Alcohol Use Disorder

CSAM Review Course in Addiction MedicineSeptember 1, 2021

Triveni DeFries, MD MPHDepartment of Internal Medicine

San Francisco General HospitalUniversity of California, San Francisco

Substance Use Warmline, National Clinician Consultation Center

CONFLICT OF INTEREST DISCLOSURE

I, Triveni DeFries, have nothing to disclose, and I will be discussing “off label” use of drugs in this presentation.

1. Describe the rising burden of alcohol-related harm in the United States and the corresponding treatment gap facing patients with alcohol use disorder (AUD)

2. Assess alcohol use with screening and diagnostic tools

3. Select medications for alcohol use disorder to match patient goals and co-morbidities

4. Describe outpatient withdrawal management considerations raised in response to an evolving care delivery landscape during Covid-19

5. Integrate harm reduction strategies into practice

EDUCATIONAL OBJECTIVES

Part I. Alcohol use in public health

Part II. How alcohol works: Pharmacology & Effects

Part III. Detecting unhealthy alcohol use

Part IV. Treatment of alcohol use disorder (AUD) and alcohol withdrawal

Part V. Implementing harm reduction

ROADMAP

Part I. Unhealthy alcohol use in public health

Question # 1

Recent studies of the US population show large increases in alcohol-induced mortality among both men and women.

a. Trueb. False

Unhealthy alcohol use

■ 93,000 deaths (255 per day) and 2.7 million years of potential life lost (29 years lost per death, on average) in the United States each year to excessive alcohol use

■ 1 in 10 deaths in US, exceeding deaths from opioid overdoses

■ Prevalence and harms are on the rise, especially among women, older adults, racial/ethnic minorities

Esser et al, MMWR, 2020

"Reflecting on the consequences of alcohol-

related morbidity and mortality through the age range, our

findings document an urgent public health crisis calling for

concerted public health action.”

Spillane et al, 2020

Alcohol-related deaths accelerating

■ Death certificates 1999-2017 showed that alcohol related deaths doubled from 35,914 to 72,558, and the rate increased 50.9% from 16.9 to 25.5 per 100,000

■ Nearly half of alcohol-related deaths resulted from liver disease (30.7%; 22,245) or overdoses on alcohol alone or with other drugs (17.9%; 12,954).

■ Rates of alcohol-related deaths were highest among males, 45-74 year olds, and AI/AN

■ Largest annual increase among NH White females

White et al, Alcohol Clin Exp Res. 2020.

Spillane et al., 2020

Noteworthy increases in deaths among women, American Indian/Alaskan Native individuals, and liver failure amongst younger age groups

And during the COVID-19 pandemic…

Barbosa C, Cowell AJ, Dowd WN. Alcohol Consumption in Response to the COVID-19 Pandemic in the United States. J Addict Med. 2020 Oct 23;15(4):341–4.

• More drinks per day after stay-at-home orders

• Exceeding recommended limits

• Larger differences for women and Black, non-Hispanic people

Pollard et al. JAMA Network Open. 2020.

Increased alcohol use during Covid-19

■ Survey of 6000 adults compared drinking and adverse consequences of alcohol use Apr-June 2019 vs May-June 2020

■ On average, alcohol was consumed 1 day more per month by 3 of 4 adults

■ For women, increase in heavy drinking 41% over baseline

■ Increased alcohol-related problems independent of consumption level for nearly 1 in 10 women

Question #1

Recent studies of the US population show large increases in alcohol-induced mortality among both men and women.

a. Trueb. False

Alcohol use and its harms are on the rise overall, though several studies find a noteworthy increase amongst women.

Part II. How Alcohol Works

Neuropharmacological Effects

Reproduced from Anton, 2008

Anton et al. Chapter 30 - Pharmacologic treatment of alcoholism, Handbook of Clinical Neurology, 2014.

Neuropharmacological Effects

Werner, 2007; De Witte, 2004.

PHARMACOKINETICS OF ALCOHOL

Absorption: From the stomach, small intestine and colon. Rate depends on gastric emptying time and can be delayed by presence of food.

Distribution: Once in the bloodstream, alcohol is distributed to all tissues including the fetus. Body weight and sex affect blood levels of alcohol. Women have less gastric metabolism of alcohol

Metabolism: alcohol is broken down by ADH (converts alcohol to acetaldehyde) and CYP2E1 via zero order kinetics

PHARMACOKINETICS OF ALCOHOL

Zero order kinetics: Alcohol levels decrease by a fixed amount over time - 0.015 BAL/hour (g/100mg/hour) or 1 oz every 3 hours

Widespread physical and psychosocial effects

• Primary care issues • Hypertension• Diabetes• Depression• Osteoporosis• GERD

• Cancer• Early pregnancy loss• Trauma• Falls• Motor vehicle accidents• Risky sex• IPV• HIV Outcomes• Poor nutrition• Firearm violence• Medication interactions• Suicide• Adverse childhood events

Ng Fat et al, 2020; Sterling et al, 2020, US Burden of Disease Collaborators, 2013

Alcohol-related liver disease

Rehm et al, 2021 Mellinger et al, 2018

Top causes of liver transplantation

Effects of alcohol on organ systems:

Effects of alcohol on organ systems: Fetal Alcohol Spectrum Disorders

■ Fetal Alcohol Syndrome: CNS, minor facial features, growth impacts

■ Alcohol Related Neurodevelopmental Disorder: Behavioral and Learning issues

■ Alcohol-Related Birth Defects: Heart, Kidneys, Bones, Hearing

■ Neurobehavioral Disorder Associated with Prenatal Alcohol Exposure

pubs.niaaa.nih.gov

Part III. Assessing Unhealthy Alcohol Use

Unhealthy Alcohol Use

■ Nearly 86% of US population reported using alcohol at least once in lifetime

NSDUH, 2019

Spectrum of Unhealthy Alcohol Use

Principles of Addiction Medicine, 6th Edition.

Unhealthy alcohol use goes undetected

■ 1 in 6 patients reports being asked about drinking

■ USPSTF recommends screenings in primary care settings in adults, and providing persons engaged in risk or hazardous drinking with brief behavioral counseling interventions (B recommendation)

Bazzi & Saitz, 2018; US Preventive Task Force, 2018; Edelman & Tetrault, 2019

Single question screener

82% sensitive, 79% specific

■ “Do you sometimes drink beer, wine or other alcoholic beverages?”

■ “How many times in the past year have you had 5 (for men) or 4 (for women or > 65yo) or more drinks in a day?”

Smith et al, 2009

AUDIT-C

Unhealthy alcohol use

At-risk drinking

Alcohol use disorder

*Note no safer use limits in pregnancy

SAMHSA, 2014

STANDARD DRINK

DSM-5: 2+ symptoms over 12 months indicate alcohol use disorder

In the past year, have you…? Interpretation Domain

Had times when you ended up drinking more, or longer than you intended? Control: exceeded own limits Impaired control

More than once wanted to cut down or stop drinking, or tried to, but couldn’t? Unable to cut back Impaired control

Spent a lot of time drinking? Or being sick or getting over the aftereffects? Compulsion Impaired control

Experienced craving — a strong need, or urge, to drink? Craving Impaired control

Found that drinking — or being sick from drinking — often interfered with taking care of your home or family? Or caused job troubles? Or school problems? Role failure Social impairment

Continued to drink even though it was causing trouble with your family or friends? Consequences: relationship trouble Social impairment

Given up or cut back on activities that were important or interesting to you, or gave you pleasure, in order to drink?

Gave up meaningful activities Social impairment

More than once gotten into situations while or after drinking that increased your chances of getting hurt (such as driving, swimming, using machinery, walking in a dangerous area, or having unsafe sex)?

Risk of bodily harm Risky use

Continued to drink even though it was making you feel depressed or anxious or adding to another health problem? Or after having had a memory blackout?

Physical/psychological consequences Risky use

Had to drink much more than you once did to get the effect you want? Or found that your usual number of drinks had much less effect than before? Tolerance Physiological criteria

Found that when the effects of alcohol were wearing off, you had withdrawal symptoms, such as trouble sleeping, shakiness, restlessness, nausea, sweating, a racing heart, or a seizure? Or sensed things that were not there?

Withdrawal Physiological criteria

Mild: 2-3Moderate: 4-5Severe: ≥6

Part IV. Treatment of Alcohol Use Disorder & Alcohol Withdrawal

Case: 40 Y patient with severe AUD seen at clinic

Which medication do you recommend?

A) acamprosateB) disulfiramC) baclofenD) naltrexone

■ They have cut back from 6-8 beers daily to 4/day

■ Severe cravings whenever they try to quit, not confident they can stop. Goal to cut back.

■ PMH: HTN, depression, knee pain

■ Meds: HCTZ, pantoprazole, sertraline, thiamine, folate, MVI

■ FH: brother and father with AUD

■ AST 88, ALT 46, Cr 0.82

AUD Cascade of Care

Mintz CM, Hartz SM, Fisher SL, Ramsey AT, Geng EH, Grucza RA, Bierut LJ. A cascade of care for alcohol use disorder: Using 2015-2019 National Survey on Drug Use and Health data to identify gaps in past 12-month care. Alcohol Clin Exp Res. 2021 Jun;45(6):1276-1286.

AUD treatment gap is massive

■ 7.6% of patients with unhealthy alcohol use receive treatment

■ 1.6% people received pharmacotherapy

■ Racial disparities in prescribing

1) Han. Key Substance Use and Mental Health Indicators in the United States: Results From the 2019 National Survey on Drug Use and Health. Substance Abuse and Mental Health Services Administration; 2020.2) Han B, Jones CM, Einstein EB, Powell PA, Compton WM. Use of Medications for Alcohol Use Disorder in the US: Results From the 2019 National Survey on Drug Use and Health. JAMA Psychiatry. 20213) Oldfield et al. Predictors of initiation of and retention on medications for alcohol use disorder among people living with and without HIV. J Subst Abuse Treat. 2020.

Unhealthy alcohol use

At-risk drinking Alcohol use disorder (moderate – severe)

Brief counseling intervention

Medication PLUS psychosocial intervention

Brief counseling intervention for at-risk drinking

10-15 minutes of counseling:• Ask permission to raise the subject• Relate drinking behavior to problems• Elicit motivations for change• Set a drinking goal• Support efforts• Refer to cognitive behavioral therapy or a mutual help group• Arrange close follow-up

National Institute on Alcohol Abuse and Alcoholism (NIAAA)

Brief Intervention vs the “Alcogenic Environment”

McCambridge, J. Reimagining brief interventions for alcohol: towards a paradigm fit for the twenty first century?. Addict Sci Clin Pract 16, 41 (2021).

Unhealthy alcohol use

At-risk drinking Alcohol use disorder (moderate – severe)

Brief counseling intervention

Medication PLUS psychosocial intervention

Medications for AUD

FDA Approved:

naltrexone

acamprosate

disulfiram

Off label (Non-FDA approved):

topiramate

gabapentin

baclofen

ondansetron

varenicline

nalmefene

FDA-approved medications for AUD:naltrexone

Dosage • Oral 50-100 mg/day• Intramuscular 380 mg/month

Mechanism Opioid receptor antagonist that reduces rewarding effects of alcohol

Effectiveness • Number Needed to Treat (NNT) = 20 to prevent return to any drinking

• NNT = 12 to prevent return to heavy drinking

Pros • OK to use if actively drinking• Daily oral AND long-acting injectable options (No RCT to compare)• Cheap and available• May combine with gabapentin

Cons • Liver concerns • Avoid if Child-Pugh C or greater, or alanine

aminotransferase (AST)/aspartate aminotransferase (ALT) >5x upper limit of normal

• Monitor liver function tests• Gastrointestinal effects, headache, dizziness• Abstinence from opioids prior to initiation• Opioids not as effective for analgesia

Jonas, JAMA, 2014; Anton et al, 2011

FDA-approved medications for AUD: acamprosate

Dosage 666 mg orally three times a day

Mechanism Modulates glutamate neurotransmission

Effectiveness Maintains abstinence, NNT = 12 to prevent return to any drinking in 8-24 weeksEffective in European studies, Abstinence prior to initiation

Pros • Safe for the liver• Can use in setting of opioid use

Cons • TID adherence• Requires renal dosing

• 50% reduction for moderate renal impairment• Contraindicated if CrCl<30

• Diarrhea in 10-15%• Takes 5-8 days for full effect• Limited to patients with goal of abstinence

Jonas, 2014; Rosner et al, Cochrane Database Syst Rev, 2010; Donoghue et al, 2015; Maisel et al, 2012

FDA-approved medications for AUD: disulfiram

Dosage 250-500 mg by mouth daily

Mechanism Inhibits aldehyde dehydrogenaseCauses aversive alcohol-disulfiram reaction

Effectiveness Meta-analysis of blind trials showed no difference than placebo though medium efficacy if open-label trials are includedMore effective in supervised administration

Pros Use in highly structured environment (e.g. opioid treatment program) or for patients with history of success with disulfiram

Cons • Very unpleasant• Adherence critical (and caution “hidden” alcohol in mouthwash, etc)• Must have goal of abstinence• Concerning in setting of pregnancy, CAD, psychosis, liver disease

Skinner et al, 2014; Jonas et al, JAMA, 2014

Non-FDA approved for AUD: topiramate

Kranzler, 2014; Feinn et al, 2016; Guglielmo et al, 2015; Blodgett et al, 2014; Jonas, 2014; Batki et al, 2014

• Goal either abstinence or nonharmful drinking. NNT = 5.29* (Adjusting with adverse events, NNT 6.12 - 7.52)

• Titrate up to 300mg/day over 8 weeks but 100-200mg/day may be effective. • To stop, taper by 25-50mg per day over 1 week

• Beneficial for people with seizures, insomnia, obesity. May be particularly useful with co-occurring PTSD, Cocaine Use Disorder, TBI.

• Significant adverse effects dose-dependent: cognitive impairment, paresthesia, sedation, appetite suppression, taste alteration, teratogenic

• Renally adjust

Non-FDA approved for AUD: gabapentin

Johnson et al., JAMA, 2006; Mason et al, 2014; Falk et al., 2019; Anton et al., 2020

• Studied at 900-1800 mg/day with mixed evidence• May be useful for people with h/o withdrawal• Can also use for non-severe alcohol withdrawal• Dose adjust for CKD• May combine with other AUD medications• May be helpful with neuropathic pain, insomnia• Misuse potential?

Non-FDA approved for AUD: baclofen

Jonas, 2014; Chaignot et al, 2018

• Safe for use in liver failure, but mixed evidence • In 165K patients in France treated with meds for AUD, baclofen was

associated with hospitalization (HR 1.1) and mortality (HR 1.3) in dose response relationship

• Concern for significant harms

Case: 40 Y female with severe AUD seen at clinic

Which medication do you recommend?

A) acamprosateB) disulfiramC) baclofenD) naltrexone

■ She has cut back from 2 bottles of wine daily to 1

■ Severe cravings whenever she tries to quit, not confident she can stop. Goal is to decrease.

■ PMH: HTN, depression, knee pain

■ Meds: HCTZ, pantoprazole, sertraline, thiamine, folate, MVI

■ FH: brother and father with AUD

■ AST 88, ALT 46, Cr 0.82

When selecting a medication for AUD:

■ Target Goals– Reduce drinking: Naltrexone, Gabapentin, Topiramate– Abstinence: Acamprosate, Disulfiram, Naltrexone, Topiramate, Gabapentin

■ Target Co morbidities– Liver Disease: Acamprosate, Gabapentin, Topiramate– Adherence Challenges: XR Naltrexone– Concurrent Opioid Use: NOT naltrexone– Renal Disease: Dose reduce acamprosate, gabapentin– Anxiety: Gabapentin– Insomnia: Gabapentin, Topiramate– H/o withdrawal: Gabapentin

Part IV.

Frontier of AUD Treatment

Bogenschutz MP, Forcehimes AA, Pommy JA, Wilcox CE, Barbosa PC, Strassman RJ. Psilocybin-assisted treatment for alcohol dependence: a proof-of-concept study. J Psychopharmacol. 2015 Mar;29(3):289-99.

Psychosocial Treatments

Clinical trials have not found any

one intervention to be superior to

the others

CBTMotivational

Enhancement Therapy

Family Behavioral

Therapy12-Step

Facilitation

Contingency Management

Community Reinforcement

Approach

Which talking therapies work for people who use drugs and also have alcohol problems? Cochrane Review, 2018

AA & 12-step mutual support groups:• A recent Cochrane review appeared to report broad AA

effectiveness in >10K people• Studies tested AA in conjunction with psychotherapy, and

had substantial risk of selection bias

Kelly, Humphreys, & Ferri, Alcoholics Anonymous and other 12-step programs for alcohol use disorder. Cochrane Database, 2020.

Virtual recovery resources• Online support groups

• 12-step, e.g., AA• SMART Recovery• LifeRing• Moderation Management• Women for Sobriety• And more

• Apps• Internet-based CBT non-inferior to face-to-face for decreasing drinks among some

treatment seeking individuals with AUD (n=301)• Podcasts

Links to more online resources:• American Society for Addiction Medicine's guidance on promoting support group

attendance during Covid-19• Accessing treatment through telehealth by National Institute on Alcohol Abuse and

Alcoholism

Johansson et al, Addiction. 2021.

Part IV. Management of Alcohol Withdrawal

State Alcohol-Related Laws During the COVID-19 Emergency for On-Premise and Off-Premise Establishments, NIAAA.

Increase in alcohol withdrawal rates among hospitalized patients during Covid-19 pandemic

Sharma RA, Subedi K, Gbadebo BM, Wilson B, Jurkovitz C, Horton T. Alcohol Withdrawal Rates in Hospitalized Patients During the COVID-19 Pandemic. JAMA Netw Open. 2021 Mar 1;4(3):e210422

Assessing safety of ambulatory withdrawal management

American Society of Addiction Medicine, 2020B Hurley and A Alvanzo, Ambulatory Alcohol Withdrawal During the Covid-19 Pandemic, ASAM, 2021

Can the patient be safely monitored in an ambulatory care setting or at home? Does the patient need inpatient care?

• Does the patient have safe housing and support?

• Can the patient maintain telephone-based contact?

• Can the patient follow medication instructions? Take orally?

• Does your clinic have the capacity to provide remote monitoring and/or accessibility for patients with alcohol withdrawal syndrome?

• Are they at risk of severe or complicated withdrawal?

• Does the patient have a history of seizures or delirium tremens?

• Does the patient have acute illness, medical co-morbidities or co-occurring substance use likely to complicate their withdrawal treatment?

• Age 65 or over?• Pregnant?• How severe are their symptoms?

Who will develop severe withdrawal?

• History of delirium tremens (DT) most predictive in hospitalized patients

• Prediction of Alcohol Withdrawal Severity (PAWSS) is a screening tool to predict severe withdrawal in a medically ill patient

• PAWSS Scores ≥4 suggest high risk. Prophylaxis and/or treatment may be indicated

Wood et al, 2018; Maldonado et al, 2014

J Blum, M Hoag, J Cram, J Bull. ASAM Workshop: Integrating Alcohol Withdrawal Management into Primary Care Settings, 2020

Part V. Harm Reduction Approaches

What is an optimal outcome in alcohol use disorder treatment?

• Total abstinence• Decrease the number of days

drinking• Decrease the number of days with

heavy drinking• Decrease the number of drinks per

day• Minimize physical, psychological,

financial, and social harm

Reduction of drinking: An appropriate clinical outcome

• Reductions in drinking levels (grams of ethanol per day) associated with decreased SBP, LFT improvements, better QOL and medication effects

• Reductions may align more with patient’s goals, recognize more people as being successfully treated, encourage more clinician confidence and encourage future medication development

Witkiewitz et al, 2021; Witkiewitz et al., 2020; Witkiewitz et al., 2019; Falk et al., 2019

Updated definitions are non-abstinence based

Remission from alcohol use disorder as defined by DSM-5 criteria Requires that the individual not meet any AUD criteria (excluding craving). Remission from AUD is categorized based on its duration: initial (up to 3 months), early (3 months to 1 year), sustained (1 to 5 years), and stable (greater than 5 years).

Recovery from alcohol use disorderRecovery is a process, achieved if both remission from AUD and cessation from heavy drinking are maintained over time. Recovery is often marked by the fulfillment of basic needs, enhancements in social support and spirituality, and improvements in physical and mental health, quality of life, and other dimensions of well-being.

Primary care for people with unhealthy alcohol use

• Up to date cancer screening• Screening: IPV, Falls, Cognitive, Depression, CV Risk• Heavy alcohol prompts osteoporosis screening before age 65• Vaccines: PPV-23 x 1 19-64yo and x2 >65yo, Tdap, HAV, HBV,

Tetanus, HPV• Consider TB risk• Assess nutritional status• Review medications for interactions with alcohol• Assess for other substance use including tobacco• Offer family planning

Comprehensive Primary Care for People who use alcohol and drugs, Workshop, California Society for Addiction Medicine, 2020

Harm reduction techniques

1) Collins SE, Duncan MH, Saxon AJ, Taylor EM, Mayberry N, Merrill JO, Hoffmann GE, Clifasefi SL, Ries RK. Combining behavioral harm-reduction treatment and extended-release naltrexone for people experiencing homelessness and alcohol use disorder in the USA: a randomised clinical trial. Lancet Psychiatry. 2021 Apr;8(4):287-300.2) Rethinking Drinking, NIAAA

Managed Alcohol Programs

Ristau J, Mehtani N, Gomez S, Nance M, Keller D, Surlyn C, Eveland J, Smith-Bernardin S. Successful implementation of managed alcohol programs in the San Francisco Bay Area during the COVID-19 crisis. Subst Abus. 2021;42(2):140-147.

Summary Points: Management of Alcohol Use Disorder

1. Screen all adults for unhealthy alcohol use2. Use brief counseling for at-risk drinking AND prescribe

medications for alcohol use disorder3. Apply a patient-centered approach to medical and psychosocial

treatment selection based on goals and co-morbidities4. Patients without history and symptoms of severe withdrawal may

be candidates for outpatient withdrawal management5. Treat to reduce harm from alcohol use disorder

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Werner D. Elucidating the role of alpha-1-containing GABA(A) receptors in ethanol action. 2007.

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