Opioid Use Disorders: Advances in Pharmacotherapy Provide Long-term Results

As opioid use disorders (OUD) have evolved, so have their treatments. For decades, patients would be given opioid agonists for withdrawal and released from inpatient rehabilitation with oral naltrexone (NTX) and adjunctive clonidine.¹ Later treatments involved daily oral medications such as opioid antagonists, but issues with treatment adherence often resulted in relapse.¹

Eventually, extended-release (XR) formulations were developed, including XR-NTX, a monthly injectable opioid antagonist; the partial opioid agonist buprenorphine-naloxone (BUP-NX), which can be taken sublingually daily; or a buprenorphine implant, which releases the drug for a duration of 6 months.^2-4 A combination of pharmacotherapy and social support is now known to be essential to treat OUD effectively.

How Extended-Release Antagonists Help Professionals With OUD

One area in which long-lasting OUD treatment might be beneficial is with licensed professionals who are trying to retain or re-enter employment.⁵ In an open-label study of 38 healthcare professionals (31 women), investigators sought to determine the long-term efficacy of XR-NTX in preventing relapse.⁵ More than half the participants received ≥12 injections, and 7 of the participants discontinued treatment because of adverse effects events (3 for anxiety, 2 for headache, 1 because of injection-site mass, and 1 as a result of derealization). None of the participants died or had a relapse.

At the end of the 2-year study, the participants’ opioid cravings were found to have decreased by a mean 45.2%, and mental health, as evaluated with the 36-Item Short Form Health Survey, improved by 31.1%. Of the 22 unemployed participants, 45.5% had raised their employment status at 24 months.

“Professionals with OUD do well with injectable [NTX] because oversight bodies for physician and nurse monitoring programs can ensure compliance,” explained lead study author Paul H. Earley, MD, an addiction specialist in Atlanta, Georgia. “There are fewer concerns that health professionals may have cognitive or other difficulties associated with partial or full agonists. Plus, the use of injectable [NTX] as a blocking agent dramatically decreases the probability of stopping medication and returning to their OUD. Thus, the public is protected.”

Induction Difficulties May Thwart Treatment

Although the XR formulations of NTX and buprenorphine implants have benefited patients who struggle with adherence and addiction, the detoxification process that precedes the first injection of XR-NTX may be insurmountable for some.⁶ When the authors of a Lancet study compared XR-NTX with sublingual BUP-NX, they found that XR-NTX treatment initiation, which requires a negative urine sample (or ≥3 opioid-free days), was an obstacle to treatment completion.

This multisite study included 570 patients (age 25-45 years; 68% men) who were randomly assigned to receive XR-NTX (n=283) or BUP-NX (n=287) for 24 weeks. Only 72% of study participants were able to start treatment with XR-NTX vs 94% with BUP-NX (P <.0001). As a result, there were fewer relapses in the BUP-NX group (57%) vs the XR-NTX group (65%). Once the participants were successfully inducted in their respective therapies, the efficacy was comparable between the 2 groups.

Stigma: An Overlooked Barrier to Treatment

Despite the 27 million people with OUD, stigma can be a tremendous barrier for individuals to seek and remain in treatment.⁷ The authors of a study on the topic found that society’s attitudes toward individuals with OUD — by labeling them as dangerous and self-destructive — can lead patients to internalize feelings of shame and guilt related to their disorder. Clinicians can help patients partially overcome such barriers by participating in shared decision-making with their patients in an effort to replace self-stigma with self-esteem.⁷

“Partner with patients to help them identify their treatment goals, learn about the strengths and weaknesses of differing interventions, and learn to compromise about treatment plan,” said study lead author Patrick W. Corrigan, PsyD, distinguished professor of psychology at the Illinois Institute of Technology in Chicago.

Preventing Future Abuses and Overdoses

Until optimal detoxification methods that would be associated with fewer or no relapses are identified, opioid overdose rescue interventions will be necessary. The authors of a 2018 study that examined the geolocation of opioid-related emergency services identified locations where NX kits might be best deployed in a municipality — akin to the defibrillator stations now commonplace in public locations.⁸ Using geospatial data based on 700 emergency calls for opioid overdoses within a 7-month period, the study authors mapped optimal locations for the NX kits where the calls had clustered.

“Given the results of our research, I hope that clinicians treating people with OUD will consider [the presence of] opioid overdose clusters in their communities as well, and, if so, whether publicly deploying NX in these hotspots could benefit their community as well,” said lead author Daniel A. Dworkis, MD, PhD, from the Keck School of Medicine of the University of Southern California, department of emergency medicine in Los Angeles.

A collaborative approach may curtail addiction at its source: the initial prescription for pain medication.⁹ Investigators at the Veterans Health System noted that, by deploying advanced practice nurses and clinical pharmacists, the interdisciplinary care teams involved in the treatment of patients with chronic pain were better able to thwart opioid abuse by managing laboratory screening, educating patients about their medications, and encouraging naloxone use and opioid tapering.⁹

“Our findings suggest there are many roles that licensed clinical pharmacists can assume on interdisciplinary primary care teams relating to pain care,” said lead author Karleen F. Giannitrapani, PhD, MPH, from the Veterans Affairs Palo Alto Health Care System’s Center for Innovation to Implementation in Menlo Park, California. “We also found that having pharmacists take on these roles may require more than simply resources. It requires culture change.”

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References

1. Bisaga A, Mannelli P, Sullivan MA, et al. Antagonists in the medical management of opioid use disorders: historical and existing treatment strategies. Am J Addict. 2018;27(3):177-187.
2. Vivitrol (naltrexone) [prescribing information]. Waltham, MA: Alkermes, Inc.; 2015.
3. Suboxone (buprenorphine HCl and naloxone HCl dihydrate sublingual tablets) [prescribing information]. Richmond, VA: Reckitt Benckiser Pharmaceuticals, Inc.; 2018.
4. Probuphine (buprenorphine implant) [prescribing information]. Princeton, NJ: Braeburn Pharmaceuticals, Inc.; 2018.
5. Earley PH, Zummo J, Memisoglu A, Silverman BL, Gastfriend DR. Open-label study of injectable extended-release naltrexone (XR-NTX) in healthcare professionals with opioid dependence. J Addict Med. 2017;11(3):224-230.
6. Lee JD, Nunes EV Jr, Novo P, et al. Comparative effectiveness of extended-release naltrexone versus buprenorphine-naloxone for opioid relapse prevention (X:BOT): a multicentre, open-label, randomised controlled trial. Lancet. 2018;391(10118):309-318.
7. Corrigan PW, Nieweglowski K. Stigma and the public health agenda for the opioid crisis in America. Int J Drug Policy. 2018;59:44-49.
8. Dworkis DA, Weiner SG, Liao VT, Rabickow D, Goldberg SA. Geospatial clustering of opioid-related emergency medical services runs for public deployment of naloxone. West J Emerg Med. 2018;19(4):641-648.
9. Giannitrapani KF, Glassman PA, Vang D, et al. Expanding the role of clinical pharmacists on interdisciplinary primary care teams for chronic pain and opioid management. BMC Fam Pract. 2018;19(1):107.