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May.12.2022

Alcohol Use Disorder

Synopsis

Key Points

  • Alcohol use disorder is a problematic pattern of compulsive and uncontrolled alcohol use associated with clinically significant impairment or distress as defined by DSM-5 criteria
  • Often heritable, chronic, and progressive; patients with continued alcohol problems experience a 3- to 4-fold increased rate of premature deathr1
  • Presentation is highly variable; however, general characterizations include inability to control drinking, continued drinking despite knowledge of consequences, and neglect of responsibilities
  • Common manifestations include cravings, obsessions and compulsions regarding alcohol use, tolerance, blackouts, withdrawal, and consequences of disease (eg, health, relationship, legal, financial, employment, educational)
  • Screening for unhealthy alcohol use is recommended by several guidelines and organizations
  • Patients with a positive screen require further evaluation to determine if patient is a risky drinker or has alcohol use disorder; diagnosis of alcohol use disorder is based on DSM-5 criteria
  • Management of patients with risky drinking behavior involves brief behavioral counseling and close follow-up
  • Management of alcohol use disorder is individualized and multidimensional; most effective strategy combines both psychosocial interventions (eg, counseling, mutual help groups) and use of medication (eg, naltrexone, acamprosate)
  • Comorbid psychiatric and behavioral issues are not uncommon in patients with disorder and often require additional specialized management
  • Complications related to alcohol use disorder are numerous and include potential serious health problems, social problems, withdrawal-related complications, and premature death
  • Disorder is not an intractable condition; patients with effectively treated disease have a promising prognosis. Various treatment approaches result in a 1- to 5-year abstinence rate between 15% and 35%r2

Urgent Action

  • Patients with moderate to severe withdrawal require urgent management of manifestations; benzodiazepines are the most commonly used pharmacotherapy for medical management of alcohol withdrawal d1
  • Certain patient populations at high risk for further disease-related health consequences (eg, pregnant patients, patients presenting with severe hepatic impairment) require urgent treatment with goal of abstinence
  • Unresponsive patients with alcohol intoxication and life-threatening high blood alcohol concentrations require emergent care to protect airway and vital functions and to monitor for hypoglycemia

Pitfalls

  • Universal screening for unhealthy alcohol use is recommended; despite recommendations, most adults are not screened for unhealthy alcohol use by medical providers in the primary care setting r2
  • Patients may not be rigorously honest (ie, may deny or minimize) in reporting amount and frequency of consumption; history obtained from family and friends may depict a more accurate account of consumption history
  • Most patients with alcohol use disorder do not receive appropriate multimodal treatment
    • Recommendations regarding appropriate counseling and mutual help group interventions for unhealthy alcohol use are in place; despite recommendations, most patients do not receive appropriate interventions r2
    • Pharmacotherapy for alcohol use disorder is appropriate and effective for many patients; despite evidence that it is effective, pharmacotherapy is often underused r3r4
  • Maintain a high degree of suspicion for alcohol use disorder in patients presenting with unexplained medical diagnosis that may represent potential complications related to disorder; patients with unhealthy alcohol consumption may not be forthright with amount and frequency of alcohol intake (minimization, denial)
    • Alcohol-related hypertension is a leading cause of reversible hypertension

Terminology

Clinical Clarification

  • Alcohol use disorder is a problematic pattern of compulsive and uncontrolled alcohol use associated with clinically significant impairment or distress, manifested by at least 2 criteria as defined by DSM-5, occurring with a 12-month period r3
  • Disease is often heritable, chronic, and progressive r5
  • Presentation is highly variable but is characterized by inability to control drinking, continued drinking despite knowledge of consequences, and neglect of responsibilities r6

Classification

  • Unhealthy alcohol use
    • An overarching term that includes risky drinking behaviors and alcohol use disorderr2r7
      • Estimated prevalence is greater than 20% among adults in the United States r2
    • Risky drinking behaviors
      • Drinking amounts of alcohol that exceed recommended limits and increase risk for health consequences without meeting DSM-5 criteria for alcohol use disorder r2
        • Maximum recommended limits for men younger than 65 years are 4 or fewer standard drinks per day and 14 or fewer per week r2
        • Maximum recommended limits for women and for men aged 65 years and older are 3 or fewer standard drinks per day and 7 or fewer per week r2
        • A standard drink is defined as approximately 14 g of absolute ethanol; this equates to approximately: r8
          • 12 oz of 5% ethanol beer
          • 5 oz of 12% ethanol wine
          • 1.5 oz of 80 proof liquor
      • Binge drinking
        • Defined as 5 or more drinks for men and 4 or more drinks for women in a day (or on the same occasion) during the preceding month r3
        • Pattern of alcohol consumption that results in elevation of blood alcohol concentration to 0.08 g/dL or more within 2 hours r9
      • Consumption of any amount of alcohol in specific patient populations (eg, pregnant patients or patients with health conditions caused/exacerbated by alcohol) may be considered risky
    • Alcohol use disorder
      • Problematic pattern of alcohol use leading to clinically significant impairment or distress as defined by DSM-5 criteria (meeting at least 2 of 11 criteria within a 12-month period); these criteria include: r10
        • Consumption of alcohol in larger amounts than intended
        • Persistent desire or unsuccessful efforts to cut down
        • Excessive time spent to obtain alcohol
        • Craving alcohol
        • Failure to fulfill major role obligation at work/home
        • Continued alcohol use despite recurrent social/interpersonal problems
        • Reduced social/occupational activities
        • Alcohol use in physically hazardous situations
        • Continued alcohol use despite knowledge of physical or psychological problem
        • Signs of tolerance
        • Signs of withdrawal
      • Classified as mild (2-3 criteria), moderate (4-5 criteria), or severe (6 or more criteria) based on number of criteria met during the past year r4
      • Previous iterations of Diagnostic and Statistical Manual of Mental Disorders (DSM-III and DSM-IV) separated diagnosis of alcohol-related disorders into alcohol abuse and alcohol dependence. This older nomenclature is now out of favor in lieu of current diagnostic terminology: alcohol use disorder with specified severity (mild, moderate, or severe). r2
        • Craving was added to the criteria in the newest classification r2
        • Previous term alcohol abuse in general correlates with milder alcohol use disorder, whereas alcohol dependence correlates with more severe alcohol use disorder r6
      • ICD-11 uses the phrases alcohol dependence or harmful pattern of use of alcohol, where the former denotes more severe manifestation r11

Diagnosis

Clinical Presentation

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:
  • 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 and Risk Factors

Causes

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

Risk factors and/or associations

Age
  • Past year prevalence estimates in the United States for alcohol use disorder:
    • Approximately 5% for 12- to 17-year-old patients r10c99
    • Overall, approximately 8.5% to 14% for adults aged 18 years and older r7r10
      • Prevalence is highest among young adults aged 18 to 29 years (approximately 16%), decreases among middle aged patients, and is lowest among patients aged 65 years and older (approximately 1.5%) c100c101c102
Sex
  • Past year prevalence estimates in the United States for alcohol use disorder are higher among men (12.4%) than women (4.9%) r10c103c104
  • Women who drink heavily are more susceptible to some physical peripheral organ consequences (eg, liver disease) than men r15
    • Higher fat content and differences in total alcohol dehydrogenase levels in women increases the risk for organ damage
Genetics
  • Family history of alcohol use disorder is a strong risk factor for development of disease r16c105
    • Disease is often familial; genetic influences account for approximately 40% to 60% of risk variance r10r17r18
    • Risk of disease is 3- to 4-fold higher in close relatives of patients with disease r10
      • Highest risk occurs in patients with: r10
        • Greater number of affected relatives
        • Closer genetic relationship with affected relatives
        • Higher severity of disorder in affected relatives
  • Details regarding specific genetic influences are evolving; some known phenotypes influenced by a number of genetic variations impart lower or higher risk for disease r10
    • Lower risk phenotypes
      • Altered function of aldehyde dehydrogenase
        • Acute alcohol-related skin flush phenomenon
          • ALDH2*2 single nucleotide polymorphism rs671 (Glu504Lys) leads to diminished activity of aldehyde dehydrogenase and impaired alcohol metabolism r5r17
          • Carriers of ALDH2*2 allele develop a disulfiramlike reaction (skin flushing, diaphoresis, tachycardia, nausea, vomiting, headache, palpitations) after consuming alcohol r16
          • Symptoms may lead to diminished future alcohol consumption, thereby protecting against development of alcohol use disorder
          • Usually noted in Asian patients and is rare in Europeans r16
      • Altered function of alcohol dehydrogenase
        • ADH1B*2single nucleotide polymorphism rs1229984 (Arg48His) leads to a fast rate of alcohol metabolism r17
        • Usually noted in Asian patients and leads to protective effect for development of alcohol use disorder r17
    • Higher vulnerability phenotypes
      • Preexisting schizophrenia or bipolar disorder c106c107
      • Low-level sensitivity (low-level response) to alcohol c108
  • Genetic variations and clinical response to certain medication
    • Single nucleotide polymorphism variant in exon 1 (Asn40Asp) in OPRM1 (μ-opioid receptor gene) is associated with greater positive reinforcing effects of alcohol consumption and greater alcohol craving, in addition to improved clinical response to naltrexone r4r19c109
    • Allele is more prevalent in White and Asian populations as compared to African population r5
  • Single nucleotide polymorphisms in several other genes may confer additional genetic risk for alcohol use disorder; genes include r20r21r22
    • GABRG1 and GARBG2, which encode for gamma 1 and 2 subunits of GABA-A receptor r20c110c111
    • COMT (Val158Met variant) and DRD2 (Taq1A variant), which affect dopamine receptor sensitivity r22c112c113
    • KIAA0040 r21c114
Ethnicity/race
  • Among 12- to 17-year-old patients in the United States, listed in order of most to least prevalent: r10
    • Hispanic individuals (approximately 6% past year prevalence) c115
    • Native American and Alaskan Native individuals c116c117
    • White individuals c118
    • African American individuals c119
    • Asian American and Pacific Islander individuals (approximately 1.6%) c120c121
  • Among adults, in order of most to least prevalent: r10
    • Native American and Alaskan Native individuals (approximately 12% past year prevalence) c122c123
    • White individuals c124
    • Hispanic and African American individuals c125c126
    • Asian American and Pacific Islander individuals (approximately 4.5%) c127c128
Other risk factors/associations
  • Increased risk of developing disease is associated with:
    • Earlier onset of first alcohol use and/or intoxication r16r17c129c130
    • Increased frequency of binge drinking r3r16c131
    • Higher number of years of heavy drinking and number of drinks per day r17c132c133
    • Accepting cultural attitudes toward drinking and intoxication r10c134
    • Easy availability of alcohol r10c135
    • Low self-control and impulsivity r16c136c137
    • Increased stress levels and suboptimal methods of coping with stress r10c138c139
    • Positive personal experiences with alcohol use and exaggerated positive expectations of alcohol effects r10c140
    • Association with peers who use alcohol and other mood-altering substances r10r16c141
    • Childhood conduct and mood disorders r16c142c143
    • Childhood and adolescent stressors (eg, verbal, physical, sexual abuse) and household instability (eg, parent or intimate partner violence, parental psychiatric illness and substance use, household member incarceration) r3r17c144c145c146c147c148c149c150c151
    • Low parental monitoring and poor family support r16c152c153
  • Additional associations include:
    • High rates of other concomitant mental health disorders such as another substance use disorder, depression and mood disorders, anxiety disorders, schizophrenia, bipolar disorder, and posttraumatic stress disorder r6c154c155c156c157c158
      • Up to 50% of patients with a lifetime history of alcohol use disorder have a least 1 other mental health disorder r16c159
      • Most patients have an additional substance use disorder: at least one-half smoke tobacco and one-third have another drug use disorder r16c160
      • Conduct disorder and antisocial behavior often co-occur in adolescents with alcohol use disorder r10c161c162
    • High rates of challenging psychosocial issues such as intimate partner violence, unstable housing, and poverty r6c163c164c165
    • High rates of concomitant chronic diseases c166
    • Marital status is associated with rate of alcohol use disorder: r3
      • Never married: highest association c167
      • Separated, divorced, or widowed: second highest association c168c169c170
      • Married or cohabitating: lowest association c171c172
    • Higher levels of impulsivity are associated with more severe and earlier onset of disease r10
    • Rates may be higher in lesbian, gay, and bisexual populations r23c173c174c175

Diagnostic Procedures

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 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.
    TestMonitor abstinenceIdentify high-risk drinkingTime to normalizeSensitivitySpecificity
    Breath or blood alcohol concentrationYesNoHoursLowHigh
    γ-glutamyltransferaseNoYesUp to 4 weeksLowModerate
    RBC mean corpuscular volumeNoYes3 monthsLowModerate
    ASTNoYes4 weeksLowLow
    Carbohydrate-deficient transferrinNoYes4 weeksModerateHigh
    Ethyl glucuronideYesNo2 daysHighHigh
    Phosphatidyl ethanolNoYes4 weeksHighHigh
    Ethyl sulfideYesNo2 daysHighHigh

Other diagnostic tools

  • DSM-5 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

Differential Diagnosis

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 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 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 criteria

Treatment

Goals

  • Start individualized treatment approach with goal of abstinence from alcohol consumption
  • Reduce or eliminate complications associated with the disorder, and improve or restore health and social well-being of patient
  • Monitor and provide follow-up in effort to prevent relapse

Disposition

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 detoxificationr6d1

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

Criteria for ICU admission
  • Alcohol use disorder does not generally require ICU level of care; however, patients with severe withdrawal manifestations or complications related to extreme intoxication may require ICU admission d1

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)

Treatment Options

Treatment of alcohol use disorder

  • Brief behavioral intervention is the initial step to define and formulate a treatment plan. Indicated for all patients with unhealthy alcohol user16r24
    • Brief intervention consists of expressing concern over alcohol consumption, advising reduction in drinking or abstinence, providing feedback linking alcohol use and health and referral to addiction treatment r24
    • Variations in content and intensity of intervention exist. Most interventions involve 1 to 3 sessions lasting 5- to 20-minutes to educate regarding safe consumption levels, set drinking goals, and provide strategies to lower intake r16
    • Clinical approach protocol is available on the National Institute on Alcohol Abuse and Alcoholism website r28
    • Intervention can be effective in reducing hazardous drinking and in encouraging patients with alcohol use disorder to engage in treatment r16
  • Several treatment options are available; no single approach has proven superior to another r2r29
    • Medically managed withdrawal and detoxification when indicated r2d1
    • Most treatment is currently delivered in specialty settings; however, treatment is increasingly available and effective from a primary care setting. Treatment via primary care generally requires coordination with behavioral/mental health services r2
    • Options for treatment settings include inpatient care, residential treatment, intensive outpatient programs, and outpatient care r2
      • Structured residential treatment in a therapeutic community or rehabilitation program may be required for patients with greater challenges (eg, more severe alcohol use disorder, little social support, unstable living conditions) and those who are unresponsive to outpatient treatment
    • Aftercare program is often a valuable adjunct to follow inpatient, residential, and intensive outpatient programs r2
  • Various treatment modalities are complementary; no single approach is universally successful or appeals to all patients
    • Ultimate treatment target of sustained abstinence from alcohol consumption is associated with best overall outcomes r16r28r30
    • Important overarching principle of treatment is to engage patient in 1 or more psychological and/or pharmacologic treatment approaches rather than advocate for a specific treatment r16
    • Most commonly recommended treatment is multimodal; ideal approach includes an individualized combination of psychiatric and/or psychosocial rehabilitation and pharmacotherapy r4
      • Common psychological and psychosocial treatment approaches include:
        • Mutual help groups
          • Used to address the psychosocial aspect of alcohol use disorder r24r28
        • Brief counseling sessions
          • Used to affect behavior: encourage abstinence, adherence to medication regimen, and participation in mutual help groups r26
        • Intensive psychological counseling
          • Used to address psychological aspects of alcohol use disorder; required particularly in those with co-occurring mental health disorders r28
        • Telehealth sessions, especially structured telephone-based care, can be a useful adjunct r24
      • Pharmacotherapy
        • Used to address the neurobiologic aspect of alcohol use disorder r28
        • Medications are usually recommended after successful cessation of alcohol use to improve ability to maintain abstinence and to enhance intensive psychological counseling r2
          • Best outcomes for patients prescribed medications occur in those who are able to abstain from consuming alcohol (even for a few days) before starting pharmacotherapy r28
        • Indications for pharmacotherapy
          • Consider for all patients with active alcohol use disorder r4r28
            • Patients with mild disease may benefit from pharmacotherapy, but data are limited r3
          • Patient who has discontinued drinking in the past few months but continues to experience intense cravings, lapses, or relapses r28
          • Patient who fails to respond to nonpharmacologic treatments approaches alone r28
          • Moderate to severe alcohol use disorder r31
            • For moderate to severe alcohol use disorder, benzodiazepines are recommended therapy for withdrawal symptoms and stabilization r24
              • If contraindicated, consider using carbamazepine, gabapentin, or valproic acid r24
            • Naltrexone or topiramate is first line therapy. Goal is to reduce consumption or achieve abstinence r24r32
            • Acamprosate can also be used r24
            • Disulfiram is for patients who prefer it or are intolerant of or unresponsive to the first line medications. Goal is to achieve abstinence
            • Gabapentin is for patients who prefer it or are intolerant of or unresponsive to other approved medications. Goal is to reduce consumption or achieve abstinence r33
        • Pharmacotherapy options
          • Approved medications include disulfiram, acamprosate, and naltrexone (oral and long-acting intramuscular injection) r2
            • Oral naltrexone and acamprosate appear similarly effective for lapse (return to any drinking) prevention and for reduction of drinking days when compared with placebo r16r30
            • Oral naltrexone appears effective for relapse (return to heavy drinking) prevention compared with placebo r30
            • Number needed to treat ranges from 9 to 20 for lapse and relapse prevention r16r30
          • Other medications with some proven efficacy include topiramate and gabapentin r2r24
            • Data supporting topiramate yield small to moderate effect size in promoting abstinence and reducing heavy drinking compared with placebo r4
            • Limited data indicate substantial effect size in promoting abstinence and reducing heavy drinking compared with placebo r4
        • Duration of pharmacotherapy
          • Optimal duration is not firmly established r4r28
          • 3 to 6 months minimum is recommended r3r28
          • Treatment continued for 1 year or more is often employed given that risk of relapse is highest in the first year of abstinence r26r28
          • Patients may require multiple episodes of pharmacotherapy or indefinite pharmacotherapy r3r26
        • Choice of medication
          • Data do not support 1 standardized approach to help guide initiation of 1 medication as opposed to another r28
            • The updated Veterans Affairs/Department of Defense guidelines recommend naltrexone and topiramate as first line agents followed by acamprosate, disulfiram, and gabapentin; tailor for each patient r24
            • Initial medication choice depends on individual treatment goals, presence or absence of comorbidity, medication adherence considerations, and other historical factors r4
            • Common considerations include:
              • Disulfiram may be helpful in a clinical scenario involving a highly motivated patient with goal of complete abstinence; however, presence of severe liver disease, myocardial disease, or psychosis may preclude its use r4r24
              • Naltrexone is not preferred/contraindicated for patients with chronic pain syndromes who may require opioids; however, in patients with concomitant opioid use disorder wishing to discontinue use of opioids, it could be used r4r24r26
              • Advanced liver disease may limit use of naltrexone r4
              • Advanced renal disease may limit use of acamprosate
              • Consider using topiramate for patients with preexisting seizure disorder and gabapentin for patients with preexisting neuropathy r4
          • Consider trial of alternate medication if patient does not respond to first choice of medication r28
          • No current data support increased efficacy of combination pharmacotherapy; however, data are limited r4r28
        • Comprehensive resource—Medication for the Treatment of Alcohol Use Disorder: A Brief Guide—is available from the Substance Abuse and Mental Health Services Administration r26
  • Most experts suggest administering a multivitamin containing thiamine, folic acid, and pyridoxine
  • Multiple treatment resources are listed in Appendix B of the Substance Abuse and Mental Health Services Administration publication, Medication for the Treatment of Alcohol Use Disorder: A Brief Guider26
  • Address comorbid psychiatric illnesses, substance use disorders, and behavioral disorders r34
  • Avoid using antidepressants to treat alcohol use disorder unless evidence exists of a co-occurring disorder for which an antidepressant is indicated (eg, anxiety disorder) r31
  • Avoid using benzodiazepines, except to treat alcohol withdrawal

Treatment of risky drinking behavior without alcohol use disorder

  • Preferred treatment approach is brief alcohol counseling intervention in the primary care setting with the goal of reducing harm by reducing alcohol consumption r2r35

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)r4
      • 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 r4r26
    • 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) r4
    • 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 every 4 weeks. Use is indicated in patients who are able to abstain from alcohol in an outpatient setting prior to treatment initiation. Patients should not be actively drinking alcohol at the time of initial naltrexone IM administration.
  • 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 kgr16) 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) r4
    • 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) r4
    • 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) r2r4
      • Avoid using other products with potential for significant alcohol absorption (eg, alcohol-based shaving creams, mouthwash, cough syrup) r4
    • 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 r4r28
    • First dose may be given after 12 hours of confirmed alcohol cessation r2r4r26
    • 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 r4
    • 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 r4
    • Initiate with gradual dose escalation over 4 weeks r4
    • 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 r4
    • Precaution: potential for drug misuse may be a concern given recent accounts of gabapentin overdose, addiction, and diversion r4
    • 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 r4r16
      • 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 r4
      • 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 websiter37 and local resources r2r37c216c217
        • SMART Recoveryr38 (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 Locatorr39 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
Procedures
c221

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 r3
  • 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

Monitoring

  • Follow-up monitoring and continued support are ongoing
    • Follow-up frequency is individualized
      • Office visits usually are scheduled weekly during initial phases of treatment then monthly when recovery process is more stabilized r40c237c238
    • Approach depends on patient's ability to meet and maintain drinking goals r28
      • Patient who is unable to meet and maintain drinking goals
        • Acknowledge that change can be difficult and support patient efforts to diminish consumption
        • Relate drinking to medical and psychosocial problems; in other words, suggest that the patient's medical and psychosocial problems are exacerbated or caused by, not solved by, alcohol use
        • Consider the following measures if they are not already in place
          • Refer to addiction medicine specialist for further recommendations and management c239
          • Recommend additional counseling (eg, add another form of counseling, increase frequency of mutual help group) c240
          • Engage family and/or significant other in treatment plan c241
          • Prescribe or change medication c242
        • Address coexisting medical and psychiatric disorders as needed
      • Patient who is meeting and maintaining drinking goals
        • Reinforce and support continued adherence to treatment plan c243c244
        • Coordinate care with addiction medicine specialist when applicable c245
        • Review medication plan c246
        • Treat coexisting nicotine dependence r44c247
        • Address coexisting medical and psychiatric disorders as needed
    • Standardized progress notes are available on the National Institute on Alcohol Abuse and Alcoholism website r45
    • Substance Abuse and Mental Health Services Administration has resources to help with monitoring health status and social functioning r26
    • Monitoring parameters depend on initial findings and patient progress, and may include: r26
      • Laboratory tests such as AST, γ-glutamyltransferase, carbohydrate-deficient transferrin, blood or breath alcohol, alcohol metabolites, and urine drug screens c248c249c250c251c252c253
      • Standardized questionnaires (eg, Alcohol Urge Questionnaire) r46c254
      • Prescription refill monitoring through pharmacy or state prescription monitoring program c255
      • Periodic reports from family members or other outside support (eg, mutual help group sponsor) with appropriate written consent
  • Specific medication-related monitoring
    • Naltrexone
      • Monitor clinically for adverse events such as nausea, hepatotoxicity (rare), and depression; injection site reactions may occur with intramuscular dosing r4c256c257
      • Some sources recommend periodically monitoring liver transaminase levels approximately every 6 months; discontinue drug if transaminase levels rise above 3 times baseline values r34r40c258
    • Acamprosate
      • Drug is well-tolerated; however, diarrhea is not uncommon r4
      • Monitor renal function in patients 65 years and older and in patients with decreased renal function (creatinine clearance rate less than 70 mL/minute/1.73 m²) r26c259
      • Clinically monitor for depression, suicidality, and ethanol withdrawal symptoms c260c261c262
    • Disulfiram
      • Monitor for idiosyncratic toxic hepatitis;r4 no rigorously standardized monitoring regimen is established
        • Substance Abuse and Mental Services Administration recommends baseline liver function tests with follow-up 10 to 14 days after starting drug, followed by continued periodic monitoring r26c263
      • Monitor clinically for other adverse events, including neuropathy and psychosis r4c264
      • Substance Abuse and Mental Health Services Administration suggests periodically monitoring CBC and serum chemistries r26c265c266
    • Topiramate
      • Monitor clinically for adverse events including paresthesias, taste disturbance, cognitive impairment, depression, weight loss, diarrhea, depression, suicidality, and visual disturbances r4c267
      • Many experts recommend periodic monitoring for metabolic acidosis by checking serum bicarbonate, electrolyte abnormalities, and ammonia levels to assess for hyperammonemia c268c269c270
      • Consider referring symptomatic patients and those at risk to an ophthalmologist to monitor for acute myopia and secondary angle closure glaucoma c271
    • Gabapentin
      • Monitor clinically for adverse events including cognitive impairment, fatigue, and ataxia r4c272

Complications and Prognosis

Complications

  • Death c273
    • Consequences related to unhealthy alcohol use are a leading cause of preventable death in the United States, behind tobacco smoking and obesity/overweight status r2
    • There is a 3- to 4-fold increased rate of premature death in patients with continued alcohol problems r1
    • Leading causes of premature death include trauma-related injury, alcoholic liver disease, heart disease and stroke, cancers, and gastroesophageal disease r16
      • Alcohol-impaired driving accounts for approximately one-third of all driving-related fatalities r4
  • Health problems associated with unhealthy alcohol use are many and include:
    • Cardiovascular problems: hypertension, ischemic heart disease, ischemic stroke, cardiomyopathy, atrial fibrillation r2c274c275c276c277c278
      • Alcohol-related hypertension is a leading cause of reversible hypertension r16c279
    • Endocrine problems: marked increase in triglycerides and LDL-C, reduced testosterone levels in males, menstrual irregularity in females, decreased bone density, diabetes r1r10r47c280c281c282c283c284c285
    • Malignancy: oropharyngeal, laryngeal, gastroesophageal, hepatic, colorectal, breast cancers r2r47c286c287c288c289c290c291
    • Gastrointestinal problems: fatty liver, liver dysfunction, cirrhosis, esophageal varices, pancreatitis, gastritis, esophagitis, ulcers r2c292c293c294c295c296c297c298c299d6
    • Mental health problems: depression, anxiety, suicide, psychosis, other substance use problems r2r9c300c301c302c303c304
    • Neurologic problems: cognitive defects, memory impairment, peripheral neuropathy, gait instability, tremor, coordination deficits, degenerative cerebellar changes, Wernicke-Korsakoff syndrome, alcohol-related seizures, dementia r2r10c305c306c307c308c309c310c311c312c313c314
    • Pregnancy related issues: fetal alcohol syndrome, fetal alcohol spectrum disorders, spontaneous abortion r2r10c315c316c317d7
    • Traumatic injury secondary to motor vehicle accidents, injuries, violence, increased risk of suicidal behavior and completed suicide r2r10c318c319c320
    • Bone marrow suppression: general bone marrow suppression, decreased erythropoiesis r7r10c321c322
    • Reproductive health: recurrent sexually transmitted disease, unplanned pregnancy r6c323c324
    • Sleep issues: insomnia, sleep apnea r6c325c326
    • Infectious disease: suppressed immune system function predisposing to infection (eg, chronic infectious disease, HIV, tuberculosis, pneumonia) r1r10r47c327c328c329c330
    • Nutritional disorders (eg, thiamine, folate deficiency) c331c332
  • Social problems associated with unhealthy alcohol use are many and may include:
    • Relationship problems: problems at home, at work, with friends c333
    • Employment, financial, and educational problems: failure to meet job or academic obligations, loss of job, dismissal from educational opportunities c334c335c336c337
    • Legal problems: operation of vehicles or machinery while intoxicated, charges related to violence (including intimate partner violence), incarceration c338c339
  • Withdrawal r48
    • Acute withdrawal phase d1
      • Usually manifests several hours after diminished alcohol consumption or abstinence and usually lasts up to a week
      • Characterized by central nervous system hyperexcitability with tremors, autonomic hyperactivity, and risk for seizures and delirium tremens c340c341c342
    • Early abstinence phase
      • May last up to 3 to 6 weeks
      • Characterized by depressed mood, anxiety, and sleep disturbances c343c344c345
    • Protracted abstinence syndrome (postacute withdrawal)
      • Some patients experience prolonged withdrawal manifestations (lasting more than 3 months) after acute withdrawal phase
      • Characterized by the following:
        • Sleep disturbances, hyperreactivity to stress and discomfort, altered emotional processing, depressed mood, and elevated anxiety c346c347c348c349c350
        • Seemingly insignificant challenges may provoke extreme anxiety and negative affect
        • Normally pleasurable events may result in attenuation or absence of expected positive responses during this period
      • Associated with increased risk of obsessions surrounding alcohol and relapse c351

Prognosis

  • Alcohol use disorder is undertreated in the United States
    • Fewer than one-third of patients receive any treatment r2
    • Fewer than 10% of patients receive a medication intended to prevent relapse or reduce alcohol consumption r2
  • Patients treated for alcohol use disorder
    • Alcohol use disorder is not an intractable condition r10
      • Typical patient with effectively treated disease experiences a promising prognosis
      • Minority of patients with severe disease experience years of alcohol-related problems
    • Various treatment approaches achieve 1- to 5-year successful sobriety rates between 15% and 35% r2
    • Patients with severe alcohol use disorder can rarely ever successfully return to controlled or moderate drinking r16
    • Better outcomes are associated with more intense treatment, less severe alcohol problems, less cognitive impairment, higher self-confidence regarding outcome, and fewer comorbid psychiatric disorders r1

Screening and Prevention

Screening

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.
            Questions0 points1 point2 points3 points4 points
            1. How often do you have a drink containing alcohol?NeverMonthly2-4 times a month2 or 3 times a week4 or more times a week
            2. How many drinks containing alcohol do you have on a typical day when you are drinking?1 or 23 or 45 or 67-910 or more
            3. How often do you have 5 or more drinks on 1 occasion?NeverLess than monthlyMonthlyWeeklyDaily or almost daily
        • Scores range from 0 to 12; higher scores indicate greater alcohol consumption r3
        • 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 disorderr54)
        • 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 r3
          • 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% r3
            • Cutoff threshold of 5 or more: sensitivity 70% to 92% and specificity 73% to 94% r3
        • 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.
          Questions0 points1 point2 points3 points4 points
          1. How often do you have a drink containing alcohol?NeverMonthly2-4 times a month2 or 3 times a week4 or more times a week
          2. How many drinks containing alcohol do you have on a typical day when you are drinking?1 or 23 or 45 or 67-910 or more
          3. How often do you have 5 or more drinks on 1 occasion?NeverLess than monthlyMonthlyWeeklyDaily 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?NeverLess than monthlyMonthlyWeeklyDaily or almost daily
          5. How often during the last year have you failed to do what was normally expected of you because of drinking?NeverLess than monthlyMonthlyWeeklyDaily 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?NeverLess than monthlyMonthlyWeeklyDaily or almost daily
          7. How often during the last year have you had a feeling of guilt or remorse after drinking?NeverLess than monthlyMonthlyWeeklyDaily 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?NeverLess than monthlyMonthlyWeeklyDaily or almost daily
          9. Have you or someone else been injured because of your drinking?NoYes, but not in the last yearYes, 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?NoYes, but not in the last yearYes, 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

Prevention

  • Educational programs are available for several target populations
    • Children and adolescents r60c360c361
      • School- and college-based interventions
      • Anticipatory guidance delivered in primary care setting
      • Community- and family-based interventions
    • Adults r60c362c363
      • Workplace and military interventions
    • All ages
      • Laws, taxes, and government regulations regarding (and legal consequences associated with) alcohol sale and consumption r61
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