#12 Listener Q & A on Substance Use Disorders

July 6, 2023 | By Kenneth Morford

Audio

Video

Put on your Primary Care Cat-Hat

We are thrilled to be back to kick off season 2! Carolyn Chan, MD (@CarolynAChan) soon to be at the University of Cincinnati, Shawn Cohen MD (@ShawnCohen_MD) at Yale University, Kenneth Morford MD at Yale University, and Natalie Stahl MD (@NanouTheNomad) at Greater Lawrence Family Health Center are back and on this episode, they answer burning questions submitted by listeners. We cover topics such as targeted naltrexone, increasing buprenorphine doses, treating kratom dependence, and so much more! 

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By listening to this episode and  completing CME, this can be used to count towards the new DEA 8-hr requirement on substance use disorders education.

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The Curbsiders Addiction Medicine are proud to partner with  The American College of Addiction Medicine (ACAAM) to bring you this mini-series.  ACAAM is the proud home for academic addiction medicine faculty and trainees and is dedicated to training and supporting the next generation of academic addiction medicine leaders. Visit their website at acaam.org to learn more about their organization.

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The Curbsiders are partnering with VCU Health Continuing Education to offer FREE continuing education credits for physicians and other healthcare professionals. Visit curbsiders.vcuhealth.org and search for this episode to claim credit. 

Show Segments

• Intro, disclaimer 0:00
• Host one-liners/lightning round  3:48
• Switching from prescription opioids to methadone or buprenorphine  8:48
• Harm reduction approach to buprenorphine 13:31
• Adjusting buprenorphine doses  18:37
• When to consider extended-release naltrexone for OUD 27:18
• Medical withdrawal management facilities 33:11
• Kratom and opioid use disorder   39:00
• Starting AUD medications in the hospital  42:38
• Targeted naltrexone for AUD  44:51
• Anxiety, PTSD, and SUDS  47:30
• MOUD & benzodiazepines 50:26
• Stimulant Use Disorder and Medications 53:61
• Changing the culture around addiction treatment:  57:16
• Outro 1:03:10

Listener Question & Answer Pearls

1. Methadone and buprenorphine are first-line treatments for OUD. Injectable naltrexone is often thought of as second line for OUD, though may be appropriate for certain patient populations.
2. Kratom is an herb that can cause physical dependence and symptoms of opioid withdrawal which can be treated with buprenorphine.
3. Naltrexone for the treatment of alcohol use disorder can be started before hospital discharge.
4. Targeted naltrexone is taking naltrexone PRN on days when an individual has alcohol cravings or anticipates an event that may trigger alcohol use.
5. When caring for individuals with co-occurring substance use and mental health disorders, such as PTSD and anxiety, be sure to adopt an integrated and comprehensive approach to treatment
6. Individuals on benzodiazepines should not have medications for opioid use disorder such as methadone or buprenorphine withheld from them.
7. Contingency management remains the gold standard in treating stimulant use disorders.
8. Promising medications for stimulant use disorders that have some evidence include extended-release naltrexone/bupropion, mirtazapine, and topiramate.

# 12 Listener Q&A – Show Notes

Opioid Use Disorder (OUD)

How do you transition from prescription opioids to methadone or buprenorphine? 

Transitioning from prescription opioids to methadone is pretty straightforward because they are both full opioid agonists. Since they have the same mechanism of action, you can start methadone on the same day as the last dose of prescription opioids. However, there are some unique characteristics of methadone. It has a long half-life and takes about 5-7 days to reach a steady state. If you increase methadone too quickly, it can result in dose stacking that may cause sedation and increase the risk of overdose. 

Calculating a morphine milligram equivalent (MME) conversion of a prescription opioid, such as oxycodone, to methadone is not always accurate (Fudin, 2017). For individuals with OUD, methadone can be started at 20 to 30mg daily and increased by 5-10mg every three days until opioid cravings and withdrawal symptoms are adequately controlled. If someone does not have OUD and is not taking high doses of prescribed opioids, starting doses are often more conservative, such as 5-10mg TID, with 5-10mg dose increases every few days.

For buprenorphine, there are two primary options for transitioning from prescription opioids. The first is called a traditional start or induction which involves stopping the prescription opioid, waiting for withdrawal symptoms to develop, and then starting buprenorphine (SAMHSA TIPS 63, 2021). It’s important to clarify whether the patient is taking a short-acting or long-acting opioid to determine how long to wait before starting buprenorphine. Patients taking short-acting opioids, such as oxycodone IR, can typically start buprenorphine 12 hours after their last dose of oxycodone. 

The second option is a low-dose initiation protocol (Cohen, 2021). With this approach, the patient continues taking their full dose of prescription opioids while buprenorphine is started at a low dose. Buprenorphine is then slowly increased each day until a dose of at least 12 or 16mg, at which point the prescription opioid is stopped. This approach takes more time but may be preferable as it avoids or reduces the need for patients to experience the discomfort of withdrawal, and reduces the risk of precipitated withdrawal.  

Can buprenorphine be used as a form of harm reduction?

Buprenorphine is a treatment for OUD and should be provided alongside a harm reduction approach. For example, while a patient’s goal may be to continue using opioids (e.g. not abstinence), they might use buprenorphine to reduce their use and/or protect themselves from developing withdrawal symptoms.

In these cases, buprenorphine can still be started via a low-dose protocol with the goal of reaching a therapeutic dose of 16-24mg daily. Ongoing opioid or other substance use should not be a reason to stop buprenorphine. 

Fentanyl is lipophilic, which has made it more challenging to start buprenorphine, as heavy, chronic fentanyl use causes this full agonist to linger in an individual’s system. Fentanyl use has increased the odds of experiencing precipitated withdrawal when taking buprenorphine within 24 hours of use (Varshenya, 2022).

When is it appropriate to increase the dose of buprenorphine in a patient who has been stable on the same dose for a long time?

Put on your primary care hat!  Are there other medical reasons why a patient is experiencing physiologic symptoms similar to withdrawal? Start by getting more history. 

• Determine whether the patient has really been on the same dose during their treatment. Have they changed formulations?
• Are they taking buprenorphine as intended for the formulation (e.g. buccal vs sublingual)?
• Are they taking buprenorphine with food, beverages, or while smoking cigarettes that can reduce the amount of active medication in their system? 
• Are there factors increasing the patient’s metabolism of buprenorphine, such as pregnancy or CYP3A4 inducers (e.g., rifampin)? 

It’s also important to clarify the patient’s symptoms. While it’s rare to develop opioid withdrawal once a patient has reached a stable dose of buprenorphine with daily adherence, they may be experiencing symptoms from another process that feel similar to withdrawal. These instances require further diagnostic workup. 

Patients may develop cravings that are no longer controlled on their current dose of buprenorphine, which is an indication to increase the dose. If a patient is on a subtherapeutic dose of less than 16-24mg daily (e.g. notably this dose is for generic SL buprenorphine and brand name Suboxone)  a dose increase may be appropriate. We typically do not increase the dose above 32mg daily due to the high receptor occupancy causing near-maximal effects of the medication (Greenwald, 2003).

After making a dose adjustment, be sure to check in with the patient to see if it helped. 

Is long-acting injectable naltrexone a good option for OUD? 

Methadone and buprenorphine are first-line treatments for OUD. However, there are instances when injectable naltrexone is an appropriate treatment. Some examples include patients who don’t want to be on an opioid agonist treatment, want to taper off methadone or buprenorphine, have co-occurring alcohol use disorder and OUD, and in some cases, adolescent patients.   

The XBOT trial compared the effectiveness of extended-release naltrexone vs buprenorphine-naloxone (Lee, 2018).  There are some nuances in the study design and clinical interpretation, which are described in this paper by Ajazi, 2022. 

How can medically managed withdrawal facilities help patients start methadone or buprenorphine and connect them to ongoing care? 

Some suggestions from the group include:

• Rapid methadone titration for patients using fentanyl
• Connect patients to ongoing OUD treatment, harm reduction services and behavioral counseling
• May be beneficial for patients who had challenges starting buprenorphine in the outpatient setting
• Can offer adjunctive medications for withdrawal symptoms such as benzodiazepines and ketamine that may be more challenging to offer in an outpatient setting. 

Do you have pearls to help patients stop using Kratom? 

Kratom is an herb that can have stimulant effects at lower doses and opioid effects at higher doses as it acts as an agonist at the mu-opioid receptor. Individuals can develop a physical dependence on kratom and experience symptoms consistent with opioid withdrawal due to its action on the mu-opioid receptor. A number of case reports have described the effect of buprenorphine/naloxone on managing symptoms of kratom withdrawal (Weiss, 2021). 

Alcohol Use Disorder & Alcohol Withdrawal 

Can naltrexone be started for alcohol use disorder before hospital discharge? 

In Dr. Cohen, Chan, Stahl, and Morford’s expert opinion, naltrexone can be started for AUD in the hospital before discharge or on the day of discharge.  There is a meta-analysis that suggests a period of abstinence before starting naltrexone may be associated with larger effect sizes for abstinence and reduced heavy drinking compared to placebo (Maisel, 2012), though this in part may just be an effect of how certain studies were designed.  Overall these medications are effective for the treatment of AUD (Jonas, 2014; Anton, 2006 ), and in our opinion, there is a lack of studies designed to specifically answer the question of whether a period of abstinence before starting MAUD medications is truly clinically beneficial. 

What is targeted naltrexone or the Sinclair method for alcohol use disorder?

Targeted naltrexone, sometimes called the Sinclair method, involves taking naltrexone only on certain days when a patient has alcohol cravings or anticipates attending an event that might trigger alcohol use (Santos, 2022). While naltrexone may benefit patients who wish to abstain from alcohol completely, it has the strongest evidence for helping patients reduce heavy drinking (Jonas, 2014). 

It’s important to recognize that non-abstinence treatment outcomes, such as reduced alcohol use, are evidence-based and can benefit patients with alcohol use disorder (Witkiewitz, 2021). Patients should be informed that naltrexone may make drinking alcohol less pleasurable, but it’s safe to combine with alcohol and will not result in an adverse reaction as is the case with disulfiram. 

How do you approach treating anxiety and PTSD in patients with substance use disorders? 

When caring for individuals with substance use disorders who also experience anxiety and post-traumatic stress disorder (PTSD) symptoms, it is crucial to adopt an integrated and comprehensive approach to treatment. Here are some general steps to consider:

• Comprehensive Assessment: Begin by conducting a thorough assessment of the individual’s substance use disorder, anxiety symptoms, and PTSD symptoms. This evaluation should include information about the person’s substance use history, trauma history, mental health symptoms, social support, and any previous treatment experiences.
• Integrated Treatment Plan: Develop an integrated treatment plan that addresses both the substance use disorder and the co-occurring anxiety and PTSD symptoms. This plan should be tailored to the individual’s specific needs and preferences. Collaboration with a multidisciplinary team, including mental health professionals, substance use counselors, and medical providers, is highly recommended.
• Stabilization: If the person is actively using substances, the initial focus should be on stabilization. This may involve medically supervised withdrawal management, in the case of an alcohol use disorder, and addressing any immediate health concerns related to substance use. It’s often challenging and may be impossible to obtain an accurate assessment of psychiatric symptoms when a patient is acutely intoxicated or experiencing withdrawal symptoms.  
• Evidence-Based Psychotherapy: Incorporate evidence-based psychotherapy approaches to address anxiety and PTSD symptoms. Cognitive-behavioral therapy, including cognitive processing therapy and prolonged exposure therapy, has shown effectiveness in treating PTSD. Additionally, treatments such as dialectical behavior therapy and acceptance and commitment therapy can be beneficial for managing anxiety symptoms.
• Dual Diagnosis Support: Provide ongoing support and education about the interaction between substance use disorders, anxiety, and PTSD. Encourage participation in support groups, peer support programs, and mutual aid groups specifically tailored to individuals with dual diagnoses.

It is crucial to remember that every individual is unique, and treatment plans should be personalized accordingly. Regular assessment and adjustments to the treatment approach may be necessary to ensure the best possible outcomes for individuals with substance use disorders and co-occurring anxiety and PTSD symptoms.

How do you approach caring for patients who are receiving MOUD and also taking benzodiazepines? 

There is limited evidence to guide care for patients receiving methadone or buprenorphine for OUD who also take benzodiazepines. In 2017, the US Food and Drug Administration released an updated drug safety communication recommending that medications for OUD should not be withheld from patients taking benzodiazepines or other sedatives (FDA, 2017).  Do not withhold MOUD from individuals with OUD who take benzodiazepines. 

Which medications have the most promising evidence for treating stimulant use disorder? 

There are currently no FDA-approved medications for treating stimulant use disorder. However, a number of medications have been studied for this indication. 

The ADAPT-2 trial was a double-blind, two-stage, placebo-controlled trial comparing the use of extended-release naltrexone (380mg Q3 weeks) plus oral extended-release bupropion (450mg per day) for moderate to severe methamphetamine use disorder (Trivedi, 2021).  The primary outcome was at least 3 methamphetamine-negative urine samples out of 4 samples obtained at the end of stage 1 or stage 2. They found that those who received ER naltrexone-bupropion (13.6%) were more likely than placebo (2.5%), to meet this clinical endpoint with an overall treatment effect of 11.1% (P< 0.001). 

Mirtazapine has also been investigated for stimulant use disorder. A study published in 2019 that included cisgender men and transgender women who have sex with men, treated with 30 mg of mirtazapine for 24 weeks in conjunction with counseling, showed a significant reduction in methamphetamine use (Coffin, 2020).

Topiramate has been studied for the treatment of cocaine use disorder with mixed results. A study investigating topiramate (titrated to 150 mg twice daily) combined with amphetamine salts found higher rates of three consecutive weeks of abstinence than placebo over 12 weeks (Levin, 2012).

For patients who use stimulants and have attention-deficit/hyperactivity disorder (ADHD), treating ADHD with psychostimulants may alleviate the need for non-prescription stimulants (Levin, 2018). Of note, psychostimulants cannot be prescribed for stimulant use disorder without co-occurring ADHD in the US. 

Contingency management, which is a non-pharmacologic behavioral intervention, remains the first-line treatment for stimulant use disorder.  The number needed to treat is 3-5 for stimulant use disorder (Crescenzo, 2018). Unfortunately, contingency management is often difficult to access in most places, despite its demonstrated cost-effectiveness (Murphy, 2015).

Goal

Listeners will learn how to address common addiction medicine topics on opioid use disorder, alcohol use disorder, stimulant use disorder, and co-occurring diagnoses.

Learning objectives

After listening to this episode listeners will…  

1. Describe how to prescribe targeted naltrexone for the treatment of alcohol use disorder.
2. Describe a medication that can be used to manage symptoms of kratom physical dependence.
3. Discuss an approach to treating co-occurring psychiatric diagnoses with substance use disorders.
4. List medications that have some evidence to support their use to treat stimulant use disorders. 

Disclosures

Drs. Chan, Cohen, Morford, and Stahl report no relevant financial disclosures. The Curbsiders report no relevant financial disclosures. 

Citation

Morford K, Cohen S, Stahl N, Roy P, Chan, CA. “#12 Listener Q and A on Substance Use Disorders”. The Curbsiders Addiction Medicine Podcast. https://thecurbsiders.com/addiction   July 6th, 2023