Frequently Asked Questions

Starting Buprenorphine Treatment In The ED

Buprenorphine is a unique schedule III opioid used for the treatment of acute and chronic pain, opioid withdrawal and maintenance treatment of opioid addiction. The most common formulations are sublingual (alone or in combination with naloxone: Suboxone), transdermal (10mcg/hr = about 0.5mg/day) and intravenous (Buprenex).

Buprenorphine has been used in clinical practice since the 1970’s. Initially, buprenorphine was used as an intravenous perioperative analgesic. Later, due to its characteristics as a long acting partial agonist, buprenorphine was found to block the euphoric effects of heroin and became used for the treatment of OUD. Sublingual buprenorphine was developed for opioid substitution treatment in the 1990s and was approved for use in the U.S. in 2002. Today buprenorphine is used to treat OUD and is increasingly used for the treatment of chronic pain.

Sublingual buprenorphine takes 15 minutes to act when held under the tongue and peaks in one hour. A typical 0.3mg IV buprenorphine begins to work immediately after an IV push with peak effect in 5-10 minutes.

If a patient that is dependent on opioids takes buprenorphine when they have opioids in their system, the buprenorphine will rapidly block the effects of their opioid, causing what is termed “precipitated withdrawal.” The severity of this effect varies from mild discomfort to severe distress. This is why there is a washout period for opioid tolerant patients before starting buprenorphine. Once significant withdrawal has begun, the administration of buprenorphine produces relief of withdrawal, anxiolysis and analgesia. Some patients with significant liver disease (ALT > 5x normal) may not be able to take buprenorphine long-term. Avoid it in patients with hypersensitivity to buprenorphine or naloxone.

Suboxone is the trademark name for buprenorphine + naloxone. The naloxone component is an abuse deterrent that is inert when the tablet is taken sublingually. The naloxone is only active if the tablet is injected. Suboxone sublingual film comes in a range of dose strengths. For example, Suboxone 8mg/2mg contains 8mg of buprenorphine and 2mg of naloxone. Other Suboxone sublingual dose options include 2mg/0.5mg, 4mg/1mg, and 12mg/3mg.

When using buprenorphine for withdrawal management, adjunctive medications are typically not needed. However, in certain cases where buprenorphine does not sufficiently control withdrawal, or when buprenorphine induces withdrawal adjunct medications such as clonidine, zofran and loperamide can be helpful. Avoid routine use of benzodiazepines.

It depends. An ED patient might receive a few doses buprenorphine to treat withdrawal and then go right back to using street opioids. Most patients with opioid use disorder don’t establish long-term abstinence on the first go around. The hope is that having a positive experience with buprenorphine treatment can be a motivation to pursue long-term treatment. The evidence is clear: the more weeks of stability on buprenorphine that a person with opioid use disorder can string together, the more their mortality risk goes down. Patients stop and start frequently, which is common. Each medical encounter is an opportunity to make another attempt at long-term recovery.

Once patients have stabilized on buprenorphine, patients should be continued on it indefinitely. When patients stop their maintenance buprenorphine or methadone, all-cause mortality more than doubles. (Sordo L, Barrio G, Bravo M, Indave B, Degenhardt L, Wiessig L, Ferri M, Pastor-Barriuso R. Mortality Risks During and After Opioid Substitution Treatment: Systematic Review and Meta-Analysis of Cohort Studies. BMJ 2017; 357:j1550.)

The underlying concept is that the neural architecture of the brain is changed by addiction and it takes years to recover. When patients are in recovery, they develop whole new patterns of behavior, stress responses and reward seeking that then get “hardwired” into the brain. This process cannot be rushed and has very little to do with patient motivation or insight.

No, MAT is not another form of addiction. Addiction differs from physical dependence in that addiction involves using a substance compulsively, using a substance despite negative consequences and using it to reach a state of euphoria. With medications to treat substance use, a patient may become physiologically dependent on the substance, but the medication is used to feel and stay well, not to achieve euphoria or a “high.” Medications, such as methadone, actually have greater chemical similarities to the brain’s natural hormones (e.g. endorphins), than other opioids.

Buprenorphine in The ED

At minimum, sublingual tablet formulations of buprenorphine should be available to be administered and/or prescribed from the ED. The most common formulations are sublingual (alone or in combination with naloxone: Suboxone), transdermal (10mcg/hr = about 0.5mg/day) and intravenous (Buprenex). Many EDs favor stocking monoproduct of buprenorphine as they are often cheaper than combination products and the risk for IV diversion when administered in the ED is negligible.

Buprenorphine will displace other drugs from opioid receptors, replacing the high-intensity stimulation from drugs like heroin or oxycodone with stable drug levels over two to three days, eliminating craving and withdrawal symptoms. Starting buprenorphine when patients have moderate withdrawal symptoms provides immediate relief, stopping withdrawal discomfort without causing euphoria or sleepiness. Do NOT start buprenorphine on opioid-dependent patients who are not in withdrawal. For these patients, the buprenorphine causes withdrawal and decreases patients’ desire to stay on buprenorphine or to try buprenorphine again.

Generally, start with 4-8 mg as sublingual tablet (Suboxone or Subutex) under the tongue. IV buprenorphine (0.3mg) can be used for patients unable to tolerate sublingual tablets. If the tablets are swallowed, very little buprenorphine gets absorbed. Repeat doses up to 32mg SL can be administered depending on the clinical situation. It is okay to administer buprenorphine in low-acuity, “fast-track” type areas of the ED. A single 8mg dose will have peak effect by about one hour and control withdrawal symptoms for 6-12 hours. Transdermal buprenorphine will generally be too weak to prevent withdrawal symptoms and is best used for patients with chronic pain. 

Always offer a naloxone prescription or kit.

    • Option 1. No DEA X waiver: Prescribe comfort meds (e.g. clonidine, loperamide, ondansetron, NSAIDS) and recommend follow-up at treatment center. It is legal in all states to offer return ED visits for buprenorphine administration for three days in a row if necessary.
    • Option 2. DEA X waiver: Give bridge script to last until outpatient visit: e.g., 8mg Suboxone, SL tabs; Take one tab under the tongue twice a day for withdrawal symptoms; Dispense #6-7.

Communication with patients
Talk to patients broadly and openly about addiction to break down stigma on the part of patients and clinicians. Daily discussion of addiction helps break down stigmatized attitudes and promote a non-judgmental medical approach.

Communication with colleagues
Getting the word out to the larger health system and the community that the ED is a setting for getting help, rather than hiding addiction and hoping to “score,” may be a potential benefit to beginning an ED MAT program. Public signage and patient handouts should be considered as part of communications plan. Provide an overview of buprenorphine treatment and what it entails – discussing risks, benefits and expectations. Widespread patient education about the neurobiological model of addiction, buprenorphine treatment and the treatment program can be provided to any patient receiving opioids. For patients identified with addiction, individually tailored educational materials can then be used.

In Colorado, Medicaid covers 100% of the cost for buprenorphine. Buprenorphine sublingual tablets without naloxone are approximately $5 and parenteral formulations are approximately $10; sublingual tablets with naloxone, patches and buccal film are much more expensive.

What is naltrexone?
Naltrexone is a medication approved by the Food and Drug Administration (FDA) to treat opioid use disorders and alcohol use disorders. It comes in a pill form or as an injectable. The pill form of naltrexone (ReVia, Depade) can be taken at 50 mg once per day. The injectable extended-release form of the drug (Vivitrol) is administered at 380 mg intramuscular once a month. Naltrexone can be prescribed by any health care provider who is licensed to prescribe medications. To reduce the risk of precipitated withdrawal, patients are warned to abstain from illegal opioids and opioid medication for a minimum of 7-10 days before starting naltrexone. If switching from methadone to naltrexone, the patient has to be completely withdrawn from the opioids. (See https://www.samhsa.gov/medication-assisted-treatment/treatment/naltrexone)

What is methadone?
Methadone works by changing how the brain and nervous system respond to pain. It lessens the painful symptoms of opiate withdrawal and blocks the euphoric effects of opiate drugs such as heroin, morphine, and codeine, as well as semi-synthetic opioids.

Patients taking methadone to treat opioid addiction must receive the medication under the supervision of a physician. After a period of stability (based on progress and proven, consistent compliance with the medication dosage), patients may be allowed to take methadone at home between program visits. By law, methadone can only be dispensed through an opioid treatment program (OTP) certified by SAMHSA. (See https://www.samhsa.gov/medication-assisted-treatment/treatment/methadone)

Addiction vs Dependence

A study by Berg et al, suggests that concerns about harm (precipitated withdrawal or drug-seeking) are likely unfounded. In a retrospective chart review of 158 patients treated at a single ED with buprenorphine for opioid withdrawal, the authors found no instances of precipitated opioid withdrawal (a potential medical complication of buprenorphine), and a greater than 50% reduction (17% vs. 8%) in return-rate to the same ED for a drug-related visit within one month, compared to return-visit rate for usual care (no pharmacologic management or supportive therapies such as anti-nausea medications and sedatives).

Buprenorphine can always be used to treat withdrawal. Anyone with an opioid use disorder who is opioid dependent and desires to get off full agonist opioids (oxycodone, hydrocodone, heroin) should be considered for buprenorphine. Typically, dosing is more frequent such as 4mg SL 3-4 times per day. Most insurance plans will only cover buprenorphine if opioid dependence is diagnosed. Whenever possible coordinate care with outpatient providers. It’s possible your patient will not view their opioid use as problematic, but they may likely meet criteria to be diagnosed with OUD based on the dependence and behaviors around obtaining the drug. Ensure you are prepared to help your patients understand the difference between addiction and dependence and how chronic pain plays a role in potentially masking OUD.

Providers cannot see over 120 patients at the same time. The DEA is only counting active prescriptions, so an ED provider who is not following patients long term would not be expected to be affected by this limit. At any given time, an ED provider would only be expected to have a few active prescriptions at the same time.

The 72-hour rule is intended to provide an emergency option for treating withdrawal as someone is getting established in treatment. It does not allow for prescribing but does allow repeat administration for three consecutive days for a given patient. The clock “resets” only after a patient has connected with a treatment program. If they relapse, they get another 72-hour emergency option. It does matter who is administering the medications. (See https://www.samhsa.gov/programs-campaigns/medication-assisted-treatment/legislation-regulations-guidelines/special).

For example:

  • Allowed: Patient “John” comes in acute withdrawal on Friday and gets buprenorphine for acute withdrawal. Then returns Saturday and Sunday to the ED and is administered Suboxone during the visit without any take home script. On Monday he sees an addiction specialist.
  • Allowed: (If there is no Suboxone on inpatient formulary) Patient “John” comes in acute withdrawal on Friday and gets morphine for acute withdrawal. Then returns Saturday and Sunday to the ED and is administered oral morphine during the visit without any take home script. On Monday he sees an addiction specialist.
  • Not allowed: Patient John sees a provider who does not have an X waiver and gets a three day prescription for Suboxone.
  • Not allowed: Patient John misses his appointment on Monday and returns to the ED asking for Suboxone. He cannot be administered or prescribed Suboxone by a NON-WAIVERED provider.
  • Not okay: John keeps the patch on for longer than three days.

Patients

Patients at risk for death from opioid overdose should be prioritized; risk factors include:

    • Injection heroin and non-medical pain reliever abuse
    • History of overdose and/or substance abuse
    • History of mental illness
    • > Morphine 100mg equivalents/day
    • Medicaid/low income patients
    • Frequent emergency department visits
      • > three in the last year;
      • ED visits with disposition of leaving without treatment or against medical advice
    • Multiple opioid prescriptions in last year and multiple prescribers. However, any patient who meets DSM 5 criteria for opioid use disorder should be strongly considered for starting buprenorphine.

There are multiple kinds of patients that can benefit from a buprenorphine treatment.

Starting a patient on buprenorphine lowers mortality from opioid addiction seven-fold. It is strongly recommended to start buprenorphine in the ED after overdose (OD), due to 10% risk of fatal OD within 12 months in these patients. Patients in opioid withdrawal, or who desire to stop using opioid pills or heroin, can work well for this program. Another type of patient that can be trickier is an individual with chronic pain. If they have a prescribing doctor, encourage them to go talk with that clinician. With these patients, it’s encouraged to start a conversation about potential transition to buprenorphine, to reduce overdose risk and possibly improve pain control. However, patients should generally be directed to discuss this option with their opioid prescriber prior to starting buprenorphine.

Yes. Buprenorphine is far safer than using street opioids. However, buprenorphine can potentiate the effects of sedatives like alcohol and benzodiazepines (but less than other opioids). Assess risk and benefit with these high-risk patients. The risk of overdose is highest when patients have binge use of alcohol and benzodiazepines. Patients should be encouraged to decrease/stop use of these substances, but often benefits of starting buprenorphine outweigh risks as the combination of illicit opioids and sedatives is riskier than buprenorphine and sedatives. See the FDA statement for further guidance:

https://www.fda.gov/drugs/drug-safety-and-availability/fda-drug-safety-communication-fda-urges-caution-about-withholding-opioid-addiction-medications

Patients who are on methadone (or on other chronic opioids) should not be started on buprenorphine while on these medications. Patients on methadone may ultimately consider transition from methadone to buprenorphine but should do so in consultation with their methadone clinic. Starts on buprenorphine for patients who took methadone within the last week is high risk for precipitated withdrawal and should only be done in consultation with an expert.

No. Offer women of childbearing age a pregnancy test. It’s encouraged to screen for HepC and HIV.

This is a case-by-case decision. Ideally ED prescriptions are short (three to seven days) with follow-up prescriptions at the outpatient treatment site. In general, most EDs will advise patients that no refills will be offered. But individual cases can be complicated and ED providers should use clinical judgement in regard to refilling prescriptions.

Yes. Buprenorphine is bought and sold on the street routinely. Most diverted buprenorphine is used for its intended purpose – avoiding dope-sickness and cravings. People who have experienced “street” buprenorphine have longer retention times in treatment, perhaps because they have experienced what buprenorphine does to increase stability and therefore are even more motivated when it comes to treatment. A reasonable balance is checking the patient drug monitoring database to confirm the patient’s opioid prescriptions and to provide a brief prescription (less than seven days). This allows time for follow-up appointments to be made with the outpatient clinic to continue buprenorphine prescribing and OUD treatment.[11]

[11] D’Onofrio G, O’Connor PG, Pantalon MV, Chawarski MC, Busch SH, Owens PH, Bernstein SL, and Fiellin DA. Emergency department-initiated buprenorphine/naloxone treatment for opioid dependence: a randomized clinical trial. JAMA. 2015;313(16):1636-44. doi:10.1001/jama.2015.3474

Regulations

There is a key difference between administration and prescription. Administration of buprenorphine in any form is allowed for any ED provider. A prescription of buprenorphine, on the other hand, is restricted. An X-waiver is needed for any prescription for SL buprenorphine for addiction. Note that anyone can prescribe buprenorphine for pain, but insurance often needs a TAR for the indication of pain. Workarounds include: A) Per title 21, §1306.07 section (c), the non-waivered prescriber can administer buprenorphine in the ED and then the patient can return for three consecutive days to get buprenorphine as they wait for an appointment. B) For healthy (ASA 1&2), young (less than 65 yrs. old) patients in moderate to severe withdrawal (at least one objective sign of withdrawal and COWS > 8), a loading dose can be used. Loading protocol = 8mg SL, assess in 30-45min, if patient feels better and no hypersensitivity, give 16-24mg SL. This will provide 72 hours of relief from withdrawal.

No. A waiver is not required to administer buprenorphine but having a clinician with an X-waiver is recommended so prescribing buprenorphine is an option on discharge.

For Patients Who Are Admitted For Medical Indication Who Are Also On Suboxone For Addiction Prior To Admission

Any MD can use any narcotic — buprenorphine, methadone, morphine, etc. — for the treatment of withdrawal (or prevention of – i.e. MAT) during the ED and inpatient course of treatment for a primary admission. There is no special certification required. Title 21, §1306.07 section (b): “If the primary admitting diagnosis is a different medical issue (other than opioid use disorder and withdrawal), the withdrawal can be treated as a part of their routine medical care. In this case, the facility is not acting as an inpatient rehab, and therefore no special certification is required.”

The 72-hour rule is intended to provide an emergency option for treating withdrawal as someone is getting established in treatment. It does not allow for prescribing but does allow repeat administration for three consecutive days for a given patient. The clock “resets” only after a patient has connected with a treatment program. If they relapse, they get another 72-hour emergency option. It does matter who is administering the medications. (See https://www.samhsa.gov/programs-campaigns/medication-assisted-treatment/legislation-regulations-guidelines/special).

Results from Buprenorphine Treatment

In a recent study of over 150,000 National Health Service patients treated for opioid dependence, followed for a total of 42,950 patient years, treatment of opioid dependence with buprenorphine was found to reduce risk for opioid overdose death by one-half versus patients with no treatment or psychosocial treatment only. In a study of 33,923 Medicaid patients diagnosed with opioid dependence in Massachusetts, mortality during the four-year study period (2003-2007) was double among patients receiving no treatment versus patients treated with buprenorphine. Additionally, patients treated with buprenorphine experienced a 75% reduced mortality versus patients treated with psychosocial interventions alone. Among the highest risk patients who inject heroin, treatment with methadone or buprenorphine for at least five cumulative years is associated with a reduction in mortality from 25% at 25 years to 6%. The association between treatment and improved survival is likely multifactorial and mediated through reduced risk of HIV infection, improved social functioning, reduced criminality and establishing long-term contact with health professionals. Importantly, survival benefit is not affected 14 15 16 17 18 19 20 21 by cessation of injection drug use.

Appendix

12 Pierce M, Bird SM, Hickman M, Marsden J, Dunn G, Jones A, and Millar T. Impact of treatment for opioid dependence on fatal drug-related poisoning: a national cohort study in England. Addiction. 2016;111(2):298-308. doi:10.1111/add.13193.

13 Clark RE, Samnaliev M, Baxter JD, and Leung GY. The evidence doesn’t justify steps by state Medicaid programs to restrict opioid addiction treatment with
buprenorphine. Health Aff (Millwood). 2011;30(8):1425-33. doi:10.1377/hlthaff.2010.0532.

14 Kimber J, Copeland L, Hickman M, Macleod J, McKenzie J, De Angelis D, and Robertson JR. Survival and cessation in injecting drug users: prospective observational
study of outcomes and effect of opiate substitution treatment. BMJ. 2010;341(jul01 1):c3172-c3172. doi:10.1136/bmj.c3172.

15 Mattick RP, Breen C, Kimber J, and Davoli M. Buprenorphine maintenance versus placebo or methadone maintenance for opioid dependence. Cochrane Database
Syst Rev. 2014;2:CD002207. doi:10.1002/14651858.CD002207.pub4.

16 Fugelstad A, Stenbacka M, Leifman A, Nylander M, and Thiblin I. Methadone maintenance treatment: the balance between life-saving treatment and fatal
poisonings. Addiction. 2007;102(3):406-12. doi:10.1111/j.1360-0443.2006.01714.x.

17 Bell J, Trinh L, Butler B, Randall D, and Rubin G. Comparing retention in treatment and mortality in people after initial entry to methadone and buprenorphine
treatment. Addiction. 2009;104(7):1193-200. doi:10.1111/j.1360-0443.2009.02627.x.

18 Gowing L, Farrell M, Bornemann R, and Ali R. Substitution treatment of injecting opioid users for prevention of HIV infection. The Cochrane Library. 2004.

19 Amato L, Davoli M, Perucci CA, Ferri M, Faggiano F, and Mattick RP. An overview of systematic reviews of the effectiveness of opiate maintenance therapies:
available evidence to inform clinical practice and research. J Subst Abuse Treat. 2005;28(4):321-9. doi:10.1016/j.jsat.2005.02.007.

20 Sporer KA. Strategies for preventing heroin overdose. BMJ. 2003;326(7386):442-4. doi:10.1136/bmj.326.7386.442.

21 Ward J, Hall W, and Mattick RP. Role of maintenance treatment in opioid dependence. Lancet. 1999;353(9148):221-6. doi:10.1016/S0140-6736(98)05356-2.

Title 21 Code of Federal Regulations PART 1306 — PRESCRIPTIONS

GENERAL INFORMATION §1306.07 Administering or dispensing of narcotic drugs.

(a) A practitioner may administer or dispense directly (but not prescribe) a narcotic drug listed in any schedule to a narcotic dependent person for the purpose of maintenance or detoxification treatment if the practitioner meets both of the following conditions:

  1. The practitioner is separately registered with DEA as a narcotic treatment program.
  2. The practitioner is in compliance with DEA regulations regarding treatment qualifications, security, records, and unsupervised use of the drugs pursuant to the Act.

(b) Nothing in this section shall prohibit a physician who is not specifically registered to conduct a narcotic treatment program from administering (but not prescribing) narcotic drugs to a person for the purpose of relieving acute withdrawal symptoms when necessary while arrangements are being made for referral for treatment. Not more than one day’s medication may be administered to the person or for the person’s use at one time. Such emergency treatment may be carried out for not more than
three days and may not be renewed or extended.

(c) This section is not intended to impose any limitations on a physician or authorized hospital staff to 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, or to administer or dispense narcotic drugs to persons with intractable pain in which no relief or cure is possible or none has been found after reasonable efforts.

(d) A practitioner may administer or dispense (including prescribe) any Schedule III, IV, or V narcotic drug approved by the Food and Drug Administration specifically for use in maintenance or detoxification treatment to a narcotic dependent person if the practitioner complies with the requirements of §1301.28 of this chapter.