AUTHOR AND EDITOR INFORMATION

Section 1 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

INTRODUCTION

Section 2 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Background

Alcoholism is common, serious, and expensive. Physicians encounter alcohol-related cirrhosis, cardiomyopathy, pancreatitis, and gastrointestinal bleeding, as well as intoxication and alcohol addiction, on a daily basis. Alcoholism is also associated with many cancers. Wernicke encephalopathy and Korsakoff psychosis are also important causes of chronic disability as well as dementia. Fetal alcohol syndrome is a leading cause of mental retardation. In addition, accidents (especially automobile), depression, dementia, suicide, and homicide are important consequences of alcoholism.

Alcohol-related diseases are discussed in separate articles. The focus of this article is screening, diagnosis, treatment, and new research findings on the natural history and heritability of alcoholism.

Pathophysiology

Alcohol affects virtually every organ system in the body and, in high doses, can cause coma and death. It affects several neurotransmitter systems in the brain, including opiates, GABA, glutamate, serotonin, and dopamine. Increased opiate levels help explain the euphoric effect of alcohol, while its effects on GABA cause anxiolytic and sedative effects.

Alcohol inhibits the receptor for glutamate. Long-term ingestion results in the synthesis of more glutamate receptors. When alcohol is withdrawn, the central nervous system experiences increased excitability. Persons who abuse alcohol over the long term are more prone to alcohol withdrawal syndrome than persons who have been drinking for only short periods. Brain excitability caused by long-term alcohol ingestion can lead to cell death and cerebellar degeneration, Wernicke-Korsakoff syndrome, tremors, alcoholic hallucinosis, delirium tremens, and withdrawal seizures. Opiate receptors are increased in the brains of recently abstinent alcoholic patients, and the number of receptors correlates with cravings for alcohol.

Frequency

United States

These statistics are based on the US National Longitudinal Alcohol Epidemiologic Study. Alcoholism is prevalent in 20% of adult hospital inpatients. One in 6 patients in community-based primary care practices had problem drinking. The following apply to the US adult population:

• Current drinkers - 44%
• Former drinkers - 22%
• Lifetime abstainers - 34%
• Abuse and dependency in the past year - 7.5-9.5%
• Lifetime prevalence - 13.5-23.5%

Alcoholism is slightly more common in lower income and less educated groups. Vaillant studied the natural history of alcoholism and the differences between college-educated and inner-city alcoholic persons. He followed 2 cohorts (over 400 patients) of alcoholic patients over many years.¹

According to Vaillant's research, inner-city men began problem drinking approximately 10 years earlier than college graduates (age 25-30 y vs age 40-45 y). Inner-city men were more likely to be abstinent from alcohol consumption than college graduates (30% vs 10%) but more likely to die from drinking (30% vs 15%). A large percentage of college graduates alternated between controlled drinking and alcohol abuse for many years. Returning to controlled drinking from alcohol abuse is uncommon, no more than 10%; however, this figure is likely to be high because it was obtained from self-reported data. Mortality in both groups was related strongly to smoking. Abstinence for less than 5-6 years did not predict continued abstinence (41% of men abstinent for 2 y relapsed).

International

The World Health Organization examined mental disorders in primary care offices and found that alcohol dependence or harmful use was present in 6% of patients. In Britain, 1 in 3 patients in community-based primary care practices had at-risk drinking behavior. Alcoholism is more common in France than it is in Italy, despite virtually identical per capita alcohol consumption.

Mortality/Morbidity

Alcohol use is the third leading cause of preventable death in the United States (after smoking and obesity). Annually, 85,000 deaths are attributable to alcohol at a cost of $185 billion.^{2, 3} Almost half of these deaths are attributable to alcohol-related injury.

Four percent of the global burden of disease is attributable to alcohol. This figure rises to 7% in North America, Europe, Japan, and Australia and to 12% in Eastern Europe and Central Asia. Worldwide, alcohol is responsible for a percentage of a number of conditions, as follows:

• Cirrhosis - 32%
• Motor vehicle accidents - 20%
• Mouth and oropharyngeal cancers - 19%
• Esophageal cancer - 29%
• Liver cancer - 25%
• Breast cancer - 7%
• Homicide - 24%
• Suicide - 11%
• Hemorrhagic stroke - 10%

Below are the statistically significant relative risks from a study by the American Cancer Society for men and women who consume 4 or more drinks daily. A drink is defined as one 12-oz beer, one 4- to 5-oz glass of wine, or one mixed drink containing 1.5 oz of spirits (80 proof). The relative risk for the noted maladies with consumption of 4 or more drinks daily is as follows:

• Cirrhosis - For men, 7.5; for women, 4.8
• Injuries - For men, 1.3
• Ear, nose, and throat cancer; esophagus cancer; liver cancer - For men, 2.8; for women, 3

Moderate alcohol consumption (1-2 drinks/d) reduces the risk of cardiovascular disease in men and women by approximately 30%.^{4, 5, 6} The effect of heavy alcohol consumption on the risk of cardiovascular disease varies in different studies. The person's drinking pattern appears to have an effect on cardiovascular disease. Drinking with meals may reduce the risk, while binge drinking increases risk (even in otherwise moderate drinkers).

Moderate alcohol consumption appears to increase the risk of breast cancer in women. Total mortality is reduced with moderate alcohol consumption but not with heavy alcohol consumption; the cardiovascular benefit is offset by cirrhosis, cancer, and injuries. The amount of alcohol associated with the lowest mortality appears to be 2 drinks per day in men and 1 drink or fewer per day in women. Moderate alcohol consumption reduces the risk of developing diabetes, but heavy alcohol consumption may increase the risk. The cardiovascular benefit becomes important in men older than 40 years and in women older than 50 years. The risk of hypertension is increased with 3 or more drinks daily.

No benefits are noted in people at low risk for coronary disease (men <40 y and women <50 y). Recent data suggest an increase in coronary calcification with moderate alcohol consumption in young adults.⁷ This effect was exacerbated by binge drinking.

Of men aged 18-25 years, 60% binge drink. (Binge drinking is defined as 5 alcoholic drinks for men [4 for women] in a row.) Binge drinking significantly increases the risk of injury and contracting sexually transmitted diseases. Women who binge drink at this age are at higher risk of becoming pregnant and potentially harming an unborn child. (Any amount of alcohol consumption during pregnancy is risky.)

More than three quarters of all foster children in the United States are children of alcohol- or drug-dependent parents. From 60-70% of reported domestic violence incidents involve alcohol. Half of all violent crime is alcohol or drug related.

Overall, morbidity and mortality are related strongly to smoking, and people who drink heavily are less likely to quit smoking. Additionally, persons who begin smoking early are more likely to develop problems with alcohol.

With regard to pregnancy, fetal alcohol syndrome is the leading known cause of mental retardation (1 in 1000 births). More than 2000 infants annually are born with this condition in the United States. Alcohol-related birth defects and neurodevelopmental problems are estimated to be 3 times higher. Even small amounts of alcohol consumption may be risky in pregnancy. A 2001 study by Sood et al reported that children aged 6-7 years whose mothers consumed alcohol even in small amounts had more behavioral problems.⁸ In a study from 2003, Baer et al showed that moderate alcohol consumption while pregnant resulted in a higher incidence of offspring problem drinking at age 21 years, even after controlling for family history and other environmental factors.⁹ All women who are pregnant or planning to become pregnant should avoid alcohol.

Race

The 2 largest studies, the US National Comorbidity Survey and the Epidemiologic Catchment Area Survey, both showed a lower prevalence of alcoholism in African Americans than in white Americans. The prevalence was equal or higher in Hispanic Americans compared with white Americans.

Studies of Native Americans and Asian Americans are smaller. These studies indicate the prevalence of alcoholism is higher in Native Americans and lower in Asian Americans when compared with white Americans.

Sex

Alcoholism is at least twice as prevalent in men as it is in women. In the National Comorbidity Survey, it was 2.5 times more prevalent in men than in women. The lifetime prevalence was 20% in men and 8% in women. For alcohol abuse or dependence in the past year, the rates were 10% for men and 4% for women.

Women do not metabolize alcohol as efficiently as men. Hazardous drinking (not alcoholism) is greater than 1 drink daily for women and greater than 2 drinks daily for men.

Problem drinking in women is much less common than it is in men, and the typical onset of problem drinking in females occurs later than in males. However, progression is more rapid, and females usually enter treatment earlier than males. Women more commonly combine alcohol with prescription drugs of abuse than do males. Women living with substance-abusing men are at high risk.

Alcohol problems are less likely to be recognized in women, and women with alcohol problems are less likely to be treated. This may be because women are less likely than men to have job, financial, or legal troubles as a result of drinking.

Age

The prevalence of alcoholism declines with increasing age. The prevalence in elderly populations is unclear but is probably approximately 3%. A study of the US Medicare population found that alcohol-related hospitalizations were as common as hospitalizations for myocardial infarction.

Among older patients with alcoholism, from one third to one half develop alcoholism after age 60 years. This group is harder to recognize. A recent population-based study found that problem drinking (>3 drinks/d) was observed in 9% of older men and in 2% of older women. Alcohol levels are higher in elderly patients for a given amount of alcohol consumed than in younger patients.

CLINICAL

Section 3 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

History

Diagnosis

Although the dangers of alcoholism are well known, data suggest that physicians frequently fail to make the diagnosis. Less than 50% of people who went to their doctor because of alcohol-related issues were asked about the problem. Multiple studies on medical inpatients and surgical patients in university and community hospitals, as well as outpatients in internal medicine and family medicine practices, show a low recognition rate and an even poorer treatment rate. The following are possible reasons that alcohol-related problems are missed during diagnosis.

• Patient factors contribute to the failure to diagnose alcohol problems. Patients frequently deny they have a problem. They might not link alcohol with its consequences. Patients may be unaware that a positive family history increases their risk for the disease. They might fear being reported to their employers. Patients might be too ashamed to report their problem.
• Physicians frequently share the responsibility for the failure to diagnose alcoholism. Many physicians have a negative attitude toward persons with alcohol problems. They view these patients as demanding and feel that they waste society's resources.
• Recognized substance abuse patients tend to have an antisocial personality disorder (type 2 alcoholism, characterized by an association with criminal behavior [sociopathy], onset in teen years, and drinking to get high), while those whose diagnosis is missed tend to have depression or anxiety. During residency training, physicians see a fair number of persons with type 2 alcoholism; these patients are often not truthful and have a poorer prognosis. This contributes to the belief among many physicians that alcoholism is not treatable, despite good evidence to the contrary (see Treatment). Also, physicians might hesitate to label a patient as alcoholic because of negative consequences. Physicians who have a problem with alcohol themselves are less likely to discuss alcoholism and its consequences with patients.
• Physicians might not know how to screen for and diagnose alcoholism. However, screening for alcoholism is important (see CAGE questionnaire and AUDIT).
• "How much do you drink?" is probably the question asked most commonly by doctors. This question has less than 50% sensitivity for alcohol problems. Blood tests, such as liver function tests and mean corpuscular volume, are not particularly effective; even the best test, gamma glutamyl transferase, has a sensitivity of only approximately 50%. Recently, sialic acid and carbohydrate-deficient transferrin levels have been touted as possible tests, but the sensitivities of both appear to be too low to be useful.

Screening

The CAGE ([need to] cut down [on drinking], annoyance, guilt [about drinking], [need for] eye-opener) questionnaire is the best-known and most-studied short screening test for alcohol problems. The CAGE questions should be given face-to-face (not as a paper and pencil test) and should be asked before questions on quantity and frequency (the sensitivity of the questions drops if quantity questions precede them).

• The following 4 questions make up the CAGE questionnaire:
• • Have you ever felt the need to cut down on your drinking?
  • Have people annoyed you by criticizing your drinking?
  • Have you ever felt bad or guilty about your drinking?
  • Have you ever had a drink first thing in the morning to steady your nerves or get rid of a hangover?
• Patients who answer affirmatively to 2 questions are 7 times more likely to be alcohol dependent than the general population. Those who answer negatively to all 4 questions are one-seventh as likely to have alcoholism as the general population.
• The sensitivity of the CAGE questionnaire was thought to be 75%. More recent studies, however, show that the sensitivity is lower, particularly in populations with a lower prevalence, such as among female and elderly populations. The CAGE questionnaire also may fail to identify binge drinkers and cannot identify those who have not experienced the consequences of alcoholism. Nevertheless, the CAGE questionnaire is brief and easy to administer
• The CAGE questions are not useful for diagnosing hazardous drinking. Women should consume no more than 3 standard alcohol drinks on any one occasion and no more than 7 drinks per week¹⁰ and men younger than 65 years should consume no more than 4 drinks on any one occasion and no more than 13 standards drinks per week. Men older than 65 years should follow recommendations for women. Other drinking considered hazardous is any use of alcohol by children, teens, by those with a personal or family history of alcohol dependence, women who are pregnant or breastfeeding, and use before or during situations requiring attention or skill (eg, driving)
• By itself, the CAGE questionnaire is not an adequate screening for alcohol problems.

The AUDIT (alcohol use disorders identification test) is the best test for screening because it detects hazardous drinking and alcohol abuse. Furthermore, it has a greater sensitivity in populations with a lower prevalence of alcoholism. One study suggested that questions 1, 2, 4, 5, and 10 were nearly as effective as the entire questionnaire. If confirmed, AUDIT would be easier to administer.

Table 1. AUDIT Questions and Scoring System

The AUDIT can be administered as a paper-and-pencil test, but the CAGE questionnaire should be administered face to face. The CAGE questionnaire is less reliable when given after asking questions on frequency. If the patient answers questions on the CAGE questionnaire or AUDIT affirmatively, following up with additional questions about circumstances and reasons is important. Additional useful questions are found below (see Additional questions).

The diagnosis of alcohol dependence relies more on the consequences of alcohol use and less on the amount of alcohol consumed. Thus, if one suspects alcohol problems from answers to screening questions, attempt to determine what consequences of alcohol abuse the patient has experienced.

Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision  (DSM-IV-TR) criteria are required to make the diagnosis of alcohol dependence. The diagnosis requires 3 of the following criteria in the DSM-IV-TR.

• A maladaptive pattern of substance use leading to clinically significant impairment or distress, as manifested by 3 or more of the following, occurring at any time in the same 12-month period:
• • Tolerance, as defined by either of the following:
  • • A need for markedly increased amounts of the substance to achieve intoxication or desired effect
    • Markedly diminished effect with continued use of the same amount of the substance
  • Withdrawal, as manifested by either of the following:
  • • The characteristic withdrawal syndrome for the substance (refer to Criteria A and B of the criteria sets for Withdrawal from the specific substances)
    • The same (or a closely related) substance is taken to relieve or avoid withdrawal symptoms
  • The substance is often taken in larger amounts or over a longer period than was intended
  • There is a persistent desire or unsuccessful efforts to cut down or control substance use
  • A great deal of time is spent in activities necessary to obtain the substance (eg, visiting multiple doctors or driving long distances), use the substance (eg, chain-smoking), or recover from its effects
  • Important social, occupational, or recreational activities are given up or reduced because of substance use
  • The substance use is continued despite knowledge of having a persistent or recurrent physical or psychological problem that is likely to have been caused or exacerbated by the substance (eg, current cocaine use despite recognition of cocaine-induced depression, or continued drinking despite recognition that an ulcer was made worse by alcohol consumption). Specify if:
  • • With physiological dependence - Evidence of tolerance or withdrawal (ie, either item 1 or 2 is present)
    • Without physiological dependence - No evidence of tolerance or withdrawal (ie, neither item 1 nor 2 is present)

The following reasons illustrate the importance of screening for alcohol and drug abuse.

• Alcoholism is common and serious.
• Failure to screen leads to misdiagnosis. Approximately 50-90% of alcohol problems are missed in the office.
• Effective and simple screening tests are available.
• Effective treatments are available, especially if the diagnosis is made early.
• Early identification can prevent physical and psychosocial problems.

Additional questions, as present below, may be helpful when screening for alcoholism.

• Have you ever had a drinking problem?
• When was your last drink? (Less than 24 h is a red flag.)
• Do you use alcohol to relieve pain, anxiety, or insomnia?
• Have you ever been arrested for drinking, such as driving under the influence?
• Have you ever lost friends or girlfriends/boyfriends because of your drinking?
• Have you ever been to an Alcoholics Anonymous (AA) meeting?
• The following are additional questions specific to the geriatric population:
• • Did your drinking increase after someone close to you died?
  • Does alcohol make you sleepy so that you often fall asleep in your chair?
• The following are additional questions specific to the adolescent population:
• • Do you drink alone?
  • Do you ever miss school to go drinking or because you have a hangover? 

Physical

• The following are signs and symptoms of alcohol withdrawal:
• • Nausea and vomiting
  • Diaphoresis
  • Agitation and anxiety
  • Headache
  • Tremor
  • Seizures
  • Visual and auditory hallucinations: Many patients who are not disoriented, and who therefore do not have delirium tremens, have hallucinations.
• The following are signs of delirium tremens (ie, alcohol withdrawal delirium):
• • Tachycardia and hypertension
  • Temperature elevation
  • Delirium
• The following are signs of chronic alcoholism:
• • Gynecomastia
  • Spider angiomata
  • Dupuytren contractures (also may be congenital)
  • Testicular atrophy
  • Enlarged or shrunken liver
  • Enlarged spleen
• Ataxia, ophthalmoplegia (usually lateral gaze palsy), and confusion indicate Wernicke encephalopathy.
• Anterograde and retrograde amnesia, often with confabulation and preceded by Wernicke encephalopathy, indicates Korsakoff syndrome.
• Asterixis and confusion suggest hepatic encephalopathy.

Causes

Patients commonly use a psychiatric disorder to deny alcohol abuse. Unless strong evidence indicates that the psychiatric disorder clearly precedes the alcoholism or is present during a long period of sobriety, the best plan is to proceed as if alcoholism is the primary diagnosis. Arrange a consultation with a psychiatrist for difficult cases because some patients who are treated for psychiatric conditions stop drinking and do very well.

The physician should, nonetheless, perform a brief mental status exam to help guide the referral process. Basic elements that should be covered in the mental status exam include an assessment of mood, perceptual problems such as hallucinations, and a safety screen. The use of a standardized instrument helps ensure important questions are asked and the results transmitted with some degree of objectivity. Several validated instruments exist, including The Patient Health Questionnaire from the Primary Care Evaluation of Mental Disorders (PRIME-MD)¹¹ and the Cornell Psychiatric Screen¹².

Genetic psychiatric disorders, such as schizophrenia and bipolar disorder, are associated with alcoholism. The presence of both a serious, persistent mental illness and alcoholism is called dual diagnosis. The physician must address both. Family history commonly reveals members with bipolar disorder, alcoholism, or both. Despite this and despite an intensive search for a gene for alcoholism, study results remain inconclusive. Nevertheless, some evidence indicates that genetics plays a major role in alcohol abuse.

• Twin studies
• • Identical twins have a higher concordance for drinking behavior and possibly alcoholism than fraternal twins.
  • In a well-conducted twin study of 542 families, a single underlying trait for conduct disorder, antisocial personality, alcohol dependence, and drug dependence was found, which was highly heritable and was observed in both sexes.¹³ Additionally, the study found that maximal alcohol consumption of fathers was predictive of their children having behavior and substance abuse problems (>24 drinks in 24 h yielded especially high risk). Not all at-risk children developed substance use or behavior problems. The environment seemed to determine which, if any, manifested. Deviant peers and poor parent-child relationships predicted early use (age <15 y) of alcohol, which predicted later alcohol abuse and antisocial personality. This study applies to early-onset alcoholism and type 2 alcoholism. More work is needed on later-onset alcoholism and type 1 alcoholism.
• Adoption studies
  
  
  • Whether reared by biologic or adoptive parents, sons of males with alcoholic problems are 4 times more likely to have problems with alcohol than sons of persons who are not.
  • Two Swedish studies have suggested the following 2 types of male alcoholism:
  • • Type 1 characteristics include (1) onset in adulthood (early twenties), (2) drinking to relieve anxiety, and (3) inherited but requires an environmental trigger.
    • Type 2 characteristics include (1) an association with criminal behavior (sociopathy), (2) onset in teen years, and (3) drinking to get high.
    • Sons of persons with type 2 alcoholism are 7 times more likely to develop type 2 alcoholism compared with the general population.
    • The theories suggested from these studies are controversial and require confirmation in additional populations.
  • Data from adoption studies on daughters of persons with alcohol problems are less clear. Daughters might be at increased risk if the biological mother has alcoholism. A recent twin study in women found higher concordance in monozygotic twins than in dizygotic twins.
• Experimental studies
• • Schuckit and Smith found that sons of persons with alcoholism respond differently to an alcohol challenge.¹⁴ They report decreased subjective ratings for feeling intoxicated, and they objectively have less body sway when given the same amount of alcohol as sons of persons without alcoholism. The study population consisted of white, male college students who drank alcohol but were not alcohol dependent themselves. The fathers in this study could not have psychopathology other than alcoholism (ie, no sociopathy, no bipolar illness).
  • Ten-year follow-up data have been published recently for the first half of this cohort. Of the sons of persons with alcoholism, 26% were alcohol dependent by age 30 years, as opposed to 9% of the control group. Furthermore, 56% of the sons of persons with alcoholism with lesser objective and subjective responses to alcohol became alcohol dependent, as opposed to 14% of the sons of persons with alcoholism who did not demonstrate these decreased responses. This also held true for the sons of fathers who did not have alcoholism, although the numbers were small.
  • Positive family history and lesser response to alcohol increased the likelihood of later development of alcohol dependence.

• Psychological studies
• • Behavioral models explain alcohol abuse in terms of learning theory. Through operant conditioning, the reinforcing elements of alcohol use become habitual.
  • Cognitive models explain alcohol abuse in terms of “automatic thoughts,” which precede the person’s more identifiable feelings about alcohol. For example, an automatic thought might be “I deserve a drink because I’ve had a rough day."
  • Psychoanalytic models explain alcohol abuse in terms of ego defenses and intrapsychic conflicts. The alcohol serves as a way to escape the uncomfortable internal conflict.

DIFFERENTIALS

Section 4 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Other Problems to be Considered

The relationship between alcohol and bipolar disorder is an important dual diagnosis. In fact, a substance abuse disorder is seen in nearly 60% of individuals with bipolar disorder.¹⁵ Any individual who presents with significant mood fluctuations must be screened for an alcohol use disorder.

Panic disorder, generalized anxiety disorder, social phobia, dysthymic disorder, major depression, bipolar mania, or primary (idiopathic) insomnia: Alcohol abuse or dependence might reflect self-treatment for these conditions.

Other drug abuse (both prescription drugs and street drugs): Consider the possibility of other drug abuse, both prescription drugs and street drugs.

Comorbid disorders: Also consider comorbid psychiatric conditions such as anxiety and depression. Depression, anxiety, and antisocial personality all are more common in persons with alcoholism than in the general population (20.5% vs 7.2%, 23.5% vs 11.1%, and 18.3% vs 3.6%, respectively).

Of particular importance is the common concurrence of posttraumatic stress disorder (PTSD) and alcohol abuse. The activating symptoms of alcohol withdrawal aggravate the PTSD, which inevitably increases the risk of relapse.¹⁶ A number of studies examined alcohol use in the aftermath of the attacks on the World Trade Center. A survey conducted 9 months after the terrorist attack found a 17.5% increase in alcohol use when compared with consumption patterns in the month preceding the attack. The same study noted that PTSD declined during those 9 months, but alcohol use remained elevated.¹⁷ Individuals glued to the television experienced higher rates of PTSD. Nationwide estimates of PTSD in the 2 months following 9/11 varied according to the television viewing time, ranging between 2.7-4.3%.¹⁸

Another study examined combat veterans of the first Gulf War. Six years after that brief war, a significant correlation still existed between alcohol use disorders and PTSD.¹⁹ The co-occurring disorders of PTSD and alcohol abuse are expressed differently between the genders. Men are much more likely to experience irritability as they drink excessively.²⁰ Women with PTSD also abuse alcohol, but are more likely to suffer from vague physical complaints and depression.²¹

WORKUP

Section 5 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Lab Studies

Biomarkers

Alcohol biomarkers are physiological indicators of alcohol exposure or ingestion and may reflect the presence of an alcohol use disorder. These biomarkers are not meant to be a substitute for a comprehensive history and physical examination by an appropriate health professional. Instead, alcohol biomarkers should be a complement to self-reported measures of drinking.²³

In a population of psychiatric patients, research evidence has shown the usefulness of biological measures in the detection of alcohol use disorders when compared with patient self-report. A 2007 study of 486 consecutively admitted psychiatric patients showed a low correlation between self-reported consumption of alcohol and illicit drugs and biological measures; 52% of the patients underreported their consumption of illicit drugs when compared with urine toxicology screening results; 56% of patients underreported alcohol use as evaluated by carbohydrate-deficient transferrin (CDT), and 37% of patients underreported alcohol use as evaluated by CDT + gamma glutamyltransferase (GGT).²² Replication of such research in a primary care population is needed to show that biological measures aid the primary care clinician in detecting alcohol use disorders.

Alcohol biomarkers are generally divided into indirect and direct biomarkers.²³

Indirect alcohol biomarkers

Indirect biomarkers suggest heavy alcohol use by detecting the toxic effects that alcohol may have had on organ systems or body chemistry.²³

• Indirect alcohol biomarkers include aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma glutamyltransferase (GGT), mean corpuscular volume (MCV), and carbohydrate-deficient transferrin (CDT).²³
• GGT, AST, and MCV are the most frequently used indirect biomarkers.²⁴ As a screen for alcohol dependence, the sensitivity/specificity of CDT is generally higher than AST, ALT, GGT, or MCV.^{23, 25, 26} (See Table 2 below.) CDT is less sensitive/specific in women than men.²⁷
• CDT is a collection of various isoforms of the iron transport protein transferrin.²⁴ Alcohol consumption above 50-80 g/d for 2-3 weeks appears to increase serum concentrations of CDT.^{26, 25} CDT tends to distinguish chronic heavy drinkers from light social drinkers.²⁴ A number of different ways are available to measure CDT; some may be better than others, depending on factors such as the type of alcohol consumption and gender.²⁸
• The combination of GGT and CDT compared with GGT or CDT alone shows a higher diagnostic sensitivity, a higher diagnostic specificity, and a stronger correlation with the actual amounts of alcohol consumption (see Table 2 below).^{25, 26} Combination GGT/CDT values appear to increase after the daily alcohol consumption exceeds a threshold of 40 g.²⁶ This approach is cost-effective, easy to manage in hospital laboratories, and should be suitable for routine clinical care.²⁶
• Other indirect alcohol biomarkers of emerging interest include total serum sialic acid (TSA), 5-hydroxytryptophol (5-HTOL), N-acetyl-beta-hexosaminidase (Beta-Hex), plasma sialic acid index of apolipoprotein J (SIJ), and salsolinol.²⁹

Direct alcohol biomarkers

Direct biomarkers are analytes of alcohol metabolism.²³

• Direct alcohol biomarkers include alcohol itself and ethyl glucuronide (EtG).²³
• A blood alcohol level might be helpful in the office if the patient appears intoxicated but is denying alcohol abuse. A blood alcohol level in excess of 300 mg/dL, a blood alcohol level of greater than 150 mg/dL without gross evidence of intoxication, or a blood alcohol level of greater than 100 mg/dL upon routine examination indicates alcoholism with a high degree of reliability. The short half-life of alcohol limits its use widely as a biomarker.²⁶ As the blood alcohol level detects alcohol intake in the previous few hours, it is not necessarily a good indicator of chronic excessive drinking.²⁴
• EtG is a minor, nonoxidative, water-soluble, stable, and direct metabolite of alcohol that is formed by the conjugation of ethanol with activated glucoronic acid.^{24, 25, 26} Shortly after alcohol intake, even in small amounts, EtG becomes positive.²⁴ After complete cessation of alcohol intake, EtG can be detected in urine for up to 5 days after heavy binge drinking^{29, 26}, making EtG an important biomarker of recent alcohol consumption.²⁴ A 2006 report by the Substance Abuse and Mental Health Services Administration states that the use of EtG should be considered as a potential valuable clinical tool, but the use of EtG in forensic settings is premature.²³
• Other direct alcohol biomarkers of emerging interest include acetaldehyde, fatty acid ethyl esters (FAEE), Ethyl Sulfate (EtS), and Phosphatidylethanol (PEth).^{23, 29}

Table 2. Sensitivity and Specificity of Alcohol Biomarkers*

Other Tests

The possibility of polysubstance abuse/dependence justifies performing a blood/urine toxicology screen for other substances of abuse.

TREATMENT

Section 6 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

A number of serious problems are closely linked to alcohol intoxication. In fact, according to the NIAAA, intoxication is present in 30% of homicides, 22% of suicides, and 33% of car crashes. Any patient who presents an imminent safety risk to themselves or another person should be considered a candidate for hospitalization. This may require the assistance of family members or medical consultation with a psychiatrist.

Medical Care

Many physicians believe no effective treatment is available for alcoholism; therefore, these physicians do not refer their patients for treatment. However, more than 13 studies representing more than 4000 patients demonstrate that brief interventions make a difference. Most of the patients in these studies drank heavily but did not yet have a problem with alcohol.

One study performed in Norway demonstrated that brief advice given early can affect gamma glutamyl transferase levels and reported alcohol consumption. Early warning makes a difference to persons who drink heavily. In a study of 200 workers with alcoholism, recalling a physician's warning about drinking at the beginning of the study was associated with a better prognosis 2 years later. Unfortunately, less than 25% had received warnings from their physicians, again illustrating the problem of missed diagnosis.

• The first step in treatment is brief intervention. The physician states unequivocally that the patient has a problem with alcohol and emphasizes that this determination stems from the consequences of alcohol in that patient's life, not from the quantity of alcohol consumed. Emphasizing the effects on family, friends, and occupation, as well as any physical manifestations, is important. Pointing out that loss of control and compulsive use indicate alcohol dependence also is important.
• • Present the diagnosis.
  • • Use explicit evidence; emphasize the consequences endured by the patient as a result of alcohol abuse.
    • Be empathic and nonjudgmental.
    • Avoid arguments about the diagnosis.
    • Avoid use of the word alcoholic.
  • Indicate the responsibility for change is with the patient. Listen to the patient's goals and point out discrepancies between his or her goals and actions.
  • Determine the patient's readiness for change. Motivating a reluctant patient is one of the great challenges in treatment. To enhance the prospects of successful treatment, the clinician needs to have a basic concept of the stages of change. The 5 stages of change (Prochaska,) provide fundamental guidance for enhancing motivation. The Substance Abuse and Mental Health Services Administration, the Center for Substance Abuse Treatment presents this concept in detail through a Treatment Improvement Protocol titled "Enhancing Motivation for Change in Substance Abuse Treatment." The 5 stages of change are precontemplation, contemplation, preparation, action, and maintenance. Specific strategies aligned with each of the 5 stages help a clinician motivate and prepare the patient for change. The 5 stages of change represent a cycle, permitting and explaining behavior that moves in both progressive and regressive directions.
  • • In the precontemplation phase, the individual does not express any interest in the need for change. Many individuals with substance use problems are firmly entrenched in this stage. The options in dealing with patients in this stage are limited and include pointing out the discrepancy between patient action and patient goals, suggesting that the patient bring a family member to the next appointment, and suggesting a 2-week abstinence trial.
    • Contemplation represents the first evidence of dynamic behavior. The individual expresses a tentative belief in the possibility that alcohol use might be harmful. The hallmark of this stage is ambivalence and skepticism. Skepticism is not the same as denial but instead allows some degree of personal reflection. The patient is receptive to new information, or just as likely reassured that current behavior is acceptable, in the absence of information. Thus, the clinician should influence the ambivalence characteristic of contemplation in a direction favoring change. This can include pointing out that the patient's actions are not congruent with their goals, giving pamphlets concerning alcohol abuse, and suggesting an abstinence trial.
    • When the clinician successfully alters the balance in favor of a healthy choice, the patient enters the preparation stage. The preparation stage is a thoughtful phase focused on making plans.
    • The action stage of change represents full recognition of a problem along with observable evidence of steps taken to reduce alcohol use. The clinician should reinforce and praise the decision to change. Emphasizing that the biggest error at this stage is to underestimate the amount of help needed to quit drinking is critical. The patient should be given a list of options for treatment including AA and pharmacotherapy.
    • Maintenance is the final and most mature stage of change. During the maintenance stage, motivational efforts are directed toward promoting hard won gains and preventing slips. Relapse prevention efforts are sustained by the patient's appreciation of specific environmental and biobehavioral triggers, which contribute to recurrence. See Follow-up.
  • As mentioned previously, the stages of change represent a cycle permitting both forward and backward movement.
• The physician must state firmly, but empathically, that alcohol is a problem for the patient and that the patient determines the solution. Patients come for treatment through several means, often from a mixture of both coercion and concern. The clinician needs to understand the extent of resistance to effectively work with the patient. A good strategy is to learn about patients' goals and indicate discrepancies between their goals and their choices. Pointing out discrepancies is more effective initially than statements such as, "You have to quit," or, "You have to go to AA."
• The patient's response determines the physician's next step. If the patient denies the problem, recommending joining AA will not work. Involving the family and/or suggesting a trial of abstinence is useful, and, importantly, the physician should follow up with the patient in a few weeks. The patient might be angry initially and storm out of the office, but then the patient might recall the physician's warning months or years later and stop drinking. For patients who recognize a problem and will consider referral, the cheapest (free) and most accessible option is AA.
• • The AA 12-step approach involves psychosocial techniques used in changing behavior (eg, rewards, social support networks, role models). Each new person is assigned an AA sponsor (a person recovering from alcoholism who supervises and supports the recovery of the new member). The sponsor should be older and should be of the same sex as the patient (opposite sex if the patient is homosexual).
  • Patients do not need a strong religious background to be successful in AA; they only need the belief in a power higher than themselves. Urge patients to use aspects of the program that can help them stay sober and ignore aspects that are not helpful.
  • Patients who have tried AA may have had a bad past experience. Patients should try at least 5-10 different meetings before giving up on the AA approach because each meeting is different. For example, women often do better at meetings for women only because the issues for female patients with alcoholism are different from the issues for male patients with alcoholism. A meeting in the suburbs might not be appropriate for someone from the inner city and vice versa.
  • The physician should have AA literature in the office (dates and places of meetings), have the AA phone number available, and know about other treatment services in the community, including referrals for medical consultants or specialists in chemical dependency. No randomized trials of AA have been performed, but a US Veterans Administration study suggested that patients who attended meetings did much better than those who refused to go.
  • AA can be reached via their Web site (Alcoholics Anonymous) or by mail (AA General Service; PO Box 459; Grand Central Station; New York, NY 10163). Physicians can order pamphlets and other patient education material from these sources.
• Additional sources of help include the Substance Abuse Treatment FACILITY LOCATOR, Self-Help Group Sourcebook Online, and SMART Recovery. The acronym SMART is for Self-Management and Recovery Training.
• Treatment of alcoholism involves the following:
• • Brief physician advice makes a difference.
  • While a trial period of controlled drinking with careful follow-up might be appropriate for a diagnosis of alcohol abuse, this approach increases a physician's professional liability. Complete abstinence is the only treatment for alcohol dependence. Emphasize that the most common error is underestimating the amount of help that will be needed to stop drinking. The differential diagnosis between alcohol abuse and dependence can be a difficult judgment call.
  • Hospitalize patients if they have a history of delirium tremens or if they have significant comorbidity. Consider inpatient treatment if the patient has poor social support, significant psychiatric problems, or a history of relapse after treatment.
  • Strongly recommend AA.
  • Encourage hospitalized patients to call AA from the hospital. AA will send someone to talk to them if the patient makes the contact. Patients need to attend meetings regularly (daily at first) and for a sufficient length of time (usually 2 y or more) because recovery is a difficult and lengthy process.
  • In the beginning of treatment, and perhaps ongoing, patients should remove alcohol from their homes and avoid bars and other establishments where strong pressures to drink may influence successful abstinence.
  • If the patient has an antisocial personality (ie, severe problems with family, peers, school, and police before age 15 y and before the onset of alcohol problems), recovery is less likely. If the patient has primary depression, anxiety disorder, or another potentially contributory disorder (the other disorder must antedate the problems with alcohol or it must be a significant problem during long periods of sobriety), treat this primary problem aggressively.
• Strongly encourage family members of patients with alcoholism to contact Al-Anon and Alateen via its Web site (Al-Anon/Alateen) or mailing address (Al-Anon Family Group Headquarters; PO Box 182; Madison Square Garden Station; New York, NY 10159-0182).

Consultations

Consultation with a psychiatrist might be indicated in cases in which questions of suicide, violence, or comorbid psychiatric disorders might be present.

Diet

Persons with alcoholism often have a poor diet. Folate deficiency is common. Advise patients to eat plenty of fruits and vegetables and consider a multivitamin supplement. Supplemental enteral nutrition improves survival in persons with advanced liver disease.

MEDICATION

Section 7 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Treatment of alcohol withdrawal is best accomplished with benzodiazepines. Avoid fixed-dose therapy, and treat patients for symptoms. This results in use of lower doses of benzodiazepines, less patient sedation, and earlier patient discharge. Lorazepam and oxazepam are preferred for patients with significant liver disease because the half-lives of other benzodiazepines can be significantly prolonged. These shorter-acting benzodiazepines require more frequent patient monitoring. Use longer-acting drugs (eg, chlordiazepoxide) when monitoring is not reliable.

Other agents that have been used with some success in the treatment of withdrawal include beta-blockers, clonidine, phenothiazines, and anticonvulsants. All can be used with benzodiazepines, but none has been proven to be adequate as monotherapy. A number of medications have been tried in the treatment of alcoholism. Disulfiram (Antabuse) has been used as an adjunct to counseling and AA with motivated patients to reduce the risk of relapse. Patients are reminded of the risks of adverse effects when tempted to drink. Disulfiram causes nausea, vomiting, and dysphoria with coincident alcohol use. In a large trial, disulfiram did not increase abstinence. If a patient asks for disulfiram and thinks it will help, it might be worth considering.

Naltrexone blocks opiate receptors and works by decreasing the craving for alcohol, resulting in fewer relapses. A recent positron emission tomography study demonstrated that persons with alcoholism have increased opiate receptors in the nucleus accumbens of the brain and that the number of receptors correlates with craving.

Most, but not all, studies found that naltrexone decreases relapses but the effect is modest (12-20%). Combining naltrexone therapy with cognitive behavioral therapy enhanced benefit. One study showed benefit with an intensive primary care intervention. Studies suggest that virtually all placebo patients who sampled alcohol relapsed, while only half the naltrexone patients who sampled alcohol relapsed.

Most studies are of short duration, and more long-term trials are needed. In short-term studies when naltrexone was stopped, patients relapsed. Naltrexone has a greater effect on reducing relapse to heavy drinking than it does on maintaining abstinence. Extended-release intramuscular naltrexone resulted in reduced relapse to heavy drinking in a large, randomized trial. Its effects on complete abstinence were more modest. The main adverse effects are nausea and/or vomiting, abdominal pain, sleepiness, and nasal congestion.

In 2001, Sinclair reviewed 8 studies and suggested that naltrexone is safe to administer in patients who are still drinking and that it will gradually result in the patient consuming less alcohol (this is the case in laboratory animals).³³ Patients should take the naltrexone daily initially and then only when they have a strong urge to drink. Patients should carry naltrexone with them indefinitely. Patients should agree to always take the naltrexone prior to drinking alcohol. Daily naltrexone may be counterproductive in patients who remain abstinent. It is most helpful in those who sample alcohol after stopping (lower chance of a relapse). More data are needed before this approach can be adapted because it challenges the conventional wisdom that complete abstinence is always the goal of treatment.

Nalmefene is another opioid antagonist, and it blocks delta, kappa, and mu receptors; naltrexone acts primarily on mu receptors. One randomized trial with 100 patients using 10 mg PO bid has been completed, and nalmefene appears to have efficacy similar to naltrexone (reduces relapse to heavy drinking in patients who sample alcohol). At present, the drug is approved only for intravenous use for opiate addiction.

A number of studies have focused on antidepressants. Early studies with the selective serotonin reuptake inhibitors (SSRIs) have been disappointing. Two fairly good studies used tricyclic antidepressants (ie, desipramine, imipramine), which showed some short-term benefit. More data are needed. SSRIs probably do not benefit patients who are not depressed but might benefit those who are depressed. Topiramate facilitates GABA function and antagonizes glutamate, which should decrease mesocorticolimbic dopamine after alcohol and reduce cravings. One double-blinded trial with 150 subjects for 12 weeks suggests this is the case (decreased drinking, decreased craving, and greater abstinence). Topiramate is not approved for this use by the US Food and Drug Administration.

The largest and longest studies on the treatment of alcohol abuse have been performed in Europe with acamprosate (Campral). At 1 year, the continuous abstinence rates were 18% in the acamprosate group and 7% in the placebo group. At 2 years, the continuous abstinence rates were 12% in the acamprosate group and 5% in the placebo group. Most patients returned to drinking while still using the drug. The drug was recently approved in the United States. It stimulates GABA transmission, inhibits glutamate, and decreases alcohol consumption in alcohol-dependent rats. The main adverse effect is diarrhea.

Two short-term trials have compared acamprosate and naltrexone. Both found naltrexone to be superior. One of these studies compared the combination with either drug alone and with placebo. The combination was statistically superior to placebo and acamprosate alone and superior (but not statistically) to naltrexone alone. Larger and longer trials of the combination therapy are needed.

Drug Category: Glutamate receptor blockers

Mechanism of action is unknown, but it enhances GABA transmission and inhibits glutamate transmission. Compared with placebo, reduces drinking frequency and effectively increases abstinence in patients with alcoholism.

Drug Category: Aldehyde dehydrogenase inhibitors

Disulfiram inhibits aldehyde dehydrogenase, and, as a result, acetaldehyde accumulates. This leads to nausea, hypotension, and flushing if a person drinks alcohol while taking disulfiram.

Drug Category: Opiate antagonists

Alcohol has been shown to bind to opiate receptors in the brain. Studies show that blocking opiate receptors decreases cravings for alcohol.

FOLLOW-UP

Section 8 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Further Outpatient Care

• Frequent follow-up is essential to support the patient in recovery. The most common mistake physicians make is assuming too soon that the patient is stable. Ask patients about attendance at AA meetings and about their relationships with their sponsors. Less than 20% of patients remain abstinent for a full year. Among patients who have been sober for 2 years, the relapse rate is 40%. Patients who have been sober for 5 years are likely to remain sober, but they are still at risk for relapse.
• Warning signs for physicians that a patient has relapsed include missing appointments or attending AA meetings less frequently. Warn patients to avoid testing themselves, particularly early in sobriety. Encouraging involvement in exercise and other leisure activities also is helpful.
• The key step for the patient is to realize that treatment does not end with sobriety. Recovery means that patients can handle the stresses of everyday life without alcohol. Therefore, the patient must develop and rehearse strategies to cope with high-risk situations.
• • Successful recovery requires the patient to be able to do the following:
  • • Learn to say no to drinking in social situations.
    • Handle heavy-drinking friends who will try to undermine the patient's sobriety.
    • Handle stress. (Patients should not ignore symptoms of anxiety.)
    • Avoid boredom. (Prior to recovery, patients spent a great deal of time drinking or recovering from drinking. Upon abstinence, patients will have more free time.)
    • Learn to get along again with family and close friends. (Family problems often increase when drinking stops.)
    • Identify other situations that can lead to drinking and develop ways to cope with them.
  • Patients should have a list of phone numbers of people they can call when they are having a difficult time coping. Importantly, patients should write out the list and put it in a convenient location because sometimes during high-stress periods they may become emotionally and mentally disorientated, necessitating written instructions.
  • Patients should spend time thinking about circumstances during which they feel at highest risk for relapse. They should anticipate these situations and make a written list. Most persons with alcoholism can quickly list the circumstances and/or emotions that led them to drink.
  • Patients need to identify specific responses (thoughts as well as behaviors) to each of these high-risk situations. Encourage patients to be very specific when considering their responses. For example, ask patients exactly what they are going to say and do when asked at parties what they want to drink. Once patients have made the list, they should practice responses to their high-risk situations.
  • When patients have the urge to drink, there are several techniques that can be used to deal with the situation, including (1) self-distraction (ie, getting involved with an alternate activity that they enjoy), (2) thought stopping (ie, patients should not dwell on thoughts of drinking but should stop these thoughts), (3) reprogramming (ie, patients should avoid activities that remind them of drinking), and (4) use of social support structure. The most common cause of relapse is failure to use coping strategies.
• If the patient has a relapse, find out what happened (make a diagnosis) in order to formulate a new treatment plan. Below is an outline for dealing with relapses. Insist that the patient be actively involved in devising solutions; do not attempt to solve the problem for the patient.
• • Make a diagnosis.
  • • How long had the patient been sober before relapse?
    • What were the circumstances of the relapse?
    • What was (were) the triggering event(s)?
    • How does the patient feel about the relapse?
    • What social support systems are available to the patient?
    • Does the patient believe that he or she can quit again?
  • Institute a treatment plan.
  • • Determine what the patient thinks is appropriate treatment.
    • Reinforce the patient's decision to seek help.
    • Emphasize that complete abstinence is the only solution.
    • Reframe the relapse as a learning opportunity.
    • Provide support and empathy. For example, reassure the patient with encouragement such as "We can do this together."
    • Have the patient come up with ways to avoid the triggering event or find alternative ways to deal with it.
    • Rehearse what to do in high-risk situations, including making use of the patient's social support system.

Prognosis

The prognosis for alcoholism should not be considered hopeless. As many as 30% of persons with alcoholism stop drinking. Even a patient with cirrhosis might have a favorable prognosis if alcohol cessation is achieved.

Patient Education

For excellent patient education resources, visit eMedicine's Mental Health and Behavior Center; Substance Abuse Center; Hepatitis Center; and Liver, Gallbladder, and Pancreas Center. Also, see eMedicine's patient education articles Alcoholism, Drug Dependence and Abuse, Alcohol Intoxication, Hepatitis B, Hepatitis C, and Cirrhosis.

Involving family in the patient’s treatment of alcoholism can be a vital step on the path toward recovery. At a minimum, the destructive behaviors that occurred before treatment should be addressed by the patient with his or her family members. This is an important acknowledgment by the patient as they begin to grapple with the significance of their previous alcohol-centered lifestyle. Family members may find support through Al Anon, a fellowship devoted to sharing experiences and learning from others how to achieve serenity when a loved one struggles with alcohol.

MISCELLANEOUS

Section 9 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Medical/Legal Pitfalls

• If a physician documents his or her diagnosis of an alcohol-related condition, efforts to educate the patient and to have the patient obtain appropriate treatment must also be documented.
• Document advice to not operate a motor vehicle or other machinery when under the influence of alcohol. Inform patients and their families that the patient is legally responsible for acts committed under the influence of alcohol.
• While a trial period of controlled drinking with careful follow-up might be appropriate for a diagnosis of alcohol abuse, this approach increases a physician's professional liability. Complete abstinence is the only treatment for alcohol dependence. The differential diagnosis between alcohol abuse and dependence can be a difficult judgment call.
• Beware of the dangers of suicide and homicide in working with a patient with an alcohol problem. Suicide is a major cause of death accounting for 30,000 deaths a year. An estimated 350,000 suicide attempts come through America's emergency departments. One third of these suicide attempts involved the use of alcohol. See The OAS Report.

REFERENCES

Section 10 of 10

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

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13. Hicks BM, Krueger RF, Iacono WG, McGue M, Patrick CJ. Family transmission and heritability of externalizing disorders: a twin-family study. Arch Gen Psychiatry. Sep 2004;61(9):922-8. [Medline].