Current Practice Guidelines

Alcohol use disorders: diagnosis, assessment and management of harmful drinking and alcohol dependence. National Institute for Health and Clinical Excellence (NICE) website. http://www.nice.org.uk/guidance/CG115. Published February 2011. Accessed July 2, 2014.

Lingford-Hughes AR, Welch S, Peters L, Nutt DJ; British Association for Psychopharmacology, Expert Reviewers Group. BAP updated guidelines: evidence-based guidelines for the pharmacological management of substance abuse, harmful use, addiction and comorbidity: recommendations from BAP [published online ahead of print May 23, 2012]. J Psychopharmacol 2012; 26:899–952. doi:10.1177/0269881112444324

Pani PP, Trogu E, Pacini M, Maremmani I. Anticonvulsants for alcohol dependence. Cochrane Database Syst Rev 2014; 2:CD008544.

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Definition

The Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5) lists diagnostic criteria for substance related and addictive disorders. The criteria are applied to all potentially habit-forming substances, of which alcohol is only one. Taken as a whole, however, the underlying problem in substance-use disorders is an inability to control substance intake with resulting social, occupational, and medical consequences.

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Epidemiology and Genetics

Alcohol use disorder affects 14% to 15% of men and 5% to 7% of women in a 12-month period. Lifetime prevalence has been reported as 41% to 43% for men and 17% to 19% for women. Meanwhile, it has been reported that 30% of the American populace engage in risky or unhealthy drinking patterns, defined as at least five standard drinks per day or 15 standard drinks per week for men, or at least four standard drinks per day or eight standard drinks per week for women. A standard drink in the United States is defined as a drink containing about 14 grams of pure alcohol, the content of alcohol in 12 ounces of beer, 5 ounces of table wine, or 1.5 ounces of 80-proof whiskey. The prevalence of alcohol use disorders in primary care settings ranges from 20% to 36%, pointing to the medical comorbidity suffered by alcohol-dependent patients and the value of screening for the disorder. Currently, it is estimated that only about 10% of patients with alcohol use disorder are recognized and receive proper intervention in primary care settings.

The role of family and genetic history in increasing the risk of alcohol use disorders cannot be overstated. Many studies have demonstrated that the presence of a first-degree relative with alcohol dependence increases the risk of the disorder from 8% to 25%. There appears to be special transmissibility of alcohol dependence when the relationship is between an alcohol-dependent father and a son. This relationship increases the risk to the son even more dramatically. A pattern of early onset (before age 25 years) and the presence of antisocial personality disorder in the alcohol-dependent parent can increase the risk even further. Children of nonalcoholics raised in adoptive alcoholic homes do not exhibit increased risk of alcohol dependence, whereas children of alcoholic parents suffer an elevated risk even if adopted by nonalcoholics at a young age.

Other significant risk factors include other psychiatric disorders, such as major depression, bipolar disorder, panic disorder, generalized anxiety disorder, attention-deficit disorder, and schizophrenia. No protection is provided by high educational level or socioeconomic status.

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Pathophysiology

Particular behaviors are associated with a higher risk of addiction. Children displaying low levels of harm avoidance and reward dependence and a high potential for novelty seeking are at high risk for at-risk drinking later in life. These children are apparently relatively less fearful of potentially dangerous activities, less interested in reward or approval from others, and attracted to unfamiliar experiences.

First exposure to alcohol seems to have less impact on a person’s risk of developing alcohol use disorders than the age at first intoxication. However, these differences are small compared with what commonly happens in young adults developing alcohol use disorders. During this time, most persons experience moderation in alcohol intake in response to negative feedback from social systems (peers, family, work, legal) and a personal recognition of transient physical and emotional consequences of drinking excessively such as depressed mood, nausea, and headache.

Many persons with a genetic predisposition to alcohol use disorders are insensitive to the unpleasant effects of alcohol intoxication such as sedation, ataxia, and incoordination. They seem to function better than their peers after an equal intake of alcohol. As their frequency and amount of drinking per occasion increase, activity in the reward centers of the brain declines. Without alcohol present, stimulation of the nucleus accumbens and activity of the prefrontal cortex are low enough to produce dysphoria and cravings. The effects of other life consequences (either positive or negative) on reward circuit functioning are diminished, so that only changes in brain alcohol concentration have reinforcing value. Eventually, the person becomes unable to function at all without constantly maintaining brain alcohol concentrations within an increasingly narrow range. Levels just below this range cause dysphoria and cravings, and levels just above this range result in unconsciousness, gait abnormalities, incontinence, or inability to function in the person’s particular environment.

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Signs and Symptoms

Box 1 lists some of the symptoms of which patients complain that should lead a health care provider to consider alcohol use disorder.

The development of tolerance is also a feature of alcohol use disorder. Tolerance is defined by DSM-5 as “either a need for markedly increased amounts of alcohol to achieve intoxication or desired effect, [or] markedly diminished effect with continued use of the same amount of alcohol.” An additional consideration when the substance abused is alcohol is switching one’s drink of choice to accommodate increasing alcohol intake. For example, a change from beer or wine as the alcoholic beverage of choice to whiskey or vodka, or a change from consuming mixed drinks to unmixed liquor suggests progression of the disease.

Early signs of excessive drinking, even legal charges like driving under the influence, domestic violence, assault and battery, or drunk and disorderly conduct are often ignored, minimized, or rationalized by patients. Although legal charges, job failures, or marital strain may lead a person to cut down on his or her drinking temporarily, many struggle to convince themselves they still can control their drinking by restricting the settings, times, or amounts they drink. For example, the alcoholic might try restricting drinking to family settings, drink only in the evening, or abstain from “hard” liquor such as whiskey or vodka.

Well-intentioned attempts to cut down or control use are often illusory and unsuccessful. Typically, after struggling to maintain previously set limits on alcohol use, persons begin violating those limits by drinking alone or in secret; hiding alcohol around the house, in the car, or at work; coming up with other reasons to explain absences from home and from work, or resorting to the use of cough syrup or mouthwash that contains alcohol.

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Diagnosis

A variety of instruments are available for detecting alcohol dependence. Perhaps the simplest and most familiar is the CAGE questionnaire. Box 2 reviews the components of the CAGE questionnaire. Answering “yes” to one of the four questions in the CAGE increases the likelihood of an alcohol use disorder to at least 90%. Although the CAGE is fast and easy to administer and score, it does suffer from some limitations. Its sensitivity varies among different cultures and it is less sensitive in women. Also, some questions are more sensitive to a diagnosis of alcohol use disorder than others.

Developed by the World Health Organization, the Alcohol Use Disorders Identification Test (AUDIT) has been validated in several cultures and provides good sensitivity in both genders. The test is a 10-item multiple-choice questionnaire that takes 5 minutes to complete and is easily scored. Scoring has been tied to intervention recommendations with several different levels of intensity. If certain questions with higher sensitivity are answered in the scored direction, it will increase the intensity of the intervention recommendation. A free AUDIT manual with guidelines for use in primary care is available online (whqlibdoc.who.int/hq/2001/WHO_MSD_MSB_01.6a.pdf).

When either the CAGE or the AUDIT raises the suspicion of an alcohol use disorder, a full alcohol and drug history should be obtained from the patient and confirmed (if possible) by a knowledgeable third party such as a spouse or parent. Especially important data are peak alcohol use, frequency and amount of alcohol use over the last month, and time and amount of last alcohol use. Also important are past consequences (legal, social, occupational), medical complications such as delirium tremens, withdrawal tremors or seizures, and longest period of abstinence from alcohol.

The DSM-5 criteria for alcohol use disorder differs significantly from the DSM-IV criteria for alcohol abuse and alcohol dependence. The DSM-IV terms were abandoned in favor of a single diagnosis with greater opportunity to describe a continuum of severity based on the number of symptoms present. Two to three symptoms is defined as “mild,” while the presence of six or more symptoms is defined as “severe” alcohol use disorder.

Laboratory Tests

Detecting acute ingestion of alcohol is a relatively simple matter. For $100 to $400, an outpatient clinic can purchase a breathalyzer that is easy to use and reasonably accurate. Confirmatory testing can be obtained through a blood alcohol level. Other procedures are rapidly gaining popularity, such as saliva test strips and sweat patch testing.

Certain blood tests can detect chronic alcohol consumption. Elevations in the level of γ-glutamyl transferase (GGT) can be caused by consuming four or more drinks per day for 4 to 8 weeks before the test. At least 4 weeks of abstinence may be required to return the GGT to the normal range. The most significant limitation of relying on the GGT is that it is elevated in other illnesses (e.g., viral hepatitis, certain prescription medications). Patients with severe liver damage might not have enough viable hepatic tissue for alcohol consumption to generate an elevated GGT. In known alcoholics without significant nonalcoholic liver disease, however, an elevated GGT should raise suspicion of relapse.

Measurement of carbohydrate-deficient transferrin (CDT) is being used more often to screen for excessive drinking. Although it may be currently less available and usually cannot be completed as quickly as a GGT, the CDT does offer some advantages. The CDT becomes elevated after 2 weeks of heavy drinking, identifying excessive drinking patterns possibly more quickly than GGT. Also, the CDT is not affected by cirrhosis or viral hepatitis.

Ethyl glucuronide is a direct biomarker of drinking because it represents a byproduct of alcohol metabolism itself. Levels may become elevated in urine after as little as a single alcoholic drink, and it is highly sensitive. Conversely, it may become elevated after ingestion of alcohol present in hygiene products, foods, or some medications.

Red blood cell mean corpuscular volume, aspartate aminotransferase, and alanine aminotransferase also may be elevated in patients engaging in heavy alcohol consumption; however, these tend only to provide supporting evidence. The sensitivity and specificity of these tests are simply too low for proof of alcohol consumption without other, more reliable evidence.

These biochemical markers of alcohol consumption cannot assess one of the key features needed for the diagnosis of alcohol use disorders: consequences. For this reason, research groups have assessed the increased sensitivity and specificity of combining self-report questionnaires with biochemical markers. For example, the combined finding of an AUDIT score greater than 8 with at least two abnormal biologic markers of heavy alcohol consumption resulted in a combined test with sensitivity and specificity greater than 90%, and it improved the positive predictive value over the AUDIT used alone.

Once a diagnosis of an alcohol use disorder is made, several tests should be performed to assess for other conditions that either commonly exist with alcohol use disorder or can exacerbate the damage caused by heavy alcohol consumption. These are listed in Box 3.

Summary

• Patients with a family history of addiction are at high risk themselves.
• Patients with any of a number of common psychiatric disorders are also at risk.
• CAGE and AUDIT are useful screening tools.
• γ-Glutamyl transferase, carbohydrate-deficient transferrin, and ethyl glucuronide can be useful markers of excessive alcohol use.

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Treatment

Intervention and Lifestyle Modifications

Once an alcohol use disorder is identified, the next step is presenting the diagnosis and recommendations to the patient. Because denial and minimization are common in addiction, the initial intervention is especially important. Depending on the situation, family members can help by reinforcing a physician’s concerns and recommendations.

The physician should start by expressing his or her concerns based on as many hard facts, specifically applicable to the patient, as are available. Next, the physician should frame the problem as a disease and absolve the patient of any sense of responsibility for the development of the disease. It should be emphasized, however, that responsibility for proper management of this disease rests with the patient. The physician should convey confidence that change is possible, and then present clear advice on what choices the patient has for addressing the problem.

Without enlisting the patient’s motivation to change the situation, treatment outcome will likely suffer. The patient must assert some control over the decision to enter treatment, but it is perfectly appropriate for that decision to be influenced by family, occupational, legal, or medical consequences if positive steps toward recovery do not occur. The goal of an intervening person (personal physician, employer, spouse, or someone else) is not to shield the patient from such consequences but to point them out and to empathize with and support the patient.

What specific recommendations should be made? In actively drinking patients with a history of withdrawal seizures or delirium tremens, immediate referral to a hospital-based chemical dependency treatment center is essential. Similarly, patients with signs of active withdrawal, such as tremor, hyperreflexia, palmar diaphoresis, tachycardia, or hypertension, are at risk for withdrawal complications and should be referred for inpatient management. Patients who have consumed alcohol in the 72 hours before assessment might still be at risk for developing withdrawal or delirium tremens and should be monitored carefully. Thiamine prophylaxis for Wernicke’s encephalopathy should begin immediately. Thiamine replacement should be via the IV route if possible.

For patients meeting the criteria for alcohol use disorder but not in danger of developing withdrawal, a strong recommendation for abstinence from alcohol should be made. All alcohol should be removed from the home. If the home environment does not facilitate sobriety, referral should be made to a residential chemical dependency treatment center where the patient can focus on recovery without distraction. Because social isolation can be a relapse trigger for many alcoholics, living alone outside the controlled environment of a residential treatment center should be discouraged. Alternatively, the patient can move to a residence with a sober, stable support system while participating in outpatient treatment.

The presence of complicating medical conditions (e.g., a preexisting seizure disorder, hepatic encephalopathy) can lead the physician to encourage a higher level of care than would be indicated without such a comorbid condition. Similarly, complex psychiatric comorbidity, limited acceptance of addiction diagnosis, nonsupportive home environment, or recent failure to maintain abstinence at a lower level of care should also lead to placing a patient at the partial hospital or inpatient levels of care. The American Society of Addiction Medicine patient placement criteria include recommendations for the correct treatment level in a particular situation.

In a patient who has agreed to enter treatment and abstain from alcohol, a critical step in early recovery is identification of triggers. Triggers are situations, people, emotions, or problems that can place a person at high risk for relapse. In the brain, the potential for reactivation of abnormal activity in reward circuitry can last many years into recovery. Common triggers are listed in Box 4. When potential triggers are identified, a relapse prevention plan particular to that trigger can be quickly developed in the office. For example, a patient identifies as a trigger the local bar where he or she engaged in after-work drinking. With the help of a physician, nurse, or counselor, the patient can develop a relapse prevention plan to attend a self-help meeting each day immediately after work instead of heading home along the usual route past the bar. A list of after-work meetings can be developed and kept in the patient’s car, purse, or briefcase.

By far the most common trigger leading to relapse is the failure to cope effectively with negative emotional states. As seen in Figure 1, negative emotional states lead to social isolation and eventual drinking. Twelve-step programs (e.g., Alcoholics Anonymous [AA]) spend a great deal of time discussing healthier coping strategies for negative emotional states. In fact, only step 1 of the 12 steps mentions alcohol at all. The other 11 steps concentrate mainly on managing anger, guilt, shame, anxiety, and social isolation.

AA and other 12-step programs attempt to create a fellowship of recovering people who support each other through the recovery process and who provide validation, a sense of social connectedness, and mentorship. The mentorship component of the program is provided by a sponsor. A sponsor is a member of the 12-step program with several years of sobriety who assists new members in finding appropriate meetings, identifying triggers, and working through the steps. Sponsors often have a great deal of contact with persons who are early in recovery or experiencing difficulty staying sober. The new member of AA may be tempted to desire a sponsor who is a relative, a neighbor, or a coworker. Unfortunately, these individual often have other agendas for us besides sobriety. For example, a neighbor is often interested in the quiet and neat maintenance of neighboring homes. A coworker might be interested in peers completing their own work duties and not interfering in the coworker’s career goals. So these agendas can interfere with the cooperative effort between sponsor and sponsee in their recovery journey. Sponsors should be someone whose only agenda with the sponsee is his or her sobriety. Persons often obtain a sponsor by informing the leaders of a recovery meeting that they need a sponsor.

As a newly recovering person begins changing his or her behavior, regular medical management interventions during early recovery can improve treatment outcomes. A typical brief intervention after an initial decision to engage in treatment includes a review of exposure to triggers and asking about any exposure to alcohol between visits. Identification of triggers associated with any relapses should lead to a relapse prevention plan to reduce the likelihood of future relapse. Recovery meeting attendance and intensity of sponsor contact should be logged. The patient is strongly encouraged to obtain a sponsor as soon as possible if he or she has not yet identified one. Adherence with medication prescribed is discussed and side effects noted. Family members are encouraged to attend family support meetings through organizations such as Al-Anon and Alateen.

Medical Options

An increasing number of medications have been approved by the U.S. Food and Drug Administration (FDA) for the treatment of alcohol dependence.

The first FDA approval was granted to disulfiram, an aversive therapy that interferes with the enzyme aldehyde dehydrogenase (ALDH), as shown in Figure 2. When alcohol is ingested, alcohol dehydrogenase metabolizes ethyl alcohol into acetaldehyde. In the presence of disulfiram, ALDH is blocked and acetaldehyde levels rise, causing tachycardia, hypertension, headache, nausea, vomiting, and in rare cases, death. Disulfiram continues to interfere with ALDH functioning up to 2 weeks after the last administered dose. Because of the potential serious consequences of drinking while ALDH is blocked, disulfiram prescription is typically restricted to alcohol-dependent physicians and others who are highly motivated, display low impulsivity, and understand the risks of such a medication in the presence of even tiny amounts of alcohol.

In 1994, the FDA approved naltrexone, an opiate-receptor antagonist, for treating alcohol dependence. In 2006, the FDA approved a depot form of the drug for once-per-month intramuscular administration. Naltrexone’s exact mechanism of action in alcohol dependence is unclear, but it might interrupt reinforcement of drinking behavior, which is mediated by the binding of endogenous opioids to receptors in central reward circuitry. Reports of hepatotoxicity warrant regular monitoring of liver function tests.

In 2004, the FDA approved acamprosate, a medication used in Europe for treating alcohol dependence since the early 1990s. Its mechanism of action is unknown, but is believed to involve modulation of the N-methyl-D-aspartate (NMDA) glutamate receptor activity. Glutamate binds to NMDA in several areas of the reward circuitry of the brain, opening a calcium channel that results in neuronal excitation. Acamprosate might reduce glutamate-mediated neuronal excitation to overexcite neurons in the most critical brain structures involved in addiction, the nucleus accumbens and the ventral tegmental area. Compared with disulfiram and naltrexone, there are fewer adverse effects and precautions associated with acamprosate. It may be taken by patients with liver dysfunction. It should not be used in patients with severe renal dysfunction.

There are no particular drug-drug interactions that would prevent otherwise healthy people from tolerating combinations of these three medications. However, evidence of added benefit conferred by coadministration of two or all three of the medications is scant.

There are a few pharmacological treatments that remain without FDA approval (“off-label”) but have demonstrated some potential in reducing relapse to alcohol use. A February 2014 Cochrane Review found insufficient evidence to support clinical use of anticonvulsants in prevention of relapse in alcohol use disorders. The agents reviewed included topiramate, valproate, gabapentin, levetiracetam, oxcarbazepine, zonisamide, carbamazepine, pregabalin and tiagabine. In the 2012 British Association of Psychopharmacology guidelines, the authors chose to review evidence of efficacy regarding baclofen, topiramate, and pregabalin, and included baclofen as a “C” rated recommendation. In the January 2014 edition of JAMA, Mason et al showed that gabapentin combined with manual-guided counseling produced statistically significant reductions in alcohol relapse and rate of heavy drinking compared with identical counseling with placebo. As further studies are published, additional evidence may clarify the role other treatments may have in the prevention of relapse of alcohol use disorders.

Treatment Outcomes

At 1 year of sobriety, the factors most associated with good outcome are AA participation, high treatment motivation, and an absence of comorbid psychiatric conditions. AA participation implies regular recovery meeting attendance, regular sponsor contact, and actively working through the 12 steps. Treatment of comorbid psychiatric disorders at the start of addiction treatment increases the likelihood of better addiction treatment outcomes.

The effect of available medications on long-term treatment outcomes is unclear. Most current studies of pharmacologic treatment followed patients for a period of 1 year or less. In a recent large study of alcoholism treatment options including oral naltrexone, acamprosate, brief medical follow-ups, or combined behavioral intervention, only acamprosate showed no evidence of improved drinking outcomes at the 1-year follow-up point. Regardless of whether any longer-term treatment effect is demonstrated, currently available medications might still provide benefits in early recovery.

Summary

• Provide patients with clear but empathic feedback on your concerns, diagnosis, and recommendations.
• Follow-up frequently during the first 6 to 12 months of recovery.
• Medication options may improve outcomes, especially in the short term.
• Long-term outcome is best in motivated patients who participate in 12-step recovery programs and are free from other psychiatric disorders.
• Patients at risk for alcohol withdrawal should be referred to an inpatient chemical dependency program.

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Prevention and Screening

The key to preventing the development of alcohol use disorders lies in identifying and educating persons most susceptible to the condition. Because of the high risk suffered by persons with a family history of addiction, family education during addiction treatment is essential. Patients in addiction treatment who have children or are planning to have children should be counseled to discourage alcohol exposure in their children. Patients struggling with other psychiatric disorders that place them at risk for developing an alcohol use disorder should be advised to abstain from alcohol for the duration of their psychiatric treatment.

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Special Populations

Pregnant women have the potential to cause the most far-reaching adverse outcomes from drinking alcohol. Beyond the specific risks to the mother, alcohol ingestion in any amount can lead to harmful effects on the developing fetus. It is very important to stress to pregnant women that there is no proven safe level of alcohol use during pregnancy.

Women in general require special attention in addiction treatment for two reasons. First, women in addiction treatment suffer a higher prevalence of comorbid psychiatric disorders than men. Careful evaluation for disorders such as depression, panic disorder, bipolar disorder, and eating disorders is especially important in women. Untreated (or ineffectively treated) comorbid psychiatric disorders will have a negative impact on treatment outcome. Second, because women make up only about one third of the population in addiction treatment, most mixed-gender treatment populations (and mixed self-help groups) contain a majority of men, and as a result tend to focus on men’s issues. It is important that women involve themselves in at least some women-only self-help meetings to ensure proper attention to their particular challenges in addiction recovery.

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Conclusion

Alcohol use disorders are common, dangerous, potentially fatal conditions that affect care in all medical settings, directly or indirectly. Often, recognizing the condition and enhancing the patient’s motivation for treatment represent the most challenging hurdles. However, there are an increasing number and variety of treatment approaches that may help more people to recover than ever before.

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Summary

• CAGE and AUDIT are useful screening tools.
• Patients with signs of active withdrawal should be referred for immediate hospitalization.
• Combinations of lifestyle changes and 12-step recovery work are often associated with better outcomes.
• Screening for co-existing psychiatric disorders with subsequent successful treatment will reduce relapse risks.
• Medication treatment aimed at reducing relapse risk is available and options may expand in the near future.

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Suggested Readings

• Agrawal A, Heath AC, Lynskey MT. DSM-IV to DSM-5: the impact of proposed revisions on diagnosis of alcohol use disorders [published online ahead of print August 18, 2011]. Addiction 2011; 106:1935–1943. doi:10.1111/j.1360-0443.2011.03517.x
• Alcohol use and alcohol use disorders in the United States—a 3-year follow-up: main findings from the 2004-2005 wave 2 National Epidemiologic Survey on Alcohol and Related Conditions (NESARC). National Institute on Alcohol Abuse and Alcoholism website. pubs.niaaa.nih.gov/publications/NESARC_DRM2/NESARC2DRM.pdf. Published September 2010. Accessed July 2, 2014.
• Alcohol use disorder: a comparison between DSM-IV and DSM-5. National Institute on Alcohol Abuse and Alcoholism website. pubs.niaaa.nih.gov/publications/dsmfactsheet/dsmfact.pdf. Published November 2013. Accessed July 2, 2014.
• American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. 5th ed. Arlington, VA: American Psychiatric Publishing; 2013.
• American Society of Addiction Medicine: Patient Placement Criteria. 2nd rev ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2001.
• Anton RF, O’Malley SS, Ciraulo DA, et al; COMBINE Study Research Group. Combined pharmacotherapies and behavioral interventions for alcohol dependence—the COMBINE study: a randomized controlled trial. JAMA 2006; 295:2003–2017.
• Babor TF, Higgins-Biddle JC, Saunders JB, Monteiro MG. The Alcohol Use Disorders Identification Test: Guidelines for Use in Primary Care. 2nd ed. World Health Organization website. whqlibdoc.who.int/hq/2001/WHO_MSD_MSB_01.6a.pdf. Published 2001. Accessed July 1, 2014.
• Dolman JM, Hawkes ND. Combining the AUDIT questionnaire and biochemical markers to assess alcohol use and risk of alcohol withdrawal in medical inpatients [published online ahead of print August 15, 2005]. Alcohol Alcohol 2005; 40:515–519. doi:10.1093/alcalc/agh189
• Fuller RK, Branchey L, Brightwell DR, et al. Disulfiram treatment of alcoholism: a Veterans Administration cooperative study. JAMA 1986; 256:1449–1455.
• Garbutt JC, Kranzler HR, O’Malley SS, et al; Vivitrex Study Group. Efficacy and tolerability of long-acting injectable naltrexone for alcohol dependence: a randomized controlled trial. JAMA 2005; 293:1617–1625.
• Mason BJ, Quello S, Goodell V, Shadan F, Kyle M, Begovic A. Gabapentin treatment for alcohol Dependence: a randomized clinical trial. JAMA Intern Med 2014; 174:70–77.
• Rollnick S, Miller WR, Butler CC. Motivational Interviewing in Health Care: Helping Patients Change Behavior. New York, NY: The Guilford Press; 2008.
• Saitz R. Unhealthy alcohol use. N Engl J Med 2005; 352:596–607.
• What is a standard drink? National Institute on Alcohol Abuse and Alcoholism website. www.niaaa.nih.gov/alcohol-health/overview-alcohol-consumption/what-standard-drink. Accessed July 2, 2014.
• Yip L. Ethanol. In: Goldfrank LR, Flomenbaum NE, Lewin NA, Howland MA, Hoffman R, eds. Goldfrank’s Toxicologic Emergencies. 7th ed. New York, NY: McGraw-Hill; 2002:952–965.