Alcohol-Related Disorders

Joseph Gary, M.D., 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 use disorders 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 (a white, light grey, or blueish ring around the edge of the cornea)
- Tremor
- Hypertension
- Rhinophyma (development of a large, bulbous nose)
- 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
- Disulfiram
  - 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-HT₃receptor 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 that 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 GABA_B 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, N-acetylcysteine (NAC)
- GLP-1 agonists show promise for treating AUD given their effect on reward pathways, but further research is needed.[1]

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.

Other

Identify and treat underlying psychiatric comorbidities such as depression, anxiety, insomnia, etc. A multi-modal and interdisciplinary approach is most effective to enact lasting change.[2]
Consider involving a hepatologist if the patient develops liver cirrhosis.

WHEN TO REFER

It is appropriate to refer someone to treatment for an alcohol use disorder whenever it is believed 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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