With this buprenor-FINE episode, you’ll become a master at office-based treatment of opioid use disorder with buprenorphine. We’ll cover the efficacy of buprenorphine, a guide to starting it, and what to think about when continuing therapy in a person-centered way. We’re joined by Dr Christine Soran, (UCSF) the medical director of the oldest buprenorphine clinic in the country – The OBIC in San Francisco.
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Three medications are approved by the FDA for the treatment of OUD. These include buprenorphine (a partial opioid agonist), methadone (a full opioid agonist, see episode 1), and naltrexone (an opioid antagonist). Methadone and buprenorphine (our full and partial agonists, respectively) reduce cravings and withdrawal and blunt the effects of other opioids. Only buprenorphine and naltrexone are available in the clinic; methadone requires almost daily visits (at least for the first three months) to a specialized opioid treatment program.
Buprenoprhine and methadone are both extremely effective – either one may decrease mortality by up to 50% (Larochelle, 2018. Sordo, 2017. Pearce, 2020, Wakeman 2020)!!!!! Buprenoprhine has also been shown to reduce non-prescribed opioid use (Mattick 2014), HIV seroconversion (MacArthur 2012), and readmission when started in the hospital (Moreno 2019).
Naltrexone is only effective for promoting abstinence from opioids in its injectable, long-acting formulation (Krupitsky 2011), not in its daily, oral form. Patients have lower retention in treatment with naltrexone compared to buprenorphine or methadone (Jarvis 2018), and evidence that naltrexone reduces the risk of overdose is lacking (Wakeman 2020, Larochelle, 2018). This is partly due to the fact that people lose opioid tolerance while taking naltrexone since it is an antagonist, so the risk of overdose is high when someone stops the medicine and starts using opioids again. Naltrexone initiation requires 1-2 weeks of total abstinence from opioids which requires many patients to go through opioid withdrawal. This process is painful and challenging, even in the clinical trial setting (Lee 2018).
Buprenorphine is a high-affinity partial agonist at the mu-opioid receptor with a respiratory ceiling effect. Each of these properties is important to the medication’s safety and efficacy. Partial agonism means that the mu-opioid receptor is roughly halfway activated, which is enough to decrease and potentially eliminate cravings and withdrawal. The ceiling effect means higher doses do not correlate with more respiratory depression, so the risk of overdose remains low. The high affinity means buprenorphine binds the mu receptor tighter than other opioids bind the receptor. This protects people whose receptors are already saturated with buprenorphine from an overdose when they take additional opioids.
You can use the analogy of a lightbulb to understand partial agonism. Full mu receptor agonists (methadone, heroin, and oxycodone, for instance) turn the light on all the way. Buprenorphine acts like a dimmer switch that turns the light to 50% of its full brightness.
Buprenorphine’s partial agonism and high affinity for the receptor also place patients at risk of precipitated opioid withdrawal when they first start the medication. If buprenorphine is started too early (when too much full opioid agonist still occupies the receptor), the high-affinity buprenorphine knocks the full agonist off the receptor. It abruptly shifts from full agonism to partial agonism. This causes severe, acute withdrawal symptoms. This is why starting buprenorphine slowly and cautiously is essential.
Buprenorphine comes in sublingual and injectable formulations. The sublingual form is easier to access from many clinics since the injectable must be dispensed from a pharmacy enrolled in the Risk Evaluation and Mitigation Strategy (REMS) Program. The injectable form lasts for a month and is a good option for people who don’t want to come to clinic or take medication regularly. Both forms are incredibly effective!
The sublingual buprenorphine is often co-formulated with naloxone (an opioid antagonist). The naloxone is not sublingually absorbed, so has no effect if the medication is taken as prescribed. The naloxone becomes active if taken intravenously, so co-formulation is merely a deterrent to IV use of the medicine (i.e., someone would precipitate withdrawal if they tried to inject their medication from the sudden opioid antagonist effect).
Until recently, prescribing buprenorphine required additional training. Now, any clinician with a DEA number can prescribe buprenorphine for to up to 30 patients with submission of a notification of intent. You can now fill out this application (SAMHSA buprenorphine notification of intent) and begin prescribing buprenorphine!
If you start prescribing and fall in love with it (as we did), you can complete the waiver training to prescribe to >30 patients (PCSS waiver training).
Every additional step we require from patients to start treatment presents a barrier that decreases the patient’s likelihood of engaging in care (Khalid 2022). We should aim to make buprenorphine available in every care setting, including the emergency room, the clinic, and the hospital.
First, starting buprenorphine requires taking a history – you need enough information to diagnose an opioid use disorder according to the Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM V) criteria, as well as information about a patient’s drug use and prior treatment attempts. Prior experience with buprenorphine (prescribed or non-prescribed) is associated with improved treatment retention so is helpful to discuss (Cunningham 2014, Williams 2022).
No labs are needed prior to starting buprenorphine. A urine drug screen can be helpful but should not delay the start of medication. Most urine drug screens do not test for fentanyl – find out if you need to order this separately at your institution and be aware that this test may take longer to result. A pregnancy test is not necessary (unless requested by the patient) because buprenorphine is safe and recommended (ACOG 2021) in pregnancy.
Most patients who start buprenorphine can do so at home, outside of the clinic, where they are more likely to feel comfortable. To avoid acute worsening of withdrawal (precipitated withdrawal), a patient should wait to start buprenorphine until they have symptoms of opioid withdrawal. If they primarily use short-acting opioids (heroin, oxycodone), they should wait 12 hours AND until they experience at least three withdrawal symptoms before taking the first dose.
Asking patients what withdrawal usually looks like (e.g., nausea, anxiety, muscle aches) can help you, and the patient delineates which symptoms they are waiting for before taking the first dose.
Once patients are experiencing significant withdrawal, they can start taking buprenorphine. The goal of the first day is to get out of withdrawal. Begin with 4-8 mg of buprenorphine, then repeat this dose every 1-2 hours until symptoms resolve (a usual daily dose is 16-24mg). In Dr. Soran’s expert opinion, the clinician should send enough to the pharmacy in the first prescription for the patient to take 24 mg daily until the scheduled follow up. For instance, a one-week prescription will include 21 x 8mg films or tabs so the patient can take three films or tabs daily. Typically the buprenorphine dose is written first, followed by the naloxone dose (e.g., 8-2mg buprenorphine-naloxone).
While traditional initiation guides recommend starting with a lower dose than the usual maximum of 24 mg/day at first (SAMHSA TIP 63), in Dr. Soran’s experience, higher starting doses may be necessary for the era of fentanyl to help people overcome withdrawal. Additionally, if someone enters precipitated withdrawal, the most helpful treatment is to take more buprenorphine, so patients should have enough to take at home if they experience this reaction.
Opioid withdrawal is incredibly uncomfortable and often a motivator to continue or return to use, even when someone wants to stop. Physicians can prescribe medications to make patients more comfortable during the withdrawal period before a patient can start buprenorphine. These medications may include ondansetron for nausea, loperamide for diarrhea, acetaminophen or NSAIDs for muscle or joint pain, or clonidine or hydroxyzine for anxiety (Charney 1981).
Dr. Chan, Dr. Cohen, and Dr. Soran all report finding this app helpful to guide patients through initiation and, more generally to learn about the process. Note that the doses are lower than those discussed above (Apple store, Google play).
Fentanyl is highly potent, lipophilic, and, like buprenorphine, has a high affinity for the mu opioid receptor (Comer 2019). Emerging data suggests that people consistently using fentanyl experience higher rates of precipitated withdrawal during buprenorphine initiation compared to people who use other opioids (Silverstein 2019, Varshneya 2021, Sue 2022).
Expert opinion: Dr. Soran generally follows the above outline for initiation but advises patients who use fentanyl to wait longer (24-48 hours) from their last use and start with a higher dose of buprenorphine (8-12 mg).
Don’t let fentanyl scare you from starting buprenorphine – remember that buprenorphine saves lives!
Buprenorphine initiation 201: low-dose induction is a newer method of buprenorphine initiation and aims to prevent withdrawal all together (Cohen 2021). More to come in season 2!!!
Ideally, the patient should follow up in one week for a check-in, discussion of the next steps, and dose adjustments.
Craving (i.e., if the patient reports an ongoing urge/ need to use or related dreams) is a reason to increase the dose of buprenorphine. Continued use of non-prescribed opioids is another reason to increase the dose. Depending on the patient’s current dose and symptoms, you can increase by 2 mg, 4 mg, or 8 mg. The maximum dose is usually 24 mg per day.
Spend time revisiting the patient’s personalized goals during every visit, especially at first. Abstinence is not the only possible positive treatment outcome. Reductions in use, safer or less chaotic use, and a greater ability to function in day-to-day life are all positive outcomes!
If a patient expresses an interest in decreasing the dose, ask why. If side effects like nausea or headaches drive a desire for a dose decrease, you can try a different formulation before reducing the dose.
Continued use of opioids or use of other substances (e.g., alcohol, benzodiazepines, cocaine) are not reasons to stop a patient’s buprenorphine! Buprenorphine does not treat substance use disorders other than OUD, so assess whether the patient is interested in discussing each separate substance at the time of the visit and assess what additional support might help. Drinking is much safer for someone who takes buprenorphine than for someone who takes non-prescribed opioids without buprenorphine.
Urine drug screens provide a snapshot of how a patient is doing at any given moment in time, and an overview of the patient’s progress over time. It is imperative to talk openly about the purpose of the test up front and obtain consent before ordering. Many patients have experienced the punitive and harmful use of urine drug screens within the context of the criminal legal system and even well-intentioned medical clinics. Discuss that you are primarily monitoring whether the patient is taking the medication that you are prescribing.
Screens that are positive for other substances can facilitate conversations about substance use if the patient would benefit from extra support, but should not affect treatment with buprenorphine. Urine drug screens can empower the patient with information about contaminants in the supply, particularly as stimulants and non-prescription benzodiazepines are increasingly contaminated with fentanyl (Armenian 2019).
Weekly visits can be helpful at first, particularly during dose titration. Visit frequency can be adapted to clinic capacity and patient preference.
Additional psychosocial interventions and counseling should be offered when available but the decision of whether or not to engage is up to the patient (SAMHSA TIP 63, ASAM National Practice Guideline). Know your local resources so you can refer appropriately if a patient is interested. A large systematic review found no improvement in outcomes with the addition of adjunctive therapy to buprenorphine for OUD but some patients find the support of individual counseling, mutual aid groups, intensive outpatient programs, or inpatient rehab to be helpful (Wyse 2021).
Telehealth can be a powerful tool to increase access to care by eliminating barriers to starting and continuing buprenorphine therapy (Wang 2021).
When people ask how long they will need to take buprenorphine, emphasize that they are in the driver seat. You can ask whether it is ok to share the data we have and your experience, and discuss that retention in buprenorphine treatment is associated with substantial reduction in mortality.
Dr. Soran frames this conversation similarly to conversations about lifestyle modifications for other chronic diseases like diabetes or hypertension. Talk through factors that have contributed to the patient’s opioid use, as well as their social supports, living environment, any physical pain, and mental health. If the patient has undergone significant positive changes since starting buprenorphine then considering a taper may be reasonable. Remind patients that taking an effective mediation is a positive outcome in its own right – if a patient experiences cravings or needs to stop a taper, this does not need to be viewed as a failure.
The patient is the expert and we are here to educate, guide, and support them in whatever ways we can!
Listeners will gain the confidence to prescribe buprenorphine to treat opioid use disorder in the clinic.
After listening to this episode listeners will…
Dr. Christy Soran reports no relevant financial disclosures. The Curbsiders report no relevant financial disclosures.
Cohen S, Soran C, Mullins K, Chan CA “#7 Do the OBOT: Buprenorphine for OUD in the Clinic with Dr. Christine Soran”. The Curbsiders Addiction Medicine Podcast. http://thecurbsiders.com/addiction 8/18/2022
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