#194 Alcohol Use Disorder Treatment with Dr. Marlene Martin

February 10, 2020 | By Carolyn Chan

Diagnose and treat patients with risky drinking and alcohol use disorder

Dismantle alcohol use disorder with evidence based tools for your tool-belt! We cover everything from ways to screen patients for risky drinking, to all the different treatment options with our guest expert Dr. Marlene Martin, @MarleneMartinMD, Director of the Addiction Care Team and Assistant Professor of Clinical Medicine at the UCSF. We learn how to initiate medications such as naltrexone and acamprosate for the treatment of alcohol use disorder, how to define treatment success, if psychosocial interventions such as Alcoholics Anonymous are effective, and what’s the deal with baclofen and gabapentin? After listening to this episode, listeners will feel ready to start prescribing medications such naltrexone to treat alcohol use disorder.  Your patients need you!

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Credits

Written and Produced by: Carolyn Chan, MD

Cover Art and Infographic: Carolyn Chan, MD

Hosts: Carolyn Chan, MD; Stuart Brigham MD; Matthew Watto MD, FACP; Paul Williams MD, FACP   

Editor: Matthew Watto MD, FACP (written materials); Clair Morgan of Nodderly.com (audio)

Guest: Marlene Martin, MD

Sponsor

ACP’s Medical Knowledge Self Assessment Program, MKSAP 18. MKSAP provides the latest and most comprehensive educational content needed by internists today. It’s THE internal medicine go-to resource for continuous learning and Board preparation. Visit http://www.acponline.org/mksapcurbsiders to place your order!

Time Stamps

• 00:00 Sponsor -ACP’s MKSAP 18 http://www.acponline.org/mksapcurbsiders 
• 00:45 Intro, guest bio
• 01:30 Guest one-liner, book recommendation, favorite failure, career advice
• Picks of the week*: Project Runway (TV show); The Quiet Place (film); Tattoos on the Heart: The Power of Boundless Compassion (book) by: Gregory Boyle; Cats (film)
• 08:20 Sponsor -ACP’s MKSAP 18 http://www.acponline.org/mksapcurbsiders 
• 09:05 Case of Mr Hops; Defining unhealthy alcohol use
• 13:37 Screening and diagnosis; assessing for tolerance; stratifying severity of AUD
• 16:56 Spiel and first steps after diagnosing a patient with unhealthy alcohol use; Motivational interviewing; Exploring motivation to change
• 22:12 Pharmacologic treatment options: Naltrexone, acamprosate, disulfiram
• 26:40 How effective are medications for alcohol use disorder; Defining success
• 29:41 Naltrexone prescribing, dose titration
• 34:25 Acamprosate prescribing; Naltrexone in advanced liver disease
• 38:05 Off label use of baclofen, gabapentin and topiramate
• 43:39 Risk stratifying for inpatient versus outpatient treatment; Non-pharmacologic interventions
• 49:26 Deciding duration of therapy
• 52:24 Take home points; Plug for AMERSA conference
• 53:57 Outro

Alcohol Use Disorder Pearls

Risky drinking is defined as more than 4 drinks per occasion or more than 14 drinks a week for men.  For women the criteria are defined as more than 3 drinks an occasion, or more than 7 drinks a week.

Screen all adults in the primary care setting for risky drinking with one of the following 3 validated tools: AUDIT, AUDIT-C and the single question screen (How many times in the past year, have you had 4 or more drinks in a day (for women), or 5 or more drinks (for men)? 

Motivational Interviewing tip: Use your OARS – Open ended questions, affirmations, reflective statements, and summarizing. 

To help remember some of the DSM-V criteria for AUD break them up into their physiologic symptoms, a) withdrawal b) tolerance and c) the 5 C’s: loss of Control, Cravings, health and relationship Consequences, Compulsion to drink, and being unable Cut back.

FDA approved medication treatment for AUD includes naltrexone PO, naltrexone LAI (long acting injectable formulation), acamprosate, and disulfiram. 

Keep in mind the patient’s comorbidities when selecting a pharmacologic treatment option.  Naltrexone is contraindicated in severe liver disease and in individuals who use opioids. Acamprosate is contraindicated in CrCl < 30, and a patient must be motivated to have adherence to daily disulfiram. 

Initiate naltrexone at either 25mg PO daily on day 1 (expert opinion, to minimize side effects), and 50mg on day 2. Follow-up to assess a patient’s success in cutting back and/or abstinence in 4-6 weeks.

These meds work! For naltrexone the NNT is 12 for return to heavy drinking, 20 for return to any drinking (Jonas, 2014).

There is some evidence to suggest gabapentin, topiramate, and baclofen may help patients cut down on their number of heavy drinking days, but these medications should be considered only if the first line medications are not an option.

Psychosocial interventions may work as well as medication treatment. Any of them can be the right one, tailor the referral based on patient preference. Options include: mutual support groups (AA), harm reduction groups, therapy (individual, family, CBT), and contingency management.      

Alcohol Use Disorder Show Notes 

Spectrum of Alcohol Use

Alcohol use is a spectrum that ranges from abstinence and/or low-risk alcohol use to severe alcohol use disorders. The spectrum range is as follows: abstinence, low-risk alcohol use. From there it turns into a category of unhealthy alcohol use which is a continuum that ranges from: risky drinking to mild-severe alcohol use disorder (Saitz, 2005).

Defining Risky Alcohol Use

For men, risky drinking is defined as more than 4 drinks per occasion or more than 14 drinks a week. For women, risky drinking is defined as more than 3 drinks an occasion or more than 7 drinks a week (NIAAA, 2005). 

Is consuming any amount of alcohol safe? 

Dr. Martin’s does not recommend that any of her patient initiate drinking alcohol strictly for health benefits -expert opinion. 

Screening for unhealthy alcohol use – “CAGE is dead”

USPSTF recommends that all adults in the primary care setting are screened for unhealthy alcohol use —USPSTF, site updated 2018. Mot screening tools have been validated in the outpatient setting, and are better when they are self-administered. The three tools the USPSTF recommends are AUDIT*, AUDIT-C and the validated single alcohol screening question (SASQ). Note*: If utilizing the full AUDIT (10 questions) to screen for unhealthy alcohol use then use a lower cutoff score of 3-5, to balance the to balance sensitivity and specificity

CAGE is no longer recommended as a first line screening tool for alcohol use disorder. 

Validated Single Question Screen

Start with a validated single question which screens individuals for unhealthy alcohol use: How many times in the past year, have you had 4 or more drinks in a day (for women), or 5 or more drinks (for men)?  If a patient answers “yes” to the question, then they have screened positive for unhealthy alcohol. This single item question has been validated, it is 82% sensitive, and 79% specific for identifying patients with risky alcohol use (Smith, 2009).

Diagnosing Alcohol Use Disorder

DSM-V is the gold standard in diagnosing alcohol use disorder. If a patient meets 2-3 criteria they a mild AUD, 4-5 criteria is a moderate AUD, and 6 + is a severe AUD (DSM-V, 2013). 

Dr. Martin recommends initiating the conversation by asking an open ended question with your patient such as “How is alcohol use affecting their lives?”. Her expert tip to remember the DSM-V criteria is to break them down into physiologic criteria of alcohol use: withdrawal and tolerance. Then remember the 5 C’s: loss of Control, Cravings, health and relationship Consequences, Compulsion to drink, and being unable Cut back. To further assess a patient’s tolerance ask if they are needing more alcohol to get the same effect or if they’ve had to increase their use over time to get to the same effect.

Your patient has a positive screen, now what?

Ask your patient for permission to discuss their alcohol use. Then, provide them specific feedback on their alcohol use, look at their motivations to change, and assist them with goal setting.  If a patient is positive for risky drinking on screening, one can utilize the Screening and Brief Intervention (SBI) model (APHA SBI manual, 2008). 

If a patient meets DSM – V criteria for alcohol use disorder, they need more support beyond a brief intervention. Dr. Martin recommends initiating medication treatment and/or referring for psychosocial intervention. 

Motivational Interviewing – Use your OARS!

Use your O.A.R.S. as a tool to jumpstart motivational interviewing.

• Open ended questions – “Tell me about your alcohol use”
• Affirmations
• Reflective statements
• Summarizing – make sure highlight any patient change talk

Motivational interviewing pearl: “Patients should be talking way more than you should.” – Dr. Martin 

For patients who are pre-contemplative. Encourage prompts such as asking the patient how alcohol use is affecting their health, if possible relate it to a current health condition, or personal issues with their relationships or job. Explore an individual’s motivation to change and be sure to highlight a patient’s “change talk” when summarizing. If an individual is pre-contemplative “roll with resistance”,  be sure to meet patients where they are at. 

Pharmacologic Treatment

The FDA  has approved 4-first line pharmacologic agents for the treatment of AUD which include: naltrexone PO, naltrexone long acting injectable (LAI), acamprosate, and disulfiram. In Dr. Martin’s opinion, naltrexone and acamprosate are her go-to first line agents.

Does the severity of the disease impact treatment? 

Most treatment studies involving medications only included patients with moderate and severe alcohol use disorder. Expert opinion: provide tailored treatment independent of severity and based on a patient’s individual goals. 

Naltrexone

Naltrexone is a mu receptor antagonist, and it works well for individuals who want to stop using alcohol, or cut back.  It works by decreasing the pleasurable effects of drinking, so individuals “unlearn” how to drink. A good option for patients with a family history of AUD and in those who have cravings for alcohol.

Contraindications to Naltrexone

• Decompensated liver cirrhosis
• Severe liver disease – CTP class C
• Co-occurring use of opioids

Of note it can be used in patients with liver disease as long as the AST/ALT are under 5 times the upper limit of normal. At high doses (300mg) naltrexone has been associated with hepatotoxicity (Mitchell, 1987).

Expert opinion: In select patients with AUD and decompensated cirrhosis it may be worth the risks vs. benefits of trialing naltrexone despite this listed contraindication.  If the patient is unable or unwilling to trial alternative first or second line therapy, and is willing to accept the risk of the medication one can consider using it. If trialed in this patient population it requires close monitoring, and approval by their hepatologist and outpatient addiction care providers. 

Initiating Naltrexone – Start tomorrow, your patients need you!

Day 1:  Start naltrexone at 25mg  (expert opinion to minimize side effects), and then increase to 50mg on day 2. Alternatively some providers may start 50mg on day 1 and continue this dose.

Common side effects include abdominal pain, nausea, vomiting, and diarrhea. Dr. Martin prefers to start at 25mg to minimize side effects, which often dissipate with time. It can be started at a dose as low as 12.5mg for 7 days if an individual has experienced adverse side effects in the past (Chapter 4: Oral Naltrexone SAMHSA/CSAT, 2009). For medication titration, assess if the patient has cut back successfully on their alcohol use while on naltrexone. If they have and would like to try to cut back further, consider increasing the dose up to 100mg daily, after 4-6 weeks.

Consider extended release naltrexone (injection) for individuals who have trouble adhering to the pill formulation. Of note the injectable formulation is expensive.

Acamprosate

Acamprosate is a glutamate antagonist that helps patients in the protracted symptoms of alcohol withdrawal that often lead people to drinking. It is good for individuals who experience dysphoric effects when they stop drinking such as insomnia. 

Initiating Acamprosate 

It’s simple to initiate, but a large pill burden for patients. The starting dose is 666 mg TID (six 333 mg pills per day!). Of note, it must be renally dosed. If  CrCl < 50, reduce the dose to 333mg TID, and if CrCl < 30 the medication is contraindicated. In contrast to naltrexone, this medication can be used in patients with end stage liver disease —Chapter 2: Acamprosate SAMHSA/CSAT, 2009. 

Disulfiram 

Disulfiram is FDA approved for the treatment of AUD but is not commonly used. Often individuals do not take it because they have  unpleasant reactions if they return to drinking. Dr. Martin’s expert opinion is to consider it for those who have not tolerated naltrexone or acamprosate, yet are highly motivated to quit drinking. In addition, one can consider in patients who are in settings where the medication is administered, such as patients going to daily methadone clinics where disulfiram could also be given. 

How effective are these medications?

One study found that less than 9% of individuals who have an AUD are treated with appropriate medication (Mark, 2009). A 2014 meta-analysis demonstrated that the NNT for acamprosate to prevent return to any drinking is 12 (Jonas, 2014)! The NNT for return to heavy drinking for naltrexone is 12 and to any drinking is 20 (Jonas, 2014). Kashlak Pearl: Even if a patient has fewer drinking days of the month, and does not achieve complete abstinence it can be counted as a success as they are less likely to have harmful complications of alcohol use. Continue to take a harm reduction approach, because decreasing alcohol use can lead to health benefits! 

Baclofen, Topiramate and Gabapentin- “Off Label”*

*none of these are FDA approved for the treatment of AUD           

A recent meta-analysis found baclofen to be associated with a delay in return to drinking and with sustained abstinence, particularly in individuals who at baseline drank very heavily, with no added benefit at a dosage greater than 60 mg/d (Pierce, 2018). This medication can be used in end stage liver disease, but has few other positive effects on drinking outcomes.

Topiramate may reduce the number of heavy drinking days and number of drinks per drinking day (Jonas, 2014).

Gabapentin can be used for the treatment of mild alcohol withdrawal (Myrick, 2009). Per Dr. Martin’s expert opinion using it in conjunction with benzos for withdrawal management may decrease benzo use. It may help with symptoms of protracted withdrawal. A small study (Anton, 2011) noted than when gabapentin was used in combination with naltrexone it lead to slightly improved drinking outcomes. Expert opinion: consider trialling gabapentin if naltrexone does not work, or add it as an additional medication  to see if can potentiate its effect.

Existing evidence from 3 RCTs (of limited quality) suggests gabapentin may decrease the number of heavy drinking days for patients with alcohol use disorder (Kranzler, 2019). One of these studies found that higher doses (800mg TID) may cause dose dependent decrease in drinking, but had a high dropout rate at 43% (Mason, 2014).

Patients with co-occurring opioid use disorder or depression

Assess which disorder is the patient’s main substance use disorder. For example, if alcohol use disorder is the main disorder (ie patient drinks daily, but uses opioids sporadically), consider trialing acamprosate for treatment of their AUD.  Naltrexone is contraindicated in individuals with opioid use disorder (OUD) or chronic opioid use.  While LAI naltrexone is FDA approved to treat both, it is often not the first line for OUD.  Dr. Martin would only consider LAI naltrexone for patients with co-occurring disorders who do not want to try buprenorphine-naloxone or methadone.  

A Cochrane review suggests if a patient has depression and co-occurring AUD, consider offering  the patient an SSRI. When started on an SSRI there is low quality evidence to support that patients may have a reduction in their alcohol consumption (Agabio, 2018) 

Psychosocial Interventions

Psychosocial interventions may work as well as medication treatment  (Anton, 2006).  “Any” of them is the right one: mutual support groups (AA), harm reduction groups, therapy (individual, family, CBT), contingency management programs. Patient needs to “buy” into the best option for them and their life. Keep in mind some residential programs can have strict and varied restrictions.

There is evidence to suggest Alcoholics Anonymous may be an effective intervention (Kashutas, 2009). If individuals choose AA, recommend they try a few meetings (all meetings can have different “flavors”), and it may take time to find the right fit. Be familiar with the local resources to help refer patients.

There is mixed evidence on the combination of medication and psychosocial interventions. Some studies show that there may be better efficacy when psychosocial interventions and medications are combined; other studies show they all perform about the same as individual components (Anton, 2006, Baldin, 2003, Kranzler, 2019).

Duration of Treatment

The optimal duration of treatment is unknown and should be tailored to individual patients (Chapter 4: Oral Naltrexone SAMHSA, 2009). During follow-up sessions assess whether the “root cause” of their drinking has been determined and stabilized. Discuss the risks vs. benefits with the patient of stopping the medication. Ask if things have changed in their environment, such as life stressors.  If they are at a point in their life where things are stable and they want to give coming off the medication a try, it’s reasonable. If not, assess if psychosocial treatment could further help support their recovery. Share concerns that stopping the medication may increase their risk to return to drinking. 

Take Home Points

1. Screen your patients for risky drinking using the single item questionnaire or the AUDIT-C.
2. Assess and diagnose AUD in your practice setting
3. Elicit your patients goals around AUD, and meet them where they are on the spectrum of their alcohol use. Offer them medication and/or psychosocial interventions based on their goals.
4. Check out AMERSA! The Association for Multidisciplinary Education and Research in Substance use and Addiction. AMERSA’s next conference is November 5-7, 2020 in Boston, MA!

Goal

Listeners will be able to screen and provide treatment for patients with alcohol use disorder.

Learning objectives

After listening to this episode listeners will…  

1. Define risky drinking and alcohol use disorder.
2. Screen patients for risky drinking.
3. List indications and contraindications of first line therapy for alcohol use disorder.
4. List indications and contraindications of second line therapy for alcohol use disorder.
5. Describe how co-occurring medical conditions affect pharmacologic treatment of alcohol use disorder.

Links*

1. Project Runway (TV show)
2. The Quiet Place (film)
3. Tattoos on the Heart: The Power of Boundless Compassion (book) by: Gregory Boyle
4. Cats (film)
5. Audit-C Calculator
6. Steven Malcom Berg-Smith Motivational Interviewing
7. AMERSA

*The Curbsiders participates in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising commissions by linking to Amazon. Simply put, if you click on our Amazon.com links and buy something we earn a (very) small commission, yet you don’t pay any extra.

References

1. Saitz, R. Unhealthy alcohol use. NEJM. 2005.[https://www.ncbi.nlm.nih.gov/pubmed/15703424]
2. National Institute on Alcohol Abuse and Alcoholism (NIAAA). Helping patients who drink too much: A clinician’s guide. NIH Publication no. 05-3769, Bethesda, MD 2005. [https://www.integration.samhsa.gov/clinical-practice/Helping_Patients_Who_Drink_Too_Much.pdf]
3. USPSTF guidelines on screening for Alcohol Use Disorder. 2018 [https://www.uspreventiveservicestaskforce.org/Page/Document/RecommendationStatementFinal/unhealthy-alcohol-use-in-adolescents-and-adults-screening-and-behavioral-counseling-intervention]
4. DSM-V: American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. 5th ed. Arlington, VA: American Psychiatric Association; 2013.
5. Smith, Peter C., et al. Primary care validation of a single-question alcohol screening test. Journal of GIM. 2009 [https://www.ncbi.nlm.nih.gov/pubmed/19247718] 
6. American Public Health Association and Education Development Center, Inc. (2008). Alcohol screening and brief intervention: A guide for public health practitioners. [https://www.integration.samhsa.gov/clinical-practice/alcohol_screening_and_brief_interventions_a_guide_for_public_health_practitioners.pdf] 
7. Mitchell, J, et al. High-dose naltrexone therapy and dietary counseling for obesity.” Biological Psychiatry. 1987 [https://www.ncbi.nlm.nih.gov/pubmed/?term=High-dose+naltrexone+therapy+and+dietary+counseling+for+obesity]
8. Hasin, D, et al. “Prevalence, correlates, disability, and comorbidity of DSM-IV alcohol abuse and dependence in the United States: results from the National Epidemiologic Survey on Alcohol and Related Conditions.” Archives of general psychiatry. 2007 [https://www.ncbi.nlm.nih.gov/pubmed/17606817]
9. Jonas et al. Pharmacotherapy for adults with alcohol use disorders in outpatient settings: a systematic review and meta-analysis.Jama. 2014 [https://www.ncbi.nlm.nih.gov/pubmed/24825644] 
10. Addolorato, G, et al. Dose–response effect of baclofen in reducing daily alcohol intake in alcohol dependence: secondary analysis of a randomized, double-blind, placebo-controlled trial. Alcohol and Alcoholism. 2011 [https://www.ncbi.nlm.nih.gov/pubmed/21414953] 
11. Myrick, H, et al. “A double‐blind trial of gabapentin versus lorazepam in the treatment of alcohol withdrawal.” Alcoholism: Clinical and Exp. Research. 2009 [https://www.ncbi.nlm.nih.gov/pubmed?term=19485969]
12. Anton, R. et al. “Gabapentin combined with naltrexone for the treatment of alcohol dependence.” American Journal of Psychiatry. 2011 [https://www.ncbi.nlm.nih.gov/pubmed/21454917]
13. Mason, B. et al. Gabapentin treatment for alcohol dependence: a randomized clinical trial. JAMA internal medicine . 2014 [https://www.ncbi.nlm.nih.gov/pubmed/24190578
14. Kranzler, H. A meta‐analysis of the efficacy of gabapentin for treating alcohol use disorder.” Addiction. 2019. [https://www.ncbi.nlm.nih.gov/pubmed/31077485]
15. Agabio, R, et al “Antidepressants for the treatment of people with co‐occurring depression and alcohol dependence.” Cochrane database of systematic reviews. 2018. [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6494437/]
16. Anton, R. et al. Combined pharmacotherapies and behavioral interventions for alcohol dependence: the COMBINE study: a randomized controlled trial.” Jama. 2006. [https://www.ncbi.nlm.nih.gov/pubmed/16670409]
17. Kaskutas, L. Alcoholics Anonymous effectiveness: Faith meets science. Journal of addictive diseases. 2009. [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2746426/]
18. Balldin, J., et al. A 6‐month controlled naltrexone study: combined effect with cognitive behavioral therapy in outpatient treatment of alcohol dependence. Alcoholism: Clinical and Experimental Research. 2003 [https://www.ncbi.nlm.nih.gov/pubmed/12878920]
19. SAMHSA TIP series No 49, Chapter 4: Oral Naltrexone. “Incorporating alcohol pharmacotherapies into medical practice.2009. [https://www.ncbi.nlm.nih.gov/books/NBK64042/

Disclosures

Dr Marlene Martin reports no relevant financial disclosures. The Curbsiders report no relevant financial disclosures. 

Citation

Martin M, Chan, C, Williams PN, Brigham SK, Watto MF. “194 Treatment of Alcohol Use Disorder”. The Curbsiders Internal Medicine Podcast. http://thecurbsiders.com/episode-list. February 10, 2020.