Showing posts with label alcohol use disorder. Show all posts
Showing posts with label alcohol use disorder. Show all posts

Metabolic Dysfunction Associated Steatohepatitis (MASLD) (Holt, 2/25/2026)

A recording of this presentation is available HERE.

Deep gratitude to Dr. Will Holt, CPMC Hepatologist, who drove to SSRRH from Piedmont at the literal crack of dawn to teach us about Metabolic Dysfunction Associated Steatohepatitis (MASLD) and Alcohol-Associated Liver Disease (AASLD) and then changed hats to spend the morning with our residency leadership as a faculty leader for graduate medical education within Sutter. 

His talk was fantastic! I recommend you watch it.

For those of you who prefer to read, the highlights:

First, MASLD

  • We all known that the prevalence of obesity and diabetes have both skyrocketed over the last several decades-- nearing 50% in some regions of our country. 
  • Along with these metabolic issues, comes MASLD-- world prevalence is estimated to be 29.8% lowest rates for those of African descent (thought to be both genetic and food access/lifestyle related)
  • Risk factors for MASLD include age >50, high BMI and DM2
    • MASLD is a risk factor for death
    • Assume that people are high risk (>50, high elevated BMI, DM2) have MASLD>> screen them for MASH with via fibroscan
  • For everyone else with any component of metabolic syndrome (e.g. overweight, a1c>6%, hypertension, HDL<40 (F) and <50 (M), triglycerides>150)>> use FIB-4 to screen first
    • if the FIB4>1.3>> Fibroscan,
    • unless they are >65yo, then use FIB-4>2.0
  • Fibroscan uses a weighted hammer/pulse to measure liver stiffness-- this is available through Sutter Airway)

  • Fibroscan <8 is normal (=reassuring, low risk), >14 demonstrates cirrhosis
    • for those with a normal fibroscan, focus on lifestyle modification for metabolic disorders
    • for those with an abnormal fibroscan, refer to hepatology
  • Fibrosis predicts liver-related mortality (see graph below from J. Hepatology 2017)
    • stage 0/1 fibrosis: no increased mortality
    • stages 2, 3, 4>> increased liver mortality 



As per the 2024 AASLD Guidelines for clinical suspicion of steatotic liver disease

What are the treatment options for MASLD and MASH?

  • Pharmacologic:
    • Vitamin E: 96 week RCT: reduced fibrosis 41% vs. 31% (placebo)
    • Pioglitazone: meta-analysis, reduced fibrosis vs. placebo OR 1.77
    • There are two FDA approved medications:
      • Resmetirom (2024): TRH-beta agonist, 52 week RCT vs. placebo, reduced fibrosis 24% vs. 14%
      • Semaglutide (2025): GLP1 agonist, 72 week RCT vs. placebo, reduced fibrosis 37% vs. 22% 
  • Non-Pharmacologic: diet/exercise/weight loss
    • weight loss improves liver histology! Even 5%!!!

Now, a little bit on ALD

  • Defining Alcohol use disorder (AUD)
  • Biomarkers for ETOH
    • Urine tests (EtG, EtS) have a very short detection window (<48 hours)
    • PEth is current "truth serum", gives us information about the last 30 days, though there are some false positives in the lower ranges (20-40). Very high results (>400-1000 are very reliable)
  • Diagnosing Alcoholic Hepatitis can be tricky!
    • elevated MCV (100), elevated WBC, jaundice
  • Treatment of alcohol-associated hepatitis with prednisolone (rather than prednisone due to first pass metabolism, when not available, prednisone is acceptable) FOR: 
    • Patients WITH Maddrey Discriminant Function >32>> 
    • AND WITHOUT
      • evidence of biliary obstruction on ultrasound
      • uncontrolled infection (especially bacteremia)
      • AKI with SCr>2.5
      • UGI bleeding
      • Severe shock/hemodynamically unstable
    • Expect 3 month recovery (bili will remain high)
    • You can wait a couple of days before starting prednisolone (e.g. if any of the above active), pts can still benefit with delayed start
    • Use the Lille score to predict (7 days) who will respond


    • N-Acetylcysteine= mixed bag, there does appear to be a mortality benefit at 30 days but not at 3 months/6 months (NEJM 2011, see image)


  • What about liver transplant (LT) in ALD?
    • 2011 RCT from France (NEJM 2011) was practice changing, randomized patients with AH without sobriety and first decompensating event  to LT vs. no LT (only <10% deemed candidates)>> found that 1 and 3 year survival was the same for patients with ALD as any other liver disease
    • This led to a change in practice in which transplant can/may be considered for alcoholic hepatitis in select patients, not specified as a specific duration of sobriety>> at CPMC, this is called the "limited sobriety pathway to LT"
    • Careful patient selection for LT (with ALD) is key. 
      • Family support
      • Absence of untreated psychiatric disorder
      • Agreement by patient with support to LIFELONG abstinence (this can be harder to get to that you might imagine)
      • This assessment is done by LT SW at CPMC (often via video visit prior to Transfer)
    • We know that patients with AUD will relapse








Phenobarbital for Severe Alcohol Withdrawal Syndrome (Aguilar & Bowen 3/12/2025)

 A recording of this presentation is available HERE

My notes:

  • 10.9% of US adults have alcohol use disorder (AUD) at some point in their lifetime (!!)
  • AUD costs the US $249 billion/year
  • 178,000 excess deaths due to AUD in the US 2021
  • Compared to opioids, higher rates of alcohol use, misuse, ED visits, and deaths see below)
A screenshot of a chart

Description automatically generated

Alcohol Withdrawal Syndrome (AWS)
  • 500,000/year episodes of AWS requiring pharmacological treatment
  • 5-20% of people admitted to the hospital have AWS
  • highest risk of seizures in first 1-2 days of AWS, DTs 4-6 days with looooooooong tail
  • Reminder of difference between hallucinosis vs. DTs (autonomic instability)
A diagram of a normal life cycle

Description automatically generated with medium confidence
Neuropharmacology of Alcohol
Dopamine>> reward>> addiction
GABA agonism during intoxication>> sedation
Chronic use>> GABA downregulation, Glutamate upregulation
Lots of other neurotransmitters involved: opiate R, serotonin R, cannabinoid R, etc
When we take away alcohol (after chronic use), our GABA system is completely depleted, and our glutamate is "going wild"


Phenobarbital is a barbiturate
  • GABA agonism, suppresses glutamate
  • PO>> onset 60 minutes, IV>> onset 5 minutes
  • metabolized in the liver, excreted renally
  • 1/2 life ~79 hours (range 53-118 hours)
    • this prolonged half life allows for a built in taper
  • has a predictable pharmacokinetics at 10mg/kg (deal body weight), though no RCTs that study "ideal drug level" for AWS
  • no documented barbiturate resistant alcohol withdrawal

Traditional treatment of AWS is with benzodiazepines. We know benzos can cause paradoxical agitation and delirium. In addition, a lack of endogenous GABA in chronic alcohol use can make benzos less useful.


What does the current  literature say about Phenobarbital vs benzos?
  • Retrospective cohort study, 42-bed ICU, 120 participants (2018, Am J of Critical Care)
    •  shorter ICU stays (2.4 vs 4.4), shorter hospital stays (4.3 vs 6.9).  lower rate of mechanical ventilation (2% vs 23%), fewer adjunctives including precedex (7% vs 28%)
  • RCT with ED pts requiring admission – single dose phenobarb vs symptom-based BZD, 102 participants (2013 Journal of Emergency Medicine)
    • decreased ICU admission rates (8% vs 25%), decreased BZD use
  • Retrospective cohort over 2 years, 606 participants (2021, Cureus)
    • shorter hospital stay (2.8 vs 3.6), lower all-cause 30-day readmission (11%  vs 19%), fewer 30-day ED visits
  • 2 different Metanalyses (2021) findings: may shorten hospital LOS, unclear if shortens ICU LOS but does decrease ICU admission, benzo sparing, may result in less intubation
Some suggestion that we should move away from CIWA for scoring AWS. One proposed alternative is RASS scoring, which should be familiar to people who work in ICUs

Proposed Phenobarbital Protocol DRAFT


Notes:
  • For HIGH risk patients (CIWA>20 OR CIWA>16 with Risk factors)
    • 10-12 mg/kg (IDEAL body weight) loading dose
    • Use ideal body weight calculator (MD Calc)
    • should happen in monitored setting (ED vs. ICU) only
  • For patients who may be at lower risk for AWS, consider lower dose than the loading dose (e.g. 130mg, 260mg IV/IM) q30 minutes-1 hour
  • Patients who have already been treated with benzos CAN receive phenobarbital but should be lower dose (due to risks of sedation)
References:
  1. SAMHSA Center for Behavioral Health Statistics and Quality. (2022). National Survey on Drug Use and Health (Table 5.9A—Alcohol use disorder in past year: among people aged 12 or older; by age group and demographic characteristics, numbers in thousands, 2021 and 2022, Issue. https://www.samhsa.gov/data/sites/ default/files/ reports/ rpt42728/NSDUHDetailedTabs2022/NSDUHDetailedTabs2022/NSDUHDetTabsSect5pe2022.htm#tab5.9a  

  2. Centers for Disease Control and Prevention. (February 29, 2024). Excessive Alcohol Deaths. Retrieved April 1 from https://www.cdc.gov/alcohol/features/excessive-alcohol-deaths.html#:~:text=About%20178%2C000%20people%20die%20from,or%20488%20deaths%20per%20day

  3. Fixed-Dose Phenobarbital Versus As-Needed Benzodiazepines for the Management of Alcohol Withdrawal in Acute Care General Internal Medicine https://pubmed.ncbi.nlm.nih.gov/38151248/#:~:text=There%20was%20no%20difference%20in,%25%2C%20P%20%3D%200.03).

  4. National Institute on Alcohol Abuse and Alcoholism. (2024). Alcohol-related emergencies and deaths in the United States. Retrieved April 1 from https://www.niaaa.nih.gov/alcohols-effects-health/alcohol-topics/alcohol-facts-and-statistics/alcohol-related-emergencies-and-deaths-united-states

  5. Maldonado, J. R. (2017). Novel Algorithms for the Prophylaxis and Management of Alcohol Withdrawal Syndromes-Beyond Benzodiazepines. Crit Care Clin, 33(3), 559-599. 

  6. Tidwell, W. P., Thomas, T. L., Pouliot, J. D., Canonico, A. E., & Webber, A. J. (2018). Treatment of Alcohol Withdrawal Syndrome: Phenobarbital vs CIWA-Ar Protocol. Am J Crit Care, 27(6), 454-460. 

  7. Rosenson, J., Clements, C., Simon, B., Vieaux, J., Graffman, S., Vahidnia, F., . . . Alter, H. (2013). Phenobarbital for Acute Alcohol Withdrawal: A Prospective Randomized Double-blind Placebo-controlled Study. The Journal of Emergency Medicine, 44(3), 592-598.e592. 

  8. Hawa, F., Gilbert, L., Gilbert, B., Hereford, V., Hawa, A., Al Hillan, A., . . . Al-Sous, O. (2021). Phenobarbital Versus Lorazepam for Management of Alcohol Withdrawal Syndrome: A Retrospective Cohort Study. Cureus, 13(2), e13282. 

  9. Murphy, J. A., Curran, B. M., Gibbons, W. A., & Harnica, H. M. (2021). Adjunctive Phenobarbital for Alcohol Withdrawal Syndrome: A Focused Literature Review. Annals of Pharmacotherapy, 55(12), 1515-1524. 

  10. Hammond, D. A., Rowe, J. M., Wong, A., Wiley, T. L., Lee, K. C., & Kane-Gill, S. L. (2017). Patient Outcomes Associated With Phenobarbital Use With or Without Benzodiazepines for Alcohol Withdrawal Syndrome: A Systematic Review. Hospital Pharmacy, 52(9), 607-616.





Phenobarbital for inpatient alcohol withdrawal (Bowen, 4/3/2024)

 A recording of this presentation can be found HERE.

***

Thanks to Dr. Anna Bowen, our future addiction medicine fellow (2024-2025), who gave an excellent talk this week on the use of Phenobarbital for Inpatient Alcohol Withdrawal. Dr. Bowen compiled the evidence for phenobarbital as well as a variety of phenobarbital protocols from different health systems. She urged us to create/modify one of our own at SSRRH, which seems like an excellent idea. 

My notes on her presentation:

  • Alcohol use disorder is very common in the US! 10.5% of the US population (+29 million people) over age 12 quality has having an AUD
  • In 2021, there were an estimated 178K deaths related to excessive alcohol use in the US. Alcohol is one of the leading causes of preventable deaths in our country
  • Complicated alcohol withdrawal syndrome (AWS) occurs in 5-20% of hospitalized patients
  • Alcohol use is responsible for nearly double the number of deaths per year as opiates
Most of us are well aware of the time course for AWS. See image below for a reminder. Remember that alcoholic hallucinosis, which often occurs early in the course, is a distinct entity from the more life-threatening delirium tremens (DTs). 

Our standard treatments for AWS include: 1) Benzodiazepines (the historic gold standard), 2) anti-epileptic drugs (including valproic acid, gabapentin, carbamazepine), and 3)Alpha-adrenergic blockers (clonidine, precedex and guanfacine).

Phenobarbital is a new old drug! It has recent (and growing) evidence for non-inferiority to the historic goal standards -- benzodiazepines-- as treatment for AWS. And in several studies, it is superior. It acts at both the GABA and NMDS receptors.

Studies of phenobarbital in AWS demonstrate:
  • shorter ICU stays, decreased ICU admissions
  • shorter hospital length of stay (LOS)
  • lower rates of mechanical ventilation
  • lower rates of adjuncts (including precedex, benzos)
Granted these studies, most recent -- between 2017 and 2023-- are all small (~100 patients each) and there are variable comparisons between different protocols, BUT in taken in totality, phenobarbital seems to have similar and/or better evidence for treatment of AWS compared to traditional treatment. If the goal is to decrease ICU admits and/or use of benzodiazepines in at-risk populations, phenobarbital is probably the tool of choice. 

So, how should it be used?

Dr. Bowen showed us 5 protocols from 5 different healthcare systems: Swedish (WA), BMC (MA), Yale (Connecticut), Contra Costa (CA) and ZSFGH (CA). While they have their own unique differences, there are three main steps to using phenobarbital in AWS:

1) Assessing risk for AWS (i.e. risk stratifying patients who screen positive for AUD for high risk AWS)
2) Understanding the risks/benefits of phenobarbital in different populations
3) Dosing protocols

Assessing for risk of Severe AWS
The benzo-sparing protocol that we currently use in the hospital -- often referred to as the Stanford Protocol --  uses the PAWSS score to risk-stratify for high risk AWS. Alternate protocols use other criteria to designate patients as high risk. These high risk characteristics include 1) a history of intubation or prior ICU stay for AWS 2) BAL>200 with signs of withdrawal despite high BAL, and/or 3) a personal history of seizures or DTs.

Whatever the methodology, the first step in treating AWS is the determination of this risk stratification. This will lead you to either treat or not treat prophylactically for AWS.

Understanding Risks/Benefits and Contraindications of Phenobarbital
Those of us who didn't "grow up" using phenobarbital may be less familiar with the pharmacology and/or risks and contraindications for phenobarbital. Here are a few important ones:
  • Concomitant high dose administration of benzodiazepines. Several protocols use <8mg lorazepam as an acceptable cut-off for liberal admin of phenobarbital. If a patient has received >20mg of lorazepam, phenobarbital is contraindicated
  • Respiratory depression (as a result of benzos or otherwise) makes patients high risk
  • Advanced cirrhosis WITH active hepatic encephalopathy and/or AMS is considered a contra-indication. But a prior history of HE or well controlled HE is not. Of note, cirrhosis itself is NOT a contraindication to use of phenobarbital
  • Patients on chronic seizure meds (including phenobarbital) is a relative contraindication
  • Pregnancy
  • Renal dysfunction (CrCl<30)
  • History of allergy and/or Steven's Johnson syndrome
It is important to check for drug-drug interactions with phenobarbital (warfarin, OCPs, furosemide). 
Also important to know that the half-life of phenobarbital is 40-140 hours, this is VERY long, which is a big reason it is desirable to use in AWS (which can go on for days), but also to know it will stay in a patient's system and can have an impact over several days time. 
Patients with cirrhosis will clear phenobarbital more slowly, so a PO taper and/or repeated doses are less needed
AND that if administered slowly (either via slow IV or IM), the risks of respiratory depression as a negative side effect are decreased. 

Phenobarbital Protocols

Actual administration and dosing protocols vary widely across systems. Variations include: 
  • Weight based vs. standard dosing
    • 5 to 10 to 15mg/kg IDEAL BODY WEIGHT loading doses vs. 130mg vs. 260mg doses
  • Single dose vs. subsequent 
    • as often as q30-60 minutes dosing with respiratory effects noted prior to additional dosing
  • IV vs. IM administration (vs. PO)
    • +/- PO taper after initial admin
  • Location of administration
    • ED vs. ICU vs. step-down units vs. medical floor patients
See images below for some of the protocols. Note variations in dosing, admin, etc. The final image is a table comparing the main components of the protocols:









summary Table comparing different phenobarb protocols in AWS


Here's what I took home from Dr. Bowen's talk:
  • Phenobarbital is a safe tool in our toolbox for management of AWS in many of our high risk patients
  • We should risk assess all patients for AWS and consider phenobarbital for patients who we deem "high risk"
  • Phenobarbital should ideally be administered early -- within the first 24 hours of that risk assessment
  • We should be careful about the use of all adjuncts -- including benzos, as well as benzo-sparing protocols -- when using phenobarbital due to its long half-life and risks for respiratory issues
  • We need a system for monitoring respiratory depression in patients who receive phenobarbital
  • We can give a large loading dose (10-15mg/kg IBW) in a highly monitored environment (e.g. ED or ICU) or lower amounts (e.g. 130-260mg x 1) with frequent rechecks for respiratory depression
  • Phenobarbital is safe in cirrhotic patients (except those with active HE) but with the understanding that it probably stays around even longer for these patients. No need for PO taper. 
I look forward to collaborating with Dr. Bowen and our ED in the coming months so that we can use phenobarbital more systematically for our high risk patients for AWS. 

An Integrative Approach to Substance Use Disorder (Adachi Serrano, 12/13/2023)

 A recording of this presentation is available HERE

***

Many many thanks to Dr. Katya Adachi Serrano, SRFMR Alumna class of 2014 and Integrative Medicine Fellow (2015) on An Integrative Approach to Substance Use Disorders. Dr. Adachi Serrano blends her family medicine background with training in herbal and integrative medicine, plus a board certification in addiction medicine. In so doing, she spoke thoughtfully on topics from buprenorphine  induction to  herbal supplements for SUD to spiritual support. This is definitely a presentation worth watching! The link is above.

For those of you who prefer the written word, my notes below:

Dr. Adachi Serrano took us through the case of a young man suffering from alcohol use disorder (AUD) and repeated episodes of alcohol withdrawal syndrome (AWS). She started by grounding us in the concept of the tribal MAT Echo Clinic Wellness Wheel (see below): consideration of the mind, body, spirit, and community, as a means to think about the care of patients with SUD. 

Tribal MAT Echo Clinic "Wellness Wheel"

The Body

Medication assisted treatment -- or medication for addiction treatment (MAT)-- is the gold standard for treatment of patients with many SUD. SUD is just like any other chronic disease, Dr. Adachi Serrano argues: SUD has a gradual onset, affects all races/ethnicities/SES, it relapses and remits, is partially relieved by lifestyle changes. And so, we should approach SUD like any other chronic disease.


AWS; Typical treatment for acute alcohol withdrawal involve either long-acting benzodiazepines (chlordiazepoxide or diazepam), or gaba-ergic meds (e.g. gabapentin) tapered by either dosing interval or amount daily. See these patients daily, says Dr. Adachi Serrano.

AUD: The best medication option we have for chronic management of AUD is naltrexone, which decreases cravings and suppresses the pleasure people get from drinking ETOH. This can be dosed 25-50mg qhs, Precaution with: acute hepatitis, liver enzymes 3-5x normal, decompensated cirrhosis, active opioid use. Common adverse events include headache, nausea, drowsiness. Some people also experience anhedonia. 

Another option is long-acting naltrexone (aka vivitrol), which is an IM injection 380mg given q4 weeks (after a 4 day PO trial of naltrexone oral). An alternative maintenance medication is acamprosate, which is dosed 666mg TID (2 tabs of 333 TID). Side effects include diarrhea and adherence. A third option is Gabapentin 100-300mg daily to TID.

OUD: Standard treatment or opiate withdrawal syndrome (OWS) is supportive measures (e.g. clonidine, hydroxyzine, trazodone, ondansetron). Maintenance for OUD is either suboxone or methadone, usually dosed 2-4mg q2-4 hours, max 8mg on D#1. Sublocade, a long-acting injectable buprenorphine, may be available to better-insured patients, dosed at 300mg SQ x 1-2 doses, then 100mg q28 days. Finally, naltrexone is a third maintenance option, but you must be opioid free for minimum of 5 days (ideally 7-10 days). This is idea for patients who do not use opioids. Clonidine is often used as an adjunct during the withdrawal phase 0.1-0.3mg q1 hour. 

Dr. Adachi went on to talk about the value of herbal supplements for SUD, as an adjunct to the standard allopathic medications. Three main categories of herbs: adaptogens, nervine, and nutritive. 

1) Adaptogens help the body to adapt to stress, "normalizing influence on physiology". They tend to be derived from the roots of plants that grow in hardy environments and rugged terrain, and their effect is thought to be due to the hormones the plants themselves have generated in these rugged environments.

  • Ashwagandha, dosed 400-500mg BID helps to normalize GABA activity in the body. This can be helpful in all forms of SUD. Precautions: nightshade allergy, hyperthyroid
  • Rhodiola, derived from arctic regions, is very stimulating. Dosed 100-200mg. Caution: can sometimes be too stimulating, especially in stimulant use, w/d and recovery. Thought to "get the fire burning again"
  • Eleutero aka Siberian Ginseng, increased dopamine, thereby increasing energy levels
  • Licorice also can be helpful, sweet and easy to take
2) Nervines: have a direct effect on the nervous system. The following nervines are considered "calming nervines" which can be helpful in recovery:
  • Skull cap, a GABA agonist, 850-1200mg daily in tincture (very concentrated)
  • Valerian, another GABA agonist
  • Lavender, 1-2 tsp in 8 oz of water
3) The last category are the Nutritives, which are nutrient rich and thought to support the body. One of Dr. Adachi's favorite is milky oats extract, which is nourishing to the nervous system and also increases dopamine. 

The Mind

Mental health treatment should be considered an essential part of MAT. All patients with SUD should be screened for underlying mood disorders (including anxiety, complex PTSD), learning disabilities, and ADHD. These underlying disorders should be treated with both medications and therapy.

Trauma: 90% of patients with OUD report a history of trauma, 80% have child sexual abuse, emotional abuse, or violent trauma. We should see SUD as a marker of trauma and work to normalize  in a therapeutic way. Here Dr. Adachi Serrano used the image of a record playing in our ear-- "our early experiences teach us messages, like a record playing in our mind" that we may not even know is playing. 


This is where mindfulness practice comes in, also CBT. Introduce the concept of brief CBT for a non-therapist (for those of working in primary care practices where mental health services can be hard to come by). Dr. Adachi Serrano took us through brief CBT (see image) and reminded us that the goal is to rewrite the core message, overwrite the music playing in our head: "I am valuable. I am loved. I matter. I am safe"


She encouraged us to teach residents to cultivate their own dopamine -- "give yourself a high five and do a little dance". But in order to prevent burnout in primary care, really important to use motivational interviewing techniques and meet patients where they are at-- know the stages of change and tailor your intervention to the patient's stage, not your desired outcome.

The Spirit

This leads us to spiritual and somatic treatments. Often in patients with SUD there is a temporal disconnect between what the body is experiencing and the present, i.e. the spirit is not living within themselves. This is categorized in different cultures with different words, including susto, soul wound, etc.

EMDR and somatic experiencing may be helpful treatment modalities.

In addition, there are many other spiritual treatments: sweat lodges, talking circles, spiritual counseling, limpiezas.

Meaning is important, and looking for ways to experience normal emotions  -- a safe space to feel both sadness and JOY. To look for one's core values, to recognize safety.

The Community

Healing community is necessary to support recovery. Patients need to ask if their community is supportive to recovery? Is their current community a barrier to recovery? Dr. Adachi Serrano described a person in recovery as being in a "bubble". When you are early in recovery, you are cleaning up your space, trying to keep your bubble strong. If your bubble doesn't have a thick shell, you don't want to be in an environment that is going to stress or test that bubble. You also need the community to provide support around that bubble, to protect the individual while they are vulnerable. This involves tending to the community, offering community -- in whatever healthy forms are available.

Group settings for SUD include: NA, AA, SMART Recovery groups, Talking circles, spiritual communities, etc. Creating connection to community, culture, family. Find space for new identity to grow. We may need to help patients guide them through a change of identity, friends/support circles to see the opportunities that are there.

Primary Care for Patients with Alcohol Use Disorder (Lund, 11/15/2023)

A recording of this presentation is available HERE

***

Deep gratitude to our Assistant Program Director and local expert, Dr. Erin Lund, for an excellent presentation on Primary Care Management of Alcohol Use Disorder (AUD). Living in the wine country, this is a medical problem that sometimes hides in the shadows of social acceptability and cultural norms. 

Dr. Lund covered a broad range of topics related to AUD, including healthy drinking, screening for risky drinking, assessing severity of the use disorder and treatment (both acute withdrawal and chronic management). Alcohol, consumed around the world, is one of the oldest-used psychoactive substances, 2/2 only to caffeine.  There is documentation of humans indulging in alcohol dating back 9,000+ years.

(Note: much of the ETOH literature includes gender-based nomenclature. In an effort to be gender inclusive, I will use the following terms in this blogpost: AMAB: assigned male at birth, AFAB: assigned female at birth)

Healthy drinking

Standard drinks vary based on alcohol content and volume: 12 oz beer, 8-9 oz malt liquor, 5 oz wine, 1.5oz distilled spirits (see image below). Healthy drinking guidelines are based on age and gender assigned at birth: for adults under age 65, no more than 4 drinks for AMAB or 3 drinks for AFAB on any one day AND no more than 14 drinks/week for AMAB and 7 drinks/week for AFAB.


Risky Drinking

Rates of risky drinking and AUD are shockingly high in the US: 12-month prevalence of 13.9% of AUD (7% mild, 3% moderate and 3% severe) and a lifetime overall prevalence of 29%. Typically people AMAB have higher rates than people AFAB, but this is changing, as alcohol becomes more socially acceptable for AFAB patients. People ages 18-35 have the highest prevalence. 

A binge episode is defined as: 

  •  >4 drinks for AFAB >5 drinks for AMAB,
  • at least one day in the last 30 days

>5 days of binge drinking=HEAVY USE

Heavy use is NOT the same as AUD, but intervention should be considered, as heavy use is associated with increased all-cause mortality, earlier death, increased automobile accidents, increased accidental and intentional injuries, and social and legal problems.

Alcohol Use Disorder

DSMV outlines AUD* as "a maladaptive pattern of alcohol use" within the past 12 months, as defined by at least two of the following criteria:

  • Drinking larger amounts/longer periods than intended
  • Efforts/desire to cut down
  • Great deal of time spent obtaining, using, recovering
  • Craving
  • Recurrent failure to fulfill role
  • Continued use despite social/interpersonal problems related to drinking
  • Activities given up (social, occupational, recreational)
  • Recurrent physically hazardous behavior
  • Continued use despite physical or psychological problems
  • Tolerance
  • Withdrawal

*Mild AUD: 2-3 criteria, moderate 4-5, severe ≥ 6

Screening for AUD

USPSTF gives a grade B recommendation to screen ALL adults for unhealthy alcohol use. Here's the good news: when we screen, it makes a difference! Patients actually cut back and change their use habits. People live longer. 

There are a variety of standardized screening tools; these include:

  • 1Q screen: How many times in the past year have you had more than 4 drinks/day (AFAB) or 5 drinks/day (AMAB). Positive with answer of >1
  • AUDIT-C (which is what is used at SRCH, see image below)
A nice thing about using the AUDIT-C is that the results can be used to guide treatment. An AUDIT-C score of 0-3 indicates low risk drinking (no intervention needed), a score 4-5 is moderate risk (brief intervention indicated). A score 6-7 merits a brief intervention + psychotherapy and consideration of pharmacotherapy. A score of 8-9 is an indication for pharmaceutical intervention + psychosocial intervention+/-specialty care management. A score of 10+ merits urgent specialty referral.

Treatment of AUD
Treatment of AUD includes both psychosocial and pharmacological treatments. It also involves both an acute stage (active use, withdrawal) and a chronic stage (maintenance, harm reduction, reduction).

Psychosocial support involves both formal treatment programs (inpatient and outpatient programs), many of which are based in Peer Support. These include but are not limited to AA, smart recovery, etc.
Pharmacological management involves, at the minimum, 1 of 3 FDA-approved medications. These meds can be started in the inpatient or outpatient setting. We have great room to improve in this area. A study in 2012 found that only 8% of US patients with AUD were being treated with medications. 

Considerations in starting meds for patients should include goals (e.g. abstinence vs. reduced use), relevant health factors (e.g. comorbidities like chronic pain, cirrhosis, etc.), and external barriers. 

Alcohol Withdrawal Syndrome (AWS)

The slide pasted below demonstrates the timeline for Alcohol withdrawal and some recommendations in terms of who can withdraw in an outpatient setting vs. those who need inpatient support.

Alcohol withdrawal is most likely to occur in patients who have been drinking for more than 2 weeks and who have abruptly stopped drinking. Once a person is 5 days past their last drink, they are outside the window of acute withdrawal. And one can move onto the maintenance stage of management of AUD. 

Providers should use standardized scores to keep an objective assessment of a patient's alcohol withdrawal. There are several, including the CIWA (10q, objective + subjective report), the SAWS (10q, patient-completed), and the SEWS (7q, clinical assessment)

CIWA: <10: very mild AWS, 10-15 mild AWS, 16-20 modest AWS, >20 severe (DTs)


SAWS: patient scores their own symptoms in past 24 hours, <12 is mild AWS, >12 is moderate to severe AWS


SEWS

The severity of AWS dictates the level of care the patient needs. Patients with mild-moderate withdrawal can be managed in the outpatient setting, assuming they can also 1) have consistent follow-up 2) take PO meds 3) have friend/relative/support person 4) have no prior hx of DTs 5) have no high risk comorbidities (physical or psychiatric) that would make home withdrawal unsafe (e.g. extreme anemia, decompensate cirrhosis) 6) do NOT have polysubstance use.

All other patients should be managed in an inpatient setting.

Pharmacotherapy for AWS

Goal of treatment of AWS is to help patients withdraw safely (prevent DTs, seizures, death) and reduce likelihood of relapse. This can be accomplished using either benzodiazepines (e.g. chlordiazepoxide or lorazepam), which was the previous gold standard, and/or with benzo-sparing protocols, most of which use anticonvulsants and anti-adrenergic medications. 

Anticonvulsants: phenobarbital, gabapentin, valproic acid, carbamazepine

Anti-adrenergic: clonidine, propranolol, guanfacine, precedex

Everyone with AWS should get folic acid (1gm/day) and vitamin B1 (thiamine, 100mg/day)

The idea behind the benzo-sparing protocols is that these medications are AS effective in safe withdrawal with less abuse potential than benzos. There are still evolving studies in this area, and some agents have more evidence than others. These protocols vary based on location and experience. 

See below the draft algorithm (not yet live) at SRCH, which screens for patients who may safely withdraw outpatient and uses fixed dose gabapentin (300mg TID vs. 600mg TID).


Older algorithms use fixed vs. on demand dosing of lorazepam and/or chlordiazepoxide. You can find a link to those older guidelines HERE

Chronic Management of AUD

Okay, finally, moving onto medications that prevent relapse and/or help people cut back and/or help people remain abstinent. Most studies look at a period of time of 12-16 weeks of reduced use and/or abstinence, but in clinical practice a minimum of a year of maintenance therapy is recommended, particularly if there is a high risk of relapse.

FDA approved: naltrexone, Acamprosate, disulfiram

  • Naltrexone: 50mg PO daily OR 380mg IM monthly, reduces risk to any drinking (NNT 10) and heavy drinking (NNT 12), injectable has evidence for reducing number of heavy drinking days. Reduces craving and pleasurable effect of drinking. Contraindicated in liver failure, concomitant opiate use (within 7 days). Pregnancy is relative contraindication.
  • Acamprosate 333mg, 2 tabs TID daily. Reduces return to any drinking (NNT 12), reduces withdrawal associated dysphoria. Has mixed evidence on efficacy compared to placebo. Contraindicated in renal failure (GFR<30) and pregnancy. 
  • Disulfiram: oldest med on the market for AUD (1949), anticipation of feeling sick discourages use. Blinded studies don't show great effect, but open label studies do show reasonable effect. 

Non-FDA approved but have some evidence: topiramate, baclofen, gabapentin, ondansetron, sertraline, semaglutide

  • Topiramate: non-FDA approved, may reduce cravings, impulsivity and post-withdrawal dysphoria, 100-300mg/day (titrated up over 6 weeks from 25mg day starting dose, increase by 50 mg per week), BID dosing recommended. Contraindicated in pregnancy and renal failure.
  • Gabapentin: non-FDA approved, may be continued after using for treatment of AWS, 300mg-600mg TID for maintenance dosing to reduce cravings and return to drinking

Alcohol Use Disorder and Alcohol Withdrawal: Outpatient Management (Robledo 3/30/2022)

Thanks to Dr. Robledo for an excellent review of AUD and AWS at Grand Rounds this week. A link to a recording of the presentation is HERE.

Note: in place of male/female to discuss gender differences, Doctor Robledo used "assigned female at birth" (AFAB) and "assigned male at birth" (AMAB). These abbreviations are included in this summary.

Alcohol use


Appropriate alcohol use is considered no more than 1 standard drink/day (=7/week) for AFAB, 2/day (=14/week) for AMAB. Risky alcohol use is anything more than this amount. 

Risky alcohol use is drinking that can lead to health consequences and may develop into alcohol use disorder. 

Alcohol use disorder is a pattern of drinking that significantly impairs health and functioning. 

Binge drinking: drinking in a way that increases blood alcohol level >0.08 in 2 hours, generally >4 drinks at once for AFAB, >5 drinks at once for AMAB

Alcohol Use Disorder (by DSM-V Criteria)
https://creativecommons.org/licenses/by/4.0/
  • mild 2-3 symptoms
  • moderate 4-5 symptoms
  • severe >6 symptoms
  • early remission: abstinent between 3-12 months
  • sustained remission: abstinent  >12 months
We all know that AUD is extremely prevalent in our society, but do you know how prevalent

29% lifetime prevalence
10.5% of children live with someone who has AUD
95K deaths/year
1/10 deaths in working age adults
$250 Billion/year in costs

COVID has been associated with alcohol use: 7.7x the odds ratio of getting COVID if you have AUD.

Screening tools for AUD 
The USPSTF recommends that all adults (>18) and all pregnant patients be screened annually for AUD. Here are some tools:
  • SASQ: "How often in the past year have you had >4 drinks at one time (if AFAB), >5 drinks at home time (if AMAB)
  • AUDIT-C: 3 questions, screening for at risk drinking (if +, should be followed by AUDIT-10)
  • ADUIT-10: 10 questions
  • CAGE questions: Cut down, Annoyed, Guilty, Eye opener (more looking at alcohol dependency)
https://www.aafp.org/afp/2013/1101/p596.html

https://www.aafp.org/afp/2002/0201/p441.html


Brief intervention for those who screen positive:
  • be empathetic and caring
  • state the medical findings in a non-judgemental way (e.g. signs of cirrhosis on exam, lab results, symptoms)
  • educate patients regarding AUD
  • advise patients to cut down/stop drinking
  • assess their stage of change/readiness for change
  • regular follow-up
Don't forget to use your motivational interviewing skills!

***

Alcohol Withdrawal Syndrome requires that someone 1) stopped after heavy/prolonged use and 2) two or more of the symptomsm describes in table 1 below:

https://www.clinicaladvisor.com/home/topics/psychiatry-information-center/alcohol-withdrawal-individualized-care-and-pharmacologic-treatment/

80% of patients will have totally uncomplicated withdrawal and do not need to be hospitalized
Higher risk folks include: those with hx withdrawal seizure or DTs, those with hx of numerous withdrawals, those with medical comorbidities (e.g. CHF, cirrhosis, traumatic brain injury)

You can use the PAWSS score or the CIWA-Ar score to predict who can safely withdraw in the outpatient setting.

  • PAWWS score available here
  • CIWA-Ar score
    • mild (<8 just need rest and hydration, 8-10 may need some PRN meds)
    • moderate 10-18 should receive standing meds iwth a taper
    • severe/complicated: >19, to hospital for monitored withdrwawa
  • SAWS score: patient self-assessment (mild <12, severe >12)
PAWSS, Maldonado 2015

SAWS: https://www.aafp.org/afp/2013/1101/p589.html


Treatment of AWS should be based on your scoring, classically using the CIWA score plus/minus the SAWSS score to determine treatment
  • Level 1: CIWA<10, SAWS <12: supportive care, prn gabapentin, carbamazepine
  • Level 2: CIWA 10-18, SAWS>12: close follow-up (daily in person, daily video), benzodiazepine (chlordiazepoxide vs. valium/lorazepam) in fixed vs. PRN dosing
  • For more information on specific drug dosing, you can refer to this paper in AAFP from 2016https://www.aafp.org/afp/2013/1101/p589.html
Supportive care for AWS in addition to medication
  • daily visits x at least 5 days
  • education
  • low stimulation home environment
  • fluids
  • 400mcg folic acid, 100mg Thiamine x 3 days
Treatment of AUD should involve CBT as well as  medication assisted therapy to help patients reduce and/or abstain from alcohol. The most commonly used option is Naltrexone (available in oral form 50-100 mg daily vs. injectable monthly form, aka Vivitrol). Additional medications to consider include acamprosate and disulfiram (less desirable, more punitive), as well as fluoxetine (if concomitant depression/anxiety and gabapentin, which has variable studies. More information in the chart below

https://www.aafp.org/afp/2016/0315/p457.html

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