Health Risks and Benefits of Alcohol Consumption

Introduction: Health Risks and Benefits of Alcohol Consumption

Look at the health risks and benefits of alcohol consumption before you pick up your next glass of beer or wine to see if it is really worth the consequences. Excessive alcohol use has significant health risks. The screening of alcohol dependence or abuse is recommended by health professionals due to large societal consequences. Alcohol use as a substance is associated with a large number of traffic deaths, homicides, and felonies. Alcohol use is excessive if one is consuming it in a manner such that it meets the criteria for misuse, abuse, or dependence. Screening once a year for alcohol misuse is covered by Medicare. One of the most common methods to screen for alcohol is by using the CAGE questionaire. Medicare also covers up to four short counseling sessions per year. During the counseling sessions, a healthcare provider may discuss the health risks and benefits of alcohol consumption with patients in the clinic setting. The counseling is not covered in the emergency room or hospital setting.

The health risks and benefits of alcohol consumption expressed here is to educate in prevention of alcohol related disease. The purpose of this information is not to reiterate commonly known risks of alcohol use such as birth defects or sequela due to impairment. It is provided to increase awareness of specific diseases directly linked to alcohol use and disease states benefited by alcohol use. Light or moderate alcohol use (especially in the form of red wine) carries health benefits, with the exception of breast cancer risk which will be explained below.

Definition of Alcohol Misuse

Alcohol misuse is one of the health risks of alcohol consumption. Alcohol misuse is defined as:

• Women under age 65 who drink over 3 drinks at a time or over 7 drinks per week.
• Men under age 65 who drink over 4 drinks at a time or over 14 drinks per week.
• Men or women over the age of 65 who drink over 3 drinks at a time or over 7 drinks per week.

Definition of Alcohol Abuse:

The American Psychiatric Association DSM-IV, the Joint Committee of the National Council on Alcoholism and Drug Dependence, and the American Society of Addiction Medicine defines alcohol abuse as alcohol use resulting in one of the following consequences within a period of 12 months:

• The inability of one to maintain obligations at home, school, or work.
• Repeated use of alcohol in hazardous or dangerous situations.
• Ongoing problems with the law due to alcohol use.
• Persistent use of alcohol despite it’s use causing concern in social relationships.

Definition of Alcohol Dependence:

Dependence on alcohol occurs if at least 3 of the following are present:

• Withdrawing from alcohol.
• A tolerance to alcohol has developed.
• Time is spent to use, obtain or recover from drinking.
• Recurrent feelings of need to cut down or limit drinking.
• Drinking a larger amount than intended.
• Loss of work, recreation, or social activities due to drinking alcohol.
• Drinking persists despite physical or psychological consequences.

The USPSTF Describes Alcohol Related Health Risks

The U.S. Preventive Services Task Force (USPSTF) describes the health risks, but does not list any benefits to alcohol consumption. The majority of alcohol related diseases are due to chronic excessive use and binge drinking. For women, according to the U.S. Preventive Services Task Force (USPSTF),“risky” or “hazardous” drinking has been defined as 8 drinks per week or 4 or more drinks per occasion. The USPSTF states that the equivalent for men is 15 or more drinks per week or 5 or more drinks per occasion. “Harmful drinking” is associated with physical, social, or psychological harm from alcohol use but the individual does not meet criteria for dependence. Alcohol dependence and abuse is associated with repeated harmful physical, psychological, and social effects due to alcohol use. Screening and behavioral counseling interventions to reduce alcohol misuse by adults, including pregnant women, in primary care settings is recommended by the USPSTF.(1)

Supplements That Support Alcohol Metabolism

Cessation of Alcohol Abuse:

Primary care physicians are recommended by the United States Preventive Services Task Force (USPSTF) to screen all adult patients for the misuse of alcohol (1).

Primary Goal for Alcoholics:

The primary goal for alcoholics is complete abstinence.

Intervention for Cessation of Alcohol:

The the United States Preventive Services Task Force (USPSTF) endorses behavioral therapy and therapy with health professionals which specialize in abuse.

Medications to Treat Alcoholism:

Medications are available which can either reduce the craving, or medication which causes an adverse physical reaction if alcohol is combined with it. Alcoholism treatment medications should not be used routinely in pregnancy due to potential risk of fetal harm.

Medications which Curb Alcohol Craving:

These include nalmefene, also known as Revex, which is category B (animal studies revealed no fetal harm) has been found to be effective for the prevention of relapse (22).

Another Anti-craving Agent:

Naltrexone (category C with embryocidal effect at high dose in animal studies) showed a significantly greater rate of abstinence than placebo (23).

Agents which Result in Aversion Reactions after Drinking Alcohol:

These include Antabuse (disulfiram) and calcium carbimide which are category C (fetal harm reported early in pregnency). These agents were also found to produce a greater than 50% rate of abstinence rate in outpatient alcoholics over a 9 year period and were tolerated well long term (24).

Health Dangers of Alcohol Abuse:

Chronic alcohol use is associated with vitamin deficiency states. Regular use of alcohol depletes vitamin B12, thiamine, folic acid, and many other nutrients. Alcohol reduces the body’s ability to absorb these nutrients. Alcohol calories are empty calories which substitute foods containing nutrients. Nutritional deficiencies may result in malnutrition and a number of diseases. In lactating mothers, folate deficiency is more pronounced due to higher folate demand by the mother.(2)

Alcohol Related Thiamine (Vitamin B1), Deficiency:

This may lead to neurological and cardiovascular problems with early symptoms including fatigue, weakness and emotional disturbance. Inflammation of several peripheral nerves, heart failure and swelling of tissues, usually in the lower limbs have been reported in people with prolonged thiamine deficiency. In severe cases of thiamine deficiency an individual may develop Wernicke’s encephalopathy (WE) which includes symptoms of eye mobility problems, uncoordinated movement, confusion, drowsiness, reduction in mental alertness, clouding of consciousness, pre-coma and coma. Among patients with developed Korsakoff’s psychosis (KP) or retrograde amnesia, disorientation, poor recall and impairment of recent memory. About 25% of patients with KP require continued hospital care. (18)

Thiamine Levels in Alcohol Users

Thiamine levels should routinely be checked in patients being treated with alcohol-related diseases. Wernicke’s encephalopathy (WE) is a neurological complication (including eye mobility problems, uncoordinated movement, confusion, drowsiness, reduction in mental alertness, clouding of consciousness, pre-coma and coma) associated with thiamine deficiency. In a study of 31 alcohol-related deaths over an 8-month period, WE was found in 17 cases and only in 2 cases were neurological symptoms reported. (19)

Thiamine levels were measured twice in 222 people over 64 years old. A total of 96 were found to have low levels at one or both measurements, and 76 of these were randomized to receive 10 mg oral thiamine or placebo daily for 3 months. Daily alcohol intake was significantly higher among those who had low thiamine levels at both measurements compared to those low at only one measure. Thiamine supplementation in those with consistently low thiamine levels (but not those with only one reduced value) improved thiamine levels and also quality of life, systolic blood pressure and weight compared to placebo. There was a trend toward improvement in energy and sleep as well in those taking thiamine. Measures of cognitive function and neuropathy symptoms were not affected by thiamine in this study. (20)

Alcohol Consumption and Risk of Breast Cancer:

Alcohol consumption was associated with an increased risk of breast cancer (BrCa) in a cohort study of 70,033 women, of whom 2,829 developed BrCa. Risk of BrCa significantly increased at a total alcohol consumption starting at 1-2 drinks/day. Specifically, at 1-2 drinks/day risk of BrCa increased by 21% (RR=1.21, p=0.01) and at > or = 3 drinks/d risk increased by 38% (RR=1.38, p=0.002). Increased BrCa risk was concentrated in women with estrogen receptor positive tumours. Estrogen is a female sex hormone that stimulates some breast cancers to grow by triggering particular proteins (receptors) in the cancer cells. Choice of wine, liquor, beer or type of wine (red, white, etc) had no major impact on results.(3)

Alcoholism and Ischemic Stroke:

Both chronic alcohol abusers and binge drinkers were found to have higher rates of brain infarction (ischemic stroke) after stopping alcohol use. Elevated platelet levels have been implicated as the etiology of these strokes. However, in a previous study, there was both high platelet levels and low platelet levels seen at the time when these strokes occur, which proposed another mechanism other than high platelet levels responsible for the stroke.(4)

In both chronic alcohol abuse and binge drinking, the increased rate of ischemic stroke may be a rebound in platelet aggregation after stopping alcohol use resulting in higher tendency of platelets to form clots.(5) This effect was not seen when wine drinkers were compared to vodka drinkers. Alcohol in the form of distilled wine and vodka both inhibited platelet aggregation, but the effect of wine on inhibition of platelet aggregation was greater than the effect of vodka on platelet aggregation.(6) After vodka drinking was stopped, an increase in platelet aggregation was seen to higher than baseline levels. This was not the case in drinkers of distilled wine. This rebound effect may be detrimental to chronic drinkers of vodka or other distilled alcoholic beverages by placing patients at risk for cardiovascular and cerebrovascular events. When it comes to mild to moderate alcohol consumption, there are beneficial effects. It is believed that HDL increases from alcohol beverages are responsible for 50% of the protective effect from coronary artery disease. The other 50% level of protection may be due to polyphenols in red wine which inhibit platelet aggregation. (7)

Alcohol Use Increases Risk of Esophageal Cancer:

Alcohol use increases risk of esophageal cancer with the exception of wine consumption which appears to reduce this risk. In a large prospective cohort study of 220,272 men and women, a higher relative risk (RR) of esophageal cancer was seen with thermal effect of hot tea, alcohol drinking, smoking and lower consumption of green and yellow vegetables. RR of esophageal cancer with a 95% confidence interval was 2.4 on average with a RR range of 1.8-3.1 for daily (4 times/week or more) alcohol drinking in comparison with non-drinking. This means that esophageal cancer is 2 1/2 times more likely to occur in an alcohol drinker than a non-drinker.(8) Esophageal and gastric cancer risk was reduced by 40% in drinkers of wine compared with twice the risk in beer drinkers and triple the risk in liquor drinkers.(9)

Alcohol Use and Psoriasis:

A meta-analysis of 15 case-control studies suggested that alcohol consumption is associated with an increased risk of psoriasis. Findings from the study showed that the odds of developing psoriasis was over 50% higher in alcohol drinkers than non-drinkers. The overall odds ratio of psoriasis for drinking persons was 1.531 (P = 0.002).(10)

Alcohol Use and Exercise:

How does alcohol affect exercise when considering the health risks and benefits of alcohol consumption? Alcohol intake has no effect on heart rate but continual use of alcohol increases blood pressure during rest and exercise. Alcohol has no effect on exercise capacity (17).

Alcohol Related Liver Disease and Cirrosis:

Alcohol interferes with folate by disrupting intestinal absorption which reduces uptake and storage of folate in the liver. This may in turn, lead to the development of alcoholic liver disease (ALD).

Benefits of Alcohol Consumption

Reducing risk of disease with alcohol intake is not routinely recommended. The ideal amount of alcohol consumption to obtain benefits of reduced risk for heart disease appears to be 2-4 drinks per day for men and 1-2 drinks per day for women. (11)

Alcohol Consumption for Cardiovascular Disease:

Drinking alcohol in moderate amounts has a protective effect on cardiovascular disease. There are both health risks and benefits of alcohol consumption for heart disease. Men who consumed light-to-moderate amounts of alcohol at 3–4 or 5–7 days per week had decreased risks of myocardial infarction and ischemic stroke compared with men who consumed alcohol less than once per week. Moderate alcohol drinking decreases the risk of cardiovascular disease by about 25%, which is linked to a decrease in the total cardiovascular disease burden in Australia of 4.7%. In Australia, 34% of the total number of deaths in 2008 were from cardiovascular disease and in 2003, it was 18% of the overall burden of disease (coronary heart disease and stroke contributed over 80% of this burden). (12)

Alcohol Intake May Increase Good Cholesterol (HDL):

It is believed that HDL increases from alcohol beverages are responsible for 50% of the protective effect from coronary artery disease. The other 50% level of protection may be due to polyphenols in red wine which inhibit platelet aggregation. (7)

Alcohol intake May Reduce Risk of Alzheimer’s disease:

An overall risk reduction in Alzheimer’s and other dementia was seen in moderate alcohol drinkers compared to nondrinkers and alcohol abusers (13).

Wine Intake Research Promising for Alzheimer’s disease:

Wine drinkers were found to have lower Alzheimer’s disease (AD) risk. The relationship between alcohol consumption and risk of dementia associated with stroke (DAS) was analyzed in a cohort study of 980 participants aged 65 and older. Dementia was diagnosed using Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, criteria and classified as AD or DAS. After 4 years of follow-up, 260 individuals developed dementia (199 AD, 61 DAS). Consumption of up to 3 servings of wine daily was associated with a lower AD risk (Hazard ratio = 0.55). Liquor, beer, and total alcohol were not associated with a lower risk of AD. Analyses of the APOE-epsilon 4 allele, a gene responsible for production of a protein which breaks down componenets of trigycerides, showed that the relationship between wine consumption and lower risk of AD was seen only in individuals without the APOE-epsilon 4 allele.(14)

Alcohol Intake May Improve Bone Mineral Density:

When examining the health risks and benefits of alcohol consumption, moderate intake of alcohol has been reported to have beneficial effects on bone mineral density. Researchers examined alcohol intake and bone mineral density (BMD) at 3 hip sites and the lumbar spine in 1,182 men and in 1,289 postmenopausal and 248 premenopausal women in this population-based study. Results showed that compared with nondrinkers, hip BMD was greater (3.4–4.5%) in men consuming 1–2 drinks/day of total alcohol or beer, whereas hip and spine BMD were significantly greater (5.0–8.3%) in postmenopausal women consuming > 2 drinks/d of total alcohol or wine. Intake of > 2 drinks/d of liquor in men was associated with significantly lower (3.0–5.2%) hip and spine BMD than was intake of 1–2 drinks/d of liquor in men. For premenopausal women, the associations were not significant. The authors conclude that there seems to be protective effects of moderate alcohol consumption on BMD in men and postmenopausal women. There also appears to be a difference in response between different types of alcoholic beverages, and between the sexes.  For men, heavier consumption of alcohol (> 2 drinks/d) may negatively affect BMD. For postmenopausal women, not only is moderate alcohol consumption good for BMD, but it also appears that larger quantities of alcohol consumption are also beneficial.  This study was also consistent with previous ones in that BMD in premenopausal women did not differ between alcohol drinkers and abstainers.(16)

Summary: Health Risks and Benefits of Alcohol Consumption

• If you drink alcohol, discuss the health risks and benefits of alcohol consumption with a qualified healthcare provider. Alcohol use is excessive if it meets the criteria for misuse, abuse, or dependence. Screening once a year for alcohol misuse is covered by Medicare. One of the most common methods to screen for alcohol is by using the CAGE questionaire.

• Alcohol Misuse is defined by the following:
  • Women under age 65 who drink over 3 drinks at a time or over 7 drinks per week.
  • Men under age 65 who drink over 4 drinks at a time or over 14 drinks per week.
  • Men or women over the age of 65 who drink over 3 drinks at a time or over 7 drinks per week.

• Alcohol dependence occurs if at least 3 of the following are present:
  • Withdrawing from alcohol.
  • A tolerance to alcohol has developed.
  • Time is spent to use, obtain or recover from drinking.
  • Recurrent feelings of need to cut down or limit drinking.
  • Drinking a larger amount than intended.
  • Loss of work, recreation, or social activities due to drinking alcohol.
  • Drinking persists despite physical or psychological consequences.

• Alcohol abuse is defined as alcohol use resulting in one of the following consequences:
  • The inability of one to maintain obligations at home, school, or work.
  • Repeated use of alcohol in hazardous or dangerous situations.
  • Ongoing problems with the law due to alcohol use.
  • Persistent use of alcohol despite it’s use causing concern in social relationships.

• Excessive alcohol use has significant health risks and screening of alcohol dependence or abuse is recommended by health professionals due to large societal consequences.

• Patients with misuse, or alcoholism should be referred for counseling and treatment to avoid alcohol dependence, prevent abuse, and reduce binge drinking.

• Primary care physicians are recommended by the United States Preventive Services Task Force to screen all adult patients for the misuse of alcohol (1).

• The primary goal for alcoholics is complete abstinence. Interventions options include behavioral therapy and therapy with health professionals which specialize in abuse.

• Medications: Medications are available to reduce the craving or cause an adverse physical reaction if alcohol is combined with it. Alcoholism treatment medications should not be used routinely in pregnancy due to potential risk of fetal harm.

• Medications which curb craving include nalmefene, also known as Revex, which is category B (animal studies revealed no fetal harm) has been found to be effective for the prevention of relapse (22).

• Another anti-craving agent is naltrexone (category C with embryocidal effect at high dose in animal studies) which showed a significantly greater rate of abstinence than placebo (23).

• Agents which cause aversion reactions after drinking alcohol include Antabuse (disulfiram) and calcium carbimide which are category C (fetal harm reported early in pregnency). These agents were also found to produce a greater than 50% rate of abstinence rate in outpatient alcoholics over a 9 year period and were tolerated well long term (24).

• Special patients populations who should abstain from alcohol use include: patients with hypertension, breast cancer or increased risk of breast cancer, pregnancy, sexually active without contraception, attempting to become pregnant, patients with psoriasis, with a history of or increased risk of esophageal or gastric cancer, with high risk of or history of stroke, patients with liver disease or hepatitis, heart failure, atrial fibrillation or other arrhythmias, patients with addiction, dependence or abuse behaviors, and other various cancers.

• Chronic alcohol abuse patients should be checked for vitamin B12, folate, thiamine, and other nutritional deficiencies. The physician should guide treatment with vitamins based on these nutrient levels as deficiency can lead to Wernicke-Korsakoff syndrome, also called Korsakoff psychosis or Wenicke’s Encephalopathy: a sub-acute dementia syndrome. Please see the section on these vitamins to increase intake of these vitamins in foods. Alcohol abuse patients should take folate (1 mg oral per day), and thiamine (100 mg oral per day) during alcohol use and several months after alcohol is stopped until good nutritional intake is resumed.

• When alcohol abuse is discontinued, an increase in risk of ischemic stroke is present. Discuss this risk with a qualified healthcare professional before quitting alcohol for possible options on how to lower this risk.

• Alcohol consumption in excess causes liver disease and cirrhosis.

• Despite benefits of alcohol in moderation, physicians are reluctant to recommend alcohol intake for health reasons. Prior to considering alcohol use daily or several times per week, discuss the risks and health benefits with the primary physician. Research supports a benefit somewhere in the range between 1-4 alcohol drinks per day for men and 1-2 drinks per day for women. 1 drink is defined as 1.5 ounces of 80-proof liquor, 5 ounces of wine or 1 can of beer. Alcohol taken for health reasons may reduce the risk of myocardial infarction, ischemic stroke, dementia associated with stroke, Alzheimer’s disease, and may improve the cholesterol profile.

• Red wine drinking in moderation has greater benefit seen in research over all other types of alcohol beverages. Benefits of red wine alone will be discussed separately and therefore please see that topic.

References: Health Risks and Benefits of Alcohol Consumption

1.Screening and Behavioral Counseling Interventions in Primary Care to Reduce Alcohol Misuse, Topic Page. October 2012. U.S. Preventive Services Task Force. http://www.uspreventiveservicestaskforce.org/uspstf/uspsdrin.htm

2.Allen LH. Causes of vitamin B12 and folate deficiency. Food Nutr Bull. 2008 Jun;29(2 Suppl):S20-34; discussion S35-7. http://www.ncbi.nlm.nih.gov/pubmed/18709879

3.Li, Y., et al. Wine, liquor, beer and risk of breast cancer in a large population. European Journal of Cancer, 2002, 45(5), 843-850. http://www.ncbi.nlm.nih.gov/pubmed/19095438

4.Numminen H, Hillbom M, Juvela S. Platelets, alcohol consumption, and onset of brain infarction. J Neurol Neurosurg Psychiatry.1996 Oct;61(4):376-80. http://www.ncbi.nlm.nih.gov/pubmed/8890776

5.Renaud SC, Ruf JC. Effects of alcohol on platelet functions. Clin Chim Acta. 1996 Mar 15;246(1-2):77-89. http://www.ncbi.nlm.nih.gov/pubmed/8814972

6.Umar A, Depont F, Jacquet A, Lignot S, Segur MC, Boisseau M, Bégaud B, Moore N. Effects of armagnac or vodka on platelet aggregation in healthy volunteers: a randomized controlled clinical trial. Thromb Res. 2005;115(1-2):31-7. http://www.ncbi.nlm.nih.gov/pubmed/15567450

7.Ruf JC. Alcohol, wine and platelet function. Biol Res. 2004;37:209–15. http://www.ncbi.nlm.nih.gov/pubmed/15455649

8.Kinjo Y, Cui Y, Akiba S, Watanabe S, Yamaguchi N, Sobue T, Mizuno S, Beral V. Mortality risks of esophageal cancer associated with hot tea, alcohol, tobacco and diet in Japan. J Epidemiol. 1998 Oct;8(4):235-43. http://www.ncbi.nlm.nih.gov/pubmed/9816815

9.Gammon MD, Schoenberg JB, Ahsan H, et al. Tobacco, alcohol, and socioeconomic status and adenocarcinomas of the esophagus and gastric cardia. J Natl Cancer Inst. 1997;45:273–6. http://www.ncbi.nlm.nih.gov/pubmed/9293918

10.Zhu KJ, Zhu CY, Fan YM. Alcohol consumption and psoriatic risk: A meta-analysis of case-control studies. J Dermatol. 2012;39:1–4. http://www.ncbi.nlm.nih.gov/pubmed/22568495

11.De Lorimier AA. Alcohol, wine, and health. Am J Surg. 2000;180:357–61. http://www.ncbi.nlm.nih.gov/pubmed/11137687

12.Stockley CS. Is it merely a myth that alcoholic beverages such as red wine can be cardioprotective? J Sci Food Agric. 2012 Jul; 92(9): 1815-21. http://www.ncbi.nlm.nih.gov/pubmed/22505227

13.Orgogozo J-M, Dartigues J-F, Lafont S, et al. Wine consumption and dementia in the elderly: A proseptive community study in the Bordeaux area. Rev Neurol. 1997;153:185–92. http://www.ncbi.nlm.nih.gov/pubmed/9296132

14.Luchsinger JA, Tang MX, Siddiqui M, Shea S, Mayeux R. Alcohol intake and risk of dementia. J Am Geriatr Soc. 2004 Apr;52(4):540-6. http://www.ncbi.nlm.nih.gov/pubmed/15066068

15.Barranco-Quintana JL, Allam MF, Del Castillo AS, Navajas RF. [Risk factors for Alzheimer\’s disease]. [Article in Spanish]. Rev Neurol. 2005 May 16-31;40(10):613-8. http://www.ncbi.nlm.nih.gov/pubmed/15926136

16.Tucker, K.L., Jugdaohsignh, R., Powell, J.J., Qiao, N., Hannan, M.T., Sripanyakorn, S., Cupples, L.A., and Kiel, D.P. Effects of beer, wine and liquor intakes on bone mineral density in older men and women. Am J Clin Nutr 2009;89:1188–1196. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2667462/

17.Gauer RL, O\’Connor FG. Department of Family Medicine Uniformed Services University of the Health Sciences. How To Write And Exercise Prescription. http://www.move.va.gov/download/Resources/CHPPM_How_To_Write_And_Exercise_Prescription.pdf

18.Agabio R. Thiamine administration in alcohol-dependent patients. Alcohol Alcohol. 2005 Mar-Apr;40(2):155-6. http://alcalc.oxfordjournals.org/content/40/2/155.long

19.D. P. Naidoo, A. Bramdev, and K. Cooper. Wernicke\’s encephalopathy and alcohol-related disease. Postgrad Med J. 1991 November; 67(793): 978–981. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2399154/

20.Wilkinson TJ, Hanger HC, Elmslie J, George PM, Sainsbury R. The response to treatment of subclinical thiamine deficiency in the elderly. Am J Clin Nutr. 1997 Oct;66(4):925-8. http://www.ncbi.nlm.nih.gov/pubmed/9322569

21.Halsted CH, Villanueva JA, Devlin AM, Chandler CJ. Metabolic interactions of alcohol and folate. J Nutr. 2002 Aug;132(8 Suppl):2367S-2372S. http://www.ncbi.nlm.nih.gov/pubmed/12163694

22.Mason BJ, Salvato FR, Williams LD, Ritvo EC, Cutler RB.A double-blind, placebo-controlled study of oral nalmefene for alcohol dependence. Arch Gen Psychiatry. 1999 Aug;56(8):719-24. http://www.ncbi.nlm.nih.gov/pubmed/10435606

23.Kranzler HR, Wesson DR, Billot L; DrugAbuse Sciences Naltrexone Depot Study Group. Naltrexone depot for treatment of alcohol dependence: a multicenter, randomized, placebo-controlled clinical trial.Alcohol Clin Exp Res. 2004 Jul;28(7):1051-9. http://www.ncbi.nlm.nih.gov/pubmed/15252291

24.Krampe H, Stawicki S, Wagner T, Bartels C, Aust C, Rüther E, Poser W, Ehrenreich H.Alcohol Clin Exp Res. Follow-up of 180 alcoholic patients for up to 7 years after outpatient treatment: impact of alcohol deterrents on outcome. 2006 Jan;30(1):86-95. http://www.ncbi.nlm.nih.gov/pubmed/16433735

25.The American Psychiatric Association Diagnostic and Statistical Manual of Mental Disorders. Fourth Edition. Text Revision (DSM-IV-TR). June 2000.

26.Morse RM, Flavin DK. The definition of alcoholism. The Joint Committee of the National Council on Alcoholism and Drug Dependence and the American Society of Addiction Medicine to Study the Definition and Criteria for the Diagnosis of Alcoholism.  JAMA. 1992 Aug 26;268(8):1012-4.

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