Clinical Roundtable

It's possible to start buprenorphine while someone is already taking full agonist opioids like oxycodone without first having them withdraw. Buprenorphine is typically dosed TID-QID for pain. The easiest way is to use a single transdermal buprenorphine patch for up to 7 days while they are quickly tapering off their full agonist opioid over a few days and starting small amounts (ex 1mg TID sublingual buprenorphine) on day 3-4. Increase SL buprenorphine over days 5-14 until withdrawal symptoms and pain are better controlled. (The buprenorphine patch is challenging to get covered by insurance. Consider 340B pharmacy or cash price for a single patch).

Bernese style microdosing only uses sublingual (SL) buprenorphine. People would continue on full agonist opioids and start taking 1/4 of a 2mg buprenorphine film at first, and then slowly increase the amount and frequency of SL buprenorphine until they are switched. Full agonist opioids typically stopped 5-7 days into starting SL buprenorphine.

Transitions from methadone would take longer and go slower, but can be successfully done, even at doses higher than 30mg.

It must be noted that this approach is based on the anecdotal reports and that there is no systematic evidence supporting the safety and effectiveness of this method.

Absolutely. The National Academy of Medicine published a 2019 report entitled "Medications for Opioid Use Disorder Saves Lives" which not only cites the evidence that "medication-based therapy is effective across all treatment setting studies to date" but goes on to state "Withholding or failing to have available all classes of U.S. Food and Drug Administration–approved medication for the treatment of opioid use disorder in any care or criminal justice setting is denying appropriate medical treatment."

Yes. Evidence from the BHLI PCARE van in Baltimore, MD demonstrates 2/3 of those initiating treatment returned for a follow-up visit and 1 in 5 were ultimately linked into long-term treatment.
(Krawczyk et al. 2019)

Low-threshold treatment is the philosophy that there should be minimal barriers to access buprenorphine and other medication for opioid use disorder treatment. Evidence supports many reasons for low-threshold treatment including new findings and recommendations: Home inductions are safe and effective, buprenorphine should not be withheld from patients taking benzodiazepines, relapse should not stop buprenorphine treatment but rather increase the level of care, behavioral treatments should only be provided as desired by patients, drug testing should not be punitive but help guide conversations.
(Martin et al. 2018)

The simple answer is education through a hospital wide initiative. It was developed by a committee of experts, led by the service chief. It was critical that the leadership of the hospital not only approved this initiative, but was involved in its development. First, we educated our providers and staff as to why we are doing this. Specifically, the benefits of buprenorphine and the dangers of OUD. Next, we educated everyone about the process to ease any discomfort and anxiety they may have had. Finally, we provided real-time support for those who had questions about the clinical use of buprenorphine.

We are fortunate that the VA has an abundance of outpatient resources. First, there is a walk-in clinic able to temporarily prescribe buprenorphine. This minimizes the need for the emergency room to write prescriptions. Next, there is a fully staffed buprenorphine-specific clinic that sees patients two days per week. Finally, there are a variety of intensive outpatient and inpatient treatment programs. Reliable outpatient follow-up is critical to the process. We ensure proper follow by providing a variety of resources (those listed). We have a cohort of providers available to prescribe buprenorphine in variety of locations around the state. We also have a walk-in clinic available M-F while awaiting for the clinic appointment.

Sublocade contains an excipient, NMP, that may cause adverse effects in pregnancy. The FDA label for Sublocade states: "In published animal reproduction studies with NMP, an excipient in SUBLOCADE, preimplantation losses, delayed ossification, reduced fetal weight, developmental delays and reduced cognitive function were reported at doses equivalent to the doses of NMP via SUBLOCADE. Decreased pup survival at 2 times the dose of NMP and malformation and postimplantation losses were reported at 3 times the dose of NMP via SUBLOCADE. In animal reproduction studies with SUBLOCADE, SUBLOCADE administered subcutaneously to pregnant rats and rabbits during the period of organogenesis at a buprenorphine dose equivalent to 38 and 15 times, respectively, the maximum recommended human dose (MRHD) of 300 mg caused embryo lethality, which appeared to be attributable primarily to the SUBLOCADE vehicle. In addition, reduced fetal body weights, increased visceral malformations and skeletal malformations were observed in rats and rabbits at a buprenorphine dose equivalent to 38 and 15 times, respectively, the MRHD. These effects were also observed with the SUBLOCADE vehicle alone, but the skeletal and visceral malformations in rat appear at least partially attributable to buprenorphine [see Animal Data]. Based on animal data, advise pregnant women of the potential risk to a fetus." Pregnancy was an exclusionary criteria for participating in the clinical trials evaluating the safety and efficacy of this medication. First-line medication treatments for OUD in pregnant women are sublingual buprenorphine or methadone (not Sublocade). Dr. Lofwall advises use of contraception among women of child-bearing age who are receiving Sublocade along with a pregnancy test prior to each Sublocade injection with the plan to switch to a non-NMP containing treatment for any woman who becomes pregnant while on this injectable monthly medication.

We consider relapse a part of the recovery process; we know that most patients take at least 3 months after starting the program to start doing well. We remind patients that relapse is part of recovery and honesty is highly valued; they must be honest with themselves and with us to fully embrace recovery and for our team and other patients to support them. We cannot help them if we do not know what’s going on. Relapse can be an important learning opportunity. It is valuable to engage in a brief discussion with the patient about the precise circumstances of the relapse. When did it occur? Where did it occur? What was the patient thinking and feeling just before the relapse? What positive and negative effects resulted from the use of the drug(s)? If the patient used opioids and felt them, strong consideration should be given to increase in buprenorphine dosage. If the patient is helped to understand the circumstances and experiences that led to the relapse, the patient can use this information to be prepared and prevent a similar relapse in the future. If patients relapse and relapse over and over, then we are clearly not helping them and they might need more support. We will then work with them to enhance their support, through such strategies as:

• Referral to higher level of care (inpatient or intensive outpatient) and once they graduate and are doing better, they can come back to our group
• Encourage attendance at 12 step programs (AA, NA) a certain number of days/week
• Encourage getting regular therapist and seeing frequently

We try not to “kick patients out of group” as we know that if they end up “back on the street and using” their prognosis is much worse, so we try to work with them and develop a plan based on where they are at.

Despite the many misconceptions about “these patients” with addiction who enter into recovery, our patients are seeking help and are generally very motivated, engaged, appreciative, and grateful. They also know that if they don’t behave they will not be welcomed into group. That being said, to minimize disruption to clinic during the time our group patient check-in at the front desk, we recommend having a separate line for group check-in or a separate space entirely (we use a computer-on-wheels to check in patients near the group room). It is helpful to have designated front desk staff who are part of your GBOT model so that they can respond to any GBOT patient needs/request appropriately without creating confusion at the front desk. It is also advisable to have security around and available, but our experience has been, again, that this group is generally VERY well behaved and creates minimal ruckus.

We have a recovery based model but we also embrace harm reduction. One good thing about motivational interviewing is that we can work with them to become less harm reductive and more recovery based. If it interferes with the group process we see them individually. We indicate that patients need to be “present” in the group setting. If they cannot be present then we refer them to individual treatment.

Some of the best groups I’ve had have been three. Optimal group size is probably 6-8 and maximum would be 10 in terms of dynamics. Small groups allow for more time with each individual and going above 10 can be problematic in that regard. However if the group is too small it can seem overwhelming to the patients to be outnumbered by the team members.

Patients sign a Group Consent Form as well as a Consent Form for Treatment. The Group Consent Form explains the treatment in a group setting. With concern about federal confidentiality regulations, it’s important to have your forms vetted by someone knowledgeable of the law to ensure that you are adhering to these regulations.

Somewhat yes. I think that’s more extensive than the actual guidelines. Fifteen minutes is a bit much. I would say five minutes beforehand. If their mouth is dry they can swish and spit just so there is some moisture. There is no talking while it’s dissolving which can take 5-10 minutes. And then I would wait five minutes afterwards before eating and drinking. However I think fifteen minutes is too much to ask in terms of what people can tolerate.

The vast majority of patients that come to me from another provider are on 24 mg of buprenorphine. There are many non-pharmacologic reasons for this: physicians read that it is the maximum dose, they feel it is the safest dose, it’s what the patient wants, etc. If they are stable on that dose, it’s usual pretty easy to get them down to 16 mg. I like to get them down to 16 so there is some wiggle room if I need to increase for pain management.

It is generally problematic to continue to use marijuana or abuse alcohol when beginning treatment for an opiate use disorder. From the harm reduction perspective, I have a degree of tolerance because for many patients who are in a dangerous situation with opioids having them enter treatment for opioids could be life or death while using marijuana is not a life threatening drug. However if patients are completely unwilling to discuss their particular use of alcohol and marijuana and consider changes, this is a red flag which suggests that more intensive treatment approach will be necessary.

No we don’t have to have those things to start treatment. For patients in dire situations, having them delay treatment to first get the lab work done would possibly lose the patient to their continued opiate abuse. Product literature says that getting liver enzymes is recommended. Is it essential? No. Some patients don’t have the money for these additional tests and trying to get these tests done would be problematic.

When someone is coming in for an induction, the assumption is that they are coming in with significant withdrawal. I don’t think they should be driving to the office if they’re that sick. So they’re at risk for that reason alone. People generally feel better by the 2nd or 3rd dose, but not everybody has the same reaction. Some people get energized from buprenorphine, some get sedated. So I think that it is a wise decision when you are giving an induction to require that they have someone drive them to and from the clinic.

The rule of thumb is that you’ll be able to wean 80% of patients off of buprenorphine after one year without too much difficulty. Of the remaining 20%, some(~10%) you will be able to wean off with more difficulty, i.e. requiring adjuvant medications, and some (~10%) you will not be able to wean off completely. Over the years, those “unweanable” patients will fill your buprenorphine slots.

I consider these based on the symptoms. I look at their patient/family history to see what has worked for them in the past. As an example, I may use mirtazepine for anxiety and sleep. It has a good sedating effect and if the patient has underlying anxiety it can to help. I may use clonidine if there are withdrawal symptoms. If they are on clonidine for over a week you should not discontinue abruptly but rather do a gradual taper mainly to avoid rebound increase in blood pressure.

In general for more minor surgical procedures such as dental work and ambulatory surgical procedures I would continue the buprenorphine and compliment with acetaminophen and NSAIDs. If the buprenorphine dose is low I would increase temporarily as needed. For patients who need major surgery, I would discuss their pain management prior to the surgery. If they are concerned about pain, I would taper them off buprenorphine (not completely), use the full agonist for pain and afterwards return them to their full dose of buprenorphine.

My opinion is that it is illegal. The Drug Treatment Act of 1972 and the DATA 2000 makes it clear that there are two medications that are currently approved by the FDA for the maintenance and withdrawal management of opioid use disorder. The first is methadone which has been in use for the past fifty years. The other drug that can be used is the sublingual formulations of buprenorphine. The use of any other opioid product to treat opioid use disorder doesn’t meet the criteria and is therefore not allowed.

I don’t believe there is a maximum dose of methadone. You may have to get permission from the state opioid treatment authority for certain amounts. The largest dose I’ve seen is 1400mg a day. The patient was functioning well and it helped his pain. Most of overdose deaths with methadone occur in the pain sector. Methadone can be very tricky and careful monitoring is necessary.

It can take a while for urine tests to become negative. People have been suffering for many years so you can’t expect this problem to go away after a few treatments. Maybe it’s an indication that the patient should be placed on maintenance rather than tapering.

Yes but not as much as when people are on chronic opiates for pain. The methadone experience has been remarkable – people who are doing well on methadone seem to be able to stay on the same dose of methadone for years. People have ascribed that to the fact that methadone is an opioid agonist but that it also has NMDA(a glutamate receptor) antagonist effects, and this may moderate the development of tolerance.

We have less experience with buprenorphine but my own experience is that people generally don’t require an increase in dose and will often go down in dose to see what happens. If they still feel good they’ll usually stay at that new dose. Generally tolerance does not create a problem for opioid agonist therapy.

Not everyone will get addicted: two people could ingest the exact same amount of substances, and one might end up addicted and the other not. What is different in the brain of the person who does get addicted? All of us will have a higher-than-usual dopamine spike in our limbic system if we are given an "abusable" substance. For some people, if that substance is given repeatedly, this will lead to a cascade of neurological changes that lead to a powerful and strong drive within the limbic system to drive the body forward to use that substance again. At the same time, the prefrontal cortex (home to our willpower and rational thinking), becomes much weaker and is no longer able to inhibit the limbic system. It's basically a situation where the "brakes are out of the car," and a person finds that even if they desire to stop using a substance, they are not able to do so. They find that they have "lost control" and that their behavior is occurring with little conscious input and with much associated shame and regret. This causes a downward spiral -- as we already know that people who are feeling ashamed are driven even deeper into shame when others punish them or shame them further.

This is a challenging patient, “late in their addiction career.” These are often the difficult questions as these are often the sickest patients. The options will be limited with a late stage case like this. Methadone doesn’t treat benzodiazepine or cocaine dependence so you’ll need other strategies, including medication, to treat these other disorders.

Discussing naloxone and overdose prevention with family is sometimes a good mechanism for expressing your concern about how he is doing. It’s a good message with which to reach him.

I prefer to refer to the sample as either positive or negative. As professionals managing patients in a medical context we should avoid street slang when discussing these as it stigmatizes the disease.

Monitoring routinely conveys an expectation. If you only monitor when you suspect something, it may stigmatize the monitoring. Watching people take the medication can be important to ensure they are taking it the right way, as it testing them afterwards to determine a baseline for their levels. Pill counting is another important tool at your disposal. By establishing an expectation of monitoring, people tend to be more honest in their self reports. It should be a normal part of what you do with all patients.

The less people adhere to a program, the more structure they need. That means seeing them more often, more frequent monitoring and perhaps intensifying treatment. I believe monthly prescriptions are a privilege and if they need to earn that privilege by doing well. It’s important to document our actions very clearly because that’s what protects us and protects our patients.

Exposure to hepatitis C virus results in development of an antibody. Antibody testing is how we screen for Hepatitis C. To determine if a patient has chronic hepatitis C infection, you must check an HCV viral RNA level. A qualitative or quantitative test can be ordered to determine presence of viremia or level of viremia, respectively. Liver function tests are not routinely helpful in determining if a patient has chronic hepatitis C infection.

Although buprenorphine is metabolized by the liver and there is a concern that it may cause liver enzyme elevation, the relative safety of use of buprenorphine in patients with chronic hepatitis C has been established. (Sokya M. et al. Am J Addict. 2014 Nov-Dec;23(6):563-9; Tetrault JM et al, J Subst Abuse Treat. 2016 Sep;68:62-7; Saxon AJ et al, Drug Alcohol Depend. 2013 Feb 1;128(1-2):71-6). Periodic monitoring of liver enzymes in patients with chronic HCV infection treated with buprenorphine is reasonable.

There is a long history of using a token economy to reward people for positive behaviors. It’s been practiced successfully for decades. Cash can be problematic as it may be used to purchase illicit substances. Rewards such as gift cards or small gift items have been demonstrated to be very effective in shaping positive behaviors as they mirror the small successes that patients experience in recovery.

There is definitely a roll and as a psychiatrist I would work collaboratively with a neurologist to order and interpret results.

We want to avoid excessive sedation when people have TBI so it’s best to start “low and go slow.” It is also important to avoid other potential CNS depressants. If a patient has co-occurring pain, consider dividing the usual buprenorphine dose into a TID schedule. In general the dose is the same and the goal is the same – to address craving and withdrawal while avoiding any significant side effects.

QID Dosing (4 times a day) is sometimes beneficial for patients with chronic pain. I had a patient with neuropathic pain and chronic headaches. Had her on 8 mg TID but we switched her to 4 QID she had an improved benefit. The total daily dose was lower but the dosing schedule change seemed to provide additional analgesic benefit.

In our practice all of our patients have some history of addiction. My view is that those co-occurring problems are so intertwined that you’re always treating both problems. Any decrease in pain or distress decreases the chance for relapse so you’re still treating the addiction. So any time you’re adjusting the buprenorphine dose for analgesic benefit you should consider the benefit or risk to the relapse prevention as well.

While the structure of daily supervised dosing is important, some patients simply feel better on methadone than buprenorphine. Some patients continue to crave (and use) opioids at even high doses of buprenorphine (e.g. ~32mg/day). Patients with more extensive histories of opioid use (higher doses, longer years, particularly if a longer history of heroin use), may be more successful on methadone than buprenorphine. The most common adverse effects of buprenorphine, for which patients in my clinic seek to transition from bupe to methadone are persistent nausea, and/or a sense of dysphoria.

No. Although methadone is a full mu agonist, with multiple medication interactions, and thus has a much narrower therapeutic index than buprenorphine, there is no special training required to “prescribe” methadone. To be specific, any provider with a DEA license can prescribe methadone for pain (which can be very problematic, see discussion below about methadone as an analgesic). However:

• Methadone for the treatment of opioid use disorder is administered in a specialized, licensed clinic, and is thus “ordered” by the clinician. No special license is required to “order” methadone in such a clinic (but getting the appropriate training/mentoring is highly advisable).
• A methadone clinic, also known as an Opioid Treatment Program, or “OTP,” (an antiquated title, as referenced in federal statutes), is required to have a physician present for a face-to-face evaluation at the time of induction into methadone treatment (but can, under certain conditions, be performed via telemedicine).
• After the induction orders are placed, NPs and PAs can order dosing adjustments without the physician present, but the clinic medical director (physician), must co-sign dosing adjustment orders.

No. It is impractical in the setting of most methadone clinics, and unnecessary to get an EKG at the time of induction for all patients. I refer to the AATOD QTc Interval Screening – Policy and Guidance Statement (2012) guidelines for EKG screening, which AATOD recommends the following for management of cardiac conduction risk in methadone maintained patients:

1. Consider a baseline and follow-up 12-lead ECG for patients with “a history of arrhythmia, prolonged QTc, a family history of premature death, and/or other significant arrhythmia risk factors” on admission or for suspected arrhythmia risks in ongoing methadone maintained patients.
2. Referral should be made for cardiac consultation for “known or detected cardiac conditions affecting heart rhythm, unexplained syncope or seizures or a significant increase in QTc from the baseline if known.”
3. Patients at-risk should be educated on cardiac symptoms to watch for e.g. “racing” heartbeat, dizziness, seizures, or fainting spells and encouraged to contact the clinic” and medical provider and/or emergency services immediately.

AATOD believes that the safeguards outlined above along with individualized induction practices will allow clinicians to optimize safety during methadone treatment. Informed and appropriate clinical monitoring and follow-up will be the best protection for patient safety. Prospective clinical trials are needed before routine ECG screening can be endorsed.’

This is not well studied, and as discussed in a very thorough review article, by Mannelli, et al (Curr Drug Abuse Rev. 2012 Mar;5(1):52-63), published guidelines are based on small studies, mostly uncontrolled investigations, and mostly on patients on low to moderate methadone doses (60-70mg daily). Furthermore, “due to differences in design and individual variability, a single protocol cannot be formulated.” Unfortunately, approximately “70% of patients receive more than 60 mg per day of methadone in the USA. Lowering the dose of methadone and/or increasing the interval between the last dose of methadone and buprenorphine may be less acceptable in this case, as it exposes patients to relapse.” There is much less data on transitioning patients at higher doses. That said, I have transitioned many patients from methadone to buprenorphine, including several patients at higher doses of methadone, for a variety of reasons. [Although more often I transition patients from bupe to methadone], By far the most common reasons for switching a patient form higher dose methadone to bupe was due to an upcoming move to an area where there was no methadone program; change in insurance status (transitioning from Medicaid to Medicare, or from Medicaid to a commercial payer); or adverse effects of decreased libido, excessive weight gain, or somnolence. [The vast majority of patients on methadone tolerate it well]. These are my overall observations and suggestions:

• Methadone is a very good medicine for treating OUD, with a longer track record than buprenorphine, and overall higher rates of patient retention than buprenorphine.
• Due to logistics, and/or patient preference/tolerance, and sometimes for compliance issues is makes sense to switch patients from methadone to bupe (particularly if planning to eventually switch the patient to an injectable form of bupe, or if transportation to a methadone clinic is an insurmountable challenge).
• In the promotion of buprenorphine (which is also an outstanding medication) sometimes methadone incorrectly gets labeled as a problematic, inferior medication, and providers seek to transition patients from methadone to bupe, even though methadone is a more appropriate medication for many patients.
• Thus, however, if the transition from methadone to bupe must proceed, from my experience I would note the following:
  • Consistent with common guidelines, the patient must achieve a state of moderate opioid withdrawal (e.g. a COWS of at least 13), before administering bupe, to avoid incurring buprenorphine precipitated withdrawal (BPW). [I have made this mistake, and have incurred substantial misery, which can last a day or more.]
  • The decision to rapidly titrate the dose downward first, vs. abruptly stopping the methadone, should be a shared decision with the patient, addressing the need for a sense of control. An example of rapidly titrating down would be dropping from 100mg of methadone daily, and dropping to 60mg on day 1, then 30mg on day 2, and 0mg on day 3, then assessing a COWS on days 4 and 5, and then dosing when moderate withdrawal is achieved. Some patients feel as sense of greater control with this type of taper. However, while some patients find this step-wise drop comforting, others find this painfully prolongs the withdrawal.
  • Plan the stop date and set realistic expectations of duration of withdrawal symptoms. Coordinate around the patient’s schedule, and the patient’s desire to withdraw either during the week, or on the weekend.
• The primary goal is to prevent relapse during the withdrawal period, and secondarily to not prolong the withdrawal period unnecessarily.
  • Prescribe anti-emetics, and other symptomatic relief medications if possible.
• Some protocols (particularly if involving higher risk patients – e.g. pregnant patients) even include using short half-life immediate release opioids or fentanyl transdermal patches.
• Some patients may require a brief hospital stay to avoid a relapse during the transition (if that is an available option).
  • Plan an appropriate dose of buprenorphine to match the patient’s opioid use history and methadone dosing, to adequately relieve withdrawal.
  • Regardless of the patient’s current methadone dose (whether that is 15mg or 200mg), patients stable on methadone are going to withdraw during abstinence (and some will supplement with heroin or other short acting opioids).
• Get to a COWS of at least 13, then administer bupe.
  • Gradually weaning down the patient’s methadone dose over many weeks (e.g. by 1-3%/week), working towards an opioid free sobriety is not applicable to this discussion.

According to the manufacturer, ER-NTX is no approved to be injected in any sites other than the upper, outer quadrant of the gluteal muscle. All clinical trials were conducted using this injection site. The manufacturer does not have clinical data to support administration outside of the approved administration site. If the patient is unable to receive intramuscular injections using the supplied needles, an alternative treatment method should be entertained.

Naltrexone would be an ideal agent in this case as long as the patient is willing to receive the injections and can abstain from opioids for the time it takes to begin induction. Naltrexone is the only medication currently approved for the treatment of both opioid and alcohol use disorder.

Patients who are already fully detoxified from opioids (in particular those in inpatient, residential, or criminal justice settings) can easily start XR-naltrexone without fear of precipitating withdrawal. The FDA-indication for XR-naltrexone is to prevent relapse to opioid use. However motivated patients with a strong preference for XR-naltrexone can undergo withdrawal management so that they are fully detoxified in order to be inducted on their first injection as well. Ideally patients would have access to all three classes of medications and be able to make an informed choice with the guidance of their care team.

Yes! Patients often discontinue oral naltrexone and this poses an increased risk of overdose death. This relative increased risk is not observed with the injectable XR-naltrexone which lasts for a month and then slowly leaves patients’ bodies. Even if patients ask for a pill, they should be encouraged to receive the injection instead.

After assessing the appropriateness of the patient for the outpatient treatment the clinician needs to determine which treatment may be most appropriate at that time and engage the patient in a shared decision-making. I would start with evaluating prior treatment history, have they previously tried any of the medication(s), was it effective and well-tolerated? If people were treated in the past with buprenorphine and were successful then that might be your first line of treatment. For those with difficulty adhering to daily buprenorphine, and those that did not stabilize (still had cravings, continued to use on top of the buprenorphine) or were misusing or diverting the medication then you might consider treatment with XR-naltrexone. Alternatively you may try a higher dose of buprenorphine or buprenorphine under supervision. Another issue is the frequency of monitoring, many patients cannot come to the clinic weekly (if necessary), and since XR-naltrexone is given once a month that gives you more flexibility for patients living in a remote areas. Insurance coverage always has to be considered as well. It’s important to explain the differences to the patient so they have a clear understanding of the differences between the medications.

Patients tend to overestimate the risk of painful conditions that would necessitate acute treatment with opioids. For acute pain, the anesthesiologist can mange pain well using high-potency opioids or non-opioid strategies. For non-acute pain, blocks work extremely well and should be recommended. For most patients we’ve treated they didn’t need acute opioid analgesia and could wait if they had to have scheduled surgical procedures.

There have been controlled trials done where patients were unaware if they are receiving active naltrexone or placebos. Within the first week, patients treated with naltrexone reported less craving, even though they did not use opioids so they had no way to tell if they were treated with active naltrexone. We often see patients with very little cravings during the first week after the injection, though they are certainly patients who continue to have cravings, albeit diministed, since they do not experience opioid withdrawal. Not every patient on naltrexone will have reduction of cravings just as not every buprenorphine patient will have reduction of cravings.

Package insert for injectable naltrexone does not specify that you need to have a trial of oral naltrexone before the injection. If the patient has a sufficient duration of abstinence from opioids (of 7-10 days) the injection can be safely given. You should carry out urine toxicology test (for morphine, oxycodone, methadone, and buprenorphine) on site right before the injection to confirm that patients did not use any opioids. Please remember that not all opioids would be detected with the rapid test so patients need to be asked about any medications taken in the previous week, to make sure they did not take opioids, and warned of the risk of precipitated withdrawal if naltrexone is given to a person taking opioids. A naloxone test can be conducted by giving 0.8-1.2 mg im and monitoring response over the next 30-45 min. If the test is negative (no change how patient feels- no withdrawal signs/symptoms on COWS scale) then it is very unlikely that withdrawal will be precipitated with injection naltrexone. However if you cannot guarantee the abstinence, and naloxone is not available then you should introduce oral naltrexone at low dose, like 12.5 mg (1/4 of the tablet) or less, at first and if no withdrawal emerges then injection can be safely given (same day few hours later or the next day. 25 mg of oral naltrexone (1/2 of the tablet) is probably too much and may precipitate severe withdrawal as the blood level is comparable to the level after the injection. It is very important to minimize the risk of withdrawal/side-effects with oral formulation since patients that have an adverse experience at the first contact with the medication might be dissuaded from continuing with it as an injection.
Giving small doses of oral naltrexone at first is necessary, but it is a barrier since naltrexone is not commercially available in smaller doses. You can always order low dose oral from a compounding pharmacy in order to get the dose to use for oral induction.

The injectable naltrexone is usually better tolerated than comparable oral doses. There’s less GI distress and nausea, possibly because much lower doses are needed as parenteral formulation bypasses the first-pass metabolism. Bioavailability of injection naltrexone is approximately 4 times greater than bioavailability of oral formulation.

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Naltrexone is an excellent option for patients who would like to discontinue treatment buprenorphine, but would like to be protected against relapse, which is seen with high frequency during the first few months after stopping buprenorphine.

Buprenorphine is best tapered down to low dose before stopping it, to reduce the level of physiological dependence and to decrease time required for elimination. Usually taper to 2 mg is sufficient, most patients find it difficult to stabilize on lower doses. Alternatively one can use adjunctive medications to minimize symptoms of withdrawal. Adjunctive medications targeting emerging symptoms are also very useful during the washout period and during initiation of treatment with oral naltrexone. Washout period of 4-6 days is usually sufficient after which naltrexone can be started, first at the low oral dose (6-12mg) followed by an injection of XR-naltrexone. With the longer washout there is less risk of withdrawal following injection but higher risk of relapse. Adjunctive medications can be continued during the first 1-2 weeks following injections (see Sigmon, Bisaga et al., 2012 for the list of medications and doses). During this transition patients need to be supported, as it is an outpatient detoxification, preferably with daily medical checkup (in person or on the phone) and psychosocial support if available.

Here are several steps that I would recommend:

• Let overdose education and Naloxone distribution be a helpful way to prioritize safety in discussions with patients and families
• Whenever possible improve non opioid options for pain prior to starting an opioid taper
• Whenever possible taper slowly and arrange for frequent follow-up based upon risk
• Make sure all comorbidities are addressed (medical, mental health and SUD)
• If a slow taper results in deterioration or if there is evidence ahead of time that a taper will result in deterioration assess and treat (when indicated) for OUD/Complex opioid dependence. In patients with chronic pain the medication of choice is usually split dose Buprenorphine/Naloxone.

Yes I have used it, it is effective but often hard to get past insurance. I like to use lactulose when others have failed. I did not find any specific articles on buprenorphine and Nalexogel but articles showing efficacy for multiple agents on OIC. Literature suggests that OIC may be less in buprenorphine but I have seen it in about 30% of patients.

The United States Federal Drug Enforcement Administration Title 21, Code of Federal Regulations 1306.07 provides guidance on this issue. It states that hospital medical clinicians may “administer or dispense narcotic drugs in a hospital to maintain or detoxify a person as an incidental adjunct to medical or surgical treatment of conditions other than addiction”. Clinicians should always ensure that patients receive seamless referral to treatment after hospital discharge.

First, it is important to treat any opioid withdrawal with medications such as methadone or buprenorphine because opioid withdrawal typically worsens other painful conditions. Second, concurrent to treating opioid withdrawal, utilize full agonist opioids for pain control recognizing that patients with OUD will likely have a high opioid tolerance and will need higher doses than opioid naïve patients. Administering opioids to a patient in the hospital will not worsen their addiction in most cases. Third, make sure you are using a multimodal approach since pain can effectively be treated by several different medications that are non-opioid. If a patient is undergoing surgery, consider anesthesia practices such as nerve blocks. Finally, if the patient presents to the hospital prescribed buprenorphine, consider continuing buprenorphine while treating pain with potent full opioid agonists like hydromorphone or fentanyl on top of the buprenorphine.

It should be a goal to reduce 'terminations' from care at all levels whether inpatient, outpatient, with or without MAT. It has been my practice to keep patients on MAT/buprenorphine even with continued use of other illicit drugs as long as there is no ongoing symptomatic safety concerns such as over sedation. For example, if someone is on a prescribed benzo from another physician but does not present as drowsy/impaired I will continue the buprenorphine. Stimulant use such as cocaine, methamphetamines, or nonmedical use of a prescription stimulant has associated risk but does not increase the risk of buprenorphine side effects. Continued use of other illicit substances needs to be addressed as part of a comprehensive treatment plan but should not lead to MAT discontinuation in someone otherwise free from opioid use. If the MAT is discontinued due to other drug use and the patient relapses to full agonist opiate use (heroin, fentanyl, oxy, etc.) the risk of overdose and death is substantial. In addition, there is no consistent data that continued use of MAT in the face of other illicit drug use contributes to diversion.

Increasing MAT access across the country will require significant participation from primary care fields of medicine (Family Medicine, Internal Medicine, OB/GYN, Pediatrics). There is often stigma associated when working with patients diagnosed with substance use disorders especially when providing MAT. First, be an example of quality practice providing evidence-based medical care to SUD patients. Second, offer your expertise to your colleagues on treating SUD patients. Third, encourage interested clinicians to review the excellent evidence-based resources provided for free on PCSSNow.org, NIDA (drugabuse.gov), and SAMHSA (SAMHSA.gov). Fourth, offer to mentor your colleagues through the process of obtaining the DATA Waiver and how to integrate the MAT practice into the daily workflow. Once clinicians see a successful integration working well, many of the barriers to becoming a MAT provider can be easily overcome.

If it’s for an emergency then you can do it. For example If a patient is suicidal or was admitted to the psychiatric floor for another reason other than drug addiction, and the patient is being maintained on buprenorphine, then any physician even if does not have the waiver to prescribe buprenorphine can continue the prescription to avoid the withdrawal. If you can see the patient that would be a better option but if it’s an emergency and the patient is at risk of relapse then at least perhaps speak with the patient on the phone and document that and give the patient a few days until the primary provider comes back. The good thing about buprenorphine is that it is Schedule III so you can order it over the phone which is good for cross-coverage issues.

We treat all ages in our clinic. For younger veterans we get a good history and prefer to start them on buprenorphine maintenance. We have a treatment agreement which covers the rules of the clinic including a call back policy. The nurse calls them and they must return to the clinic within 24 hours with their buprenorphine pills. We take urine checks and do pill counts. We check their buprenorphine and norbuprenorphine levels to make sure they are taking it and not selling it. We do this randomly.

During the induction phase they have to come a few days in a row. Then weekly. We don’t give more than a week’s prescription at a time. After the first month we can decide if they need more intensive treatment or not.

I have the same experience. It’s supported by the literature – a study showed that at the maintenance level relapse was about at 10% whereas at the taper it was 50%. It’s my clinical experience as well. I tell people that it’s their choice and I can’t force them to stay on suboxone but if they relapse it’s okay, they can come back in and we’ll start them again.

We rely on the norbuprenorphine to buprenorphine ratio. The norbuprenorphine should be double the buprenorphine. If the norbuprenorphine is low and the buprenorphine is high, then the patient may not have been taking it for several days and restarted before coming to the screening.

You don’t want to be the only provider treating these co-morbidities. You’ll want to collaborate with primary care, pain specialists, etc to combat these problems. My role is to determine if the patient meets the criteria for opioid use disorder. If not then I would refer them to another provider since it is not my area of expertise.

Yes. Cohort studies find that having OUD is associated with 13 times greater risk for suicide, even controlling for co-occurring mental health disorders. Suicide is undercounted in deaths of opioid-related overdose, and the risk for suicide in OUD is probably underestimated.

This depends on your care setting. Health care providers who evaluate patients in acute care settings, with no prior care relationship and unlikely to become involved in a longer-term care relationship, can effectively use validated brief screenings tested for use in these settings. Examples include the ED Safe Patient Safety Screener (PSS-3) for emergency department care, or the Ask Suicide Screening Questions Toolkit (ASQ) for inpatient medical and surgical settings and primary care. Keep in mind that although item 9 on the Patient Health Questionnaire (PHQ-9) relates to suicide screening, the PHQ-9 was developed as a screen for major depressive episode and as such is less well-validated for suicide screening compared with other brief screens noted above. For behavioral health settings and longitudinal care, the Columbia-Suicide Severity Rating Scale (C-SSRS) is well-validated for monitoring enduring suicide risk. In all cases, clinical concern based on risk factors and/or positive screening results should be immediately followed by comprehensive mental health safety evaluation and safety planning, including means reduction, such as removing the person from unsafe access to opioid analgesics, drugs and alcohol and educating family on the use of naloxone rescue for opioid-related overdose. Further materials may be found at the Suicide Prevention Resource Center (sprc.org) and in the downloadable pdf, National Action Alliance for Suicide Prevention: Transforming Health Systems Initiative Work Group. (2018). Recommended standard care for people with suicide risk: Making health care suicide safe. Washington, DC: Education Development Center, Inc.

No. Safety planning has elements that are universal to all patients, such as education about suicide warning signs, lethal means reduction, and access to suicide prevention supports, hotlines, and health care. There are also personalized aspects to safety planning. The following are examples of patient-specific planning: determining patient-specific warning signs and patterns, engaging collateral supports from family and peers, working with the person to understand what he or she is willing to do to reduce suicide risk and entering these plans on a pocket reminder, provision of caring outreach contacts, and prescribing medications that target stabilization and reduction of suicide risk (e.g., MOUD for OUD, appropriate antidepressant therapies for depressed individuals).

Each individual must be carefully evaluated and an individual treatment plan developed. For some patients who use benzodiazepines while in MAT, continued monitored prescribing is indicated and the best choice. These should be patients who have tried other treatments and have unsuccessfully attempted tapering. Ultimately, the benefits must outweigh the risks.

The research is split of the potential benefits of gabapentin in assisting with benzodiazepine tapering. Some feel it is an abused medication and should not be used. Whether it is used or not, its use should follow a careful individual assessment and the development of a treatment plan taking into consideration the patient’s issues (biological, psychological, social and spiritual).

The obvious concerns revolves around the risk of synergism leading to overdose, respiratory depression, and death. Interestingly, a recent study by Bakker and Streel (2017) found that despite this concern, benzodiazepine maintenance treatment was associated with longer retention in treatment and a lower death rate for those in treatment, and for those who left treatment, a higher death rate. How to manage MAT patients who use/abuse benzodiazepine is a controversial topic and one with limited research to provide guidance. Treatment needs to be individualized taking into account each patient’s clinical picture.(Martin et al. 2018)

Group psychotherapy can reduce the stigma of addiction, particularly the stigma of MAT within some parts of the Twelve Step community. It can also reduce the isolation of the patient and increase the psychosocial support using both the resources of the therapist and fellow group members. This support can orient group members to the mechanisms of mutual support that promote recovery. This all improves the cost-effectiveness of treatment.

Yes. The four components of a behavioral protocol (skill building and practice, introducing alternative reinforcers, having clinical conversations in an Motivational Interviewing style, and building social supports), can be implemented by the same treatment provider and within the same treatment context that a MAT protocol is being utilized. For example, a Motivational Interviewing stance (and conversational strategies) can be utilized in conversations about medication adherence and address ambivalence a patient may have about their behavioral change plans. In addition, it can be useful to check-in with patients about high-risk situations they may come into contact with between appointments and spend some moments problem solving about ways to handle these situations. In addition, discussing strategies for coping with cravings and urges can be a helpful conversation. It can be also useful to ask patients to outline and record their goals in between sessions and checking back in with them at the next appointment.

There is evidence to suggest utility in adding a psychosocial intervention in conjunction with MAT. However, the specific structure of the behavioral treatment plan can look different. Many controlled studies of Buprenorphine maintenance include structured and weekly Medication Management sessions that can explicitly discuss issues around adherence and addressing barriers to adhering to a change plan. Structured medication management protocols are rarely utilized in many medical settings, although can be an active component in the change process. Further, other factors such as high levels of opiate use at the time of seeking treatment, polydrug use, psychiatric distress, and continued opiate use in the context of MAT over time may be important indicators that augmenting MAT with a behavioral treatment platform would be beneficial to the patient. From a motivational standpoint, requiring participation in a behavioral health protocol should not serve as a barrier to initiating a MAT protocol. Addressing a patient’s ambivalence around a behavioral treatment component could be a topic to address within a regularly scheduled, structured medication management sessions with the goal of having a patient decide that the benefits of having more support and a skills oriented component can outweigh the cons.

Evidence suggests that including family members in the treatment process confers a better prognosis. This involvement has included family members just attending 1 or 2 counseling sessions to discuss the concerns they may have and ways they can support the patient’s change plan. It can also involve family members attending CRAFT sessions to learn a range of skills and strategies to support the patient’s change process. For patients with limited social support building a supportive structure is critical. Counseling sessions can incorporate elements of a 12-step facilitation protocol to help patient’s connect with a social support system. The SAMSHA website offers links to various peer-to-peer and self-help groups which can be an important component for improving long term outcomes. It is important to discuss the types of peer support groups with the patient and check-in with the patient’s experiences while attending these meetings. The messaging around MAT is not always consistent across groups and patients may receive mixed messages (e.g. MAT is not being in recovery; is not the proper way to change). Thus, regularly checking in with the patient can correct any misinformation and help prepare them with communication strategies to respond to treatment-interfering messages.

We use the disease model and approach each separately. For example, if we have a patient with diabetes and asthma, we won’t stop treating the diabetes if they start smoking again and the asthma gets worse. Likewise, we try not to tie buprenorphine treatment to poorly controlled cocaine or alcohol use disorder. The other rationale for the harm reduction approach as opposed to the abstinence model is that the longer someone is in treatment the higher the odds of them getting better. We use motivational interviewing and try to let natural consequences be a platform for discussion. We also use relapse prevention groups and we see people more frequently if they continue to use other substances to try to provide an incentive to decrease use. Often, we will require group 3x weekly along with weekly scripts with the aim of helping them reduce use.

We get a urine test as early as possible since many people don’t expect it the first visit. That helps us understand what substances we need to be concerned about. We will still enroll people with other substance misuse but advise them we will be dealing with their other substance problems and we won’t be able to progress (to monthly scripts for example) if those don’t improve. We get releases from their other physicians. We won’t treat if they won’t let us talk to their physician and we prefer to take over all their psychiatric prescriptions. We also use mouth swabs on occasion as those are harder to alter – not to be punitive but to understand the problem. And we let them know the dangers of combining substances. A huge risk factor for any substance use disorder is untreated ADHD so we do want to treat it, if it is legitimate but we do need to be meticulous with the diagnosis and with ongoing monitoring to make sure that amphetamines are being used therapeutically. We try to document functional improvement with the amphetamines and use the ones with the lowest abuse potential.

Building rapport with the OUD patient is an essential first step and should be reinforced at every level, from reception to physician and follow-up care. Rapport can best be built by things such as welcoming the patient, listening and giving eye contact to the patient, showing appreciation for the patient making the appointment, and focusing on patient-friendly strategies such as safety and “warm hand-offs”.

Difficult & complex OUD patients may have significant issues of comorbid conditions, untreated or unresolved trauma, and difficulties in taking care of basic survival needs. We need to adjust expectations for progress with these patients, and focus on 1 or 2 key outcome variables that might represent smaller but measurable steps to indicate progress that can be “celebrated” with the patient – even while other indicators might still show significant concerns.

It is acceptable to use the buprenorphine/naloxone combination product in pregnancy. There is essentially no absorption of naloxone sublingually: naloxone was added to the buprenorphine when the FDA formulated the medication to lower the abuse potential (IV and snorting, the naloxone is active). Many institutions prescribe only the combination product and many patients prefer no changes to medications. Since there is no maternal absorption, there is no passage from mother to breastmilk: therefore women are strongly encouraged to breastfeed if no other contraindications (ie: HIV or active cocaine/methamphetamine abuse).

Intrapartum pain control can be managed with IV full opioid agonist (if desired) in early labor and epidural analgesia (PCEA) during labor. Nalbuphine and butorphanol are contrainidicated: they are both partial opioid agonists and will precipitate withdrawal in women with opioid dependence (if withdrawal is inadvertently precipitated, administer enough full opioid agonist (morphine, dilaudid) to make the patient more comfortable and the fetal effects should be reversed as well). Intraoperative pain can be managed with spinal and/or epidural anesthesia. Opioids are rarely indicated followed routine vaginal birth and should not be routinely prescribed in the hospital or at discharge without other circumstances (such as extensive perineal laceration). Following cesarean delivery, patients may need 50-70% more opioid medication for pain control, but adherence to the current opioid-sparing guidelines is also appropriate with the use of long acting intrathecal opioids (ie: morphine, although whether they are as effective in the setting of MAT is unknown), NSAIDS, and acetaminophen. Transverse abdominal plane (TAP) blocks can be considered in place of intrathecal opioids but the impact of this intervention on post-operative opioid use in the non-opioid dependent patient is equivocal. Discharge prescribing for a limited number of pills of full agonist with close follow-up is prudent.

The provision of safe care through the prenatal and postnatal period is more dependent on the clarity transparency of the protocol used, and the monitoring applied to validate compliance, than it is to the degree of specialty care available. If the provider managing the opioid use disorder is not also managing the pregnancy, it is critical that the pregnant patient be receiving pre-natal services from a qualified obstetrician or family medicine physician.

The context of pregnancy frequently creates an atmosphere of motivation to change behavior. However, in the case of newly discovered pregnancy, the dynamics of caring for only one of the two people involved with the conception can undermine progress of the pregnant partner. Seeing the entire household as contributors to success frequently requires engaging multiple household members.

There is no data to suggest that reduction of dose prior to delivery will reduce the frequency of Neonatal Abstinence Syndrome. ON the other hand, a motivated patient who wishes to reduce their dose should always be allowed to make that decision. Frequently volume of distribution changes during pregnancy result in a need for increased dose to reduce cravings, but when a patient declares that the dose is not necessary to control cravings and asks to reduce the dose, there is no discrete data to suggest that this should be refused.

Buprenorphine is FDA approved for adolescents 16 years and older, and naltrexone is FDA approved for young adults 18 years and older. Methadone is available to adolescents under 18, but regulatory restrictions make accessing methadone very difficult. (Adolescents under 18 need to demonstrate two prior documented ‘unsuccessful’ attempts at addiction treatment that did not involve a medication, after which they need to locate an opioid treatment program that accepts adolescents under 18, which are exceedingly rare.) Despite these age cutoffs, in some clinical practices, buprenorphine and naltrexone are used off-label for ages younger than those approved by the FDA. However, any prescriber considering this should be aware that the lack of FDA approval for younger ages is due to insufficient clinical trial data for these younger ages.

The American Academy of Pediatrics and other professional organizations recommend that adolescents and young adults receive the same evidence-based treatment for opioid use disorder as adults (including use of pharmacotherapy with buprenorphine, naltrexone, or methadone). Options for pharmacotherapy, therefore, are the same for adolescents as for adults. Where treatment differs is often with regard to developmental considerations. Adolescents are in a transitional age in which they are experiencing substantial change. This includes increasing autonomy in health care decisions; often navigating health insurance and medication copays for the first time; and potentially experiencing changes in housing, education, and employment as high school comes to an end. Additionally, many adolescents have ambivalence surrounding addiction treatment, particularly if they have been brought into treatment by a concerned parent or other trusted adult, rather than choosing to come to treatment themselves. Thus, motivation for treatment can fluctuate, and providers may need to be prepared to provide treatment ‘on demand’, recognizing that the ability to pursue treatment could change from moment to moment. Nonetheless, many teens are very early in the trajectory of addiction and its harms, and thus might be more treatment-responsive than many adults with much longer histories of substance use. Additionally, since many adolescents with opioid use disorder have never received a medication for addiction treatment previously, you may be the first provider to offer them evidence-based pharmacotherapy, offering a significant opportunity for successful treatment.

Yes. Methadone and buprenorphine are both evidence based treatments for women with OUD who are pregnant. The developing fetus is at risk if the mother is in withdrawal. Maintained on MAT most women with OUD have a healthy pregnancy. It is not medically appropriate to detox a pregnant patient on buprenorphine or methadone during the pregnancy.

No. The incidents of NAS in pregnant women maintained on methadone or buprenorphine is approximately 60-80%. There is no correlation between the main dose of methadone or buprenorphine and the incidents or severity of NAS. Recent evidence has shown that neonates born to mothers on buprenorphine have a less severe NAS, require less medication treatment and have a shorter length of stay in the NICU.

Yes. MAT in adolescents is appropriate. Buprenorphine is currently the treatment of choice in adolescents. Naltrexone and methadone are reasonable options as well. In all ages, but this group in particular, it is also critical they engage in groups and other behavioral health treatments.