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)

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)

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.

Vaping: Medicine or Menace (Ling, 11/13/2024)

 A recording of this presentation is available HERE.

***

This was a mind-blowing and practice-changing Grand Rounds this week -- so much to learn and understand about vaping (aka e-cigarettes) as primary care providers. The speaker, Dr. Pamela Ling, is the Director of the UCSF Center for Tobacco Research and Education, and she shared so much valuable data and on-the-ground information about the current state of vaping. The title of her talk was Vaping: Medicine or Menace?

Here's what I learned:

First off, the vaping industry is rapidly evolving. Unfortunately, the science, while forthcoming, lags behind an agile and sneaky industry. The first e-cigarettes came on the market in 2009 and looked like little "fake cigarettes" (they even featured a puff of smoke). Now, vapes come in a shapes and sizes and with increasingly concentrated (and flavored) solutions and changing delivery devices. 

E-cigarettes create an aerosol by using a battery to heat up liquid that usually contains nicotine, flavoring, and other additives. Users inhale this aerosol into their lungs. E-cigs can also be used to deliver cannabinoids, such as marijuana and other drugs. 

OMG check this out! These are vaping products confiscated from high schools in California and North Carolina (1000 products from 25 high schools) from an MMWR publication.

While cigarette smoking levels are down in California (and SoCO), vaping is on the rise, and the youngest have the highest rates.

In fact, SoCo teens seem to have higher rates of vaping than California teens overall.

And, unsurprisingly for those of us who care for marginalized populations, more vulnerable kids (based on gender identity, race, etc) have even higher rates of e-cigarette use

Note that while Sonoma County average of e-cigarette use is 12%, certain groups have MUCH higher rates, namely: SoCo gender questioning kids and kids who identify as black/African American, and Native American.

In addition to vaping nicotine, cannabis is increasingly popular; almost as many people use cannabis as tobacco now in the US. And while smoking is still the most common way to consume cannabis, edibles and vaping are both increasing.

Of note, older generation vapes contained far LESS nicotine. Newer vapes include chemicals that make higher concentrations more palatable and more appealing. As you can see in the image below, whereas older versions (The JUUL) contained the equivalent of about 1 pack of cigarettes, newer versions (e.g. Flum pebble) now contain up to 30 packs of cigarettes. This leads to increased nicotine consumption and dependence. And because of price controls and taxation cigarettes, vaping can save money, which certainly also influence habits and behaviors. Whereas a carton of cigarettes may cost upward of $50-85, a single vape (the equivalent of 3 cartons) costs less than $20 online. 

The same is true for rising THC concentrations in cannabis vapes. 

Do E-cigarettes help people quit smoking?

It is important to understand that there is SOME evidence of the use of e-cigarettes to promote smoking cessation, though the evidence is weak at best. E cigarettes are not approved by the FDA for smoking cessation, though they are recommended by the UK NHS due to this evidence. Under RCT conditions, earlier generations of vape products have been shown to be more effective than nicotine replacement therapy. You can see this data below summarized in the Cochrane review below. 

This has not borne out in population level observational studies-- in other words, when used as a consumer product, e-cigarettes do not help with cessation. Also important to note that the e-cig market is evolving extremely rapidly and the products are increasingly appealing to young people (this is not a coincidence).

Isn't vaping better for us than smoking?

Stella Tomassi and colleagues published a study of young adult vapers who never smoked compared to smokers using quantitative PCR to detect DNA damage (as a marker for future cancer).  They found a dose-dependent formation of DNA damage in oral cells of vapers who had never smoked tobacco cigarettes as well as exclusive cigarette smokers. They also found more damage seen in heavier users, users of pod vapes and sweet flavors) independent of nicotine levels.  

Recent studies of the epigenetic effects of tobacco smoking and e-cigarette use found similar changes in DNA methylation among people using cigarettes and people using e-cigarettes, changes that were associated with lung carcinogenesis.

While we do not have direct human data on vaping and lung cancer outcomes, these newer biomarkers of DNA damage and epigenetic changes are likely to be informative for lung cancer risk.

When people switch completely from cigarettes to e-cigs, there is definitely a decline in those biomarkers. So maybe vaping IS better than cigarette smoking. Unfortunately, many people try to convert to vaping but then continue intermittently also smoking cigarettes. Interestingly, the evidence shows that these "dual users" do not reduce their exposures to carcinogens.  

In terms of cardiovascular disease: a recent study published in NEJM 2024 found that CV disease risk from vaping was NO different than CV disease risk from smoking. So for CV risk the answer is NO.

But here's perhaps one of the most important take home points: dual use (using BOTH vapes and cigarettes) is definitely the worst for patients. Check out this summary table below showing the risk of disease appears higher for dual users. . .

Dr. Ling's closing advice to clinicians:

• Ask about vaping to engage in a cessation conversation
• Ask about both nicotine and cannabis vaping
• Encourage to treat nicotine vapes like any tobacco product
• Encourage complete switching not dual use
• Longer term transition off vaping products (using nicotine-replacement)

Ariel Thomas-Urlik, MPH from the Sonoma County Department of Public Health, who helped make this presentation possible, also shared some local information about local laws aimed at preventing widespread sales of nicotine products to children and adults.  

Did you know that SoCo has a minimum price of $10/pack for cigarettes? No coupons or discounts are allowed to be applied. 

Also California law currently prevents flavored tobacco products from being sold in physical retail stores, and a new law going into effect this week prohibits County of Sonoma do NOT ALL e-cigarette sales in physical retailers that sell tobacco (cannabis dispensary do not apply). While retailers continue to sell, DPH is using volunteer decoys to catch retailers who are violating this law. There is less access in SoCo, and we know that when access goes down, people become more interested in quitting. 

A new state law CA AB3218 which goes into effect on January 1, 2025 makes online purchase of vapes illegal in the state of California!

Methadone in Hospitalized Patients (Bowen & Aguilar 11/6/2025)

 A recording of this presentation is available HERE. 

Deep gratitude for our two Addiction Medicine Fellows, Drs. Bianka Aguilar and Anna Bowen, for an important and concrete presentation this week on Methadone in Hospitalized patients. They will be back in the spring with another Addiction Medicine presentation!

Here are my favorite pearls:

1) Starting methadone in the hospital decreases self-directed (AMA) discharges (30% vs. 59.6%), reduces all-cause readmission rates (27% vs. 41%), and decreases risk of endocarditis, osteomyelitis, and septic arthritis. I was taught that we should be "cautious" in the hospital about starting methadone if there wasn't a long-term plan for follow-up, but this is no longer true. If a patient is motivated to start methadone and it is indicated, we should do it. There are many new algorithms that can cross taper people easily from methadone to buprenorphine IF they are unable to get methadone through an outpatient treatment center.

2) Fentanyl in our drug supply has changed the treatment of opioid use disorder (OUD).  Recent studies are showing the methadone may be superior to buprenorphine in terms of treating OUD in fentanyl users. Methadone for OUD also appears to have higher retention rates. 

3) Traditional methadone induction involved weeks of up titrating doses until methadone was at therapeutic levels; newer studies, particularly in the fentanyl era, have found that quick starts--  higher starting doses, 30-40mg on D#1, and quicker up-titrating, increasing by 10-15mg, per day is safe and effective.

4) While methadone is known to lengthen the QT interval, not everyone on methadone needs serial or even baseline EKG monitoring. Most guidelines recommend an EKG at initiation of methadone only for patients with other cardiac risk factors (e.g. known prolonged QT, CAD, CHF, etc.)  AND once methadone doses near 100mg daily. This is a dose response side effect. We should remember to look at other medications that can also prolong QTc to see if those can be altered/discontinued. A QTc of >500 is not an absolute contraindication to treating with methadone, but the clinical scenario merits review (e.g. medication review)

4) Some people are "rapid metabolizers", meaning that single daily dose of methadone may be insufficient to help with cravings and treat their opiate use disorder. This is known to be true in pregnancy, but can also occur in some patients. Rapid metabolizing most often manifest as someone who appears appropriately treated by a certain methadone dose by 2-4 hours after their dose (maybe even a little sedated), but then 12 hours later is experiencing s/sx of withdrawal or cravings. We can potentially help their case to receive methadone BID by checking "peak" (2-4 hours after the dose) and "trough" (right BEFORE their dose) serum level of methadone.

Practical tips for methadone in hospitalized patients:

• Consult the addiction medicine fellows (on call schedule on Epic)
• Document a 1 year history of OUD
• Use the COWS score to monitor s/sx of withdrawal
• We have 2 Methadone clinics in Santa Rosa: DAAC and SRTP. When initiating methadone, contact one of these clinics ASAP to arrange intake.
• There is a federal 3 day exception for patients being discharged from the hospital, to whom we can prescribe methadone. Current local help is available via Creekside Pharmacy vs. SSRRH ER.
• Offer all patients naloxone on discharge. 
• Use the California Bridge website for help, including guidelines and algorithms.
• 
  
  
  
• Keep your eye out for newer studies showing quick start algorithms

• 

  Toronto Perinatal Addiction Medicine Team
  
  

  
  
  

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. 

Addressing Benzodiazepines in Primary Care (Threlfall, 2/28/2024)

A recording of this presentation is available HERE.

***

Many thanks to local psychiatrist, Dr. Alex Threlfall for an excellent Grand Rounds presentation this week: Addressing Benzodiazepines in Primary Care. As we all know, benzodiazepines (heretofore BZD) play a major role in the national opioid epidemic, and despite lack of organized attention to the issue, addressing concomitant BZD use and misuse is an important public health and safety issue for all our patients.

My summary:

BZD were historically the number one prescribed medication in the world (in 1960s and 1970s). They are frequently involved in opiate overdose deaths. The combination is very dangerous. After opioids, BZD are the most commonly caused agent involved in intentional and unintentional overdoses. 

Let's start with six areas of risk (i.e. patients in which you should NOT start BZD).

History of:

• Mental health conditions associated with trauma
• Substance use disorder (SUD)
• Elderly (>65)
• Chronic pulmonary disease (e.g. COPD)
• Women of child-bearing age
• Chronic pain (with or without opiate use)

Trauma

Trauma is rampant in our patient population, upwards of 20-50% of the general US population report a history of childhood physical or sexual abuse. It's even higher -- 70%-- in populations with depression/anxiety, SUD, chronic pain and functional pain disorders like IBS. Sexual abuse directly influences development of SUD.

**THERE IS NO EVIDENCE SUPPORTING THE USE OF BZD in TRAUMA or PTSD (either acute trauma or long term treatment). In fact, there are  studies that suggest that adding benzos at the time of a traumatic event can increase PTSD, can lead to addiction, and that benzos can even reduce the efficacy of psychotherapy by blunting therapeutic effect.

Benzodiazepines are highly addictive. 

VA data from 2016 shows that 58-100% of patients prescribed BZD will become physically dependent, 50% of patients with a pre-existing SUD will develop a BZD use disorder, and 5-10% of patients newly on BZD will develop SUD. 

Benzodiazepines are particularly risky for older adults.

We have not paid attention to our patients as they have aged. People prescribed a BZD were often not offered a safer alternative. In a study of geriatric patients on BZD, <1% had been referred for psychotherapy, 10% were co-prescribed an opioid. The most common indication for BZD in these patients were insomnia and anxiety. Despite this evidence of harm, population studies show increasing rates of BZD rx in elderly patients and failure to discontinue, particularly in people >80 years old and Trend women>> men.

All adults on new or continuous BZD rx

The older you are, the more likely you are to be on a BZD. This is a problem. White people have "better access" to BZD than their non-white cohorts and higher rates of BZD misuse. 

Risks of BZD are real.

Falls, hip fractures, sedation, cognitive impairment, motor vehicle accidents. While an observational study from ~10 years ago found that being on BZD, people were more likely to develop dementia. It is not true that BZD causes dementia, but it does cause cognitive impairment. All BZD are on the Beer's list of medications not safe for elderly patients. Number needed to harm is 2: for every person you successfully treat with BZD, you will harm two. 

As in everything, prevention in the best strategy. In other words, avoid new starts of BZD.

Okay, so when are BZD actually indicated as first-line therapy?

• Acute crisis setting (e.g. patient floridly manic, psychotic, agitated patient => 2mg lorazepam)
• Bipolar mania
• Severe panic
• Alcohol withdrawal (though we are moving away from BZD use)
• Seizure disorders
• Procedures & planned events (e.g. for patients with intellectual disability who need sedation)
• Phobias (e.g. flying, but beware)

If prescribing BZD for these conditions, you should use the lowest effective dose, avoid alprazolam (aka xanax) whenever possible (super short, very fast acting, too much reinforcement) and restrict prescription for 2 weeks or less.

Of note, BZD are THIRD line treatment for anxiety

First line is pharmacotherapy -- SSRI, SNRI-- and/or evidence based psychotherapy (CBT, mindfulness). 

• SSRIs/SNRIs are all effective for anxiety disorders. Dr. Threlfall's favorites are escitalopram and sertraline. Start super low (2.5 or 5mg escitalopram=> target 5-20mg 25 mg sertraline, target 100-200mg). People with anxiety will often respond sooner than with depression. If they tolerate, will respond within 1-2 weeks. 
• Part of efficacy is you! You need to reassure patients, check in (1 week to be sure started/tolerating), then see again in 2-4 weeks. You hold them psychically through the process
• Buspirone can be effective either standing or PRN. Literature doesn't do it justice. Titrate 10-30mg TID. Watch for serotonin syndrome. 
• uses for Vets for prn to cross the GG bridge, take prn
• It's not sedating, but still helps with anxiety.

Second line: gabapentin>>pregabalin>>propranolol>>clonidine

                    amitriptyline*>>nortriptyline

                    hydroxyzine*>> diphenhydramine

• clonidine for pts with extreme anxiety 0.1mg TID can be pretty effective (BP and adherence and rebound BP issues). Can use 0.1mg patch, can co-treat hypertension
• *DON'T use amitriptyline in EVER elderly b/c of anti-cholinergic effects
• *DON'T use hydroxyzine and diphenhydramine in older adults >65 (people with cognitive impairment). Effects wear off pretty quickly, get tolerant quickly

Another note, BZD is NOT FIRST LINE TX for INSOMNIA (per all professional societies)

First line

All recommend CBTi as first-line treatment for insomnia

VA has a free app, free to download, easy to use, is effective: "CBTi coach"

Free app from the VA

Second line options

• Melatonin: 1-2mg max (long acting)
• Prazosin (if nightmares/trauma or waking startled): 1mg to start, up by 1mg every 4 days, as much as tolerated, stop at 3mg to see again. VA says 12-18 is safe dose (Threlfall maxes out at 8mg). Side effects: orthostasis, sedation, congestion
• Trazodone, low dose, start at 25mg, rarely go about 150mg. Above 200mg getting into anti-depressant range. Can get serotonin syndrome if on SSRI. People don't like hangover effect
• Mirtazapine: more sedating at lower dose 7.5-15mg, above that lose the sedation effect (but keep increased appetite). People when starting mirtazapine can experience heavy sedation during the day for 3-5 days. Try it when that sedation is not going to be too bothersome. Restless legs
• Doxepin: recent study 3-6mg safe and effective in older adults. On Beer's list, anti-cholintergic but at low dose, better safety profile
• Amitriptyline/nortriptyline 

Third line

• Hydroxyzine, diphenhydramine
• Ambien (Zolpidem) or Temazepam if you really need to, particularly if concomitant bipolar disorder

How to initiate BZD:

1. Rare if you ever do

2. Short symptomatic relief 1-2 weeks

3. Get psychiatry consult

4. Make sure you have the conversation with the patient, "This is going to be short term"

5. Be very clear about the risks

6. Discuss exit strategies (taper, switch)

7. Be the only prescriber

8. Document failure of other trials of meds

9. CURES, urine drug screen

10. BZD treatment agreement if going more than 2 weeks

Use these only Total Daily Dose (TDD): Lorazepam 2mg TDD, Clonazepam 1.5 TDD, Diazepam (he doesn't like, people seek out the effect, 15mg TDD), Temazpeam 30mg TDD

There is evidence that if patients are informed of the risks of BZD, they want off them. In one study in which pharmacy sent patients taking BZD information on the risks of BZD: 62% self-started BZD taper, 21% were completely off at 6 month follow-up. Give people the opportunity to get off with education, encouragement and support. 

One final note, getting people off BZD is not not without risk. In fact, there is new evidence that there is real risk in discontinuing BZD. When people are taken off BZD, they die more, fall more, go to the hospital more, have more suicide attempts and non-fatal overdoses. We have to pay attention to the effects of long-term BZD on their neurophysiology. When people are really attached, get them on the lowest dose possible. And don't use them every day -- intermittent use is MUCH safer than chronic use. 

Tapering is a team-based approach. Use your nurse, your MA, a colleague, behavioral health. Don't start right away. Establish relationship. You ARE the medicine in the room. Establish that before making any changes. It goes a long way. 

Multidisciplinary Pain Management (Revelis 12/6/2023)

 A recording of this presentation is available HERE. 

***

Thank you to Dr. Yulia Revelis, SMGR Pain Management physician, for an excellent Grand Rounds presentation this week on Multidisciplinary Pain Management. Dr. Revelis, who is fellowship trained in pain management, is a relatively new addition to SMGR. Dr. Revelis took us systematically through how she assesses and treats pain complaints in her clinic. I was most impressed with her pragmatic approach to pain and her simple advice to believe patients when they complain of pain.

Here are the rest of my notes:

• Acute pain: days to weeks (after acute injury, surgery, etc.)
• Subacute pain: <3 months
• Chronic pain: >3 months

Most common pain, no surprise, is low back pain, followed by neck pain, joint pain (knee, shoulder, hip), and TBD or "total body dolor", which is all-body pain.

Dr. Revelis encouraged us to always go back to the history and physical when assessing pain. Also consider imaging, medications/interventions/treatments, social components, and psychiatric components ("depression and anxiety go hand in hand with chronic pain, and it is a vicious cycle")

She covered a few key tools to help in your assessment of pain. These include the following (links are live when possible)

• Oswestry Low Back Pain Disability Questionnaire
• SF-36
• McGill Pain Assessment
• Fibromyalgia Questionnaire
• Pain in Advanced Dementia (PAINAD)

These are all tools to quantify pain, its impact on activities of daily living and quality of life, and can often be used to track benefit of interventions offered.

To evaluate pain, Dr. Revelis encouraged us to go back to the history: get detailed description of the pain, its location, associated factors, chronicity, family history and social history. Then do a focused exam including inspection, palpation and any indicated special testing. "You don't always have to get imaging," she cautioned, "only when it is clinically appropriate to do so." 

Pain management is multifactorial

• Physical therapy
• Medications 
• Interventional options
• Counseling/CBT

Physical therapy offers long-term solutions gives people autonomy and self-determination with regards to their pain. She is a big big fan.

Medication options are many:

• topical meds (including lidocaine patches, Voltaren gel, and compounded creams including ones that have TCA or topical gabapentin)
• NSAID (care with elders, contraindications)
• Acetaminophen is an excellent pain med and is often under-dosed!
• Anti-spasmodic (including cyclobenzaprine, baclofen, tizanidine) her first line is cyclobenzaprine (Flexeril) 5mg at bedtime x 2 weeks max, "start low, go slow". Only rx'd as needed and should almost always be rx'd in conjunction with PT
• Gabapentinoids (gabapentin and pregabalin), particularly for neuropathic or radicular pain
• TCA/SSRI/SNRI: duloxetine particularly helpful in fibromyalgia
• Opioids should be A LAST RESORT, really only indicated for cancer-pain and acute pain, not adequately treated with all of the above

Dr. Revelis is able to over her patients injections, when appropriate, using either ultrasound or x-ray guidance. These include injections of neck, epidural injections, knees, hips, etc. 

It is important to screen for addiction/addictive behaviors in patients with chronic pain and remember that chronic pain specialists are not the same as addiction specialists. Pts with chronic pain exhibiting addictive behaviors should be evaluated by addiction specialists.

When to refer to pain specialist?

• chronic non-cancer pain
• cancer pain
• acute on chronic pain
• most importantly, patients who WANT to be helped

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