Prolonged Cessation of Chronic Opioid Analgesic Therapy: A Multidisciplinary Intervention

, ,

This article evaluates the immediate and long-term efficacy of a group multidisciplinary program for chronic opioid analgesic therapy cessation in the setting of chronic, noncancer pain.

ABSTRACT

Objectives: To contribute to the literature of best-practice approaches to promote full mu agonist chronic opioid analgesic therapy (COAT) cessation in a population with chronic, noncancer pain by describing initial and extended follow-up outcomes from a limited group program that utilized a standardized, multidisciplinary curriculum containing robust complementary care access in a private practice setting.

Study Design: A retrospective review of data from electronic health records and the California Prescription Drug Monitoring Program for program participants between October 2017 and December 2019.

Methods: Daily oral morphine milligram equivalent (MME) dose use upon entry, at program graduation, at 6 months post graduation, and at extended follow-up of 7 to 24 months post graduation were compared and reported for program participants.

Results: A total of 109 program participants with incoming daily COAT use amounts as high as 600 MME (median, 60 MME; 25% quartile, 36.5 MME; 75% quartile, 90 MME; interquartile range, 53.5 MME) had a successful COAT cessation rate of 90% at program graduation, which was maintained at 6 months and extended follow-up at 95% and 97%, respectively.

Conclusions: This pilot study contributes to the literature by documenting a successful and potentially generalizable strategy to promote COAT cessation, and by providing unusually lengthy follow-up for postintervention COAT cessation monitoring.

Am J Manag Care. 2022;28(2):In Press

_____

Takeaway Points

Building on articles previously published in this journal, this research suggests a potential path toward an effective and sustained clinical approach to decrease chronic opioid analgesic therapy use in the population of patients with chronic, noncancer pain.

  • We retrospectively examine the initial and sustained success rates of full mu agonist chronic opioid analgesic therapy (COAT) cessation in the setting of chronic, noncancer pain (CNCP) through voluntary participation in a pilot program—implemented via 2 sites and care teams—that provided a standardized, multidisciplinary curriculum containing robust complementary care.
  • This study provides unusually lengthy follow-up for postintervention COAT cessation monitoring of up to 24 months.
  • Initial COAT cessation success rates were high, and sustained success at 6 months and beyond was even higher (90%, 95%, and 97%, respectively), indicating that the program curriculum may be an effective strategy for broader application for sustainable COAT cessation in the setting of CNCP.

_____

A recent CDC report suggests that years of nationwide medical and managed care regulations to limit prescription opioid access, dose, and time exposure have had minimal positive impact on life expectancy in the United States.1 Despite the wide abandonment of opioid prescriptions by the medical community, opioid-related mortality and morbidity have continued to rise, a trajectory that has accelerated due to the COVID-19 pandemic.1-3 Aside from being a contributor to overdose-related death, full mu agonist chronic opioid analgesic therapy (COAT) has been shown to impede vocational and social return to function and to increase length of disability.1,3,4 Managed care charges for patients with opioid dependency are more than 550% higher than the average annual per-patient charge.5 Also, the population of “opioid refugees” is gaining numbers—patients who were made dependent upon opioids by recent, but now out-of-favor, prescribing practices for the management of chronic pain and are now abruptly unable to find a medical source for the same medications.6 This has moved many patients with chronic pain dependent upon opioids to drastic measures such as seeking new or multiple prescribers, emergency medical care, or even illicit opioid sources.7

The medical community has been trialing and comparing several approaches to combat the ineffective use of COAT for chronic, noncancer pain (CNCP). Some managed care institutions have attempted a model of coverage cessation for these medications, resulting in paradoxically increased costs as patients struggle to cope.3 Clinicians have reported varying levels of success to promote COAT cessation through outpatient weaning8-12 and single-modality approaches of cognitive behavioral therapy (CBT),13,14 acupuncture,10 interdisciplinary programing,15-24 and buprenorphine substitution.20,25-27 None of the data present a definitive, best-practice approach to the challenge of the opioid epidemic in the setting of chronic pain.

The Present Study: The Focus on Opioid Transitions (FOOT Steps) Program

This study aims to present outcomes from the Focus on Opioid Transitions (FOOT Steps) Program. FOOT Steps was created to be a practical, implementable intervention to help patients with CNCP cease COAT reliance by using a robust combination of interventions usually applied individually. This paper describes not only how well the program achieved the objective initially, but also how well such results were maintained at an extended look back of up to 24 months of retrospective follow-up.

METHODS

Study Design

The intervention. A standardized curriculum was implemented within a multidisciplinary program designed to transition patients with CNCP off COAT. It contained group CBT emphasizing pain coping skills and mood regulation, complementary care modalities delivered in a group setting (biofeedback, mindfulness, acupuncture, and gentle motion), and individualized medication management providing the option of buprenorphine for COAT cessation, either as an alternative or as a transitional medication. Every activity was designed for home exercise and was led by a licensed or credentialed expert in that field, such as a physician, nurse practitioner, psychologist, licensed acupuncturist, physical therapist, or licensed physical therapy assistant. The program commenced in 6-hour sessions, 10 times, approximately weekly. The Table shows an example of a typical session schedule. Patient adherence was corroborated through mandated extended-panel urine drug screen at every meeting. Discharge planning occurred with the offer of continued care plan consultation to the referring clinicians upon graduation, as needed.

Buprenorphine was offered as an alternative to COAT, as it is a partial mu agonist in the opioid family.28 The danger of respiratory depression and overdose-related death associated with opioid use is thought to be conferred by the mu receptor, making partial mu agonist opioids significantly safer than full mu agonist opioids,29,30 which are the opioids predominantly used for analgesia. As a reflection of the superior safety profile of buprenorphine, in 2018 the CDC removed the associated oral morphine milligram equivalent (MME) conversion factor—signifying the relative potency of the opioid compared with the standard of morphine—stating that buprenorphine is “not expected to be associated with overdose risk in the same dose-dependent manner as doses for full agonist opioids.”31

FOOT Steps was a circumscribed, higher-acuity outpatient treatment within the auspices of a larger multicenter private practice specializing in CNCP, which received patient referrals from the surrounding geographical area of primary and specialty care offices in Northern California. These referral sources were diverse and included federally qualified health care centers, private practices, hospital-affiliated clinics, occupational medicine providers, and workers’ compensation entities. Patients were referred to FOOT Steps from within the larger CNCP specialty practice for COAT cessation when they were not meeting realistic analgesic and/or functional goals or were experiencing negative sequelae from COAT and could not cease COAT use via more traditional therapies. Two centers and clinical teams participated in administering the program. Funding occurred via routine medical fee-for-service billing. The researchers analyzed the present data through the course of program-related quality assurance measures. No other funding was present for this study. This study was reviewed by a private institutional review board and was determined exempt from full review.32

Measures. This is a retrospective review of electronic health records (EHRs) and California Prescription Drug Monitoring Program (PDMP) data—decoupled from identifying features—of patients who participated in the FOOT Steps Program from October 2017 to December 2019. Because the PDMP is ubiquitous as a record of presence and volume of prescribed controlled substances in California, with few exceptions (see Discussion), lack of an entry in the PDMP was interpreted as that subject not using opioids. No participant was lost to follow-up in this manner. COAT MME, as defined by the CDC,31 was noted upon entry, at graduation, 6 months post graduation, and at the extended follow-up point of December 2019 using the measures described. Extended follow-up length varied based on the rolling admission design of the program, from 7 to 24 months after graduation date. Participants were determined to have successfully graduated from the program if COAT cessation was achieved in 1 of 4 ways: a complete transition to a topical or sublingual form of buprenorphine, a COAT abstention without the aid of a transitional medication, a maintenance of recent COAT abstinence in the context of reported struggle with craving or coping, or a reduction of incoming buprenorphine dose by more than 50% in incoming patients not using full mu agonist opioids for analgesia. For the purposes of this paper, graduation and COAT cessation, as defined by the pathways above, are synonymous.

Participants. The subjects of this study were chosen via a semistructured motivational interviewing–style evaluation between individual participants and one of the qualified program clinicians, after a medical records review, to ensure that they met the inclusion criteria of the clinical program: adults who voluntarily consented to a group program for the purpose of COAT cessation and carried a diagnosis of CNCP from any etiology; had used COAT daily at the time of admission or had struggled to maintain recent opioid cessation; had tried and failed or plateaued on a previous opioid wean; and were failing to meet realistic functional and analgesic goals, as determined by the individual patients and/or their CNCP care teams. COAT used by participants at program initiation was any form of commercially available oral or transdermal long- and short-acting full mu agonist opioids obtained while under the care of a physician.32

Exclusion criteria from the program were candidates who did not carry a diagnosis of CNCP; were actively engaging in opioid diversion; had an active substance use disorder or biomedical or psychological comorbidity of significant acuity to be appropriate for higher than level 1 (outpatient) services as defined by the American Society of Addiction Medicine33 during the proposed time of program participation; or had a neurocognitive or neurodegenerative disorder that precluded the ability to actively participate in care-planning decisions and/or reliably follow written instructions.

Methodology

The outcomes data are reported using descriptive statistics.

RESULTS

Data on 109 FOOT Steps participants treated between October 2017 and December 2019 were included in this study. Initially, 113 participants entered the program from the pool of evaluated candidates, but 4 were referred out for higher-acuity care after appearing to meet the exclusion criteria after starting the program, and thus were not included in the outcomes data set. Incoming MME used by participants is represented in Figure 1, showing a range up to 600 MME (median, 60 MME; 25% quartile [Q1], 36.5 MME; 75% quartile [Q3], 90 MME; interquartile range [Q3-Q1], 53.5 MME). Anyone included in the study who did not successfully graduate from the program was included in the tally of “unsuccessful.” Causes for unsuccessful graduation noted in the EHR included 1 lack of consent for treatment after orientation, 1 adverse outcome of intolerable COAT withdrawal symptoms, and 1 adverse reaction to buprenorphine, and the remainder were cases of patient-initiated care plan changes resulting in a return to COAT. Noted reasons given by patients to return to COAT included complaints of pain, psychosocial stressors, and lack of buprenorphine coverage by insurance companies.

Limited demographic information was retrievable due to omissions and variations present in EHR demographics data, which were inputted across multiple systems and clinics. A total of 109 participants ranged in age from 27 to 88 years, and 69% of the participants were identified as female. Some inferences can be made about the socioeconomics of the studied population based on insurance sources: approximately 30% Medicare, 25% worker’s compensation, 10% Medicaid, less than 1% cash pay, and the remainder were commercial insurances. Narrative reports from the EHR revealed that patients typically had been exposed to multiple medications, surgeries, and treatment modalities prior to their referral to FOOT Steps. Most participants had experienced chronic pain for a period of years to decades. A majority also identified their work status as “disabled” or “retired,” when noted.

Figures 2, 3, and 4 summarize the program’s initial successful COAT cessation and follow-up maintenance rates. Ninety-eight participants (90%) ceased COAT by program graduation (Figure 3). Sixty-three of 66 (95%) and 64 of 66 (97%) successful graduates either maintained their successful graduation medication regimen or continued to make further progress on their own by also weaning off buprenorphine entirely at 6 months (Figure 4) and at extended follow-up after graduation (Figure 5), respectively. It should be noted that the look-back groups contain fewer subjects than the initial graduation group as an effect of rolling program admissions. Thus, some graduates graduated too recently to meet look-back time frames. It should also be noted that there were a few participants included in the population of those who maintained successful COAT cessation at follow-up whose PDMP showed a brief return to classic opioid use. A cross-reference with the EHR showed that these patients underwent a surgical procedure necessitating a limited exposure to classic opioids. If such patients had subsequently returned to buprenorphine or had ceased all opioids at the time of look back, they were included in the successful COAT cessation group.

DISCUSSION

Contribution to the Field

This study reports outcomes from a group program that yielded high COAT cessation rates for patients with CNCP by combining a standardized limited multidisciplinary curriculum, rich in complementary care, with buprenorphine access. The review of the program’s outcomes showed not only high initial success rates of COAT cessation, but also high sustained success for up to 24 months. This sustained success is especially significant to the field, as such follow-up outcomes are scant and are typically poor in response rate and results. Also significant is the implication that a cumulation of individual approaches that have previously been shown to be somewhat effective can lead to additive higher success when packaged together into a single intervention.

Comparison With Previously Documented COAT Cessation Approaches and Outcomes

The most abundantly available approach to COAT cessation for patients with CNCP is gradual outpatient opioid weaning. Studies observing the efficacy of this approach have shown some success of decreasing opioid dose, but complete cessation is reported to be closer to only 10%.9,11,12 Often, these marginal successes are documented as taking a year or more to achieve.9,12

Success rates of varying amounts have been documented using complementary interventions such as acupuncture, CBT, and interdisciplinary programming. One acupuncture study noted COAT cessation for 66% of participants but a significant return to opioids upon follow-up.10 In the same study, limiting generalizability, it was reported that only 10% of participants were taking “strong opioids.” Outcomes of CBT-based interventions for opioid cessation have also varied. One study reported opioid cessation rates as high as 55%, but the average MME in that study was only approximately 30,13 whereas another CBT-focused study in which some patients (albeit only 27%) were taking more than 100 MME had a dropout rate of 78% and documented success with a qualitative survey.14 As can be seen, FOOT Steps participants used MME as high as 600, and a previous study exploring factors potentially relating to initial COAT cessation found that MME amount was noncontributory.32 Interdisciplinary programs have reported the highest COAT cessation, but these successes have also been inconsistent (from 20% to 97%) at the culmination of the intervention, which is typically only a 3- to 4-week observation period.15,17,19,21,23,24 Studies that have tracked long-term opioid cessation success rates from interdisciplinary programming have documented that poor follow-up response and opioid backsliding are common findings.15,19,21,24

Similarly, reports about the role of buprenorphine for COAT cessation in CNCP have vastly different outcomes.15,25-27 One study reported only a 33% success rate with simultaneous adverse effects of 83%.27 Another study reported inverse findings: high COAT cessation and few adverse effects.25 When reported, long-term maintenance of COAT cessation varies greatly as well.15,34

Generalizability

Features of this study show promise for the generalizability of FOOT Steps’ outcomes. Clearly the study had no placebo arm; however, all participants had previously attempted and failed a traditional outpatient COAT wean, which suggests that the selected participants in this study were potentially skewed unfavorably toward the outcome of COAT cessation. Additionally, whereas it is a common model to parse out only 1 type of injury or etiology of pain to study the effectiveness of interventions, all CNCP etiologies were accepted in this study. Diagnoses of mild and moderate opioid use disorder in conjunction with chronic pain diagnoses were accepted, which may further broaden applicability. Also promising is that the intervention was successful in a population that contained users of high MME. Finally, the consistent success of program results from 2 separate centers and clinical teams is an encouraging foundation for replication elsewhere.

An especially noteworthy outcome of this study is the length of time that success was sustained, with no patients lost to follow-up. Features that likely contributed to successful long-term outcomes are both internal, relating to curriculum, and external, relating to program integration within the larger medical community. The curriculum encouraged participant-motivated emotional and physical problem-solving techniques. Upon graduation, discharge planning occurred with continued consultation offered to the referring clinicians. This communication network was only occasionally utilized, but continued access to consistent treatment and medication regimens must be underscored as an important reinforcement to the participants’ extended success.

Limitations

Assessment of internal validity of the present study must consider the limitations inherent in a retrospective study of a clinical treatment program within a private practice. For example, nonparticipant screening data are not available for comparison, and selected participants were those who expressed motivation to cease COAT use via a motivational interviewing–style initial evaluation for the program, representing a potential selection bias. Likewise, there was an inherent treatment bias, as the intervention was designed to produce successful results for patients. An argument could be made for reporting bias as well, as the clinical team spent significant time with the participants, and this allowed for 4 inappropriate candidates to be readily identified and referred to a higher level of care after entering the program (such as a psychological or substance-related inpatient treatment program). There is a possibility that this population gets missed and goes untriaged in shorter studies, leading to lower interventional success rates. Finally, the relatively small pool of 109 participants, with only modest demographic information to identify them, may affect the generalizability of the study results.

It must be discussed that a potential weakness exists in follow-up measurements pertaining to limitations inherent in the PDMP. The PDMP report appears blank if no controlled substances are being administered during the queried time period. Thus, blank PDMP reports were read as complete opioid cessation, including buprenorphine. However, the PDMP may also give a blank report in a few instances when the subject may still be using controlled substances, such as when they are prescribed from another state, the Veterans Health Administration, or a methadone treatment center or accessed illicitly. These scenarios are unlikely in the present study, as monthly case tracking within the PDMP showed internal consistency in the refill behavior of the participants. PDMP results were also cross-referenced with prescribing and drug screening records in the EHR, which provided a necessary confirmation to validate the PDMP presumptions. These extended and cross-referenced look-back methods make aberrancies highly unlikely in this study. Further, because the participant group in this study with blank PDMP reports was very small (only 4 and 12 participants in the 6-month and extended follow-ups, respectively), PDMP report misrepresentation would not skew results substantially.

CONCLUSIONS

This pilot study contributes to the literature by documenting a successful and potentially generalizable strategy to promote COAT cessation, and by providing unusually lengthy follow-up for postintervention COAT cessation monitoring.

Acknowledgments

The authors thank their exceptional clinical colleagues, especially Kaitlin Doran, PsyD; Jessica Goza, NP; Kelly Rumrill, NP; Tatiana Hernandez, CCA; and Julie Ginsberg, LAc, for their teamwork and assistance with data collection and organization.

Author Affiliations: Integrated Pain Management Medical Group (MJS), Walnut Creek, CA; University of Arizona (ZHC), Tucson, AZ; Azusa Pacific University (CHY), Azusa, CA.

Source of Funding: The researchers analyzed the data presented here through the course of clinically related quality assurance measures. No other funding was present for this study. This study was reviewed by a private institutional review board and was determined exempt from full review. In the spirit of disclosure, the primary investigator of this study was the creator and medical director of the multidisciplinary program studied. Because the program is no longer in session, no financial gain can be foreseen due to inadvertent publicity from this article.

Author Disclosures: The authors report no relationship or financial interest with any entity that would pose a conflict of interest with the subject matter of this article.

Authorship Information: Concept and design (MJS); acquisition of data (MJS, ZHC); analysis and interpretation of data (MJS, ZHC, CHY); drafting of the manuscript (MJS, CHY); critical revision of the manuscript for important intellectual content (MJS, ZHC, CHY); statistical analysis (MJS, CHY); provision of patients or study materials (MJS, ZHC); obtaining funding (MJS); administrative, technical, or logistic support (MJS, ZHC); and supervision (MJS).

Address Correspondence to: Marcelina Jasmine Silva, DO. Email: mjsilvado@gmail.com.

REFERENCES

1. Xu J, Murphy SL, Kockanek KD, Arias E. Mortality in the United States, 2018. NCHS Data Brief. 2020;(355):1-8.

2. Alter A, Yeager C. COVID-19 impact on US national overdose crisis. Overdose Detection Mapping Application Program. June 2020. Accessed March 9, 2021.http://www.odmap.org/Content/docs/news/2020/ODMAP-Report-June-2020.pdf

3. Silva MJ, Kelly Z. The escalation of the opioid epidemic due to COVID-19 and resulting lessons about treatment alternatives. Am J Manag Care. 2020;26(7):e202-e204. doi:10.37765/ajmc.2020.43386

4. Dowell D, Haegerich TM, Chou R. CDC guideline for prescribing opioids for chronic pain — United States, 2016. MMWR Recomm Rep. 2016;65(1):1-49. doi:10.15585/mmwr.rr6501e1

5. The impact of the opioid crisis on the healthcare system: a study of privately billed services. FAIR Health. September 2016. Accessed August 29, 2020. https://s3.amazonaws.com/media2.fairhealth.org/whitepaper/asset/FH%20White%20Paper%20-%20The%20Impact%20of%20the%20Opioid%20Crisis%20on%20the%20Healthcare%20System%20-%20Sept%202016-5972407510d1f.pdf

6. Zaman T, Striebel J. Opioid refugees: a diverse population continues to emerge. CSAM News. 2015;41(1):1,6-7. Accessed March 15, 2021. https://cdn.ymaws.com/csam-asam.org/resource/resmgr/docs/csamnews_newsletter/csamnews_fall2015_v41_n1.pdf

7. Achenbach J, Bernstein L. Opioid crackdown forces pain patients to taper off drugs they say they need. The Washington Post. September 10, 2019. Accessed October 19, 2020. https://www.washingtonpost.com/health/opioid-crackdown-forces-pain-patients-to-taper-off-drugs-they-say-they-need/2019/09/10/3920f220-c8da-11e9-a4f3-c081a126de70_story.html

8. Frank JW, Lovejoy TI, Becker WC, et al. Patient outcomes in dose reduction or discontinuation of long-term opioid therapy: a systematic review. Ann Intern Med. 2017;167(3):181-191. doi:10.7326/M17-0598

9. Harden P, Ahmed S, Ang K, Wiedemer N. Clinical implications of tapering chronic opioids in a veteran population. Pain Med. 2015;16(10):1975-1981. doi:10.1111/pme.12812

10. Heiwe S, Lönnquist I, Källmén H. Potential risk factors associated with risk for drop-out and relapse during and following withdrawal of opioid prescription medication. Eur J Pain. 2011;15(9):966-970. doi:10.1016/j.ejpain.2011.03.006

11. Weimer MB, Hartung DM, Ahmed S, Nicolaidis C. A chronic opioid therapy dose reduction policy in primary care. Subst Abus. 2016;37(1):141-147. doi:10.1080/08897077.2015.1129526

12. Schneider JP, Kirsh KL. Defining clinical issues around tolerance, hyperalgesia, and addiction: a quantitative and qualitative outcome study of long-term opioid dosing in a chronic pain practice. J Opioid Manag. 2010;6(6):385-395. doi:10.5055/jom.2010.0036

13. Nilsen HK, Stiles TC, Landrø NI, Fors EA, Kaasa S, Borchgrevink PC. Patients with problematic opioid use can be weaned from codeine without pain escalation. Acta Anaesthesiol Scand. 2010;54(5):571-579. doi:10.1111/j.1399-6576.2009.02164.x

14. Whitten SK, Stanik-Hutt J. Group cognitive behavioral therapy to improve the quality of care to opioid-treated patients with chronic noncancer pain: a practice improvement project. J Am Assoc Nurse Pract. 2013;25(7):368-376. doi:10.1111/j.1745-7599.2012.00800.x

15. Huffman KL, Sweis GW, Gase A, Scheman J, Covington EC. Opioid use 12 months following interdisciplinary pain rehabilitation with weaning. Pain Med. 2013;14(12):1908-1917. doi:10.1111/pme.12201

16. Maclaren JE, Gross RT, Sperry JA, Boggess JT. Impact of opioid use on outcomes of functional restoration. Clin J Pain. 2006;22(4):392-398. doi:10.1097/01.ajp.0000208250.15572.01

17. Rome JD, Townsend CO, Bruce BK, Sletten CD, Luedtke CA, Hodgson JE. Chronic noncancer pain rehabilitation with opioid withdrawal: comparison of treatment outcomes based on opioid use status at admission. Mayo Clin Proc. 2004;79(6):759-768. doi:10.4065/79.6.759

18. Townsend CO, Kerkvliet JL, Bruce BK, et al. A longitudinal study of the efficacy of a comprehensive pain rehabilitation program with opioid withdrawal: comparison of treatment outcomes based on opioid use status at admission. Pain. 2008;140(1):177-189. doi:10.1016/j.pain.2008.08.005

19. Vines SW, Cox A, Nicoll L, Garrett S. Effects of a multimodal pain rehabilitation program: a pilot study. Rehabil Nurs. 1996;21(1):25-30, 40. doi:10.1002/j.2048-7940.1996.tb01669.x

20. Wakeman SE, Larochelle MR, Ameli O, et al. Comparative effectiveness of different treatment pathways for opioid use disorder. JAMA Netw Open. 2020;3(2):e1920622. doi:10.1001/jamanetworkopen.2019.20622

21. Kidner C, Mayer T, Gatchel R. Higher opioid doses predict poorer functional outcome in patients with chronic disabling occupational musculoskeletal disorders. J Bone Joint Surg Am. 2009;91(4):919-927. doi:10.2106/JBJS.H.00286

22. Cowan DT, Wilson-Barnett J, Griffiths P, Allan LG. A survey of chronic noncancer pain patients prescribed opioid analgesics. Pain Med. 2003;4(4):340-351. doi:10.1111/j.1526-4637.2003.03038.x

23. Crisostomo RA, Schmidt JE, Hooten WM, Kerkvliet JL, Townsend CO, Bruce BK. Withdrawal of analgesic medication for chronic low-back pain patients: improvement in outcomes of multidisciplinary rehabilitation regardless of surgical history. Am J Phys Med Rehabil. 2008;87(7):527-536. doi:10.1097/PHM.0b013e31817c124f

24. Darchuk KM, Townsend CO, Rome JD, Bruce BK, Hooten MM. Longitudinal treatment outcomes for geriatric patients with chronic non-cancer pain at an interdisciplinary pain rehabilitation program. Pain Med. 2010;11(9):1352-1364. doi:10.1111/j.1526-4637.2010.00937.x

25. Malinoff HL, Barkin RL, Wilson G. Sublingual buprenorphine is effective in the treatment of chronic pain syndrome. Am J Ther. 2005;12(5):379-384. doi:10.1097/01.mjt.0000160935.62883.ff

26. Daitch D, Daitch J, Novinson D, Frey M, Mitnick C, Pergolizzi J Jr. Conversion from high-dose full-opioid agonists to sublingual buprenorphine reduces pain scores and improves quality of life for chronic pain patients. Pain Med. 2014;15(12):2087-2094. doi:10.1111/pme.12520

27. Rosenblum A, Cruciani RA, Strain EC, et al. Sublingual buprenorphine/naloxone for chronic pain in at-risk patients: development and pilot test of a clinical protocol. J Opioid Manag. 2012;8(6):369-382. doi:10.5055/jom.2012.0137

28. Lutfy K, Cowan A. Buprenorphine: a unique drug with complex pharmacology. Curr Neuropharmacol. 2004;2(4):395-402. doi:10.2174/1570159043359477

29. Dahan A, Yassen A, Romberg R, et al. Buprenorphine induces ceiling in respiratory depression but not in analgesia. Br J Anaesth. 2006;96(5):627-632. doi:10.1093/bja/ael051

30. 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

31. Opioid oral morphine milligram (MME) conversion factors. HHS. Accessed August 30, 2021.
https://www.hhs.gov/guidance/sites/default/files/hhs-guidance-documents/Opioid%20Morphine%20EQ%20Conversion%20Factors%20%28vFeb%202018%29.pdf

32. Silva MJ, Coffee Z, Yu CH, Martel O. Anxiety and fear avoidance beliefs and behavior may be significant risk factors for chronic opioid analgesic therapy reliance for patients with chronic pain—results from a preliminary study. Pain Med. 2021;22(9):2106-2116. doi: 10.1093/pm/pnab069

33. About the ASAM Criteria. American Society of Addiction Medicine. Accessed December 1, 2020. https://www.asam.org/asam-criteria/about

34. Gatchel RJ, Okifuji A. Evidence-based scientific data documenting the treatment and cost-effectiveness of comprehensive pain programs for chronic nonmalignant pain. J Pain. 2006;7(11):779-793. doi:10.1016/j.jpain.2006.08.005