Alcohol Use Disorder

Etiology

Although the exact etiology of alcohol use disorder remains unknown, susceptibility to the disorder is likely multifactorial. According to twin and adoption studies, approximately 50% of the liability is genetic, with the remaining 50% attributed to environmental factors.[3] Neurobiological and epigenetic adaptations likely play a role in the development of AUD, but further research is needed.[4]

Epidemiology

Alcohol is the most commonly used substance in the United States, with 67.4% of those 18 and older reporting alcohol use in the past year, according to the 2022 National Survey on Drug Use and Health. In terms of risky drinking patterns, 23.5% of those 18 and older reported binge drinking in the past month, and 6.3% reported heavy alcohol use. The prevalence of AUD is estimated to be 29.5 million among those 12 and older as of 2022, and, as of 2019, AUD was the most commonly diagnosed substance use disorder, according to the Substance Abuse and Mental Health Administration.[SAMHA. Age Groups and Demographic Characteristics] 

Pathophysiology

Alcohol use disorder involves a loss of control over the ability to drink moderately. This loss of control results in negative consequences that impact relationships, physical and mental health, and the ability to fulfill role obligations. Alcohol is used in increasing amounts to achieve the same effect, a phenomenon known as tolerance, and its absence results in withdrawal symptoms. Patients with AUD experience intense cravings for alcohol that drive ongoing consumption.

Alcohol causes the release of dopamine in the ventral tegmental area, which is a part of the reward pathway. Alcohol also affects other reward systems, such as the endogenous opioid system, γ-aminobutyric acid (GABAergic) system, glutamate, and serotonin.[5] The reinforcing effects of alcohol include the ability to induce euphoria and anxiolysis. The fact that not every person who drinks alcohol will necessarily experience a loss of control and progression to addiction indicates that AUD is not solely driven by exposure to alcohol. As mentioned, genetic and environmental susceptibilities are not fully understood.

History and Physical

The United States Preventive Services Task Force recommends screening adults for unhealthy alcohol use in the primary care setting. This grade B recommendation can be accomplished using either the 1-item Single Alcohol Screening Question (SASQ) or the 3-item Alcohol Use Disorders Identification Test-Consumption. [USPSTF. Unhealthy Alcohol Use in Adolescents and Adults] Those who screen positive should be evaluated for AUD using the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DMS-V) criteria.

The diagnosis of AUD is established using the criteria in the DSM-V. Two or more criteria indicate mild AUD, 4 to 5 indicate moderate AUD and 6 or more criteria are consistent with severe AUD. These criteria, gleaned from the clinical history and collateral sources, generally assess the impact of alcohol on a patient’s relationships, health, activities (ie, employment), and the ability to moderate their drinking. The 2 criteria to make the diagnosis center around the patient experiencing withdrawal symptoms when not drinking alcohol and tolerance or requiring an increasing amount of alcohol to achieve the same effect.

While the diagnosis of AUD relies primarily on the history, labs may have utility in certain scenarios. The blood alcohol level can be used to evaluate for acute intoxication. To assess for alcohol use in the past 5 days, a serum ethyl glucuronide can be used. The carbohydrate deficient-transferrin can detect alcohol use from the past 2 weeks. The accuracy of the ethyl glucuronide and the CDT is limited by false positives.[1] The PeTH (phosphatidylethanol) can also be used to detect alcohol use from 3 weeks prior.[6]

Evaluation

Clinicians in the general medical setting should evaluate for sequelae of chronic alcohol use, which are many, given alcohol’s widespread effects on various organ systems. Alcohol causes and worsens many medical conditions, as discussed below.

Gastrointestinal system: Alcohol is well known for its hepatotoxicity, which is reversible with cessation up until the point of cirrhosis. Hepatotoxicity secondary to alcohol use can be detected on liver enzyme testing that may show an elevation in alanine aminotransferase and aspartate aminotransferase as well as gamma-glutamyl transferase. Alcohol can cause alcohol-related hepatitis (formerly alcoholic hepatitis) and present with jaundice, fever, ascites, and leukocytosis. Patients with alcohol-related cirrhosis may exhibit some or all of the classic stigmata, such as spider angiomas, palmar erythema, and ascites, to name a few. Like all patients with cirrhosis, those with alcohol-related cirrhosis should be screened for hepatocellular carcinoma and, if appropriate, esophageal varices. They should also be vaccinated against hepatitis A and B if non-immune.[6] In addition to liver disease, alcohol can cause both acute and chronic pancreatitis as well as exocrine insufficiency. Finally, alcohol contributes to the development of gastritis and acid reflux.

Hematologic system: Alcohol causes bone marrow suppression, which is reflected in the complete blood count as leukopenia, thrombocytopenia, and anemia. Thrombocythemia may also be driven by underlying liver disease. Macrocytosis with or without anemia may be seen due to deficiencies in B12 and folate.

Neuropsychiatric system: Chronic alcohol use leading to thiamine deficiency can result in Korsakoff syndrome marked by antero- and retrograde amnesia. Alcohol can also cause peripheral neuropathy of small fibers in a “stocking-glove” distribution. Gait abnormalities may be seen in the presence of thiamine deficiency that affects large fibers. Alcohol can worsen various psychiatric diseases, such as depression, and increase the risk of stroke and dementia.

Cardiovascular system: Acutely, alcohol can trigger atrial fibrillation. Chronic alcohol use can accelerate coronary artery disease and cause dilated cardiomyopathy.[1] Alcohol use and withdrawal worsen hypertension.

Oncologic system: The risk of certain cancers is increased by chronic alcohol use, including breast, esophageal, oral cavity, pharyngeal, liver, colorectal, gastric, and pancreatic.[7]

Endocrine system: Chronic alcohol use impairs bone health, leading to osteoporosis. Through a variety of mechanisms, alcohol can also lead to hypothyroidism.

Pulmonary system: Alcohol worsens sleep apnea physiology in those with obstructive sleep apnea but also increases the risk of sleep apnea.[8] The use is also associated with an increase in pulmonary infections such as pneumonia.

Immune system: Alcohol impairs the function of B and T cells, thereby increasing the risk of both bacterial and viral infection.[9]

Treatment / Management

The goal of AUD treatment is to reduce alcohol intake or have complete cessation; this includes pharmacotherapy with or without behavioral treatments. Three US Food and Drug Administration (FDA)-cleared medications for AUD are discussed below:

Naltrexone: Naltrexone is a mu-opioid receptor antagonist that can be taken daily by mouth or as a monthly intramuscular injection administered in the clinic setting. The medication works by inhibiting the pleasurable and reinforcing effects of alcohol that patients experience, such as decreased drinking days and/or drinking amounts. Naltrexone also decreases craving for alcohol and rates of returning to drinking after cessation.[10] Naltrexone is a first-line medication for AUD and should be considered, barring any contraindications such as concurrent use of opioid agonist medications for pain or opioid use disorder. Naltrexone should be used cautiously and in collaboration with the patient’s hepatologist if used in patients with decompensated cirrhosis.

Acamprosate: Acamprosate is another effective, first-line medication for alcohol use disorder. However, the 2 tablets 3 times a day dosing increases the pill burden and may be difficult for patients to take consistently.[11] The medication cannot be used in renal failure and requires dose reduction in renal insufficiency. Acamprosate’s mechanism of action is unknown but likely modulates the GABAergic system. Ideally, the medication is started after a patient is abstinent from alcohol.  

Disulfiram: The third FDA-approved medication for AUD, disulfiram, is an aversive therapy that causes an unpleasant reaction when alcohol is ingested. Mechanistically, the medication inhibits the enzyme acetaldehyde dehydrogenase, which causes an accumulation of acetaldehyde. Acetaldehyde causes the disulfiram reaction, including flushing, nausea, vomiting, tachycardia, palpitations, and diaphoresis. Because of the cardiac stress a disulfiram reaction induces, the medication should be avoided in those with significant cardiac disease. Treatment with disulfiram is best suited to those with a support person who can help administer or observe the patient taking the medication. After starting disulfiram, liver enzymes should be checked in the following weeks as it rarely can cause idiopathic hepatitis.[1] For this reason, disulfiram should also be avoided in patients with hepatic impairment. 

Additional medications for alcohol use disorder: Though not FDA-approved to treat AUD, medications such as gabapentin, topiramate, or baclofen may be used in the treatment of AUD. Generally, these medications have less robust evidence and outcomes supporting their efficacy in treating AUD. When using gabapentin to treat AUD, the optimal dosing for gabapentin is 600 mg 3 times daily.[12] Due to the adverse event profile, topiramate use for AUD is limited.[13](A1)

Behavioral treatment: Multiple behavioral treatment options exist for patients with AUD; however, they should not be pursued at the exclusion of pharmacotherapy. Behavioral treatment may occur in various settings, from inpatient rehabilitation to outpatient individual therapy. Various types of group options exist, including intensive outpatient treatment or self-help groups such as Alcoholics Anonymous or SMART Recovery. 

Differential Diagnosis

Various psychiatric conditions may present with unhealthy alcohol use; therefore, clinicians must screen for the following:

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

Prognosis

AUD is a chronic condition where the prognosis is variable. In some, the course follows a relapsing-remitting course, while others are abstinent without participating in formal treatment. Factors that increase the risk of relapse include psychiatric comorbidities and other substance use disorders.[14]

Complications

Alcohol use disorder can contribute to a host of complications as listed below:

• Accidental injuries (falls, car accidents, etc)
• Non-accidental injuries
• Malignancy (oropharyngeal, esophageal, gastric, breast, colorectal, hepatocellular, pancreatic)
• Periodontal disease
• Nutritional deficiencies
• Gastroesophageal reflux disorder
• Gastritis
• Mallory-Weiss tears
• Delayed gastric emptying
• Cirrhosis
• Acute and chronic pancreatitis
• Exocrine pancreatic insufficiency
• Upper gastrointestinal bleeds
• Stroke
• Coronary artery disease
• Atrial fibrillation
• Dilated cardiomyopathy
• Hypertension
• Immunosuppression
• Sleep apnea
• Aspiration
• Bacterial pneumonia
• Malabsorption
• Sexually transmitted infections
• Wernicke-Korsakoff syndrome
• Neuropathy
• Dementia
• Hypothyroidism
• Osteoporosis
• Megaloblastic and sideroblastic anemia
• Thrombocytopenia
• Acute alcohol-related hepatitis [9]