • Acamprosate
      • Dosage: 666 mg PO tid
      • Mechanism of action is unclear, but it probably helps restore GABA/glutamate balance after prolonged drinking.
      • Side effects: GI complaints (diarrhea)
      • Excreted unchanged in the urine, so useful in patients with liver impairment
  • Medications used off-label for treatment of alcohol dependence:
    • Ondansetron
      • Dosage: 4-8 μg/kg PO bid
      • Selective 5-HT3 receptor antagonist
      • May be more effective in patients with early-onset alcoholism and with the LL (long) variant of the presynaptic 5-HT transporter gene
      • Side effects: headache, GI disturbances, tachycardia, prurititis, insomnia
    • Topiramate
      • Dosage: start at 25 mg PO daily, and titrate to 150 mg bid over 12 days
      • Anticonvulsant which enhances GABA function
      • Side effects: paresthesias, weight loss, dysgeusia, concentration or memory impairment, fatigue
      • Excreted unchanged in the urine, so useful in patients with liver impairment
    • Baclofen
      • Dosage: 5-10 mg PO tid
      • Presynaptic GABAB receptor agonist
      • Randomized controlled trials show mixed results in reducing alcohol intake
      • Side effects: headache, nausea, insomnia, hypotension, urinary frequency
      • Excreted through kidneys, so useful in patients with liver impairment
    • Other medications used: gabapentin, varenicline, prazosin, levetiracetam

Psychotherapy

  • Treatment generally starts with the individual’s recognition that the disorder is present.
  • Referral to a 12-step program (Alcoholics Anonymous) is probably the best known psychological intervention.
  • Cognitive-behavioral therapy: focuses on situations and triggers for use
  • Motivational enhancement therapy
  • Brief interventions: counseling and therapy provided by primary care providers targeted at reducing risky or hazardous drinking
  • Relapse prevention therapy: helps patients identify and cope with high-risk situations and manage cravings
  • Project Match conducted a randomized-controlled trial to compare 3 treatments: motivational enhancement therapy, cognitive behavioral therapy, and 12-step facilitation. All treatment modalities were equally efficacious, and >50% of patients remained abstinent or reduced their drinking at 1 and 3 years post-treatment.

WHEN TO REFER

It is appropriate to refer someone to treatment for an alcohol use disorder whenever it is felt that alcohol consumption is interfering with normal functioning.

FOLLOW UP

  • Follow-up should occur frequently after the initial cessation of alcohol consumption and be tapered as felt to be appropriate by an addictionologist or other trained health care professional.
  • Maintenance of sobriety requires lifelong vigilance, and individualized care is necessary.

COMMENTS

  • Despite advances in the treatment of alcohol use disorders, individuals often relapse several times before obtaining abstinence.
  • There may be some advantages to a harm reduction approach that aims to reduce alcohol consumption to non-pathologic levels while maintaining the ultimate goal of abstinence.

References

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Last updated: May 2, 2017