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:

• Day 1: Give 2–4 mg, then repeat every hour up to 12 mg or until withdrawal is relieved
• Day 2: Give the total taken on Day 1, then give additional doses up to a total of 16 mg or until cravings are relieved
• Day 3: Give the total taken on Day 2, then give additional doses up to a total of 24 mg or until cravings are relieved
• Most patients will require 16–24 mg to relieve withdrawal symptoms and cravings

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:

• Day 1: 0.5 mg once (obtain by cutting a 2 mg film into quarters)
• Day 2: 0.5 mg BID
• Day 3: 1 mg BID
• Day 4: 2 mg BID
• Day 5: 2 mg TID
• Day 6: 2 mg QID
• Day 7: 4 mg TID and stop opioid agonists

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:

• Give 4–8 mg, then wait 30–60 minutes
• As long as there is no withdrawal, give a single dose of 16–24 mg
• The patient has now received a large cumulative dose of buprenorphine and can be discharged, ideally with follow-up care

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:

• Constipation: We recommend all patients on buprenorphine get a standing bowel regimen. Avoid bulk formers, such as psyllium, which can worsen constipation. We use the approach outlined in the “Recommended Bowel Regimen” table (www.tinyurl.com/yc65htxx).
• Dental issues: The topic of buprenorphine-induced dental issues is controversial (for more information, see our interview with Dr. Puzantian in The Carlat Addiction Treatment Report, January 2023). Patients are recommended to wash out their mouth with water once the buprenorphine is dissolved and to avoid eating, drinking, or brushing their teeth for one hour. Whenever possible, ensure regular dental follow-up.
• Naloxone sensitivity: Very little naloxone is absorbed sublingually, but some patients may experience headache, nausea, anxiety, or flushing. If your patient reliably develops these symptoms immediately after taking a dose of buprenorphine/naloxone, consider switching to monoproduct.
• Sedation: Sedation usually is not a problem, though some patients will feel tired after taking buprenorphine. This tends to go away after a few weeks, but if not, consider minimizing other sedating medications and switching buprenorphine to evening.

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.