Update on Buprenorphine for the Treatment of Opioid-Use Disorder

In the year leading up to July 2022, more than 107,000 persons in the United States died of a drug overdose, and 81,000 of those deaths involved opioids.[1] Those numbers have increased during the COVID-19 pandemic despite substantial efforts by public health officials and many others to reverse this preventable trend in “deaths of despair.”[2]

Treatment of opioid-use disorder is an essential part of the public health response to the opioid scourge that continues to plague the United States. Formulations (including pills or films) of buprenorphine (BELBUCA, BUTRANS) were first approved by the Food and Drug Administration in 1981. Since 2002, the fixed-combination product buprenorphine/naloxone (SUBOXONE, ZUBSOLV) has been added, and buprenorphine drugs have specifically been approved to treat opioid dependence.[3] The labeling for both types of medication states that they “should be used as part of a complete treatment plan that includes counseling and psychosocial support.”[4],[5]

Recent research continues to support buprenorphine’s effectiveness and safety as a treatment for opioid-use disorder.

Background on opioid-use disorder and buprenorphine

In 2021, an estimated 2% of persons in the United States who were 12 years of age or older had an opioid-use disorder.[6] Widely deployed assessment criteria require the presence of at least three of the following six signs for the formal diagnosis of opioid-use disorder: 1) strong desire to use, 2) difficulty controlling use, 3) withdrawal symptoms upon ceasing, 4) tolerance to the effects (need for ever-increasing doses), 5) neglecting pleasures or interests because of opioids and 6) persistent use despite clearly harmful consequences.[7]

Buprenorphine is a partial opioid agonist, which means that it partially activates the brain receptors that trigger the euphoria, analgesia, breathing depression and other effects of opioids. As a partial (rather than a full) opioid agonist, buprenorphine can be therapeutic for those with opioid-use disorder because it reduces the negative symptoms of withdrawal while minimizing the dramatic emotional swings that feed dependence. Naloxone, the commonly used and highly effective nasal spray (KLOXXADO, NARCAN) or injectable (ZIMHI) antidote to opioid overdose, is often coformulated with oral buprenorphine (for example, in Suboxone) to reduce the risk of overdose in case buprenorphine intended for oral use is mistakenly administered by injecting or snorting.[8]

Previous articles in Worst Pills, Best Pills News have described notable but largely addressable — with clinical monitoring and other healthy behaviors — risks of buprenorphine, including addiction, overdose, liver toxicity, serotonin syndrome (when taken with certain antidepressants or migraine medications), dental problems, and reduced libido and fertility.[9],[10]

More permissive prescribing during the COVID-19 pandemic

As COVID-19 emerged, buprenorphine became more widely available via remote prescribing to treat opioid-use disorder. Accordingly, some health professionals were concerned that this expanded flexibility might lead to increased abuse and put some patients at risk of overdose and death. An observational study published in 2023 suggests otherwise.[11]

The study reviewed data from 31 U.S. states for the period from July 2019 through June 2021. The data included 74,474 unintentional opioid overdose deaths, of which 1,955 were buprenorphine-involved overdose deaths. Although all opioid-involved overdose deaths increased by about one-third over the first year of the COVID-19 pandemic, the study found no similar increase in buprenorphine-involved deaths. Moreover, 93% of the buprenorphine-involved deaths also involved other hazardous drugs (such as benzodiazepines and gabapentin), compared with 67% of the other opioid-related deaths, indicating that buprenorphine alone is less dangerous than other opioids such as heroin or fentanyl.

Review study of buprenorphine to treat prescription-opioid-use disorder

A 2022 expert review of randomized clinical trials (RCTs) considered the role of opioid agonists, including methadone (METHADOSE) and buprenorphine, for opioid-use-disorder patients whose dependence was principally on prescription pain medications. Of the eight relevant RCTs involving 709 patients, there was “low to moderate” (for example, small samples and none were fully blinded) quality evidence that methadone kept more people in treatment, whereas buprenorphine otherwise seemed similarly effective. Buprenorphine also was superior to other treatment options such as detoxification (removal of opioids only), opioid antagonists (inhibitors such as naltrexone [VIVITROL]) or psychosocial treatments. Unfortunately, this evidentiary synthesis offered only “low” or “very low” quality evidence regarding adverse effects and no data regarding the important outcomes of employment and quality of life.

Use in pregnancy

Prior research demonstrates the benefits of methadone or buprenorphine treatment for opioid-use disorder in pregnancy.[13] A 2023 medical-records study, however, found that use of these medications during pregnancy was associated with risks to the new mother and infant.[14] The nonrandomized retrospective (look-back) study used Rhode Island data from 2008 to 2016 and was limited to women with continuous Medicaid enrollment from three months before to one month after a live birth who also had an opioid-use disorder. These selection criteria identified the following three groups for comparison: those prescribed buprenorphine (n=85), those prescribed methadone (n=137) and those prescribed no medication for their opioid-use disorder (n=152).

Adjusted comparisons indicated that, as compared with those exposed to neither medication, both methadone- and buprenorphine-exposed infants had higher neonatal abstinence (withdrawal) syndrome and intensive care unit admission rates, were small for their gestational age and had more lengthy hospital stays. Methadone-exposed infants further were more likely to have low birth weights, whereas buprenorphine-exposed infants were less likely to experience preterm births. New mothers also were more likely to have longer hospital stays if they had prescriptions for methadone or buprenorphine during their pregnancy. Overall, the maternal and newborn outcomes were worse for methadone than for buprenorphine. Therefore, the study authors concluded that if medication treatment is needed for opioid-use disorder during pregnancy, buprenorphine is preferred over methadone.

What You Can Do

If you are concerned that you are misusing opioids, including pain medications, you should consult with a doctor about treatment that may include buprenorphine therapy. Such treatment planning will likely be more intense and complex for pregnant women. Medication for opioid-use disorder should always be combined with other psychosocial supports and counseling. Opioid-use disorders typically are persistent and cycling, so relapses are common.

Finally, note that if you or someone close to you is being treated with buprenorphine or methadone for opioid-use disorder or has an elevated predilection for misusing opioids (originally obtained via legal prescription to treat pain or otherwise), you should keep doses of the opioid antidote naloxone handy in case of overdose emergencies. Naloxone nasal spray was approved for prescription use in 2015 and for over-the-counter use in March 2023.
 

References

[1] Tanz LJ, Jones CM, Davis NL, et al. Trends and characteristics of buprenorphine-involved overdose deaths prior to and during the COVID-19 pandemic. JAMA Netw Open. 2023;6(1):e2251856.

[2] Mattson CL, Tanz LJ, Quinn K, et al. Trends and geographic patterns in drug and synthetic opioid overdose deaths - United States, 2013-2019. MMWR Morb Mortal Wkly Rep. 2021;70(6):202-207.

[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 10;6:100133.

[4] Indivior Inc. Label: buprenorphine (SUBUTEX). June 2022. https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/020732s027s028lbl.pdf. Accessed May 2, 2023.

[5] Indivior Inc. Label: buprenorphine and naloxone (SUBOXONE). June 2022. https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/020733s031s032lbl.pdf. Accessed May 2, 2023.

[6] Substance Abuse and Mental Health Services Administration. 2022. Key substance use and mental health indicators in the United States: Results from the 2021 National Survey on Drug Use and Health (HHS Publication No. PEP22-07-01-005, NSDUH Series H-57). Center for Behavioral Health Statistics and Quality, Substance Abuse and Mental Health Services Administration. https://www.samhsa.gov/data/report/2021-nsduh-annual-national-report. Accessed May 2, 2023.

[7] Nielsen S, Tse WC, Larance B. Opioid agonist treatment for people who are dependent on pharmaceutical opioids. Cochrane Database of Syst Rev. 2022;9(9):CD011117.

[8] Gregg J, Hartley J, Lawrence D, et al. The naloxone component of buprenorphine/naloxone: discouraging misuse, but at what cost? J Addict Med. 2023;17(1):7-9.

[9] FDA warns that buprenorphine medications dissolved in mouth increase risk of dental problems. Worst Pills, Best Pills News. July 2022. https://www.worstpills.org/newsletters/view/1475. Accessed May 2, 2023.

[10] Buprenorphine for opioid addiction. Worst Pills, Best Pills News. February 2017. https://www.worstpills.org/newsletters/view/1086. Accessed May 2, 2023.

[11] Tanz LJ, Jones CM, Davis NL, et al. Trends and characteristics of buprenorphine-involved overdose deaths prior to and during the COVID-19 Pandemic. JAMA Netw Open. 2023;6(1):e2251856.

[12] Nielsen S, Tse WC, Larance B. Opioid agonist treatment for people who are dependent on pharmaceutical opioids. Cochrane Database of Syst Rev. 2022; 9(9):CD011117.

[13] Ordean A, Tubman-Broeren M. Safety and efficacy of buprenorphine-naloxone in pregnancy: a systematic review of the literature. Pathophysiology. 2023;30(1):27-36.

[14] Wang S, Meador KJ, Pawasauskas J, et al. Comparative safety analysis of opioid agonist treatment in pregnant women with opioid use disorder: a population-based study. Drug Saf. 2023;46(3):257-271.