Continuing Education Activity

Alcohol use disorder (AUD) remains a significant issue in the United States, affecting many individuals. Although the exact cause of AUD is not fully understood, several factors are believed to contribute to its development. These factors include the home environment, peer interactions, genetic predisposition, cognitive functioning, and the presence of certain personality disorders. This activity provides a comprehensive review of the evaluation and management of AUD, emphasizing the crucial role of the interprofessional team in recognizing and effectively managing this condition.

Objectives:

• Screen patients for alcohol use disorder using validated assessment tools (eg, AUDIT and CAGE questionnaire) to identify individuals at risk.
• Apply appropriate pharmacological and non-pharmacological treatments (eg, Alcoholics Anonymous or 12-Step programs) for individuals with alcohol use disorder.
• Collaborate with interdisciplinary teams of healthcare providers to develop comprehensive treatment plans and provide integrated care for individuals with alcohol use disorder.
• Coordinate and facilitate appropriate follow-up care, relapse prevention strategies, and ongoing support and counseling services for individuals with alcohol use disorder.

Introduction

Alcohol use disorder (AUD) is a prevalent psychiatric condition in the United States, characterized by problematic and unhealthy patterns of alcohol consumption. It is a well-recognized disorder that encompasses a broad spectrum of symptoms and behaviors associated with alcohol misuse. AUD affects a significant portion of the population, making it one of the most widespread psychiatric disorders in the country. The consequences of alcohol misuse extend beyond individual health, impacting various aspects of society, including social dynamics, economic factors, and public health.

Estimates of complications related to alcohol misuse vary; however, certain studies indicate that up to 40% of individuals have experienced adverse effects associated with alcohol misuse. According to the data obtained from the 2015 National Survey on Drug Use and Health, it was found that out of the surveyed population, approximately 138.3 million individuals aged 12 and older reported active alcohol use in the United States. Among this group, 48.2% of individuals admitted to having engaged in binge-drinking episodes within the 30 days preceding the survey. Among those who reported binge drinking, 26% of individuals acknowledged heavy alcohol use, defined as engaging in binge drinking for 5 or more days within the previous 30 days, accounting for 12.5% of the total alcohol users surveyed. These data indicate that 5.9% (or 15.7 million) of individuals in the United States aged 12 and older meet the criteria for AUD (refer to the image for the specific criteria). In addition, alcohol-related issues contribute to more than 85,000 deaths annually in the country.[1][2][3]

Furthermore, motor vehicle accidents, dementia, depression, homicide, and suicide have all been linked to AUD.

Diagnosis of AUD

According to the Diagnostic and Statistical Manual of Mental Disorders (DSM-5), AUD is classified based on the presence of 2 or more of the following criteria within 12 months:

• Alcohol is often taken in more significant amounts or consumed longer than intended.
• A persistent desire or unsuccessful efforts exist to reduce or control alcohol use.
• A significant amount of time is spent on activities necessary to obtain or use alcohol or recover from the effects of alcohol.
• Craving or a strong desire or urge to consume alcohol.
• Regular alcohol use leads to an inability to meet essential responsibilities at work, school, or home.
• Continued use of alcohol despite having persistent or recurrent social or interpersonal problems caused or exacerbated by the effects of alcohol.
• Significant reduction of important social, occupational, or recreational activities due to alcohol use.
• Recurrent alcohol use in situations in which it is physically hazardous.
• Continued use of alcohol despite knowing a persistent or recurrent physical or psychological issue is likely to have been caused or exacerbated by alcohol.
• Tolerance is characterized by either of the following:

  • The need for significantly increased amounts of alcohol to attain intoxication or the desired effect.
  • A substantial reduction in the desired effect even with continued use of the same amount of alcohol.
• Withdrawal, demonstrated by either of the following:

  • The presence of the typical withdrawal syndrome of alcohol.
  • Frequent consumption of alcohol (or a closely related substance, such as a benzodiazepine) to alleviate or prevent the onset of withdrawal symptoms.

Based on the number of criteria met, a patient can be classified as having a mild AUD (if they meet 2 or 3 criteria), moderate AUD (if they meet 4 or 5 criteria), or severe AUD (if they meet more than 6 criteria).

According to the 2015 National Survey on Drug Use and Health, 11.8% of survey respondents met the criteria for AUD. Among individuals with AUD, the severity of the disorder varied. Specifically, 67.4% had mild AUD, 18.8% had moderate AUD, and 13.8% had severe AUD.[4] Notably, patients with the most severe form of AUD often seek treatment more frequently and experience a chronic relapsing course.[5]

Etiology

Although the pathogenesis of AUD is not completely understood, multiple factors are believed to contribute to its development. These actors encompass environmental influences such as home environments, peer interactions, genetic elements, and cognitive functioning. AUDs also occur with psychiatric disorders such as schizophrenia, depression, and various personality disorders.[6][7][8][9] Co-occurrence of these psychiatric disorders and AUDs often leads to a worsened prognosis for both disorders.[7]

Evidence supports the influence of specific genes on an individual's susceptibility to developing AUDs. Variants of alcohol dehydrogenase (ADH1B) and aldehyde dehydrogenase (ALDH2) genes are considered to have a protective effect against the development of AUDs.[10][11] Certain genes identified as potential risk factors associated with increased susceptibility to developing AUDs include, but are not limited to, GABRG2 and GABRA2, COMT Val 158Met, DRD2 Taq1A, and KIAA0040.[12][13][14][15]  

Epidemiology

According to the 2016 National Survey on Drug Use and Health conducted by the Substance Abuse and Mental Health Administration, an estimated 43 million individuals in the United States aged 12 and older were reported to have a substance use disorder. Among them, 29 million individuals had an AUD, while 2.7 million had a disorder related to illicit drug use. These statistics establish alcohol as the most prevalent substance misused in the United States.

Among individuals diagnosed with both AUD and an illicit drug disorder, 1.8 million were adolescents (aged 12-17), 5.5 million were young adults (aged 18-25), and 16.8 million were adult individuals (aged 26 or older). Furthermore, out of those with a substance use disorder, 19.4 million individuals (aged 18 or older) also experienced a co-occurring mental illness.[16][17][18]

In general, AUDs tend to be more prevalent in individuals with lower levels of education and lower income.

On a global scale, AUDs impact a significant number of people, with an estimated 240 million individuals being affected worldwide, notably in regions such as Europe and the Americas.

Pathophysiology

Multiple theories have been proposed to explain the development of AUDs in individuals. Some evidence-supported theories include positive-effect regulation, negative-effect regulation, pharmacological vulnerability, and deviance proneness.

Positive-effect regulation theory suggests that certain individuals consume alcohol to seek positive rewards, such as to experience euphoria or pleasure. They may use alcohol to enhance positive emotions or social experiences.

Negative-effect regulation theory suggests that individuals may turn toward consuming alcohol to cope with negative emotions or distressing situations.[19] Alcohol consumption can be a self-medication strategy to alleviate symptoms of depression, anxiety, or feelings of worthlessness.

Pharmacological vulnerability theory emphasizes individual differences in how they respond to the acute and chronic effects of alcohol. Specific individuals may be more susceptible to the rewarding effects of alcohol or have a reduced capacity for efficient alcohol metabolism, thereby increasing their vulnerability to developing AUDs.

Deviance proneness theory proposes that individuals with a history of deviant behavior or inadequate socialization during childhood may be more prone to developing an AUD. In this theory, alcohol consumption can become a strategy for self-medication to alleviate symptoms of depression, anxiety, or feelings of worthlessness. 

In addition, an individual's gender can also influence the development of AUDs.[20] 

Toxicokinetics

The metabolism of alcohol (ethanol) primarily occurs in the liver by the enzyme cytosolic alcohol dehydrogenase (ADH). This enzymatic reaction involves the reduction of nicotinamide adenine dinucleotide (NAD+) and produces acetaldehyde as a byproduct.

Acetaldehyde is subsequently metabolized by the enzyme aldehyde dehydrogenase (ALDH), which oxidizes it to form acetate. Acetate then enters into various metabolic pathways. ADH is also present in the gastrointestinal tract, contributing to the initial metabolism of ethanol during its ingestion, also known as first-pass metabolism.[21][22] 

The cytochrome P450 system, particularly the enzyme CYP2E1, plays a role in alcohol metabolism, although to a lesser extent than ADH. In chronic alcohol users, this pathway is upregulated, leading to an increased rate of alcohol metabolism.[21][22][23]

The metabolism of alcohol is affected by various factors. Generally, females tend to eliminate alcohol consumption faster than males. However, females have a slower first-pass metabolism due to lower levels of ADH, resulting in higher initial blood alcohol concentration following alcohol consumption.[24] 

During pregnancy, the fetal liver metabolizes alcohol slower due to incomplete expression of enzymes CYP2E1 and ADH. As a result, the developing fetus is exposed to alcohol for a prolonged period, increasing the risks of fetal alcohol spectrum disorders.

In addition, there is evidence of a potential age-related decline in alcohol elimination.[22] Furthermore, certain studies propose that Native Americans may metabolize alcohol faster due to the expression of beta-3 Class 1 ADH isoforms than individuals who express only the beta-1 Class 1 ADH isoform.

Alcohol metabolism is generally slower in a fasting state, which is attributed to the decreased levels of ADH observed during fasting.[25] Conversely, consuming food can enhance liver blood flow, and the presence of sugars, such as fructose, allows a substrate for the regeneration of NAD+ from ADH. This conversion enables NAD+ to participate in the oxidation of alcohol.[25]

The time of day also impacts alcohol elimination from the body, with the highest rates of elimination observed late in the evening. Heavy drinking can affect the rate of alcohol elimination from the body, which is likely attributed to the increased expression of the CYP2E1 enzyme. However, this increase in alcohol elimination rate eventually slows down in individuals with advanced liver disease.[22]

Medications that function as ADH inhibitors can slow down the rate of alcohol elimination. H2 receptor blockers can also inhibit ADH, thereby reducing the first-pass metabolism in the stomach and potentially increasing blood alcohol levels.[22]

History and Physical

While gathering patient history, it has been observed that individuals with AUDs often report engaging in binge drinking episodes of consuming 4 or more drinks in a single session. To further assess the likelihood of AUDs in individuals, healthcare professionals may utilize screening tools such as the CAGE questionnaire. A score of 2 or greater on the CAGE questionnaire typically indicates the need for further evaluation and potential diagnosis of AUDs. The CAGE questionnaire comprises 4 questions as listed below:  

1. Have you ever felt the need to Cut down on your drinking?
2. Have you ever been Annoyed by people criticizing your drinking?
3. Have you ever felt Guilty about your alcohol consumption?
4. Have you ever felt the need for an Eye-opener to steady your nerves or get rid of a hangover?

Patients with AUDs may report additional symptoms, including frequent falls, blackout spells, instability, or visual impairment. They may also report experiencing seizures, tremors, confusion, emotional disorders, and a pattern of frequently changing jobs following a few days of abstinence from alcohol. Social challenges such as job loss, separation or divorce, estrangement from family, or homelessness may also arise. In addition, sleep disturbances are also frequently reported.

Patients may be asymptomatic or present with hypertension or insomnia in the early stages. In the later stages, as the condition progresses, patients may report additional symptoms such as nausea or vomiting, hematemesis, abdominal distension, epigastric pain, weight loss, jaundice, or other signs of liver dysfunction.

To screen for AUDs, the US Preventive Services Task Force recommends the following tools:

• The 10-Question AUDIT (AUDs Identification Test)
• The 3-Question AUDIT (AUDIT-C)
• Single-Question Screening Test

During an examination, patients with AUDs may display signs of cerebellar dysfunction, such as ataxia or difficulty with fine motor skills. They may also exhibit other physical manifestations, including slurred speech, tachycardia, memory impairment, nystagmus, disinhibited behavior, or hypotension. Tremors, confusion or changes in mental status, asterixis, ruddy palms, jaundice, ascites, and other indications of advanced liver disease may also be observed in patients with AUDs. Other signs of liver disease associated with AUD may include hepatomegaly or splenomegaly in the early stages and the presence of spider angiomata, the development of cirrhosis, and liver shrinkage in the advanced stage of liver disease. 

Complications arising from alcohol usage may manifest as bleeding disorders, anemia, gastritis, ulcers, or pancreatitis. Laboratory tests may indicate anemia, thrombocytopenia, coagulopathy, hyponatremia, hyperammonemia, or decreased vitamin B12 and folate levels as the advanced liver disease progresses.

Evaluation

Evaluation of patients with suspected AUDs should involve a comprehensive assessment of their alcohol consumption habits. It is essential to inquire about the frequency and quantity of alcohol consumed by the individual. Standardized screening tools, such as the CAGE questionnaire and the screening questions for AUD (see Image. DSM 5 Criteria for Alcohol Use Disorder.), can help identify problematic drinking patterns in individuals with AUDs. Furthermore, obtaining a detailed family history of AUDs and substance use disorders, as well as personal and family history of any psychiatric disorders, is essential for the evaluation process.

The evaluation should include screening for any medical or behavioral complications related to alcohol use. This comprehensive evaluation may involve assessing for potential issues such as macrocytic anemia, elevated liver enzymes, coagulation disorders, pancreatitis, frequent falls, occupational difficulties, relationship issues, and aberrant behaviors (such as risky sexual activity or impulsiveness).[26][27]

Alcohol biomarkers can assist in the evaluation process in patients with AUDs. Indirect biomarkers, including AST, ALT, GGT, mean corpuscular volume (MCV), and carbohydrate-deficient transferrin (CDT), can provide insights into the extent of alcohol-related organ damage. Direct biomarkers, such as alcohol and ethyl glucuronide levels, can help in the detection of recent alcohol consumption directly. Measuring CDT and phosphatidylethanol (PEth) can serve as a marker for long-term alcohol use or to monitor prolonged abstinence.[28][29]

Treatment / Management

Treatment approaches for substance use disorders, including AUDs, often involve a combination of nonpharmacological and pharmacological interventions. Nonpharmacological or psychologically based treatment methods include motivational interviewing, motivational enhancement therapy (MET), and cognitive behavioral therapy (CBT).

Motivational interviewing is a counseling approach that aims to assist individuals in recognizing and addressing their current problems and encourages them to make positive changes in their behavior. This approach is particularly effective for individuals who may feel ambivalent or uncertain about changing their behavior or quitting alcohol.

The primary objective of motivational interviewing is to enhance an individual's intrinsic motivation for change by addressing and resolving their ambivalence. Motivational interviewing is a therapeutic approach that aims to elicit and enhance an individual's intrinsic motivations or self-motivations for making positive changes in their lives.[30][31] A Cochrane review conducted on the topic concluded that motivational interviewing is a more effective approach compared to no treatment when it comes to reducing the severity of substance use.[32] 

MET is a manual-based intervention that incorporates the principles of motivational interviewing. It aims to strengthen the motivation and commitment of an individual to change their alcohol use behaviors. Through a personalized assessment, MET helps individuals to explore their alcohol use patterns. On the other hand, CBT is a therapeutic approach that emphasizes the connection between thoughts, behaviors, and emotions. CBT aims to assist patients in recognizing triggers and underlying factors that influence their behavior.[33][34]

In addition to MET and CBT, other therapies are available to treat patients with AUDs. One of the therapies includes 24-hour residential facilities, commonly known as "inpatient rehab," which provide comprehensive treatment for individuals with alcohol-related medical and psychiatric complications or comorbidities. Furthermore, there are various programs, such as Alcoholics Anonymous (AA) or 12-Step programs, that focus on group support and mentorship. These programs can be valuable sources of assistance for individuals in maintaining abstinence. AUD is a chronic condition; many individuals may experience lapses or setbacks during recovery. Therefore, the intensity and duration of therapy may vary based on individual needs and circumstances.[35][36]

Several pharmacological options can be combined with nonpharmacological approaches to enhance the treatment outcomes of AUDs. These medications include naltrexone, acamprosate, and disulfiram.[37] 

Naltrexone is a primarily mu-opioid receptor antagonist. It was initially approved by the US Food and Drug Administration (FDA) in 1994 as a pill that can be administered daily.[38] In 2006, an extended-release injectable formulation of naltrexone was also approved by FDA, which can be administered once every 30 days. Naltrexone works by reducing the effects of endogenous opioids on the reinforcement of drinking alcohol.[39] Numerous studies have demonstrated the effectiveness of naltrexone in reducing the frequency of drinking days and median drinking days and increasing the number of days of abstinence and continuous abstinence.[40][41][42] Caution should be taken when administering naltrexone to patients with a co-occurring opioid-use disorder, as improperly timed medication administration can result in significant opioid withdrawal.

Acamprosate is a medication approved by the FDA in 2004 to treat AUDs. It is derived from taurine and is believed to function as a glutamate agonist.[43]  Although the exact mechanism by which acamprosate works remains unclear, it is believed to involve the modulation of inhibitory and excitatory neurotransmitters in the brain, promoting a balanced state between them.[44] Based on a Cochrane review comprising 24 randomized clinical trials, it has been observed that acamprosate reduces the risk of relapse to drinking and enhances cumulative abstinence rates.[45] 

Disulfiram, approved by the FDA in 1951, functions by inhibiting ALDH, resulting in the accumulation of acetaldehyde in the body. When individuals consume alcohol while taking disulfiram, they experience a disulfiram reaction characterized by symptoms such as flushing, headache, shortness of breath, dizziness, and diaphoresis, among other symptoms. In severe cases, these reactions can lead to shock and subsequent death. The primary purpose of disulfiram is to create a fear of these adverse reactions, thereby motivating patients to abstain from alcohol.[46]

Other medications that have demonstrated efficacy in treating patients with AUDs, but have not yet received FDA approval, include gabapentin and topiramate. Gabapentin is typically prescribed as an anticonvulsant and for neuropathic pain management. It is believed to modulate central stress systems and correct dysregulation caused by alcohol use and cessation.[47] There is also evidence that suggests that gabapentin decreases alcohol cravings.[48] Topiramate, another anticonvulsant medication, has demonstrated mechanisms of action that make it effective for treating patients with AUDs. However, current literature indicates that topiramate is associated with a reduction in drinking days, an increase in abstinent days, and an overall decrease in alcohol cravings.[47][49]

According to the American Psychiatric Association practice guidelines:[50]

• Patients with suspected AUDs should undergo evaluation for other psychiatric illnesses and co-occurring substance use.
• Physiological biomarkers should be used as an adjunct to assess the severity of a patient's alcohol use.
• The treatment goals should be discussed and agreed upon between the patient and the healthcare provider.
• The potential risks to oneself and others from continued alcohol use should be openly discussed.
• Hospitalization is recommended for patients experiencing severe alcohol withdrawal symptoms. Admission should also be considered for those with no social support, major psychiatric disorders, and a history of relapse.
• Patients should receive a person-centered treatment plan that includes pharmacological and nonpharmacological treatments, eg, the AA program.
• Patients should be encouraged to remove all alcohol from their homes as a positive step toward supporting their recovery process.
• Naltrexone and acamprosate are first-line pharmacotherapy options for patients who prefer medication and have not responded to nonpharmacological methods.
• Disulfiram can be used for patients who have not responded to naltrexone or acamprosate.
• Second-line medications of choice include gabapentin and topiramate.

Differential Diagnosis

AUDs often occur concurrently with other conditions as individuals attempt to self-treat 1 or more of these conditions. Common disorders include:

• Posttraumatic stress disorder
• Bipolar disorder
• Panic disorder
• Anxiety disorder
• Dysthymic disorder
• Major depression
• Insomnia

Prognosis

AUD is a significant and potentially harmful condition. According to the World Health Organization (WHO), AUDs are responsible for at least 3 million deaths annually, with a higher prevalence in men than women. In addition to the risk of death, AUDs are associated with various adverse outcomes, including:

• Motor vehicle collisions
• Cirrhosis
• Esophageal, oral, liver, and breast cancers
• Homicide and suicide
• Hemorrhagic stroke

Identifying and treating AUDs early can help minimize the risks associated with this condition. Early intervention and timely treatment offer several advantages in mitigating the negative consequences and potential harm caused by AUDs.

Deterrence and Patient Education

Patient education and deterrence play essential roles in addressing AUDs.

• Individuals with alcohol use disorder often display poor dietary choices, which can result in deficiencies of essential nutrients such as folate. Therefore, addressing and educating patients about the importance of maintaining a healthy diet is crucial.
• While engaging with patients who consume alcohol, it is essential to have open discussions about the risks they pose to themselves and others, including their physical and mental health.
• Patients with AUDs often benefit from regular and frequent engagement to make progress and stay motivated in their treatment.
• Discussions about a patient's AUD should be approached in a non-confrontational and non-judgemental manner to enhance the therapeutic relationship.
• Encouraging a healthy diet comprising fruits and vegetables is essential for individuals with AUDs for their overall well-being.

Pearls and Other Issues

Here are some additional considerations related to AUDs:

• Complications arising from AUDs extend beyond physical health. They can significantly impact various aspects of a patient's life, including their socioeconomic status, mental health, interpersonal relationships, employment, and overall physical well-being.
• Early intervention in AUD is crucial for preventing further harm and promoting recovery. Regular and ongoing non-judgemental discussions between the patient and healthcare provider are vital.
• Acknowledging the patient's successes along their recovery journey and providing appropriate resources to support their continued efforts during each visit are essential for their well-being.
• Discussions should focus on identifying and addressing the barriers that may prevent individuals with AUDs from seeking cessation or assistance. By understanding these barriers, healthcare providers can collaborate with patients to explore new approaches that can improvise the likelihood of successfully overcoming the challenges associated with AUDs.

Enhancing Healthcare Team Outcomes

AUD is a highly prevalent condition in the United States. Unfortunately, many individuals with this disorder do not seek medical attention until they encounter health issues or become entangled in legal complications. The consequences of AUDs extend beyond mere addiction, profoundly impacting the lives of family members and friends and causing disruptions in interpersonal and professional relationships.

It is uncommon for individuals with AUDs to seek help on their own proactively. Most alcoholics never receive necessary medical attention due to a lack of screening by healthcare providers. However, considering the increasing prevalence of AUDs, a national agenda has been established to address this issue. As part of this agenda, all healthcare professionals must be vigilant in identifying individuals with AUDs and making appropriate referrals to ensure they receive the necessary support for their recovery.

Primary care physicians, nurse practitioners, and pharmacists are pivotal in educating patients and raising awareness about the detrimental effects of alcohol consumption. Within inpatient settings, it is essential to offer counseling services, especially to individuals who are identified as having AUDs. Considering many individuals with AUDs may also experience psychiatric issues, including a mental health nurse in their outpatient care is highly beneficial for comprehensive patient support. 

Clinicians should encourage patients to attend AA meetings and consider involving their family members in recovery. If AA attendance alone proves insufficient, clinicians may need to explore pharmacological therapies as an additional intervention to assist patients with AUDs. CBT should also be offered to patients with AUDs. To ensure comprehensive care, adopting an interprofessional team approach involving various healthcare professionals to support individuals with AUDs is necessary.  

AUDs have no therapeutic benefits and pose significant disruptions in families and relationships. By providing appropriate interventions, support, and education, clinicians can actively contribute to the well-being and recovery of individuals affected by AUDs.

Outcomes

The prognosis for many patients with AUDs is challenging, with less than 20% to 30% achieving abstinence. In addition, the organ damage caused by alcohol is irreversible, further emphasizing the urgency of addressing the issue. To mitigate the impact of alcohol, it is crucial to provide comprehensive education to the patient and their family members about the destructive consequences of alcohol use. Referring patients to AA programs is a recommended course of action, as AA provides a supportive community and a structured approach to recovery. However, it is worth noting that compliance with AA attendance is often low, and alternative interventions may be necessary to enhance treatment outcomes.[1][26] 

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Disclosure: Sara Nehring declares no relevant financial relationships with ineligible companies.

Disclosure: Richard Chen declares no relevant financial relationships with ineligible companies.

Disclosure: Andrew Freeman declares no relevant financial relationships with ineligible companies.