TCPR: When buprenorphine was first approved, the government made it difficult to prescribe, but that’s changed.

Dr. Capurso: When buprenorphine was first released two decades ago, the fear was that it would fuel the opioid epidemic kicked off by drugs like oxycodone (OxyContin). But we’ve since learned that, as a partial agonist, buprenorphine is much safer than we once thought. We’ve also learned how effective it is for opioid use disorder (OUD). Between its safety profile, its efficacy, and the worsening overdose crisis, regulations like prescribing caps and X-waiver requirements have been lifted.

TCPR: Can clinicians opt out if they aren’t comfortable prescribing buprenorphine?

Dr. Capurso: Not really. Anyone with a DEA license is expected to learn how to prescribe buprenorphine through eight hours of required education. To my knowledge, this hasn’t been tested in courts, but if a patient with OUD comes into your office and you refuse standard of care, which is buprenorphine, and the patient dies of an opioid overdose, I think you could be held liable (Marsden J et al, eClinicalMedicine 2023;66:102311). And in my view, it’s a moral obligation to treat the disorder.

TCPR: I’ve heard clinicians say, “I don’t see those kinds of patients,” but you’re saying this is an epidemic—we can’t avoid them.

Dr. Capurso: We need to correct the stereotype that patients who take buprenorphine are somehow all unstable or difficult. These “kinds of patients” cross all levels of society and are as varied as patients with mood or anxiety disorders. I treat many stable high-functioning patients on buprenorphine.

TCPR: What do we need to do before starting buprenorphine treatment?

Dr. Capurso: Requirements have become less restrictive—we used to check complete blood count, liver function tests, electrolytes, renal function, and an ECG before the first dose, but we’ve learned that’s unnecessary for otherwise healthy patients.

TCPR: What about a urine drug screen (UDS)?

Dr. Capurso: As we’ve moved toward a harm reduction model, fewer providers are requiring a UDS at every appointment, which used to be standard. I think that change makes sense. If we find cocaine or even opioids on the UDS, are we going to refuse buprenorphine? No. Most patients with OUD will use drugs at some point in their treatment. In older models of care, these patients might have been discharged or tapered off the medication. To me, that’s like withholding antidepressants because a patient is depressed. It’s completely backward logic.

TCPR: What do you use the UDS for, then?

Dr. Capurso: It’s an assessment tool, like a depression rating scale in a mood disorder clinic. If we detect nonopioids, it opens a discussion about treating those. If we find opioids, we discuss why the medication is not working optimally—maybe we need to increase the dose, switch formulation, add supports, or seek a higher level of care. We might consider switching to methadone.

TCPR: What if the patient refuses your recommendations?

Dr. Capurso: How many of us follow all the diet and exercise advice that our doctors give us? That’s not grounds to discontinue treatment. My philosophy is that some buprenorphine is better than no buprenorphine. Even if the patient continues to use, buprenorphine provides some degree of overdose protection and may help keep them engaged in treatment. In OUD, the evidence is pretty clear that the key ingredient is the medication. That’s not true for other addictions. For cannabis, cocaine, and stimulant use disorders, the main treatment is the psychotherapy. Alcohol is somewhere in the middle.

TCPR: What if the UDS is negative for buprenorphine?

Dr. Capurso: I simply point out that the UDS is negative for buprenorphine and ask the patient why that might be. You’d be surprised how open patients are, especially ones with whom you have an established rapport. And while we don’t want to encourage diversion, I’m less concerned with buprenorphine diversion than other controlled substances. Evidence shows that when it’s diverted, it is mostly used by other people to treat their own OUD, and as I said before, it is safer than opioid agonists (Cicero TJ et al, Drug Alcohol Depend 2018:193:117–123).

TCPR: How often should we check the UDS?

Dr. Capurso: Ideally once a month, but I don’t let it get in the way of access to treatment. Think of it like a mood rating scale. Checking it at every visit is ideal, but you wouldn’t withhold treatment if you can’t get one. The goal is to assess if our treatment is working.

TCPR: Can we use outside labs for the UDS?

Dr. Capurso: Yes. Directly observed screens used to be standard, but we’ve mostly given that up. The added value there, if any, is questionable. Plus, observing patients while they are urinating can be invasive, and many patients have trauma histories.

TCPR: What if a patient keeps having excuses for not doing the UDS?

Dr. Capurso: If they repeatedly dodge giving a sample, I assume they’re using. But that too can open a conversation. “Let’s say your UDS is positive. What can we do about it? One thing that we are not going to do is kick you out of treatment.” Once patients understand that a positive screen doesn’t mean discharge or punishment, usually all of a sudden they can provide a sample.

TCPR: How often should patients be seen?

Dr. Capurso: Typically, a buprenorphine script is limited to 30 days, so you’d want to see them at least once a month. I see them more often, typically weekly, in the beginning as we are finding the right dose or if they otherwise are not doing well. If you can’t see them within four weeks, you should have a colleague cover before refilling.

TCPR: What if they miss an appointment?

Dr. Capurso: If there’s a good reason, I’ll refill the script. But if I don’t hear from them, or they miss repeated appointments, I like to send a shortened script. For example, if I see them every two weeks, I’ll send them four days. That ensures they aren’t suddenly cut off, which usually results in return to use, but it serves as a reminder that they need to come in. Most clinics have a policy about discharge—in mine, it’s three no-shows.

TCPR: Does the law require in-office visits?

Dr. Capurso: Not currently. Buprenorphine can be prescribed via telehealth, which helps with access. But while it's permitted, I’ve found that initiating treatment via telehealth can be tricky because of the risk of precipitating withdrawal.

TCPR: Tell us about that.

Dr. Capurso: Buprenorphine is a partial agonist with a relatively high affinity, so if the patient has opioids in their system when buprenorphine is initiated, it can knock those agonists off the receptor, resulting in withdrawal.

TCPR: There is a sense that this problem is worse in the age of fentanyl.

Dr. Capurso: There are reports that buprenorphine-precipitated withdrawal is more common in people using fentanyl (Varshneya NB et al, J Addict Med 2022;16(4):e265–e268). But that hasn’t been my personal experience. Fentanyl sold on the street is not pure pharmaceutical-grade stuff—it’s an unpredictable mix of heroin, fentanyl, fentanyl derivates, all sorts of fillers, that have a variety of potencies and half-lives. As a result, the time course of withdrawal has become very unpredictable. You just have to watch the patient clinically and start buprenorphine when they’re ready (Editor’s note: The accompanying article on page 1 discusses how to time the initial dose of buprenorphine to minimize precipitated withdrawal).

TCPR: Are the symptoms the same as opioid withdrawal?

Dr. Capurso: Yes. Buprenorphine-precipitated withdrawal tends to be on the severe side—vomiting, diarrhea, diaphoresis, achiness, extreme levels of anxiety and restlessness. Patients are really miserable.

TCPR: Is it dangerous?

Dr. Capurso: Not directly. It isn’t lethal under most circumstances. The risk here is that withdrawal is so uncomfortable that the patient will give up on treatment, and that can have fatal consequences.

TCPR: How do you manage those symptoms?

Dr. Capurso: There are several ways to go regarding symptom management. We don’t have head-to-head comparisons, but the best approach is probably to give more buprenorphine (Spadaro A et al, Am J Emerg Med 2022;51:5822–5826). It’s a bit like ripping off the Band-Aid, and patients may be hesitant, but when you flood the receptors with buprenorphine, you’re providing a reasonably good agonist signal, which eliminates many of the withdrawal symptoms. I just give the full 24 mg dose and patients feel quite a bit better.

TCPR: What other strategies are available?

Dr. Capurso: Another way—which is generally less effective—is to treat symptomatically: clonidine 0.1–0.2 mg PRN for vital sign elevations, ondansetron 4 mg for nausea, trazodone 50 mg for insomnia, hydroxyzine 50 mg, or lorazepam 0.5–1 mg PRN for anxiety. Sometimes a precipitated withdrawal will turn a patient off from buprenorphine altogether. In that case, you can pivot away from buprenorphine and start methadone instead. An initial dose of 20–30 mg is common, and you can give another 10 mg to address additional symptoms up to a total of 40 mg in the first 24 hours. Remember that methadone will need to be continued by a federally recognized opioid treatment program, so be sure that follow-up will be available before going down this road.

TCPR: Could you have avoided the problem by starting with a high dose of buprenorphine, like 24 mg?

Dr. Capurso: Some think this is the way to go. The standard procedure is to give up to 8 mg in the first 24 hours, based on the theory that large doses are more likely to precipitate withdrawal. But this may not be the case. A “macroinduction” technique is being developed that gives 24–32 mg in the first visit (Herring AA et al, JAMA Netw Open 2021;4(7):e2117128). On the flip side, “microinduction” aims to minimize withdrawal by giving very small doses and gradually building up (Editor’s note: See a review of all three methods in the April/May/June 2024 issue of The Carlat Addiction Treatment Report).

TCPR: In this issue, you wrote about how to start buprenorphine at home. Are there situations when home induction isn’t safe?

Dr. Capurso: Most patients can tolerate home induction (Lee JD et al, J Gen Intern Med 2009;24(2):226–232). For those who have unstable home environments, who have cognitive impairment, or who are withdrawing from another substance in addition to opioids, I’d recommend starting in an ED or inpatient unit.

TCPR: Are there situations when you wouldn’t use buprenorphine for OUD?

Dr. Capurso: For some, the partial agonism of buprenorphine just doesn’t seem to be sufficient. In my personal experience, these are people who have been using high doses for a long time. I’ll refer these patients to methadone, but ultimately, it comes down to patient preference. We lack data to predict which patients will do better on which medications.

TCPR: What about patients who are taking prescribed stimulants or benzodiazepines without a clear indication?

Dr. Capurso: I don’t worry too much about stimulants, at least when it comes to interactions with buprenorphine. I’m more cautious about benzos, just because they can synergistically suppress breathing. I’ll work with the patient to minimize benzo use, but I don’t withhold buprenorphine because of it. For many patients, your choice is benzo with buprenorphine or benzo with street fentanyl. Clearly the buprenorphine option is the safer way to go.

TCPR: So, in the end, it comes down to risk and benefit.

Dr. Capurso: Yes, exactly. And just as with any medical decision, document that carefully. The goal is not to avoid all risk—that’s not possible here. Patients with OUD have a high risk of death, and buprenorphine lowers that risk. We just need to document our thinking.

TCPR: Thank you for your time, Dr. Capurso.