Buprenorphine After the X-Waiver

April 2, 2024


By Sarah M. Jackson

Peer Reviewed

During the COVID-19 pandemic, opioid overdose deaths increased from 50,000 in 2019 to 80,000 in 2021, largely driven by synthetic opioids such as fentanyl.1 Despite the escalating use of synthetic opioids, medication for opioid use disorder (MOUD) has remained elusive to many. Nearly 90% of people with opioid use disorder do not receive MOUD, including methadone, naltrexone, and buprenorphine.2 The chasm between the need for treatment and the lack of prescriptions has been partially attributed to federal regulations, in particular the need for an “X-waiver.” For decades, doctors without board certification in addiction could only prescribe buprenorphine if they completed training and registered for the waiver. This opt-in process has been blamed for siloing buprenorphine prescriptions to the specialties of addiction medicine and psychiatry. Fortunately, the X-waiver was eliminated in December 2022, paving the way for all providers with a DEA license to prescribe buprenorphine. With the regulations lifted, one might anticipate a spike in buprenorphine orders to match the high prevalence of opioid use disorder. But, as all providers become capable of prescribing buprenorphine, the question emerges— was the lack of treatment just about the X-waiver?

Buprenorphine was first synthesized in 1966 from an initiative to create a safer codeine alternative, but it became recognized as an effective treatment for patients undergoing detoxification from heroin.3 It is classified as a partial mu opioid receptor agonist with stronger binding affinity than recreational opioids. As a result of partial agonism, buprenorphine is thought to have a “ceiling effect” in terms of euphoria and respiratory depression,4 reducing the risk of overdose. Additionally, buprenorphine is commonly prescribed in a combination product as buprenorphine with naloxone (SuboxoneÒ). This results in opioid antagonism by the naloxone if the product is not used as directed (sublingually) and, instead, is diverted and used intravenously.5 The safety measures and partial agonism serve as advantages over methadone. Methadone, a full opioid receptor agonist, has to be given through opioid-treatment programs (OTP), requiring patients to travel to a site for monitored medication administration. On the other hand, the profile of buprenorphine creates flexibility and increased access, reaching patients who cannot go to an OTP by giving them a month’s worth of medicine from a provider’s office.6 Given the safety, efficacy, and logistical advantages over methadone, the insufficient prescribing of buprenorphine is all the more striking.

The X-waiver, which is now viewed as a regulatory roadblock, was intended to expand the availability of buprenorphine providers beyond those who are board-certified in addiction. Created under the Drug Addiction and Treatment Act of 2000, the X-waiver could empower clinicians with whom patients regularly come in contact; primary care providers, emergency practitioners, and dentists could initiate treatment. However, buprenorphine is classified as a Schedule 3 narcotic by the Drug Enforcement Administration (DEA), signaling a potential for abuse, thus requiring an eight-hour training for physicians to prescribe safely and prevent misuse. Once applicants were approved by the Substance Abuse and Mental Health Services Administration (SAMHSA) for the waiver, providers received a DEA number with the titular “X” at the front. Prescribers had limits on the number of patients they could have on buprenorphine treatment at a given time and were required to keep meticulous records.

While it is easy to sanitize the lack of buprenorphine treatment by blaming it on the bureaucratic hurdles, a study of doctors without X-waivers found that the reasons go beyond the regulatory requirements. The main reasons for not seeking the waiver were: 1) providers did not want floods of requests for buprenorphine, and 2) they were concerned about diversion of the medication for misuse.7 Of these participants, over a third of them reported that “nothing would increase their willingness to prescribe buprenorphine.”7 Such concerns about misuse are surprising given the evidence that suggests that buprenorphine is safe and reduces all-cause mortality,8 especially weighed against the unequivocal danger of fentanyl.

Even when efforts have been made to increase the proportion of providers with the X-waiver, it was clear that there were other factors contributing to the reluctance to prescribe. In Rhode Island, there was a systemic endeavor to increase the number of doctors with an X-waiver, resulting in a 200% increase in physicians with waivers from 2016-2022.9 However, the number of patients being treated did not follow the same trend; it has declined between 2020 and 2023.10 In a survey of physicians with waivers, over 56% reported that they were not prescribing at capacity. Over half of those indicated that nothing would increase their willingness to prescribe, which was driven by 1) lack of belief in agonist treatment, 2) lack of time for more patients, and 3) beliefs that reimbursement rates are insufficient.7 With these attitudes, it is evident that simply having the ability to prescribe buprenorphine will not automatically translate into this life-saving therapy being more readily available.

When Congress eliminated the X-waiver in December, it only removed a superficial obstacle to prescribing buprenorphine. Addiction is difficult to treat. It is a relapsing and remitting condition associated with significant medical and psychiatric comorbidity. Opioid use disorder is stigmatized in society and, clearly, in medicine. It is hard to imagine physicians choosing to routinely withhold evidence-based treatments for other conditions that are as common and deadly. As all physicians gain the ability to prescribe buprenorphine, more has to be done to support doctors, especially primary care and emergency physicians, in including the medication as part of their practice. Whether through education on the evidence for agonist therapy, improving reimbursements, or reflections in quality metrics, efforts to expand access to buprenorphine are only beginning with the end of the X-waiver.

Sarah M. Jackson is a Class of 2025 medical student at NYU Grossman School of Medicine

Peer reviewed by Ann Garment, MD, Clinical Associate Professor, Department of Medicine, NYU Grossman School of Medicine Co-Director, Addiction Medicine Fellowship Program,  Section Chief, General Internal Medicine, Bellevue Hospital Center

Image courtesy of Wikimedia Commons, Buprenorphine naloxone Tablets Bottle.jpg

References

1. National Institute on Drug Abuse. Drug overdose death rates. National Institute on Drug Abuse. https://nida.nih.gov/research-topics/trends-statistics/overdose-death-rates Published February 9, 2023. Accessed May 25, 2023.

2. Krawczyk N, Rivera BD, Jent V, Keyes KM, Jones CM, Cerdá M. Has the treatment gap for opioid use disorder narrowed in the U.S.?: A yearly assessment from 2010 to 2019. Int J Drug Policy. 2022;110:103786. doi:10.1016/j.drugpo.2022.103786  https://pubmed.ncbi.nlm.nih.gov/35934583/

3. Heidbreder C, Fudala PJ, Greenwald MK. History of the discovery, development, and FDA-approval of buprenorphine medications for the treatment of opioid use disorder. Drug Alcohol Depend Rep. 2023;6:100133. Published January 10, 2023. Accessed May 25, 2023. doi:10.1016/j.dadr.2023.100133  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10040330/

4. Walsh SL, Preston KL, Stitzer ML, Cone EJ, Bigelow GE. Clinical pharmacology of buprenorphine: ceiling effects at high doses. Clin Pharmacol Ther. 1994;55(5):569-580. doi:10.1038/clpt.1994.71  https://pubmed.ncbi.nlm.nih.gov/8181201/

5. Sivils A, Lyell P, Wang JQ, Chu X-P. Suboxone: History, controversy, and open questions. Front Psychiatry. 2022;13:1046648. Published October 28, 2022. doi:10.3389/fpsyt.2022.1046648  https://pubmed.ncbi.nlm.nih.gov/36386988/

6. Jones CW, Christman Z, Smith CM, et al. Comparison between buprenorphine provider availability and opioid deaths among US counties. J Subst Abuse Treat. 2018;93:19-25. doi:10.1016/j.jsat.2018.07.008

7. Huhn AS, Dunn KE. Why aren’t physicians prescribing more buprenorphine?. J Subst Abuse Treat. 2017;78:1-7. doi:10.1016/j.jsat.2017.04.005

8. Sordo L, Barrio G, Bravo MJ, et al. Mortality risk during and after opioid substitution treatment: systematic review and meta-analysis of cohort studies. BMJ. 2017;357:j1550. Published April 26, 2017. doi:10.1136/bmj.j1550

9. Bebinger M. A roadblock to life-saving addiction treatment is gone. Now what? NPR. https://www.npr.org/sections/health-shots/2023/03/06/1159225349/roadblock-to-

10. RI Department of Health (RIDOH), Behavioral Healthcare, Developmental Disabilities and Hospitals (BHDDH), Brown University (brown edu). Medication for opioid use disorder data–Prevent Overdose RI. https://preventoverdoseri.org/medication-for-opioid-use-disorder-data Published November 30, 2022. Accessed May 25, 2023.

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