Noah Capurso, MD, MHS. Associate Professor of Psychiatry, Yale University, New Haven, CT; Editor-in-Chief, The Carlat Addiction Treatment Report.
Dr. Capurso has no financial relationships with companies related to this material.
Buprenorphine was approved for the treatment of opioid use disorder (OUD) in 2002 and quickly emerged as a first-line treatment, but strict prescribing rules limited its reach. This changed in January 2023 when the so-called “X-license” requirement was dropped. Now, anyone qualified to prescribe controlled substances can also prescribe buprenorphine. However, many prescribers are new to doing so. Here, we’ll guide you through how to prescribe buprenorphine effectively so that you can treat your patients struggling with OUD.
Formulations
There are a lot of formulations of buprenorphine out there (see the “Buprenorphine Formulations” table). Breaking them down into a few simple categories can help you keep them straight:
Dose: High-dose formulations are used to treat OUD. They come as sublingual tablets or films each containing 2 mg or 8 mg of buprenorphine. Low-dose formulations are only approved for the treatment of chronic pain. They are available as transdermal patches (Butrans), buccal films (Belbuca), and short-acting injections (Buprenex), each of which contain <2 mg of buprenorphine.
Naloxone content: Naloxone is added to some sublingual formulations in order to deter misuse. The reasoning is that naloxone causes withdrawal if snorted or injected, but its poor sublingual bioavailability ensures that someone taking it properly won’t feel naloxone's effects.
Duration of action: Sublingual tablets and films have a half-life around 36 hours and are typically taken daily or several times a day. There are two long-acting injectable forms: Sublocade, which is given every one to two months, and Brixadi, which is given weekly or monthly.
Induction
It’s important to carefully time the first few buprenorphine doses—a process called induction. As a high-affinity mu-opioid partial agonist, buprenorphine can precipitate withdrawal symptoms if given while full-agonist opioids are still in the system (for further details, see The Carlat Addiction Treatment Report, November/December 2021). Here are three methods to consider:
Standard induction: This is the most common strategy and has the most evidence, so it's the one we usually recommend. Here, a medium dose of buprenorphine is given once the patient is in moderate opioid withdrawal, and the dose is escalated over two to three days. Start by quantifying withdrawal severity via the Clinical Opiate Withdrawal Scale (COWS) (www.mdcalc.com/calc/1985/cows-score-opiate-withdrawal). Once COWS ≥8–10:
Microinduction: Developed to get patients onto buprenorphine without withdrawal, this method introduces very small doses while the patient continues opioid agonists. Avoiding withdrawal may sound appealing, but the process takes a week or more, leaving your patient vulnerable and undertreated. Therefore, reserve this approach for patients who are in a controlled setting or who can’t abstain long enough for standard induction. Microinduction also works well for transitioning patients from prescription opioids like methadone. Many protocols have been described (Ahmed S et al, Am J on Addict 2021;30(4):305–315), but here is a good starting point:
Macroinduction: This approach gets patients onto a high dose of buprenorphine as quickly as possible, even within a few hours. Macroinduction is the newest approach of the three and has only been studied in ED settings (Herring AA et al, JAMA Netw Open 2021;4(7):e2117128). Consider it for patients in an emergency setting who are unlikely to engage in follow-up treatment. Like the standard induction, start once COWS ≥8–10:
Maintenance
Once induction is completed, buprenorphine should be continued as a daily medication. Taking it this way has been associated with decreases in opioid use, substance-related mortality, and all-cause mortality, among other positive outcomes (Santo Jr T et al, JAMA Psych 2021;78(9):979–993). Here are some pointers to help you maintain your patients on buprenorphine over the long term:
Dose: Typically 8–24 mg daily, though patients tend to do better with higher doses. Only when the daily dose is ≥16 mg does buprenorphine work as well as methadone (Mattick RP et al, Cochrane Database Syst Rev 2014(2):CD002207). There can be variability, however, so ask whether your patient is experiencing opioid cravings. If they say “yes,” increase the dose. When dosed properly, buprenorphine should suppress cravings.
Frequency: Buprenorphine can be taken once, twice, or three times daily. Its analgesic properties tend to be relatively short-lived, so patients with comorbid chronic pain may do better with smaller and more frequent doses.
Formulation: Sublingual buprenorphine/naloxone is the most widely available formulation and therefore the default first-line choice. Buprenorphine alone, or “monoproduct,” can be used in pregnancy or for patients sensitive to naloxone. Buprenorphine/naloxone and buprenorphine monoproduct are interchangeable in terms of dosing.
Managing side effects: Here are a few common side effects and how to manage them:
Consider long-acting: Long-acting injectable buprenorphine is usually recommended for patients with poor adherence, though we don’t have studies showing this definitively. How the two long-acting options, Sublocade and Brixadi, compare to each other remains to be seen. For more about long-acting injectable buprenorphine and a detailed guide on how to use Sublocade, see “What to Know About Injectable Buprenorphine” in The Carlat Addiction Treatment Report, January 2023.
Discontinuing
There is no evidence indicating that there is a safe time to stop buprenorphine. On the contrary, data show that mortality increases six-fold in the month after stopping OUD treatment and that longer duration of buprenorphine treatment is associated with better outcomes, at least for the first year. Providers should encourage patients doing well on buprenorphine to stay on buprenorphine (Santo T Jr et al, JAMA Psychiatry 2021;78(9):1–15; Hasan NM et al, AM J Drug Alcohol Abuse 2022;48(4):481–491).
Nonetheless, some patients will insist on coming off medication. Most patients will experience withdrawal symptoms when the dose is lowered, so for these patients, prescribe a medication taper. Slower tapers are associated with lower rates of opioid use (Dunn KE et al, Drug Alcohol Depend 2011;119(1–2):1–9), so we recommend no more than a 20% reduction at any one time. Check in with your patients frequently during the process and adjust the taper schedule accordingly.
Carlat Verdict
Buprenorphine is a first-line treatment for OUD and now can be prescribed by anyone able to write for controlled substances. Patients should start with a carefully timed induction and increase the dose until they are free from withdrawal symptoms and opioid cravings. Consider long-acting injectable formulations for patients with poor adherence. Finally, encourage your patients to stay on buprenorphine.
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