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Alcohol use is associated with a wide range of medical and behavioral disorders. An estimated 4% to 40% of medical and surgical patients experience problems related to alcohol. Alcohol and its associated health problems have a major impact on the practice of generalists and other physicians.

Patients with alcohol problems present several unique challenges for physicians. As with other chronic diseases, alcohol-use disorders range in clinical severity from relatively a symptomatic to severe and do respond to treatment. To manage patients effectively, physicians should be able to recognize all forms of alcohol problems from the earliest stages to the more advanced stages, and they should be able to participate in the management of patients along the entire spectrum of the disease process.

The National Institute on Alcohol Abuse and Alcoholism (NIAAA) recently published guidelines for use by physicians in the management of patients with alcohol problems. The guidelines address the identification and treatment of alcohol problems, which encompass behavioral and social problems as well as medical manifestations of excess alcohol use. This subsection provides an overview of the major clinical features and recent developments in the identification and management of alcohol problems in clinical practice.

Approximately 73% of adults in the United States use alcohol. When considering the spectrum of clinical manifestations in patients who may have alcohol problems, it is helpful to distinguish nonproblematic, moderate drinking; hazardous drinking, which places patients at risk for alcohol problems; and harmful drinking, which directly causes specific alcohol problems. Patients with more advanced alcohol problems may meet criteria for alcohol abuse or alcohol dependence.

The NIAAA has defined moderate drinking in terms of the average number of drinks consumed a day that places an adult at relatively low risk for developing alcohol-related health problems. For men younger than 65 years, moderate drinking is drinking an average of no more than two drinks a day. For men over 65 years and for all women, moderate drinking is defined as drinking less than two drinks a day. In contrast, at-risk drinking (which corresponds to the category of hazardous use in the schema developed by the World Health Organization [WHO]) occurs when those moderate drinking levels are exceeded or when the number of drinks consumed during a single occasion exceeds a specified amount (four drinks per occasion for men and three drinks per occasion for women). These definitions are based on epidemiological studies that demonstrate an association between specific levels of alcohol consumption and increasing health problems and mortality.

Specific criteria for diagnosing alcohol abuse have been developed by the American Psychiatric Association (APA). In the Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV), alcohol abuse is defined as a maladaptive pattern of alcohol use leading to clinically significant impairment or distress, manifested in a 12-month period by one or more of the following problems: (1) failure to fulfill role obligations at work, school, or home; (2) recurrent use of alcohol in hazardous situations; (3) legal problems related to alcohol; and (4) continued use despite alcohol-related social problems.

By APA criteria, alcohol dependence is manifested by a maladaptive pattern of use over a 12-month period that includes three or more of the following problems:
(1) physiologic tolerance, characterized either by an increase in the amount of alcohol consumed or by a decrease in the effects of the amount of alcohol customarily consumed.
(2) symptoms of withdrawal.
(3) use of greater amounts of alcohol over a longer period than intended.
(4) a persistent desire or unsuccessful attempts to control use.
(5) a great deal of time spent obtaining alcohol, using alcohol, or recovering from use.
(6) reducing important social, occupational, and recreational activities
(7) continued use despite knowledge of physical or psychological problems.

The term alcoholism, which is perhaps the most widely used term to describe patients with alcohol problems, has lost much of its usefulness because of the imprecision in its definition and the stigma associated with the term. A panel of 23 experts convened by the National Council on Alcoholism and Drug Dependence and the American Society of Addiction Medicine defined alcoholism as follows: "...a primary, chronic disease with genetic, psychosocial, and environmental factors...often progressive and fatal... characterized by impaired control over drinking, preoccupation with the drug alcohol, use of alcohol despite adverse consequences, and distortions in thinking, most notably denial...." However, more precise terminology for specific alcohol problems is more clinically useful.

Evidence from family, twin, and adoption studies supports a strong genetic component for the risk of alcohol dependence. In general, most studies of twins have demonstrated a higher concordance of alcohol dependence in monozygotic twins than in dizygotic twins. Adoption studies generally document that adopted children with a biologic parent who is alcoholic have a twofold to threefold greater risk of alcoholism than adopted children whose biologic parents are not alcoholic. Some studies suggest that there may be at least two distinct genetic risk patterns, variously referred to as type I (late-onset, milieu-limited) and type II (early-onset, male-limited). Studies of nonalcoholic adolescents and young adults with and without a family history of alcoholism provide evidence for a variety of electroencephalographic differences and differences in behavioral and physiologic responses to test doses of alcohol that may be related to the increased risk. The search for the gene responsible for transmitting risk of alcoholism has focused largely on the human D₂ dopamine receptor gene (DRD2). Although one group that studied deceased alcoholics reported an association with this gene, others have found no such association. Other putative alcoholism vulnerability genes include alcohol dehydrogenase-2 (ADH2), aldehyde dehydrogenase-2 (ALDH2), and the serotonin auto receptor HTR1B. Although genetic predisposition is clearly a major risk factor for alcohol problems, environmental influences may also impart risk. Such environmental influences include negative life events, occupational stress, expectancies about alcohol, personality factors (e.g., problem-prone behavior during adolescence), and interpersonal influences (e.g., the behavior of family or peers).

Familiarity with the wide variety of medical, behavioral, and psychiatric complications of heavy drinking or alcohol dependence facilitates detection and management of alcohol problems in patients.

The numerous medical complications associated with problem drinking have been the subjects of several reviews. Patients may present to physicians with acute and chronic clinical signs and symptoms that are the direct or indirect results of alcohol use. The most common medical effects of alcohol are seen in the central and peripheral nervous systems; these effects are intoxication, withdrawal, seizures, delirium and dementia, stroke, and peripheral neuropathy. Similarly, alcohol has a wide variety of effects on the GI system; these effects include esophageal diseases (e.g., Mallory-Weiss tears and carcinoma), gastritis, and peptic ulcer disease. Liver diseases, including acute alcoholic hepatitis and cirrhosis, are also highly prevalent. Acute and chronic pancreatic disease is also a common manifestation of alcohol use. Finally, the cardiovascular system may suffer a wide range of alcohol-related problems, such as hypertension, left ventricular hypertrophy and cardiomyopathy, arrhythmias, and sudden death.

Along with causing major neurological, digestive system, and cardiovascular effects, alcohol use is associated with a variety of other organ-based effects. Heavy drinking is associated with cancer of the upper digestive and respiratory tracts, the liver, and, in at least one study, the prostate, pleura, and cervix. Data linking alcohol to cancers of other organs (e.g., pancreas, colon, and breast) have been less convincing. Alcohol use may present as bleeding because of dysfunction of hepatic synthesis or thrombocytopenia. Alcohol use has also been associated with metabolic and endocrine abnormalities, such as osteoporosis, disturbances in lipid metabolism, menstrual dysfunction, male hypogonadism, and thyroid and adrenal dysfunction. Gout is associated with alcoholism and may occur at serum urate levels lower than those seen in nonalcoholic patients. Toxic effects of alcohol on the kidney are generally subclinical or secondary to other alcohol-related effects. Alcohol has been related to important dermatological problems, such as psoriasis and the dermatological findings associated with chronic liver disease. Finally, high levels of dental and periodontal disease have been documented in populations of alcoholic patients.

Epidemiological surveys have demonstrated high rates of psychiatric illness in persons diagnosed with alcohol abuse or dependence. Data from the Epidemiological Catchment Area Study demonstrated that 45% of such persons had a lifetime psychiatric diagnosis. The most common disorders were anxiety and affective and antisocial personality disorders. The National Comorbidity Study found a high 12-month prevalence of anxiety disorders (36.9%) and affective disorders (29.2%) in alcohol-dependent patients. Thus, patients with alcohol problems require careful evaluation for comorbid psychiatric symptoms and problems. Similarly, patients with psychiatric disorders are at high risk for having comorbid substance-use disorders.

Family problems, employment and legal problems, and social dysfunction may be more prevalent than specific medical or psychiatric diagnoses, and alcohol-induced behaviors may result in other specific problems.

Alcohol use is the leading cause of accidents (most notably, automobile accidents), injuries, and trauma (e.g., drownings, head injuries, burns, and spinal cord injuries). Alcohol use is associated with more severe injury in trauma patients. In addition, emergency departments are important sites for intervention in patients with alcohol problems. In one study, however, emergency physicians did not refer any patients with an elevated blood alcohol level to alcohol treatment. Treatment of patients convicted of driving under the influence of alcohol may decrease their likelihood of accidental or violent death. Minor accidents are also more prevalent among alcohol users.

Alcohol use is associated with injuries and trauma related to acts of violence; such acts include assault and homicide, as well as the domestic abuse of children and spouses. In one study of urban trauma center patients, victims of violence were more likely to use alcohol, to be male, and to possess a knife or gun. A history of childhood victimization has been identified as a predictor of the development of alcohol problems in women. Thus, a history of violence or abuse should prompt a careful assessment of drinking behaviors, and problem drinkers should be assessed carefully for these problems.

HIV seroprevalence may be higher in patients with more severe impairment from alcohol, and women may be at especially increased risk. In one alcohol-treatment setting, HIV seroprevalence in heterosexual, non-drug-injecting patients was 5%. Heavy drinkers are more likely to engage in high-risk sexual behaviors, such as having increased numbers of sexual partners, engaging in sex without condoms, and using injection drugs. Counseling patients about the association of alcohol use and high-risk sexual behaviors may result in safer sexual practices.

Alcohol-dependent persons are more likely to smoke tobacco than the general population. Alcohol acts as a co-carcinogen with tobacco, substantially increasing the risk of head, neck, and lung cancers. Alcohol-dependent patients who stop drinking may be up to 60% more likely to quit smoking than those who continue to drink.

Despite the prevalence of alcohol problems and their impact on health, most studies demonstrate that alcohol problems are not routinely detected in primary care settings. Rates of failure to detect alcohol problems vary by setting and level of practitioner training. Alcohol abuse or dependence is most likely to be identified in patients experiencing severe medical complications, such as alcoholic hepatitis or cirrhosis, and is less likely to be detected in women. Earlier detection of medically hazardous levels of drinking before the onset of organ damage or of alcohol abuse or dependence may be critical in preventing late sequelae. Simple, brief interventions are effective in reducing heavy drinking in high-risk drinkers.

Easy-to-use techniques for screening patients for alcohol-use disorders are currently available; these techniques should be incorporated into the routine care of all patients. One such screening technique involves a four-step process for identifying and diagnosing alcohol problem .Step 1 is to inquire about current and past alcohol use in all patients. Patients with alcohol problems may be somewhat sensitive about these and other alcohol-related questions. It is therefore critical that the patient be approached in a nonjudgmental manner. In addition, these questions may need to be asked on multiple occasions to obtain an accurate history of the patient's alcohol use. The questioner needs to be specific about current and past alcohol use. Because genetic predisposition and family environment are important risk factors for alcohol problems, inquiries into family history should routinely include questions about relatives with alcohol problems.

Steps 2 through 4 apply to all patients who report a history of alcohol use. In step 2, a more detailed history regarding quantity and frequency of alcohol use is obtained. The type of alcohol consumed is critical. Some patients may consider beer a safer form of alcohol and may not report its use unless specifically asked. Questions can help establish the frequency of alcohol use (e.g., daily as opposed to less frequent use) and a baseline of the amount of alcohol usually consumed. It is also important to establish other patterns of alcohol consumption; for example, a patient may have only two drinks a day from Monday through Thursday but may consume 10 to 15 drinks on Friday and Saturday nights. Questions about the quantity and frequency of alcohol use may help distinguish moderate drinking from at-risk and problem drinking and may help identify specific patterns of use, such as binge drinking.

In step 3, a standardized questionnaire is used to detect possible alcohol problems. The most commonly studied screening instrument in primary care settings is the CAGE questionnaire . This questionnaire screens for lifetime alcohol problems. It consists of four questions designed to identify ongoing alcohol use and withdrawal phenomena that demonstrate alcohol dependence. In scoring the CAGE questionnaire, each "yes" response counts as 1 point. A score of 2 or more is generally considered to be a positive result. The CAGE questionnaire is useful in identifying patients with alcohol problems who are seen in primary care settings; its sensitivity ranges from 60% to 95%, and its specificity ranges from 40% to 95%. Supplementing the four questions of the CAGE questionnaire with additional questions about tolerance (e.g., "How many drinks can you hold?") and substituting a question about whether any of the patient's friends or family members have expressed worry or concern about the patient's alcohol use may improve the usefulness of the CAGE questionnaire. Although it has been studied in a variety of health care settings, there are specific patient groups in whom the CAGE questionnaire may be less useful as a screening instrument. In one study of patients older than 60 years, the CAGE questionnaire performed poorly in identifying heavy drinkers or binge drinkers, among whom less than half had a positive CAGE score. In a more recent study, investigators demonstrated that the CAGE questionnaire may perform less well among women and within specific ethnic groups.

The Alcohol Use Disorder Identification Test (AUDIT) may provide additional useful information when patients are being screened for alcohol problems in primary health care settings. AUDIT was developed by the WHO and was designed to iden-tify hazardous and harmful drinking, as well as alcohol dependence. Among the 10 AUDIT questions are three quantity and frequency questions regarding current drinking and seven questions regarding past drinking. Each question is scored on a scale of 0 to 4; a total score of 8 or greater is considered to be a positive result. AUDIT has demonstrated a sensitivity of 92% to 96% and a specificity of 94% to 96%. Other screening instruments such as the TWEAK test and the Short Michigan Alcoholism Screening Test (S-MAST) have potential for use in primary health care settings but require further testing in those settings before their applicability can be determined.

Step 4 involves asking further questions with regard to potential alcohol problems. It is applied to those patients who were identified in steps 1 through 3 as having potential alcohol problems. A diagnosis of alcohol abuse or dependence is made on the basis of the criteria described in DSM-IV. The examination for evidence of specific alcohol-related medical and psychiatric problems should include a thorough history and physical examination. Although not useful as screening tests for alcohol-use disorders, laboratory tests, such as liver enzyme assay, may be useful in identifying undiagnosed alcohol-related medical problems. Questioning patients about alcohol-related behavioral and social problems is also essential when evaluating patients suspected of having alcohol-related problems. In addition, knowledge of previous treatment of alcohol problems is essential when referring patients for treatment.

Screening and diagnosis of alcohol problems represents a basic initial step in the management of patients with alcohol problems. Factors such as patient denial may make the initiation of a treatment plan very challenging. In addition, as with all chronic health problems and diseases, treatment is no guarantee of cure. Although the benefits of the treatment of alcohol-use disorders may be temporary, such treatment can be of great benefit to patients and to society as a whole. Patients with more severe alcohol problems, such as alcohol dependence, may require treatment from alcohol treatment specialists, whereas those in the at-risk and problem-drinking categories may be managed in primary care settings. The primary care physician can play a critical role in the management of all patients with alcohol problems, regardless of the severity of those problems. For patients with more severe alcohol dependence, the primary care physician's role includes identifying patients with severe dependence, referring such patients to treatment specialists, evaluating those patients for medical complications, providing support for ongoing treatment, and monitoring for signs of relapse .

A six-stage model has been proposed for assessing patients' readiness for behavior change and treatment . These stages represent a continuum, and patients may move from one stage to another. Physician assessment of readiness for behavior change may be helpful in tailoring the advice given to patients with alcohol problems. The overall goal is to move patients from the precontemplation stage to the action stage so that maintenance can be achieved.

Brief intervention therapy typically involves providing patients with feedback about the problems associated with their drinking habits and advising them to reduce their alcohol consumption to levels considered medically safe (i.e., below the level of at-risk drinking). The FRAMES acronym (feedback, responsibility, advice, menu, empathy, self-efficacy) summarizes a counseling strategy commonly used in brief interventions . This counseling strategy, as well as others commonly employed in brief intervention therapy, are useful for primary care physicians, and their use in primary care settings has been advocated by government agencies and experts in the field.

Two meta-analyses have examined the efficacy of brief intervention therapy. One such study concerned over 40 controlled trials that enrolled over 6,000 patients; it concluded that brief intervention therapy is more effective than no counseling at all and is often as effective as more extensive treatment. Another recent meta-analysis of eight studies demonstrated that patients who received brief intervention therapy were almost twice as likely to decrease their drinking as those who did not receive such therapy.

A recent study illustrates the process and value of brief intervention therapy. In this study, a sample of 723 persons were recruited from 17 primary care practices in Wisconsin. The group receiving brief intervention therapy was given a health booklet on general health issues and also received structured counseling about their drinking behaviors during two visits with a physician . After each visit to the physician, the patients received a telephone call from a nurse who reinforced the advice given by the physician. The control group received only the health booklet. Patients were followed for 1 year; the main outcomes used to evaluate the brief intervention therapy were measures of alcohol use (i.e., drinks per week and episodes of binge drinking), the number of emergency department visits, and the number of days spent in hospital. A 12-month follow-up evaluation showed that the mean number of drinks consumed per week decreased by more than 7.5 drinks in the group receiving brief intervention therapy, compared with a decrease of just over three drinks a week in the control group. The treatment group also had significantly fewer episodes of binge drinking over a 30-day period and experienced fewer episodes of excessive drinking. In addition, men in the treatment group had a significantly shorter length of hospitalization than men in the control group.

This study, along with many of the others reviewed in the two meta-analyses (see above), demonstrates that relatively simple clinical interventions that take a minimum amount of time and are well within the skill level of most primary care physicians can effectively improve patients' drinking behaviors. Important questions remain to be studied. The effectiveness of brief intervention therapy over time is unknown. In addition, the optimal number of brief interventions, the optimal length of time over which brief interventions should be made, and the optimal frequency of repeated brief interventions are uncertain. Other aspects of brief intervention therapy that have not yet been determined are the long-term benefits of such therapy and the effect that brief interventions have on progression to more severe alcohol problems.

Alcoholics Anonymous (AA) and similar groups, such as Rational Recovery and Narcotics Anonymous, are based on a 12-step recovery model. In this model, 12 steps describe specific attitudes, beliefs, and actions that are regarded as critical to the recovery process. Meetings are held 7 days a week in multiple locations throughout the country and include both open meetings, which are open to everyone, and closed meetings, which are restricted to group members.

Physicians interested in encouraging their patients to attend AA meetings should obtain an AA meeting schedule from their local AA organization. In addition, it is often recommended that physicians attend at least one open meeting so that they can better counsel their patients on how AA works. AA chapters and other 12-step groups are widely available and are free of charge.

Recently, attention has been paid to the question of the effectiveness of 12-step approaches. Several studies have demonstrated that attendance at AA meetings correlates with positive drinking outcomes. In addition to attendance, the patient's degree of involvement in AA (e.g., whether the patient has a program sponsor and the degree to which the patient participates in meetings) appears to correlate with decreased alcohol consumption. In one study, participants in an employee assistance program were given compulsory treatment on an inpatient basis, were required to attend AA meetings, or had a choice of these two options. All three groups improved, and no significant differences in job-related outcome variables were found among the groups. Although AA was less costly than inpatient treatment, a significant number of AA patients were subsequently referred for inpatient treatment; those who received inpatient treatment had the best outcomes. Future research on AA that is methodologically rigorous and attends to important clinically oriented outcomes is needed.

In addition to providing office-based evaluation, management, and referral to self-help groups, primary care physicians will often need to provide more intensive services to patients who meet criteria for alcohol abuse and dependence. These can include management of the alcohol withdrawal syndrome and referral to an alcohol treatment program.

Signs and symptoms of alcohol withdrawal, which can occur in alcohol-dependent persons who stop taking alcohol or who reduce their alcohol intake, include abnormalities in vital signs (e.g., tachycardia, hypertension, and fever), other symptoms of autonomic hyperactivity (e.g., tremor, diaphoresis, and insomnia), GI symptoms (e.g., nausea, vomiting, and diarrhea), and central nervous system effects (e.g, anxiety, agitation, hallucinations, seizures, and delirium). Withdrawal severity and response to treatment may be assessed using the revised Clinical Institute Withdrawal Assessment (CIWA-Ar). This instrument describes 10 clinical features of withdrawal that are rated by the clinician on the basis of observation of the patient. Although many patients presenting with mild withdrawal can be managed as outpatients, those with more severe withdrawal or with significant comorbid medical or psychiatric problems may require inpatient care.

When managing alcohol withdrawal, physicians should keep the following specific goals in mind. First, patients' symptoms should be monitored closely and treated in a manner that minimizes discomfort. Inadequate treatment of withdrawal symptoms may be a major stimulus to return to drinking. In addition, patients need to be monitored for major withdrawal complications such as seizures or delirium and treated accordingly. Withdrawal treatments are designed to decrease the occurrence of these complications. Entry into withdrawal treatment is also an opportunity to fully evaluate patients for other alcohol-related problems and to assess their general health status. It is critical to immediately plan for postwithdrawal treatment of alcohol problems to help patients maintain abstinence. All patients who are treated for alcohol withdrawal should be referred for ongoing treatment.

Pharmacologic therapies for alcohol withdrawal syndrome have been the focus of much research over the past 40 years. A variety of drugs, including the barbiturates, phenothiazines, carbamazepine, and alcohol itself, have been used. The benzodiazepines (e.g., chlordiazepoxide, diazepam, lorazepam, and oxazepam) are the safest and most effective medications for this purpose. In addition to preventing or alleviating withdrawal symptoms, benzodiazepines may also decrease the incidence of seizures and possibly delirium tremens.

Recently, a working group assembled by the American Society of Addiction Medicine reviewed the world literature on pharmacologic therapy for alcohol withdrawal syndrome to provide an evidence-based guideline for clinicians. Their review of over 130 papers yielded 65 prospective, controlled trials, which examined over 40 drugs. This review provided strong evidence in favor of the benzodiazepines over placebo and all other drugs and suggested that the longer-acting benzodiazepines provide a smoother withdrawal and may be more effective in preventing seizures. Generally, however, shorter-acting benzodiazepines are considered to be safer in the elderly and in patients with severe liver disease. Older benzodiazepines, such as chlordiazepoxide and diazepam, are the best studied and are also the least expensive. Recent research has suggested that newer approaches using clonidine, beta blockers, and carbamazepine are effective in decreasing the severity of certain withdrawal symptoms but are not as effective as the benzodiazepines and presumably do not protect against seizures, as do benzodiazepines. Thus, these alternative treatments are generally considered to be adjuvants to benzodiazepines.

Problem drinkers and drinkers who are at risk for alcohol problems who do not respond to brief intervention therapy, as well as patients who meet criteria for alcohol abuse and dependence, may require referral to specialists and formal alcohol treatment programs. This is particularly true of patients who are suffering significant medical, psychiatric, or social comorbidity that is related to their alcohol use or patients who are alcohol dependent. The referral process can be more successful if the physician is familiar with the structure and types of treatment used in their local programs. It is important to communicate effectively with alcohol treatment program caregivers and to reinforce their treatment strategies when patients present for follow-up medical care.

Most patients can be managed safely and effectively in an outpatient treatment environment. Criteria have been developed by the APA and the American Society of Addiction Medicine that are designed to aid in patient placement. Clinical variables that are important in determining level of service needed include the presence of medical or psychiatric comorbidity, the risk of withdrawal, the level of social support available, and previous treatment experience.

The psychotherapeutic approaches used in alcohol treatment programs may vary from one program to another. Common approaches may be administered either as individual therapy or as group therapy. Activities commonly seen in alcohol treatment programs include (1) motivating patients to change their behavior and lifestyles; (2) teaching patients coping skills to avoid alcohol use; (3) encouraging patients to develop activities that do not reinforce drinking and that reward abstinence; (4) helping patients to improve interpersonal interactions; and (5) promoting compliance with pharmacotherapy and medical care. Treatment typically occurs over a long period and becomes less intensive as patients demonstrate prolonged abstinence.

Three commonly used psychotherapeutic approaches were recently evaluated in a randomized clinical trial. The three approaches studied were cognitive-behavioral coping-skills therapy, motivational-enhancement therapy, and 12-step facilitation. In each program, therapy was administered for 12 weeks. Two parallel but independent randomized clinical trials assessed these approaches in inpatients and outpatients. Both inpatients and outpatients experienced significant and sustained improvements in drinking outcomes, as measured 1 year after treatment. The groups did not differ in their degree of improvement. In the inpatient arm of the study, patients experienced a 70% increase in the percentage of days they were abstinent (from 20% to 90%); 35% remained completely abstinent. In the outpatient arm, patients experienced an 80% increase in the percentage of days they were abstinent; 19% maintained complete abstinence. Of note was the large percentage of both inpatients and outpatients (25% and 35%, respectively) who had a "slip" but did not relapse (with relapse being defined as 3 consecutive days of heavy drinking). For the majority of patients enrolled in this study, treatment resulted in significant improvement.

Pharmacotherapy is a useful adjunct to psychotherapy in helping patients drink less. Three medications have been studied extensively for this purpose: disulfiram, naltrexone, and acamprosate. Disulfiram was the first of these medications to become available. It works through the inhibition of the enzyme alcohol dehydrogenase. Patients who are receiving disulfiram and who subsequently drink alcohol are at risk for a severe adverse reaction, which includes flushing, nausea, vomiting, and diarrhea. Patients on disulfiram need to avoid unintended alcohol consumption, which may occur through the consumption of alcohol-containing foods or medications. Disulfiram has demonstrated limited effectiveness in decreasing alcohol use. Its use requires aggressive supportive treatment and monitoring, and it appears to be most effective in highly motivated patients.

Naltrexone is an opioid antagonist that was originally developed for the treatment of opioid dependence. Subsequently, naltrexone was shown to decrease the pleasurable effects and craving associated with alcohol use. Two randomized, placebo-controlled trials assessed the effectiveness of naltrexone therapy; in these studies, alcohol-dependent persons were given naltrexone at a dosage of 50 mg/day, were treated either on an outpatient basis or through day-hospital treatment programs, and were followed for 12 weeks. When the data from the two studies were combined, it was found that 54% of patients who received naltrexone remained abstinent, compared with 31% of patients who received placebo. Although these studies focused on patients enrolled in formal alcohol treatment programs, a subsequent study found that naltrexone can be effectively administered in primary care settings. In this study, 29 alcohol-dependent persons received naltrexone at a dosage of 50 mg a day for 10 weeks. The majority of patients (72%) completed treatment; 35% relapsed to heavy drinking. When compared with baseline values, all drinking behaviors improved significantly in these individuals, including the percentage of days in which the patients were abstinent, which increased from 36.6% to 88.8%, and the mean number of drinks consumed per occasion, which decreased from 9.5 drinks to 2.5 drinks.

Acamprosate has been studied extensively in Europe and is currently under investigation in the United States. In a recent analysis of 11 randomized, placebo-controlled trials involving a total of 3,338 patients with alcohol dependence, patients who received acamprosate demonstrated superior abstinence rates and duration of abstinence during a 6-month to 12-month posttreatment follow-up period. In one study of 272 persons, 43% of those who received acamprosate remained abstinent for 48 weeks, compared with 21% of those who received placebo. In clinical trials of acamprosate, dosages have ranged from 1.3 to 2.0 g/day in divided doses, and side effects (most commonly diarrhea) have been minimal. Concomitant administration of disulfiram has improved the effectiveness of acamprosate without adverse interactions between the drugs. Research is also under way to evaluate the effectiveness of acamprosate in combination with naltrexone.

Additional information on the treatment of alcohol problems may be obtained from the National Institute on Alcohol Abuse and Alcoholism (http://www.niaaa.nih.gov) , the National Clearinghouse for Alcohol and Drug Information (http://www.health.org) , and Alcoholics Anonymous (http://www.alcoholics-anonymous.org) .