Alcohol Use Disorder (AUD)

Alcohol Use Disorder (AUD)

Alcohol Use Disorder (AUD)

Primer

Alcohol Use Disorder (AUD) is a substance use disorder characterized by repeated use of alcohol despite significant problems associated with its use.

Epidemiology

Alcohol use is a leading risk factor for premature death and disability worldwide. It remains the leading cause of mortality for people aged 15 to 49 years old worldwide.
- 3.8% of all deaths worldwide and 4.6% of disability-adjusted life-years are attributable to alcohol use.^[1]
In the United States, the prevalence of alcohol use disorder is estimated to be 12.4% for adult men and 4.9% for adult women.^[2]
- The prevalence is thought to be highest in individuals between 18 to 29 (16.2%), and is the lowest in individuals age 65 and older (1.5%).^[3]
- Males have higher rates of alcohol use related disorders than females.
- It is important to note that prevalence rates also vary greatly between different ethnicities and countries around the world, highlighting the important social-cultural aspects of alcohol use.
Most individuals who develop an alcohol use disorder do so by their late 30s.^[4]

Prognosis

In the elderly, cancers are the leading cause of alcohol-related death.
Alcohol also plays a significant role in the progression of cardiovascular diseases, cancer, diabetes, respiratory infections, unintentional, and intentional injuries (suicide).^[5]
Despite early reports suggesting the benefits of moderate wine drinking, there is no level of alcohol consumption that improves health.^[6]
Individuals severely intoxicated on alcohol are at higher suicide risk (both intentional and unintentional), as there can be an alcohol-induced depressive and/or bipolar disorder.^[7]^[8]
Alcohol use is estimated to account for up to 55% of fatal driving events.^[9]
Importantly, alcohol use disorder is not an intractable, nor an incurable condition. Most typical individuals with a disorder have a promising prognosis, and can recover. There is a minority of individuals with severe alcohol use disorder, who do have a very poor prognosis however.^[10]

Comorbidity

Long term, high doses of alcohol use affects every organ system, in particular the gastrointestinal tract, cardiovascular system, and the central/peripheral nervous systems.
- GI effects include cancer of the esophagus/stomach, gastritis, stomach/duodenal ulcers, liver
- Cardiac effects include hypertension, cardiomyopathy, increases in triglycerides and low-density lipoprotein cholesterol.
- Peripheral neuropathy can include muscular weakness, paresthesias, and decreased sensation
- Central nervous system impacts include the risk for alcohol-induced dementia, mild cognitive impairment, degenerative changes in the cerebellum, and severe memory impairment.
  - Wernicke-Korsakofff syndrome, is an alcohol-induced permanent amnestic disorder, due to vitamin B1 (thiamine) deficiency from excessive alcohol use.
Bipolar disorders, schizophrenia, antisocial personality disorder are all associated with a significant rate of alcohol use disorder.
Anxiety and depressive disorders are also associated with alcohol use disorder, but the role of temporary alcohol-induced depression and withdrawal symptoms can make the cause difficult to determine.^[11]
In antisocial personality disorder with comorbid alcohol use disorder, it is associated with increased criminal activity, including homicide.^[12]

Risk Factors

Cultural attitudes towards drinking, the availability of alcohol, and peer pressure are environmental risk factors for alcohol use disorder.^[13]
Alcohol use disorder is highly heritable, with around 50% of the variance of risk explained by genetic factors.
- Individuals with close relatives of alcohol use disorder have a 3 to 4 times higher risk of developing it themselves.
Individuals of Asian ethnicity, with the aldehyde dehydrogenase 2 (ALDH2) deficiency (“Asian flush/glow syndrome”) have lower risk for alcohol use disorder.
Individuals with schizophrenia or bipolar disorder, as well as high impulsivity are at higher risk for alcohol use disorder.^[14]

DSM-5 Diagnostic Criteria

Criterion A

A problematic pattern of alcohol use leading to clinically significant impairment or distress, as manifested by at least 2 of the following, occurring within a 12-month period:

Alcohol is often taken in larger amounts or over a longer period than was intended
There is a persistent desire or unsuccessful efforts to cut down or control alcohol use
A great deal of time is spent in activities necessary to obtain alcohol, use alcohol, or recover from its effects
Craving, or a 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 the effects of alcohol
Important social, occupational, or recreational activities are given up or reduced because of alcohol use
Recurrent alcohol use in situations in which it is physically hazardous
Alcohol use is continued 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:
- A. A need for markedly increased amounts of alcohol to achieve intoxication or desired effect, or
- B. A markedly diminished effect with continued use of the same amount of alcohol.
Withdrawal, as manifested by either of the following:
- A. The characteristic withdrawal syndrome for alcohol (refer to Criteria A and B of the criteria set for alcohol withdrawal), or
- B. Alcohol (or a closely related substance, such as a benzodiazepine) is taken to relieve or avoid withdrawal symptoms.

Mnemonic

The mnemonic WILD and ADDICCTeD can be used to remember the criteria for alcohol use disorder.

W - Work, school, home obligations failure
I - InterpersonaL or social consequences
D - Dangerous use

and

A - Activities given up or reduced
D - Dependence (tolerance)
D - Dependence (withdrawal)
I - Internal consequences (physical or psychological)
C - Can't cut down or control use
C - Cravings
T - Time-consuming use
e
D - Duration or amount is greater than intended

Specifiers

Remission Specifier

Specify if:

In early remission: After full criteria for alcohol use disorder were previously met, none of the criteria for alcohol use disorder have been met for at least 3 months but for less than 12 months (with the exception that Criterion A4, “Craving, or a strong desire or urge to use alcohol,” may be met).
In sustained remission: After full criteria for alcohol use disorder were previously met, none of the criteria for alcohol use disorder have been met at any time during a period of 12 months or longer (with the exception that Criterion A4, “Craving, or a strong desire or urge to use alcohol,” may be met).

Environment Specifier

In a controlled environment: This additional specifier is used if the individual is in an environment where access to alcohol is restricted.

Severity Specifier

Specify if:

Mild: Presence of 2 to 3 symptoms
Moderate: Presence of 4 to 5 symptoms
Severe: Presence of 6+ symptoms

Signs and Symptoms

See main article: Alcohol Intoxication

Alcohol use disorder is defined by a cluster of behavioural and physical symptoms, which can include withdrawal, tolerance, and craving.
- Withdrawal symptoms can begin 4 to 12 hours after the reduction of intake after a prolonged period of heavy alcohol ingestion.
- Some withdrawal symptoms such as insomnia can persist for months and contribute to relapse.^[15]
Depending on the severity of the use, individuals may use alcohol in physically hazardous circumstances (e.g. - driving a car or operating machinery while intoxicated).^[16]
Often times, intoxication can result in significant distress or even physical harm to others around the individual.

Alcohol Use History

Important questions to ask on alcohol use history include:

Frequency
- Age of first drink
- Age of first problematic drinking (“When did it start having an impact on your function?”)
- How often do you drink any alcohol? (“Every day? Once a month?”)
- Longest period of abstinence (“Longest period of time where you did not use alcohol?”)
- Time of last drink (to assess for the presence of withdrawal symptoms)
Triggers
- Location (e.g. - in a bar/parties/home?)
- Symptoms (depression/anxiety)
Quantity
- What do you usually drink? (wine? beer? spirits?)
- How much do you drink? (How much will you drink at a time?)
- How much do you usually spend on alcohol in a week?
- Binge drinking?
Treatment
- Medications
- Inpatient/outpatient treatment
Goals
- “What would you like to see happen with your drinking?” (e.g. - complete abstinence, harm reduction)

Type A vs. Type B Alcohol Use

Historically, different phenotypes of alcohol use can predict response to medications and treatment. Alcohol use has been classically divided into:^[17]

Type A alcoholism = later age of alcohol use disorder, less family history (i.e. - fewer first degree relatives with alcohol use disorder), less severe dependence, fewer co-morbid psychiatric disorder and symptoms, and less psychosocial impairment
Type B alcoholism = more severe alcohol use disorder, characterized by earlier age of onset, a strong family history, childhood conduct and behavioural problems, polysubstance abuse, more co-morbid psychiatric disorders (in particular anti-social personality disorder)

Type A alcoholism individuals typically respond better to sertraline, compared to Type B who have no improvement.^[18]

Standard Drink

See also: Rani, S., & Laupacis, A. (2023). “Less is better” is the best message when talking to patients about alcohol. CMAJ, 195(36).

Quantifying alcohol use can be hard, given the wide range of alcoholic beverages, shapes, and sizes.
A standard drink (SD) is a unit that is used to quantify alcohol intake in a systematic way (however, a standard drink varies from country to country).
- In Canada, a standard drink is any drink that contains 13.6 grams of pure alcohol, or 0.6 ounces of 100% alcohol.
Different alcoholic beverages have different concentrations of alcohol:
- Most beers contain 5% alcohol
- Most wines contain 12 to 13% alcohol
- Spirits can contain 40% alcohol or more
In addition, different shapes and sizes of containers will contain different volume of alcoholic drinks (see figure 1).
In Canada, along with recent WHO recommendations, indicate that there is no “safe” level of alcohol consumption, with health risks starting at as low as 3 standard drinks per week (for both female and male sex).^[19]
- This is significantly lower than previous Canadian guidelines that recommended no more than 10 drinks a week for females and 15 drinks for males.

Fig. 1

Screening and Rating Scales

Alcohol Use Disorder Screening and Rating Scales

Name	Rater	Description	Download
CAGE	Patient	The CAGE Questionnaire is an acronym formed from the 4 questions on the questionnaire (Cutting down, Annoyed, Guilty, Eye opener). The CAGE is a simple screening questionnaire for alcohol use disorder. Two “yes” is a positive screen for males; one “yes” is a positive for females.	Download
AUDIT	Patient	The Alcohol Use Disorders Identification Test (AUDIT) is a 10-item self-report questionnaire. It asks questions about past-year quantity and frequency of drinking, consequences of drinking (e.g., blackouts), and questions similar to the CAGE. It may be more accurate than the CAGE in identifying alcohol use disorders. Also, unlike the CAGE, it can help distinguish alcohol dependence from hazardous or at-risk drinking.	Download

Pathophysiology

See main article: Introduction to Addiction Medicine: Conceptualizing Addiction

Like with all substance use disorders, there is a complex interplay between biological, social, psychological, and cultural factors.

Differential Diagnosis

Non-pathological use of alcohol.
- The key criteria for alcohol use disorder is the use of heavy amounts of alcohol with repeated and significant distress or impaired functioning. While most alcohol users sometimes consume enough alcohol to feel intoxicated, only a minority (<20%) ever develop alcohol use disorder. Therefore, daily drinking in low doses and intoxication alone does not make the diagnosis for alcohol use disorder.
Sedative, hypnotic, or anxiolytic use disorder
- The signs and symptoms of alcohol use disorder can be similar to those seen in a sedative, hypnotic, or anxiolytic use disorder.
Conduct disorder in childhood and adult antisocial personality disorder
- Alcohol use disorder (and other substance use disorders) is present in the majority of individuals with antisocial personality and conduct disorder.

Investigations

Serum γ-glutamyltransferase (GGT) is a sensitive indicator of recent alcohol use (>35 units)
- At least 70% of individuals with a high GGT level are chronic heavy drinkers (i.e. - 8 or more drinks daily on a regular basis).^[20]
Carbohydrate-deficient transferrin (CDT) (>20 units or higher) is also a high sensitivity and specificity test.^[21]
Both GGT and CDT levels typically return back to normal within days to weeks of stopping drinking, which make the markers a useful method for monitoring abstinence
Elevated ALT (x2 upper limit of normal can also indicate alcohol related liver injury)
MCV may also be elevated in heavy drinkers and is an indication of the direct toxic effects of alcohol on erythropoiesis.^[22]
Other non-specific changes include elevated triglycerides, elevated high-density lipoprotein cholesterol), and high-normal levels of uric acid.^[23]

Neuroimaging

Although nonspecific, the combination of frontal and superior vermian atrophy may be found in alcohol disorder.^[24]

Physical Exam

Individuals may have tremors, difficulty with gait
Exam for stigmata of liver disease including hepatomegaly, spider angiomas
Esophageal varices and hemorrhoids may be present
Examine for asterixis if concerned about hepatic encephalopathy
Males with chronic alcohol use disorder may have decreased testicular size due to the feminizing effects associated with reduced testosterone levels.^[25]

Treatment

Pharmacotherapy

There is the most evidence for naltrexone and acamprosate
- disulfram is one of three Health Canada-approved medications for treatment of AUD in adults but is not commercially available in Canada and must be compounded by specialty pharmacies, based on the review of available evidence, it is not recommended over other available pharmacotherapies for AUD, but may be used in the cases of patient preference.
- Topiramate and gabapentin are suggested as second-line medications for patients with moderate to severe alcohol use disorder, but typically only after trying naltrexone and acamprosate first.
Naltrexone is recommended for patients who have a treatment goal of either abstinence or reducing alcohol consumption.^[26]
Acamprosate is recommended for patients who have a treatment goal of complete abstinence.^[27]

Alcohol Use Disorder Treatment (First Line)

Name	Mechanism	Dose	Adverse Events, Side Effects	Contraindications	Notes
Naltrexone	• Blocks mu opioid receptor and reduces the euphoria of EtOH	• 25mg PO daily x 3 days, then increase to 50mg PO daily (recommended daily dose) • Can titrate up to 150mg PO daily • No need to abstain before starting	• Nausea, headache, dizziness, GI side effects • Can cause reversible elevations in AST/ALT, order first at baseline, and check again in 1 month's time. Stop if more than 3x LFT elevation.	• Current prescribed/non-medical opioid use (due to it competitively displacing opioid medications from their binding sites and precipitating withdrawal), hepatitis, liver failure, naltrexone hypersensitivity	Particularly effective for those who report a high euphoria immediately after drinking. Naltrexone has a NNT of about 12 to prevent heavy drinking.
Acamprosate (“Campral”)	• Glutamate antagonist, mimics GABA • Not entirely understood • Restores normal balance of neuronal excitation?	• 666mg TID • 333mg TID if renal impairment • No need to abstain before starting	• Diarrhea, vomiting, abdominal pain, anxiety	• Severe renal impairment (if GFR < 30)^[28] • Breastfeeding	Can be an expensive medication

Alcohol Use Disorder Treatment (Second Line)

Name	Mechanism	Dose	Adverse Events, Side Effects	Contraindications	Notes
Gabapentin	• GABA agonist	• Initial dosing varies, can start between 100-300 mg TID • Optimal dose is 600 mg TID (max 1800 mg daily)^[29] • Safe to start while using alcohol, but may be more effective if patients are abstinent for ≥ 3 days	• Low side-effect profile and very well tolerated • Mild headache, fatigue	• Gabapentin hypersensitivity	Gabapentin decreases heavy drinking days with a medium effect size, but difference with placebo on more important aggregate measures of abstinence and consumption outcomes.^[30]
Topiramate	• Alters GABA receptors	• Start: 50mg PO daily • Titrate to: 50mg PO BID; max 300mg daily	• Dizziness, numbness in hands/feet • Drowsiness, fatigue, psychomotor slowing, difficulty concentrating, speech or language problems • Somnolence, anxiety, mood disturbances • Starting at low dose and titrating up can reduce adverse effects	• Topiramate hypersensitivity • Pregnant or planning pregnancy • Narrow-angle glaucoma • Nephrolithiasis • Caution in concomitant use of valproic acid	Like most anticonvulsants, there is an associated risk of birth defects. Taking topiramate in the 1st trimester of pregnancy may increase risk of cleft lip/cleft palate in the infant.

Alcohol Use Disorder Treatment (Other)

Name	Mechanism	Dose	Adverse Events, Side Effects	Contraindications	Notes
Disulfram (“Antabuse”)	• Inhibits aldehyde dehydrogenase to cause an extremely unpleasant physiological reaction if alcohol is consumed (i.e., an alcohol-disulfiram reaction) • Increases serum acetaldehyde causing toxic symptoms - nausea, tachycardia	• 125mg PO daily, increase to 250mg daily if reports no reaction to NNT = 9	• With EtOH: vomiting, flushed face, headache • Without EtOH: headache, anxiety, garlic-taste, acne, peripheral neuropathy, depressive symptoms • Can cause severe hypotension and arrhythmias • To avoid a severe reaction, wait at least 24-48 hours between the last drink and the first drink • May trigger psychosis at high doses	• Liver cirrhosis • Pregnancy • Unstable cardiovascular disease	Relatively poor evidence for efficacy. The alcohol-disulfiram reaction can potentially be fatal, patients must never be administered disulfiram without full consent and knowledge of its effects.
Baclofen	GABA agonist	• Initial dose 5mg TID, increase to 10mg TID • Maximum daily dose 80mg	• Drowsiness, dizziness, weakness, fatigue, headache, insomnia, paraesthesias, vertigo, nausea and vomiting, urinary retention, or constipation.	• Baclofen hypersensitivity	Hallucinations and seizures have occurred on abrupt withdrawal of baclofen. Therefore, except for serious adverse reactions, the dose should be reduced slowly when the drug is discontinued.

Thiamine

See main article: Wernicke Encephalopathy and Korsakoff Syndrome

Thiamine 100mg TID should be prescribed as ongoing supplementary therapy in alcohol use disorder patients identified as at risk for thiamine deficiency. ^[31]

Psychotherapy

Various psychosocial interventions can be highly effective for alcohol use disorder including:

Cognitive behavioural therapy with a relapse prevention focus
Community reinforcement approach (CRA)
Motivational interviewing (MI) is a key approach towards addressing ambivalence and making changes in substance use.
Peer support groups (e.g. - Alcoholics Anonymous)

Guidelines

Alcohol Use Disorder Guidelines

Guideline	Location	Year	PDF	Website
Canadian Guideline for the Clinical Management of High-Risk Drinking and Alcohol Use Disorder	Canada	2023	Link (see also: comment on sertraline use in AUD)	Link
Canadian Guidelines on Alcohol Use Disorder Among Older Adults	Canada	2020	-	Link
British Columbia Centre on Substance Use (BCCSU)	Canada	2019	Link	Link
National Institute for Health and Care Excellence (NICE)	UK	2011	-	Link
American Psychiatric Association (APA)	USA	2018	-	Link
European Federation of Neurological Societies (EFNS) - Wernicke Encephalopathy	Europe	2010	-	Link

Resources

For Patients

For Providers

Swift, R. M., & Aston, E. R. (2015). Pharmacotherapy for alcohol use disorder: current and emerging therapies. Harvard review of psychiatry, 23(2), 122.

Articles

Research

¹⁾ American Psychiatric Association. (2013). Diagnostic and Statistical Manual of Mental Disorders (5th ed.). Arlington, VA.

²⁾ American Psychiatric Association. (2013). Diagnostic and Statistical Manual of Mental Disorders (5th ed.). Arlington, VA.

³⁾ American Psychiatric Association. (2013). Diagnostic and Statistical Manual of Mental Disorders (5th ed.). Arlington, VA.

⁴⁾ American Psychiatric Association. (2013). Diagnostic and Statistical Manual of Mental Disorders (5th ed.). Arlington, VA.

⁵⁾ GBD 2016 Alcohol Collaborators. Alcohol use and burden for 195 countries and territories, 1990–2016: a systematic analysis for the Global Burden of Disease Study 2016. The Lancet, 2018; DOI: 10.1016/S0140-6736(18)31310-2

⁶⁾ Burton, R., & Sheron, N. (2018). No level of alcohol consumption improves health. The Lancet, 392(10152), 987-988.

⁷⁾ American Psychiatric Association. (2013). Diagnostic and Statistical Manual of Mental Disorders (5th ed.). Arlington, VA.

⁸⁾ GBD 2016 Alcohol Collaborators. Alcohol use and burden for 195 countries and territories, 1990–2016: a systematic analysis for the Global Burden of Disease Study 2016. The Lancet, 2018; DOI: 10.1016/S0140-6736(18)31310-2

⁹⁾ American Psychiatric Association. (2013). Diagnostic and Statistical Manual of Mental Disorders (5th ed.). Arlington, VA.

¹⁰⁾ American Psychiatric Association. (2013). Diagnostic and Statistical Manual of Mental Disorders (5th ed.). Arlington, VA.

¹¹⁾ American Psychiatric Association. (2013). Diagnostic and Statistical Manual of Mental Disorders (5th ed.). Arlington, VA.

¹²⁾ American Psychiatric Association. (2013). Diagnostic and Statistical Manual of Mental Disorders (5th ed.). Arlington, VA.

¹³⁾ American Psychiatric Association. (2013). Diagnostic and Statistical Manual of Mental Disorders (5th ed.). Arlington, VA.

¹⁴⁾ American Psychiatric Association. (2013). Diagnostic and Statistical Manual of Mental Disorders (5th ed.). Arlington, VA.

¹⁵⁾ American Psychiatric Association. (2013). Diagnostic and Statistical Manual of Mental Disorders (5th ed.). Arlington, VA.

¹⁶⁾ American Psychiatric Association. (2013). Diagnostic and Statistical Manual of Mental Disorders (5th ed.). Arlington, VA.

¹⁷⁾ Babor, T. F., Hofmann, M., DelBoca, F. K., Hesselbrock, V., Meyer, R. E., Dolinsky, Z. S., & Rounsaville, B. (1992). Types of alcoholics, I. Evidence for an empirically derived typology based on indicators of vulnerability and severity. Archives of general psychiatry, 49(8), 599–608.

¹⁸⁾ Dundon, W., Lynch, K. G., Pettinati, H. M., & Lipkin, C. (2004). Treatment outcomes in type A and B alcohol dependence 6 months after serotonergic pharmacotherapy. Alcoholism, clinical and experimental research, 28(7), 1065–1073.

¹⁹⁾ Rani, S., & Laupacis, A. (2023). “Less is better” is the best message when talking to patients about alcohol. CMAJ, 195(36), E1232-E1233.

²⁰⁾ American Psychiatric Association. (2013). Diagnostic and Statistical Manual of Mental Disorders (5th ed.). Arlington, VA.

²¹⁾ American Psychiatric Association. (2013). Diagnostic and Statistical Manual of Mental Disorders (5th ed.). Arlington, VA.

²²⁾ American Psychiatric Association. (2013). Diagnostic and Statistical Manual of Mental Disorders (5th ed.). Arlington, VA.

²³⁾ American Psychiatric Association. (2013). Diagnostic and Statistical Manual of Mental Disorders (5th ed.). Arlington, VA.

²⁴⁾ Shanmugarajah, P. D., Hoggard, N., Currie, S., Aeschlimann, D. P., Aeschlimann, P. C., Gleeson, D. C., Karajeh, M., Woodroofe, N., Grünewald, R. A., & Hadjivassiliou, M. (2016). Alcohol-related cerebellar degeneration: not all down to toxicity?. Cerebellum & ataxias, 3, 17. https://doi.org/10.1186/s40673-016-0055-1

²⁵⁾ American Psychiatric Association. (2013). Diagnostic and Statistical Manual of Mental Disorders (5th ed.). Arlington, VA.

²⁶⁾ British Columbia Centre on Substance Use (BCCSU), B.C. Ministry of Health and B.C. Ministry of Mental Health and Addictions. Provincial Guideline for the Clinical Management of High-Risk Drinking and Alcohol Use Disorder. 2019. Vancouver, B.C.: BCCSU.

²⁷⁾ British Columbia Centre on Substance Use (BCCSU), B.C. Ministry of Health and B.C. Ministry of Mental Health and Addictions. Provincial Guideline for the Clinical Management of High-Risk Drinking and Alcohol Use Disorder. 2019. Vancouver, B.C.: BCCSU.

²⁸⁾ Incorporating Alcohol Pharmacotherapies Into Medical Practice.

²⁹⁾ Mason, B. J., Quello, S., Goodell, V., Shadan, F., Kyle, M., & Begovic, A. (2014). Gabapentin treatment for alcohol dependence: a randomized clinical trial. JAMA internal medicine, 174(1), 70-77.

³⁰⁾ McPheeters, M., O’Connor, E. A., Riley, S., Kennedy, S. M., Voisin, C., Kuznacic, K., ... & Jonas, D. E. (2023). Pharmacotherapy for Alcohol Use Disorder: A Systematic Review and Meta-Analysis. JAMA, 330(17), 1653-1665.

³¹⁾ RebelEM:Should You Prescribe Oral Thiamine for Chronic Alcoholics?

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