Alcoholism — When does Drinking Become a problem?

Alcoholism is a global public health problem, with around 2.5 million deaths per year caused by alcohol worldwide. According to the World Health Organization’s 2011 global status report, alcohol is the world’s third largest risk factor for disease and disability. Alcohol dependence is a chronic, relapsing disorder, with most patients never receiving treatment. Almost one-third of Americans consume enough alcohol to be considered at risk for alcoholism.

Alcohol use disorder is characterized by continuous or periodic use:

• Impaired control over drinking
  • 15 or more drinks/week for men*
  • 12 or more drinks/week for women
  • 5 or more drinks at a time at least once a week
• Preoccupation with alcohol
• Use of alcohol despite adverse consequences
• Increased tolerance to alcohol
• Distortion of thinking or Denial

*one drink = 12-ounce beer, 5-ounce glass of wine, 1.5 ounce shot of liquor

According to the Centers for Disease Control and Prevention (CDC), the number of alcohol-induced deaths totaled 26, 256 for 2011, higher than in 2010. This trend suggests that alcoholism is increasing in the United States, and as health professionals it is pertinent that we do our part to effectively treat and combat this disease.

Alcoholism affects patients both mentally and physically. Both mind and body must be treated to overcome alcohol dependence. Combination therapy with both medication and psychosocial treatment can help change behavior and help patients cope with problems without using alcohol. Examples of psychosocial treatments include Alcoholics Anonymous (AA) meetings, group therapy, counseling, or hospital treatment. The support and commitment to change is very important in overcoming alcohol dependence.

What are Treatments for Alcoholism?

Treatment for alcohol dependence involves a combination of counseling and a structured 12-step treatment program. Medication treatment regimens are given as part of treating alcoholism.

• See a counselor
• Take medications
• Join a support group

How do Medications Help Treat Alcohol Dependence?

Medications can help treat alcoholism by working in the body in different ways:

• Change the way the brain responds to alcohol so that it elicits less of a response
• Reduce craving for alcohol
• Cause awful side effects if alcohol is consumed
• Reduce symptoms of alcohol withdrawal

The US Food and Drug Administration (FDA) has approved these three medications for treating alcohol dependence:

• disulfram (Antabuse)
• naltrexone (Trexan)
• acamprosate (Campral)

About 20% of eligible patients receive these medications. Serotonergic and anticonvulsants are used off-label for alcohol dependence. Studies have shown that these medications can increase abstinence rates and decrease drinking.

Prescription Drugs for Alcoholism Treatment

Disulfram (Antabuse)

Disulfram (Antabuse) is an alcohol-sensitizing agent that creates an unpleasant reaction when drinking alcohol, thus reducing the desire to drink. It blocks acetaldehyde dehydrogenase (an enzyme that helps break down alcohol). This disrupts the metabolism of alcohol and causes palpitations, flushing, nausea, vomiting, headache. Disulfram is given to patients after they have abstained from alcohol for at least 12 hours. Liver function tests should be monitored.

Disulfram was approved by the FDA in the 1950s for the treatment of alcohol dependence and has been shown to improve rates of alcohol abstinence. There are advantages and disadvantages to taking disulfram. The severe reaction when mixing both disulfram and alcohol is thought to increase patient’s motivation to remain abstinent. Disulfram is only effective when patients are compliant and motivated.

Dose: Patients begin with 250 mg once per day and increase to 500 mg per day.

Side effects: Disulfram-alcohol interaction (palpitations, flushing, nausea, vomiting, headache).

Contraindications: Alcohol, metronidazole (Flagyl), or paraldehyde use psychosis; cardiovascular disease

Cost: Average wholesale price is $154.49 for a 250 mg bottle of 100 tablets. Average wholesale price is $247.10 for a 500 mg bottle of 100 tablets.  

Naltrexone (ReVia, Trexan)

Naltrexone was FDA approved in 1994 and is an anti-craving agent. It is an opioid receptor blocker that competitively binds to opioid receptors, reducing the pleasant and reinforcing effects of alcohol. Unlike disulfram, naltrexone does not make you feel sick if you drink alcohol, instead it directly targets the learned association of experiencing pleasure following alcohol use. Naltrexone is effective in reducing relapse rates and increasing abstinence rates. In a meta-analysis study of 50 randomized controlled trials, 7793 patients with alcohol dependence found that naltrexone reduced the risk of heavy drinking by 83% and decreased drinking days by 4% compared to a placebo.

Dose: Patients take 50 mg once per day.

Side effects: Nausea, Headache, Anxiety, Sedation, abdominal pain

Contraindications: Narcotic use, acute opioid withdrawal, acute hepatitis, liver failure. Liver function tests should be monitored for hepatotoxicity.

Cost: Average wholesale price is $427.51 for a 50 mg bottle of 100 tablets.

Acamprosate (Campral)

Acamprosate was FDA approved in 2004 and is an anti-craving medication. Acamprosate is thought to promote a balance between excitatory and inhibitory chemical messengers called glutamate and gamma-aminobutyric acid (GABA), respectively. Acamprosate helps individuals by changing learned responses to alcohol cues and reducing distress associated with alcohol withdrawal. In double-blind, 24 randomized controlled study of 6894 patients that compared acamprosate to a placebo, receiving acamprosate significantly reduced the risk of returning to drinking by 86% and increased abstinence by 11%.

Compared to naltrexone and disulfram, acamprosate is not metabolized by the liver and is not affected by alcohol use. Naltrexone can be given to patients with hepatitis or liver disease. It can also be given to patients who continue drinking alcohol.

Dose: 333 mg enteric coated tablets. Adults ≥ 132 lbs (60 kg): 2 tablets three times daily; Adults ‹ 132 lbs: 2 tablets with the morning meal, one with the midday meal, and one with the evening meal.

Side effects: Diarrhea, headache, flatulence, nausea, vomiting, dyspepsia

Contraindications: Severe renal impairment (Creatinine Clearance ‹ 30 ml per minute or 0.5 mL per second)

Cost: Average wholesale price is $249.50 for a 333 mg bottle of 180 tablets.

Efficacy of Drugs for Treatment of Alcohol Dependence

Acamprosate was the least effective of the three FDA approved treatments for alcohol dependence. The average number of days until the first heavy drinking days was 17.6 days for acamprosate, 46.6 days for dilsulfram, and 22 days for naltrexone.

Genetic factors may play a role in patient response to different medications. Knowledge of genetic risk factors and gene polymorphisms can be used to match treatments to patients and increase the margin of success. Although more studies need to be conducted, pharmacogenomics research looks promising.

In the Pipeline — An Experimental Vaccination for Alcoholism

In February of 2013, scientists began preclinical trials for the world’s first alcoholism vaccine. The vaccine is said to deliver an “instant hangover” if the patient uses alcohol. Researchers will first test the vaccine on mice and human trials will follow. This innovative idea would be helpful to people struggling with alcohol dependence, but would also require patient motivation.

References

Centers for Disease Control and Prevention. (2014) Alcoholism. Retrieved from http://www.cdc.gov/alcohol/

Hamreus K., Saville K, Witkiewitz K. Acamprosate for treatment of alcohol dependence: mechanisms, efficacy, and clinical utility. 2012: 8 45-53.

RED BOOK Online. ACAMPROSATE. Truven Health Analytics, Inc,; 2014.

RED BOOK Online. DISULFRAM. Truven Health Analytics, Inc.; 2014.

RED BOOK Online. NALTREXONE. Truven Health Analytics, Inc.; 2014.