Alcohol Use Disorder

History

• General
  • Ignorance about and stigma surrounding this disease are barriers to obtaining accurate history
    • Patients may not be forthright with amount and frequency of alcohol consumption; denial and minimization are common ^c1c2
    • Provider must develop a positive and supportive relationship and not show bias
    • History obtained from family and friends may provide a more accurate account of consumption history
  • Clinical presentation is highly variable ^r5
• Course and development of disease
  • First episode of intoxication often occurs in middle teen years ^r10c3
  • Most patients who develop alcohol use disorder do so by their late 20s; approximately 10% develop the condition after age 40 years ^r10
  • Earlier onset of disease is associated with patients who start becoming intoxicated younger and who had conduct problems before they began drinking ^r10
  • Disease course is highly variable but often is marked by periods of remission and relapse
    • Characteristic remission and relapse pattern:
      • Stop drinking in response to crisis or serious consequence
      • Resume drinking after a period of abstinence with an initial, brief period of more controlled drinking
      • Rapid escalation in consumption ensues and severe problems again develop
• Typical drinking behavior characteristics and other manifestations based on severity of unhealthy alcohol use ^r6
  • Risky drinking behavior
    • Patients often do not regularly drink much above maximum recommended limits
  • Mild alcohol use disorder
    • Patients often drink more heavily than patients with risky drinking behavior but may not drink daily
    • Typical consumption is fewer than 40 drinks per week, and serious withdrawal manifestations are often lacking
  • Moderate alcohol use disorder
    • Patients usually drink daily and may have some withdrawal manifestations when they stop
    • Some do not drink daily but have heavy binge drinking behavior
  • Severe alcohol use disorder
    • Patients are usually daily drinkers who consume more than 40 drinks weekly
    • Significant withdrawal symptoms usually are present, and serious life consequences develop
• Primary manifestations consistent with alcohol use disorder include:
  • Craving phenomenon
    • Patients are unable to reliably stop drinking once they start ^c4c5
  • Obsessions and compulsions surrounding alcohol
    • Strong desire and preoccupation with planning next drinking event, obtaining alcohol, and hiding alcohol, and seeming inability to avoid initiating consumption ^c6
    • Patients often report unsuccessful attempts to cut back or quit drinking ^c7
  • Tolerance
    • Require increased amounts of alcohol to achieve intoxication or desired effect, or there is diminished effect with continued use of same amount of alcohol ^c8
  • Blackouts ^c9
    • Manifest as complete or partial amnesia for events during any part of a drinking episode without loss of consciousness and without relative loss of other skill deficits (eg, maintain relative ability to perform other functional skills such as walking, talking, and even driving) ^r12
    • Relatively rapid increase in blood alcohol concentration is most consistently associated with increased likelihood of blackout ^r12
  • Withdrawal ^d1
    • Often one of the last manifestations of disease to appear after other aspects of disease have developed ^r10
    • Minor (eg, headache, tremor, insomnia, nausea, vomiting, anxiety) or major (eg, hallucinations, seizure, delirium tremens) withdrawal symptoms may be reported with diminished alcohol use or abstinence ^{c10c11c12c13c14c15c16c17c18}
    • Symptoms may be relieved by drinking alcohol (eg, early morning or afternoon alcohol consumption) or by taking another drug closely related to alcohol (eg, a benzodiazepine)
• Additional manifestations that often occur secondary to progression of disease
  • Use of alcohol in hazardous situations (eg, driving car, operating machinery, swimming) ^c19c20
  • Life consequences commonly develop; continued consumption of alcohol may occur despite consequences
    • Common consequences
      • Legal (eg, arrests, incarceration) and conduct (eg, violence) problems ^c21c22
      • Relationship strains (eg, marital discord, estrangement from close relatives or friends) ^c23
      • Employment, financial, and educational consequences (eg, absences, failure to meet responsibilities, poor performance and productivity, job related accidents, loss of job) ^{c24c25c26c27c28c29c30c31c32c33}
      • Organ changes (eg, liver disease, gastritis, endocrine disturbance, persistent insomnia, and depression) ^c34c35c36c37
  • Hopelessness, depression, and anxiety ^c38c39c40
    • Often accompanied by overarching feelings and emotions such as:
      • Guilt, shame, and remorse secondary to perceived harm caused to self and others while drinking ^c41c42c43
      • Deep anger and resentment ^c44c45
      • Intense fears ^c46
  • Isolation ^c47
    • From people (eg, family, friends, colleagues) and from social and/or recreational activities previously enjoyed
• Common personality traits and characteristics in patients with active disorder (occur and/or worsen as a result of the disorder) may include:
  • Negative temperament ^r13c48
  • Disinhibition and impulsivity ^r13c49c50
  • Manipulativeness ^r13c51
  • Extroversion ^r14c52
  • Neuroticism ^r14c53
• Initially, patients may present with symptoms secondary to complications related to alcohol use disorder, such as:
  • Unexplained primary medical complications (eg, hypertension, pancreatitis, elevated liver function test results, fatty liver) ^c54c55c56c57
  • Child born with fetal alcohol syndrome or fetal alcohol spectrum disorder ^c58c59
  • Falls associated with significant injury (eg, extensive bruising, epidural hematoma) ^c60c61
  • Traumatic injury associated with operating machinery or vehicles while intoxicated ^c62
  • Traumatic injury associated with violence while intoxicated ^c63
  • Mental health problems (eg, depression, anxiety, attempted suicide) ^c64c65c66
  • Gastrointestinal issues (eg, gastritis with dyspepsia, nausea, bloating) ^c67c68c69
  • Neurologic problems (eg, gait instability, peripheral neuropathy) ^c70c71
  • Reproductive health issues (eg, recurrent sexually transmitted infections, unplanned pregnancy, erectile dysfunction, menstrual irregularity) ^c72c73c74c75
  • Sleep problems (eg, insomnia, sleep apnea) ^c76c77

Physical examination

• Initially, patients may present with findings secondary to complications related to alcohol use disorder
  • Elevated blood pressure and/or tachycardia ^c78c79
  • Hepatomegaly, which may indicate alcohol-induced liver disease ^c80
  • Epigastric abdominal tenderness, which may indicate pancreatitis or gastritis ^c81
  • Decreased testicular size and feminization in men, associated with reduced testosterone levels ^c82c83
  • Evidence of unexplained trauma ^c84
• Patients may present with characteristic signs of alcohol withdrawal syndrome
  • Unsteady gait ^c85
  • Fine action tremor ^c86
  • Seizures ^c87
  • Mild peripheral edema ^c88
  • Restlessness ^c89
  • Tachycardia or hypertension ^c90c91
• Patients may present with signs of intoxication
  • Ataxia ^c92
  • Nystagmus ^c93
  • Slurred speech ^c94
  • Inappropriate affect ^c95

Causes

• A combination of genetic, physiologic, and environmental factors ^r10c96c97c98

Risk factors and/or associations

Primary diagnostic tools

• Suspect diagnosis based on clinical presentation or positive response to screening tool ^c176
• Conduct secondary assessments to confirm screening results, determine type of unhealthy alcohol use (eg, risky drinking, alcohol use disorder), establish baseline behavior, and identify particular concerns for further discussion during treatment phase ^r2
  • May use a second tier screening tool (eg, AUDIT full version [Alcohol Use Disorders Identification Test]) to follow initial positive first tier screen (eg, single question, AUDIT-C [Alcohol Use Disorders Identification Test–Consumption]). AUDIT score can then help guide further assessment and subsequent plan ^r2
  • For patients in general medical and mental healthcare settings, it is recommended that they be screened for unhealthy alcohol use periodically using the 3-item Alcohol Use Disorder Identification Test-Consumption or Single Item Alcohol Screening Questionnaire ^r24
  • Alternately, National Institute on Alcohol Abuse and Alcoholism's checklist may help guide further assessment with a systematic evaluation for maladaptive patterns of alcohol resulting in clinically significant impairment or distress ^r25
• Confirm alcohol use disorder with a diagnostic interview to establish DSM-5 TR criteria ^r10
• Baseline and adjunct studies obtained at time of diagnosis are nondiagnostic but may confirm heavy drinking and identify alcohol-related peripheral organ damage; tests to consider include: ^r26
  • Baseline renal function testing, serum glucose level, liver function testing, and CBC on all patients to assess for potential alcohol-related complications ^{r6r16c177c178c179c180}
  • Pregnancy test in women of childbearing years ^r26
  • Some sources recommend urine toxicology screen to assess for other substances that may affect treatment approach ^r26c181
  • Adjunct tests and findings that may be helpful during evaluation include:
    • Blood alcohol concentration may help in assessing tolerance and recent alcohol consumption ^r10c182
    • γ-glutamyltransferase and carbohydrate-deficient transferrin levels may be elevated in heavy drinkers; both tests combined improve test characteristics (sensitivity/specificity) compared with either test alone ^r27c183
      • Although combining tests is the most useful, carbohydrate-deficient transferrin is more expensive, so many use γ-glutamyltransferase alone
    • Other test results that may be altered in heavy drinkers include: ^r10
      • Elevated triglyceride and HDL-C levels
      • High reference range levels of uric acid
      • Elevated mean corpuscular volume
    • Testing for breath or blood alcohol concentration and alcohol metabolites (eg, ethyl glucuronide, phosphatidylethanol) may be useful in certain monitoring scenarios ^r26c184

Laboratory

• Liver function testing ^c185
  • Liver function testing can identify consequences of liver injury secondary to heavy drinking ^r10
  • AST level is characteristically elevated more than ALT level in patients with alcohol-related hepatocyte damage ^r6
    • AST to ALT ratio greater than 2 raises the possibility of alcoholic hepatitis, particularly when each enzyme level is lower than approximately 400 units/L ^r1
  • Use of certain drugs (eg, naltrexone, disulfiram) is cautioned in patients with liver disease ^r26
  • AST and ALT elevations usually normalize approximately 4 weeks after cessation of drinking ^r16
• γ-glutamyltransferase ^c186
  • Modest elevation or high reference range levels (more than 35 units) are consistent with persistent heavy drinking (8 or more drinks daily on a regular basis) ^r10
  • Levels return toward reference range within days to weeks of abstinence from drinking ^r10
  • Sensitivity and specificity to identify heavy drinking overall is poor; detects approximately 20% of heavy drinkers ^r16
• Renal function testing ^c187
  • Baseline renal function testing can help direct appropriate choice of pharmacotherapy ^r26
  • Use of certain drugs (eg, naltrexone, acamprosate) is cautioned in patients with impaired renal function ^r26
• Mean corpuscular volume ^c188
  • Macrocytosis with elevated or high reference range mean corpuscular volume values may be present in heavy drinkers secondary to direct toxic effects of alcohol on bone marrow erythropoiesis ^r10
  • Elevations may persist in times of abstinence for up to 3 months owing to long half-life of erythrocytes ^r16
• Blood alcohol concentration ^c189
  • Most individuals without tolerance will demonstrate severe signs of intoxication with levels at 200 mg/dL or more ^r10
  • Some degree of tolerance likely exists when blood alcohol concentration exceeds 150 mg/dL without signs of intoxication ^r10
  • Blood or breath alcohol concentration may be a helpful measured parameter to monitor for abstinence ^r16
• Carbohydrate-deficient transferrin ^c190
  • Levels of 20 units or more are consistent with persistent heavy drinking (8 or more drinks daily on a regular basis) ^r10
  • Levels return toward reference range within days to weeks of abstinence from drinking ^r10
  • Sensitivity is moderate and specificity is high for detection of high-risk drinking; may be helpful parameter to identify heavy drinking ^r16
  • Testing is not widely available and usually is performed in specialized laboratories ^r16
• Alcohol metabolites
  • Ethyl glucuronide ^r27c191
    • Urine is the most widely used sample for testing
    • Test is highly sensitive; false positives are not infrequent because even trace amounts of alcohol exposure (eg, in cosmetics) can result in positive test ^r26
    • False positives can occur from other conditions (eg, bacterial hydrolysis from Escherichia coli causing a urinary tract infection)
    • Time for levels to normalize after alcohol consumption is approximately 2 days ^r16
    • Measured parameter may be helpful to monitor for abstinence ^r16
    • Testing is not widely available and usually is performed in specialized laboratories ^r16
  • Ethyl sulfate ^r27c192
    • Ethyl sulfate and ethyl glucuronide are both products of ethanol metabolism and levels are often measured together in the urine to detect recent ethanol use
    • Unlike ethyl glucuronide, ethyl sulfate occurs in the urine only as a result of alcohol consumption
  • Phosphatidyl ethanol ^c193
    • Blood is the most widely used sample for testing
    • Sensitive and specific marker to detect chronic drinking (eg, 3 or more drinks a day for 1-2 weeks); may be helpful parameter to identify heavy drinking ^r16r26
    • Marker may be detected for 2 to 4 weeks in blood after drinking has stopped ^r26
    • Testing is not widely available and usually is performed in specialized laboratories ^r16

• Common biologic markers of alcohol use.

  Test characteristics (sensitivity/specificity) apply to usefulness for detection of high risk drinking.

  Adapted from Connor JP et al: Alcohol use disorders. Lancet. 387(10022):988-98, 2016, Table 2.

  Test	Monitor abstinence	Identify high-risk drinking	Time to normalize	Sensitivity	Specificity
  Breath or blood alcohol concentration	Yes	No	Hours	Low	High
  γ-glutamyltransferase	No	Yes	Up to 4 weeks	Low	Moderate
  RBC mean corpuscular volume	No	Yes	3 months	Low	Moderate
  AST	No	Yes	4 weeks	Low	Low
  Carbohydrate-deficient transferrin	No	Yes	4 weeks	Moderate	High
  Ethyl glucuronide	Yes	No	2 days	High	High
  Phosphatidyl ethanol	No	Yes	4 weeks	High	High
  Ethyl sulfide	Yes	No	2 days	High	High

Other diagnostic tools

• DSM-5 TR diagnostic criteria for alcohol use disorder ^r10c194
  • Diagnosis of alcohol use disorder may be assigned based on meeting at least 2 of the following 11 symptom criteria occurring within a 12-month period
  • Symptom criteria include: ^r10
    • Alcohol consumed in larger amounts or over a longer period than intended
    • Persistent desire or unsuccessful efforts to cut down or control alcohol use
    • Much time spent in activities necessary to obtain, use, or recover from effects of alcohol
    • Craving, strong desire, or urge to use alcohol
    • Recurrent alcohol use resulting in a failure to fulfill major role obligations at work, school, or home
    • Continued alcohol use despite having persistent or recurrent social or interpersonal problems caused or exacerbated by effects of alcohol
    • Important social, occupational, or recreational activities given up or reduced owing to alcohol use
    • Recurrent alcohol use in situations in which it is physically hazardous
    • Continued alcohol use despite knowledge of having a persistent or recurrent physical or psychological problem that is likely to have been caused or exacerbated by alcohol
    • Tolerance, as defined by either of the following:
      • Need for markedly increased amounts of alcohol to achieve intoxication or desired effect
      • Markedly diminished effect with continued use of the same amount of alcohol
    • Withdrawal, as manifested by either of the following:
      • Characteristic signs of alcohol withdrawal syndrome
      • Consuming alcohol or a closely related substance (eg, a benzodiazepine) to relieve or avoid withdrawal symptoms
  • Specifiers ^r10
    • Severity
      • Mild: presence of 2 to 3 DSM-5 symptom criteria
      • Moderate: presence of 4 to 5 DSM-5 symptom criteria
      • Severe: presence of 6 or more DSM-5 symptom criteria
    • Remission status
      • Early remission
        • None of the criteria previously met for alcohol use disorder are present for at least 3 months but less than 12 months (except for craving phenomenon, which may still be present)
      • Sustained remission
        • None of the criteria previously met for alcohol use disorder are present at any time for a period of 12 months or longer (except for craving phenomenon, which may still be present)
    • Presence in a controlled environment
      • Specify if patient is in a controlled environment (eg, locked hospital unit, therapeutic community, correctional facility) where access to alcohol is restricted

Most common

• Nonpathologic use of alcohol ^c195
  • Similar presentation, with repeated (sometimes daily) and occasionally heavy use of alcohol in quantities sufficient to cause intoxication ^r10
  • As opposed to patients with alcohol use disorder, use does not result in repeated and significant distress or impaired functioning in these people ^r10
  • Differentiate clinically with DSM-5 TR criteria
• Sedative, anxiolytic, or hypnotic use disorder ^c196c197
  • Presenting signs and symptoms are nearly identical to manifestations of alcohol use disorder
  • Concurrent use of sedative, anxiolytic, or hypnotic medications is not uncommon in patients with alcohol use disorder
  • As opposed to alcohol use disorder, mild decrease in autonomic system functioning (eg, bradycardia, hypotension) is more characteristic of sedative, anxiolytic, or hypnotic use
  • Differentiation can be difficult and disorders may be comorbid. Clinical history, urine drug testing, and application of DSM-5 TR criteria can aid in differentiation
• Depressive and anxiety disorders ^c198c199d2
  • May present similar to alcohol use disorder with mood changes in conjunction with heavy or frequent alcohol use ^d3
  • People with mental health conditions may self-medicate with alcohol in effort to blunt severity of psychiatric symptom manifestations ^d4
  • Alcohol-induced depression and anxiety are common in patients with active alcohol use disorder and initially can complicate the differentiation process ^d5
  • True comorbid psychiatric illnesses, rather than alcohol-induced effects, are often noted before onset of heavy alcohol use and persist after recovery from alcohol use disorder is achieved ^r6
  • Diagnosis of comorbid depressive and anxiety disorders may require a period of abstinence to determine whether manifestations are secondary to alcohol-induced effects, primary mental health issue, or both
  • Diagnoses are based on DSM-5 TR criteria

Admission criteria

Admit patients with moderate to severe withdrawal and those who are at risk for severe withdrawal (eg, history of severe withdrawal, withdrawal seizures) for inpatient detoxification^r6d1

Admit patients with significant medical or psychiatric comorbidity, patients who lack social support, and patients who are pregnant for further evaluation and management ^r6

Admit patients at risk for suicide for further evaluation and treatment

Admit any heavily intoxicated patients who cannot be cleared in the emergency department after period of observation for airway protection, hydration, seizure precautions, and monitoring for glucose abnormalities, ketoacidosis, potential trauma, and development of withdrawal ^r16

Patients with serious health consequences related to alcohol use (eg, significant trauma, cardiac complications, liver failure, pancreatitis, pneumonia) may require admission for further diagnostic and management considerations

Recommendations for specialist referral

• Consider evaluation and treatment in consultation with an addiction medicine specialist for patients at risk for severe withdrawal course, moderate to severe alcohol use disorder, and inability to maintain sobriety secondary to frequent relapse
• Psychiatric evaluation is required for patients at risk for suicide (eg, ideations with plan, ideations with past attempt) and patients with likely psychiatric comorbidity
• Pregnant patients require care in consultation with high-risk obstetrician and may require evaluation and management by an addiction medicine specialist
• Consider evaluation and treatment in consultation with an adolescent addiction medicine clinician for adolescent patients
• Consult appropriate specialist for patients presenting with serious health consequences related to alcohol use (eg, gastroenterologist for liver failure, cardiologist for cardiomyopathy)

Drug therapy

• Naltrexone (oral and long-acting intramuscular injection) ^c200
  • Contraindications
    • Acute hepatitis or liver failure;^r2however, drug is safe in patients with mild to moderate liver disease (up to Child-Pugh Class B cirrhosis or transaminases less than 5 times upper limit of reference range)^r3
    • Patients taking opioids or opioid agonists such as buprenorphine (drug precipitates opioid withdrawal) or anticipated need for opioids (drug blocks effects of opioids) ^r2
      • Opioid abstinence for several days to a week (approximately 5 times half-life of opioid taken) is recommended before starting naltrexone ^r3r26
  • Use with caution in patients with moderate to severe renal impairment ^r26
  • Most data support best efficacy in patients not currently drinking alcohol (number needed to treat is 12 to prevent return to heavy drinking compared with placebo) ^r3
  • Predictors of positive therapeutic response to naltrexone may include positive family history for alcohol use disorder and strong cravings for alcohol ^r36
  • Oral dosage
    • Naltrexone Hydrochloride Oral tablet; Adults: 50 mg PO once daily with food for 12 weeks. Other regimens include 50 mg PO once daily on weekdays and 100 mg PO on Saturdays; 100 mg PO every other day; or 150 mg PO every third day. Some patients may require 100 mg/day PO. Initially, patients may require 3 to 6 months of treatment. Certain patients may benefit from up to 1 year of treatment. Titrate dose from 12.5 mg to 25 mg PO once daily to minimize GI upset; gradually titrate the dose, split the daily dose, or adjust the administration times.
  • Intramuscular injection dosage
    • Naltrexone Suspension for injection, Extended Release; Adults: 380 mg IM as deep gluteal injection every 4 weeks. Use in patients who are able to abstain from alcohol in an outpatient setting and who are not actively drinking.
• Acamprosate ^c201
  • Precaution: dose reduction required for patients with moderate renal impairment (use 333 mg dose PO 3 times a day) and low body weight (less than 65 kg^r16) ^r2r26
  • Contraindicated in patients with severe renal impairment ^r2r24
  • Safe to use in patients with mild to moderate liver disease (Child-Pugh class A or B cirrhosis) ^r3
  • May be most effective in patients not currently drinking alcohol; effective for both maintaining abstinence and reducing heavy drinking days (number needed to treat is 12 to prevent return to drinking compared with placebo) ^r3
  • Acamprosate Calcium Gastro-resistant tablet; Adults: 666 mg PO three times per day. Initiate treatment as soon as possible after the period of alcohol withdrawal, when abstinence is achieved, and maintain treatment even if the patient relapses. Lower doses may be effective in some patients. Efficacy in promoting abstinence has not been demonstrated in patients who have not undergone detoxification or achieved alcohol abstinence; therefore, acamprosate is indicated only in patients who are abstinent at the time of treatment initiation. Acamprosate should be used as a part of a comprehensive program that includes psychosocial support and treatment.
• Disulfiram ^c202
  • Precautions: causes symptoms with alcohol exposure (eg, flushing, headache, nausea and vomiting, diaphoresis, lightheadedness); may cause medically dangerous symptoms with significant alcohol exposure (eg, hemodynamic instability) ^r2r3
    • Avoid using other products with potential for significant alcohol absorption (eg, alcohol-based shaving creams, mouthwash, cough syrup) ^r3
  • There is potential for drug interactions with disulfiram use (eg, benzodiazepines, isoniazid, rifampin, metronidazole, warfarin, oral hypoglycemics, phenytoin, theophylline) ^r26
  • Contraindicated in patients who plan to continue consuming alcohol; have severe cardiac disease, psychosis, or cognitive dysfunction; are pregnant or breastfeeding; or are highly impulsive ^r24r31r34
    • Cardiac function assessment may be indicated before initiating treatment with disulfiram, depending on patient's history ^r31
  • Effectiveness is improved when patient dosage is monitored. Best reserved for highly motivated patients and patients with significant external pressure to maintain sobriety with goal of abstinence ^r3r28
  • First dose may be given after 12 hours of confirmed alcohol cessation ^r2r3r26
  • Disulfiram Oral tablet; Adults: 500 mg PO once daily every morning for 1 to 2 weeks, then reduce to 250 mg PO once daily. The dose may be taken in the evening if drowsiness occurs. Recommended maintenance dosage range: 125 mg to 500 mg PO once daily. Max: 500 mg/day PO.
• Topiramate ^c203
  • Consider for patients with comorbid seizure disorder ^r3
  • Precaution: titrate dose escalation more slowly and diminish total daily dose by 50% in patients with creatinine clearance of less than 70 mL/min; taper is required when medication is discontinued ^r3
  • Initiate with gradual dose escalation over 4 weeks ^r3
  • Topiramate Oral tablet; Adults: 25 mg PO once daily, initially. Titrate dose according to response and tolerability. Max: 300 mg/day in divided doses.
• Gabapentin ^c204
  • Consider for patients with comorbid neuropathy ^r3
  • Precaution: potential for drug misuse may be a concern given recent accounts of gabapentin overdose, addiction, and diversion ^r3
  • Gabapentin Oral tablet; Adults: Use not FDA-approved, but has been studied. Initially, 300 mg PO at bedtime on day 1; then 300 mg PO twice daily on day 2; then 300 mg PO 3 times per day on Day 3; and then titrated upward over days 4 to 7 to reach final dosage. Doses from 600 mg/day to 1,800 mg/day PO have improved abstinence rates and relapse-related symptoms (i.e., insomnia, dysphoria, craving) in some patients.

Nondrug and supportive care

Alcohol use disorder

• Brief intervention defines problem and formulates treatment plan; steps for initial brief intervention:
  • Clearly state diagnosis ^r28
  • Negotiate a realistic drinking goal with abstinence being the safest option ^r28
  • Recommend treatment plan that involves counseling and/or medication with or without medically assisted withdrawal management ^r28
  • Motivate patient to engage in decision making about medication and treatment plan ^r16
• Abstinence is the ultimate goal for optimal outcome ^r28c205
  • Abstinence is not the initial expressed goal of many patients ^r3r16
    • When a patient with alcohol use disorder initially is unwilling to commit to abstinence, best approach is to set the goal of reducing drinking, while continuing to reinforce that a goal of abstinence has best outcome ^r28
    • Alternate outcome goals, at least initially, can include reducing cravings, quantity consumed, and number of heavy drinking days ^r3
    • Need for abstinence is suggested by failure to control drinking ^r16
  • Some slightly different initial approach models for patients unable to or unwilling to abstain: ^r2
    • Shared decision-making model ^c206
      • Support patient as preferences, values, and goals are clarified
    • Harm reduction model ^c207
      • Controversial approach involves main treatment goal of reducing heavy drinking (controlled drinking) rather than complete abstinence
  • Provide suggestions for strategies to help maintain abstinence and cope with urge obsessions ^r34c208
• Psychiatric and psychosocial rehabilitation
  • Modalities
    • Intensive counseling programs
      • May occur in a variety of settings (eg, inpatient, outpatient) and with a number of approaches (eg, individual, group) ^{r2c209c210c211c212c213}
      • Most commonly recommended techniques include motivational enhancement therapy and cognitive behavioral therapy ^r2c214c215
    • Brief counseling sessions
      • May occur in primary care setting; motivational interviewing technique is often employed ^r35
      • Weekly or biweekly, brief (15-20 minutes), and may be effective when combined with medication use ^r26
    • Mutual help groups
      • Mutual help groups can help maintain long-term sobriety and improve quality of life in patients who attend regularly and actively participate in discussion ^r26r34
      • Most commonly recommended programs include 12-step–based programs such as Alcoholics Anonymous; meetings can be located through the Alcoholics Anonymous website^r37 and local resources ^{r2r37c216c217}
      • SMART Recovery^r38 (Self-Management and Recovery Training) is an alternative for patients who reject the spiritual recovery angle offered by most Alcoholics Anonymous programs ^r16c218
    • Telehealth ^r24c219
      • Technology-based interventions such as automated text/voice messaging or smart phone apps can be added to usual care of alcohol use disorder
      • The current recommendation is to use structured telephone-based care as an adjunctive tool rather than unstructured interventions
  • Substance Abuse and Mental Health Services Administration provides a Behavioral Health Treatment Services Locator^r39 to help find addiction and mental health services throughout the United States
• Relapse prevention ^c220
  • Involves frequent monitoring and follow-up
  • Goals include maintaining high motivation and accountability for treatment, promoting and maintaining positive attitudes toward recovery, and diminishing risk for relapse ^r1
• Adjustments to treatment plan
  • Depend on patient progress, specific pitfalls encountered (eg, problems adhering to treatment plan, medication tolerance), and evolving treatment goals
  • In the event of relapse, consider the following treatment options ^r26
    • Assess and address social, medical, or behavioral factors that contribute to patient’s alcohol consumption
    • Increase monitoring
    • Adjust medication dose
    • Increase or change intensity of psychosocial services
    • Refer patient for specialty care to addiction medicine specialist, if not already done

Treatment of risky drinking behavior without alcohol use disorder

• Behavioral counseling interventions may reduce or eliminate behavior ^r2
• Data support brief (5-15 minutes) multicontact (2 or more) intervention as the most effective approach ^r2
  • Clinical approach protocol is available on the National Institute on Alcohol Abuse and Alcoholism website, and structured questions are available ^r7r28r40
  • Key components of brief intervention include raising subject, providing feedback, enhancing motivation, negotiating, and advising ^r40
• Effective counseling techniques use motivational interviewing, advising, feedback, alcohol consumption diaries, self-help materials, and problem-solving exercises ^r2
  • Motivational interviewing techniques are particularly promising and are designed to guide and facilitate behavioral changes
    • Focus is to elicit patient motivation for change and to aid exploration and resolution of ambivalence
    • Techniques used include reflective listening, open-ended questions, elicit-provide-elicit strategy, asking permission, importance exercises, and confidence exercises. Uses REDS strategy (roll with resistance, express empathy, develop discrepancy, support self-efficacy)
  • Advice regarding strategies to reduce alcohol intake in patients with risky drinking behavior is available ^r34
• Follow-up to review alcohol intake and continue support at each patient visit

Comorbidities

• Psychiatric illnesses and behavioral disorders
  • Mental health conditions (eg, anxiety disorders, depressive disorders, conduct disorders, schizophrenia, bipolar disorder, antisocial personality disorder, substance use disorders, eating disorders, posttraumatic stress disorder) are observed with increased frequency in patients with alcohol use disorder ^{c222c223c224c225c226c227c228c229c230}
  • Integrated treatment is the most effective and preferred treatment method; assumes that each disorder is primary and requires simultaneous care ^r26
  • Primary caregiver can be most effective coordinating and streamlining care through specialists (eg, psychiatrists, addiction medicine specialists) ^r26
  • Both naltrexone and acamprosate may be used in combination with psychiatric medications; disulfiram is contraindicated in the presence of psychosis and may increase tricyclic antidepressant and long-acting hepatically metabolized benzodiazepine levels ^r26
  • Treatment of depression is individualized given that substance-induced depression and comorbid chronic depression may be difficult to differentiate ^r26
    • Consider antidepressant when
      • Symptoms limit recovery potential and there are limited or no contraindications (eg, history of mania or hypomania) ^r26
      • Depressed mood does not improve or resolve with reduction in heavy alcohol use or abstinence ^r4
• Renal impairment ^r31c231
  • Severe renal impairment: acamprosate is contraindicated
  • Mild to moderate renal impairment: do not use acamprosate as first line treatment
• Acute hepatitis or hepatic failure ^r31c232c233
  • Naltrexone is contraindicated
• Anticipated need for opioids or other opioid requirement ^r31
  • Naltrexone is contraindicated
• Co-occurring opioid use disorder ^r31c234c235
  • Naltrexone is indicated for patients (whose goal is abstinence from both opioids and alcohol) who are able to abstain from opioid use for a clinically appropriate time before starting naltrexone
• HIV ^r40c236
  • Ineffective treatment of alcohol use disorder can adversely affect HIV treatment secondary to suboptimal antiretroviral therapy adherence
  • Intramuscular dosing of naltrexone may be preferred to ensure administration and diminish pill burden in patients opting for pharmacotherapy

Special populations

• Pregnant patients
  • 11.5% of pregnant women report drinking alcohol and 3.9% report binge drinking in the past 30 days, according to data from the Behavioral Risk Factor Surveillance System obtained between 2015 and 2017 ^r41
  • Alcohol consumption during pregnancy is associated with fetal alcohol spectrum disorders including birth defects involving the central nervous system, behavioral disorders, and impaired intellectual development
    • May also be a risk factor for other adverse pregnancy outcomes such as miscarriage and stillbirth ^r41
  • Strict abstinence from alcohol consumption is the primary goal for pregnant patients and women trying to conceive; no amount of alcohol is known to be safe for developing fetus ^r26
  • Screening questions and tools require incorporation of assessment for any alcohol use during pregnancy; several adapted screening tools are validated for use in pregnant patients
  • Manage patients in consultation with an addiction medicine specialist and/or obstetrician specializing in high-risk pregnancy ^r26
  • Medication use in pregnant patients is controversial; none of the medications approved for treatment of alcohol use disorder have been definitively shown to be safe for pregnant or nursing patients ^r26r42
    • Medications should be used only when probable benefits outweigh potential risks ^r26
    • The American Psychiatric Association, the International Task Force of the World Federation of Societies of Biological Psychiatry, and the International Association for Women's Mental Health recommend against use of medications (other than benzodiazepines) to treat alcohol withdrawal in pregnant and breastfeeding patients ^r31r43
    • Disulfiram is contraindicated in pregnancy ^r26
    • Low doses of benzodiazepines used for the shortest duration may be used to prevent alcohol withdrawal symptoms if high chronic alcohol intake is ceased (hospitalization is recommended in this scenario) ^r43
  • Assess newborns for fetal alcohol spectrum disorders and measure alcohol metabolites in meconium if fetal alcohol exposure is suspected ^r43
• Adolescents and young adults
  • None of the available medications are approved for use in patients younger than 18 years with alcohol use disorder ^r26r42
  • Ideally, refer patients to a clinician or program specializing in adolescent addiction for treatment planning ^r26
  • In practice, because medications have no specific contraindications in this population, judicious use of medication may be necessary when psychosocial interventions alone are not effective or when there is evidence of moderate to severe alcohol use disorder ^r26
  • Specific screening questions and tools are useful in adolescents; several adapted screening tools are validated for use in this population
• Older adults
  • Several diagnostic challenges exist in this age group. Accurate diagnosis may be difficult owing to: ^r26
    • Pronounced patient and family member shame, denial, and minimization regarding disorder
    • Misdiagnosis of alcohol use disorder as another condition common in this age group (eg, depression, dementia)
  • Treating with medications must be done carefully because there is increased likelihood of concomitant comorbidity and diminished renal clearance of medications ^r26
    • Acamprosate may require dose reductions and frequent renal function tests
    • Disulfiram requires dose reduction; maintain care when prescribing to patients taking multiple medications because potential exists for multiple drug interactions with disulfiram

At-risk populations

• Several guidelines and task force recommendations advocate for universal screening of all adults for unhealthy alcohol use ^r2
  • Yearly screening is recommended by most experts;^r24r6 however, it may be impractical in some instances ^r8
  • Some experts recommend targeted yearly screening for certain patients at increased risk for disease or disease consequences such as: ^r8
    • At high risk for unhealthy drinking (eg, smokers, adolescents, young adults) ^r8
    • With symptoms that may result from heavy drinking (eg, depression, anxiety, insomnia, tremor, elevated transaminases) ^r8
    • Who will be taking prescription medication ^r8
    • Who may become pregnant ^r8
    • Who present to emergency department ^r8
    • Who are older adults, particularly with initiation of any new medication and significant change in health status ^r49
    • With family history of alcohol use disorder or addiction ^r49
    • Who have conditions that can be caused by alcohol use
  • Despite recommendations, most adults are not asked about alcohol use by medical providers ^r2
• Specific screening recommendations and suggestions for appropriate intervention for patients who screen positive are provided by several organizations, including:
  • Substance Abuse and Mental Health Services Administration
    • Recommends SBIRT approach (screening, brief intervention, and referral to treatment) ^r50
  • US Preventive Services Task Force ^r51
  • US Department of Veterans Affairs ^r24
  • National Institute on Alcohol Abuse and Alcoholism ^r28
  • National Institute for Health and Care Excellence ^r32

Screening tests

• Validated screening tools for unhealthy alcohol use (risky drinking) and alcohol use disorder include: ^r2
  • First tier screening tools
    • Single question screen ^c352
      • Questioning process
        • First ask if patient sometimes drinks beer, wine, or other alcoholic beverages
        • When affirmative, follow-up with single question asking how many times in the past year patient has had 5 or more drinks in a day (men younger than 65 years) or 4 or more drinks in a day (all women and men aged 65 years and older) ^r2
      • Results and test characteristics
        • Response of 1 or more times establishes a positive screen ^r2
        • Sensitivity is around 82% and specificity is around 79% for detecting unhealthy alcohol use ^r2r6r7
        • Sensitivity is around 87% and specificity is around 67% for detecting alcohol use disorder ^r6
    • AUDIT-C (Alcohol Use Disorders Identification Test–Consumption) ^c353
      • 3-question tool (first 3 questions of the AUDIT); takes approximately 1 to 2 minutes to complete ^r2

        • AUDIT-C (Alcohol Use Disorders Identification Test–Consumption).

          AUDIT-C consists of the first 3 AUDIT questions. Threshold for positive screen is variably defined. Many sources use a cut point score for positive screen in women of 3 or more and in men of 4 or more.

          Data from Babor TF et al: AUDIT: The Alcohol Use Disorders Identification Test: Guidelines for Use in Primary Health Care. 2nd ed. WHO; 2001.

          Questions	0 points	1 point	2 points	3 points	4 points
          1. How often do you have a drink containing alcohol?	Never	Monthly	2-4 times a month	2 or 3 times a week	4 or more times a week
          2. How many drinks containing alcohol do you have on a typical day when you are drinking?	1 or 2	3 or 4	5 or 6	7-9	10 or more
          3. How often do you have 5 or more drinks on 1 occasion?	Never	Less than monthly	Monthly	Weekly	Daily or almost daily

      • Scores range from 0 to 12; higher scores indicate greater alcohol consumption ^r4
      • Results
        • Threshold for positive screen is variably defined
        • Some sources consider a score of 3 or more for women and 4 or more for men a positive screen ^r2r7
        • Other sources report that a cutoff score of 3 suggests hazardous drinking and 4 or more suggests possible alcohol use disorder ^r16
      • Test characteristics
        • Sensitivity and specificity for unhealthy alcohol use depend on cutoff threshold used and population screened
          • Using threshold score of 4 in men, sensitivity is approximately 86% and specificity ranges from 72% to 89% ^r2
          • Using threshold score of 3 in women, sensitivity ranges from approximately 60% to 73% and specificity ranges from 91% to 96% ^r2
    • CAGE questionnaire (cut-down, annoyed, guilty, eye-opener) ^r52c354
      • Reasonable tool for identifying alcohol use disorder; however, CAGE questionnaire is considered inferior to single question screen and AUDIT-C (Alcohol Use Disorders Identification Test–Consumption) for detecting full range of unhealthy alcohol use ^r2
      • Questions ^r52
        • Cut down: have you felt you should cut down on your alcohol consumption?
        • Annoyed: have people annoyed you by criticizing your drinking?
        • Guilt: have you felt guilty about your drinking?
        • Eye opener: have you ever had a drink first thing in the morning (ie, had an eye opener) to steady your nerves or to get rid of a hangover?
      • Results ^r53
        • Any affirmative response suggests possible unhealthy drinking behavior and requires further evaluation for alcohol use disorder
        • 2 or more affirmative answers are suggestive of probable alcohol use disorder (patients with 2 or more affirmative answers are up to 7-fold more likely to have alcohol use disorder^r54)
      • Test characteristics
        • CAGE (cut-down, annoyed, guilty, eye-opener) tool has a lower sensitivity for detecting risky drinking behavior compared with other first tier screening tools but will identify most patients with alcohol use disorder ^r2r6
        • 2 or more affirmative answers suggests a clinically significant alcohol use problem with a measured sensitivity range of 78% to 81% and specificity of 76% to 96% in various populations and settings ^r55
  • Second tier screening tool
    • AUDIT full version (Alcohol Use Disorders Identification Test) ^c355
      • Some experts suggest using AUDIT instead of abbreviated first tier tools when clinical suspicion of alcohol use disorder is high for improved test characteristics ^r6
      • 10-question tool; takes approximately 5 minutes to complete ^r2
      • Results
        • All results must be combined with a thorough patient history and physical examination to be useful
        • Scores range from 0 to 40; higher scores indicate increased likelihood of harmful drinking ^r4
        • Positive screen with high likelihood of hazardous drinking is indicated by:
          • Score of 8 or more for men up to age 60 years or 4 or more for women, adolescents, and men older than 60 years ^r28
        • High likelihood of alcohol use disorder is indicated by either:
          • Total score of 13 or more in women and 15 or more in men ^r2
          • Subscore of at least 2 points total from questions 4, 5, and 6 (total score of less than 13 for women, less than 15 for men) ^r2
      • Test characteristics
        • Sensitivity and specificity for heavy alcohol use are variably reported and depend on cutoff threshold used and population screened ^r28
          • Cutoff threshold of 4 or more: sensitivity 84% to 85% and specificity 77% to 84% ^r4
          • Cutoff threshold of 5 or more: sensitivity 70% to 92% and specificity 73% to 94% ^r4
      • Suggested response to scores in a primary care setting from 1 source includes ^r16
        • Score 0 through 7: provide basic alcohol education
        • Score 8 through 15: advise about reducing hazardous drinking behaviors
        • Score 16 through 19: impose brief intervention and provide advice about reducing hazardous drinking behaviors. Strongly encourage patient to diminish intake. Continue monitoring
        • Score 20 through 40: refer to specialized treatment

      • AUDIT (Alcohol Use Disorders Identification Test).

        Total score of 13 or higher for women and 15 or higher for men indicates a high likelihood of alcohol use disorder. A subscore of at least 2 points (total) from questions 4, 5, and 6 indicate a high likelihood of alcohol use disorder in women with a total score below 13 and men below 15.

        Data from Babor TF et al: AUDIT: The Alcohol Use Disorders Identification Test: Guidelines for Use in Primary Health Care. 2nd ed. WHO; 2001.

        Questions	0 points	1 point	2 points	3 points	4 points
        1. How often do you have a drink containing alcohol?	Never	Monthly	2-4 times a month	2 or 3 times a week	4 or more times a week
        2. How many drinks containing alcohol do you have on a typical day when you are drinking?	1 or 2	3 or 4	5 or 6	7-9	10 or more
        3. How often do you have 5 or more drinks on 1 occasion?	Never	Less than monthly	Monthly	Weekly	Daily or almost daily
        4. How often during the last year have you found that you were not able to stop drinking once you had started?	Never	Less than monthly	Monthly	Weekly	Daily or almost daily
        5. How often during the last year have you failed to do what was normally expected of you because of drinking?	Never	Less than monthly	Monthly	Weekly	Daily or almost daily
        6. How often during the past year have you needed a first drink in the morning to get yourself going after a heavy drinking session?	Never	Less than monthly	Monthly	Weekly	Daily or almost daily
        7. How often during the last year have you had a feeling of guilt or remorse after drinking?	Never	Less than monthly	Monthly	Weekly	Daily or almost daily
        8. How often during the last year have you been unable to remember what happened the night before because of your drinking?	Never	Less than monthly	Monthly	Weekly	Daily or almost daily
        9. Have you or someone else been injured because of your drinking?	No	—	Yes, but not in the last year	—	Yes, during the last year
        10. Has a relative, friend, doctor, or other health care worker been concerned about your drinking or suggested you cut down?	No	—	Yes, but not in the last year	—	Yes, during the last year

  • The US Preventive Services Task Force recommends the AUDIT (Alcohol Use Disorders Identification Test), AUDIT-C (Alcohol Use Disorders Identification Test–Consumption), or the single-question National Institute on Alcohol Abuse and Alcoholism screen as the most accurate means of assessing for unhealthy alcohol intake ^r51r56
    • CAGE (cut-down, annoyed, guilty, eye-opener) screening tool has low sensitivity at lower levels of alcohol intake
• Screening in special populations
  • Adolescents
    • CRAFFT Screening Interview was developed specifically for adolescents. It screens for alcohol and drug use and has been validated ^r57c356
      • Made up of 6 questions. If 2 or more are answered affirmatively, test is considered positive and further evaluation should be done
        • C: have you ridden in a car driven by someone (including yourself) who was high or had been using alcohol or drugs?
        • R: do you ever use alcohol or drugs to relax, feel better about yourself, or fit in?
        • A: do you ever use alcohol or drugs while you are by yourself, alone?
        • F: do you ever forget things you did while using alcohol or drugs?
        • F: do your family or friends ever tell you that you should cut down on your drinking or drug use?
        • T: have you ever gotten in trouble while you were using alcohol or drugs?
    • Single-question screening ^r58
      • In the past year, how many times have you used alcohol?
        • If answer is "none," screen is considered negative. Any amount of alcohol consumption is considered a positive screen and requires further discussion and advice
    • 2-question screening tool; specific questions vary based on patient age. Questions for high schoolers include: ^r25
      • In the past year, on how many days have you had more than a few sips of beer, wine, or any drink containing alcohol?
        • Any number of days drinking suggests need for further discussion and advice
      • If your friends drink, how many drinks do they usually drink on an occasion?
        • Friends drinking 3 or more drinks suggests need for further discussion and advice
  • Pregnant patients
    • T-ACE (tolerance, annoyance, cut down, eye-opener), TWEAK (tolerance, worry, eye-opener, amnesia, k/cut down), and AUDIT-C (Alcohol Use Disorders Identification Test–Consumption), are examples of tools validated for use in this population ^{r59c357c358c359}
    • Include or modify at least 1 item while questioning pregnant patients to assess for any consumption of alcohol, regardless of tool used
• Provide appropriate interventions for patients who screen positive for unhealthy alcohol use or potential alcohol use disorder
  • Risky drinking behavior
    • Brief behavioral counseling provided in primary care setting may reduce self-reported unhealthy alcohol use ^r2r7
    • Clinical approach protocol is available on the National Institute on Alcohol Abuse and Alcoholism website ^r28
  • Potential alcohol use disorder
    • Diagnosis requires clinical interview to assess for fulfillment of DSM-5 criteria ^r2
    • Treatment requires more intensive interventions with counseling and medications ^r2
• Implementing screening and appropriate interventions in the primary care setting
  • Implementation may require additional support systems, changes in staffing or staff roles, formal protocols, and additional provider and staff training ^r2
  • Health care provider may run into barriers, including lack of training and expertise, competing priorities, misconceptions about benefits of interventions, lack of confidence about ability to help patients with unhealthy alcohol use, and inadequate infrastructure ^r2