• Research

    Advancements in opioids research, beyond surgical prescribing practices

head and torso portrait of Dr. Gazelka by glass wall windows
Halena Gazelka, M.D. is chair of Mayo Clinic's Opioid Stewardship Program — a Quality initiative.

In "An Institutional Approach to Managing the Opioid Crisis," the authors describe the elements of Mayo Clinic's Opioid Stewardship Program. The study's first author, Halena Gazelka, M.D., an anesthesiologist, is chair of the program. She works together with the study's senior author, Elizabeth Habermann, Ph.D., deputy director of research in the Mayo Clinic Robert D. and Patricia E. Kern Center for the Science of Health Care Delivery, and many others across Mayo Clinic, to identify prescribing practices for opioids — in both acute and chronic pain situations. Together the team has led transformation of postsurgical prescribing patterns — developing, implementing and validating patient-centric guidelines.

"The opioid crisis had not escaped the attention of anyone, and we stepped up quickly to find out where we could make a difference," says Dr. Gazelka. "Mayo Clinic was in the same place as everyone else — we didn't know how many opioids were being prescribed, how much variance we had between providers, procedures or conditions — or frankly, how much waste and potential for misuse was occurring on our watch."

Under Dr. Gazelka's leadership, Mayo began reviewing current practices, workflows, and internal and external guidelines.

"Very little evidence was out there about opioids," says Dr. Habermann. "We realized very quickly that we, Mayo Clinic, needed to build the evidence to not only guide our prescribing clinicians regarding the needs of our patients, but prescribers and patients everywhere."

This is where the Mayo Clinic Kern Center for the Science of Health Care Delivery came into play. Center-based work (center co-authors identified with bold type) has helped determine Mayo's baseline prescribing habits across practices and specific surgeries.

"Center colleagues partnered across the surgical practices to first determine the baseline, and then implement and validate evidence-based prescribing guidelines specific to each practice," says Dr. Habermann. Read more about that work in Advancements in opioids research, transformations in postsurgical prescribing.

Dr. Habermann posing at counter in the Pharmacy, with several bottles of opioids on the counter and one in her hand
Elizabeth Habermann, Ph.D.

As these efforts were ongoing, in Minnesota, Twin Cities Public Television (TPT) ran an award-winning, several segment program, The Opioid Fix, which included an episode with Drs. Habermann and Gazelka describing some of the center's research, along with two other patient care and education-focused segments originating at Mayo Clinic.

"We are continuing our efforts, refining postsurgical prescribing, expanding our patient and provider education, and building tools and processes to reduce excess opioids in our communities," says Dr. Gazelka.

Now research efforts are moving into non-surgical prescribing practices, and the center is expanding collaborations with Pharmacy.

"Initially a lot of the center's opioid work came out of the Surgical Outcomes Program, and was focused on post-operative prescribing," says Dr. Habermann. "We have a number of our surgical outcomes team and other Kern Center faculty and analysts who have been collaborating to examine the appropriateness and effectiveness of opioids in other pain management contexts."

Some of those non-surgical publications are described here:

Engstrom K, Brown CS, Ubl D, Hanson K, Bates R, Cunningham J. J Gen Intern Med. 2021 Aug 11.

This 6-month-long quality improvement retrospective study sought to characterize the quantity, type and indication of opioids prescribed for non-surgical patients upon hospital discharge and how the patients actually used those prescriptions.

A median of 112.5 total morphine milligram equivalent (MME) quantities were prescribed to patients at hospital discharge. Of the 200 patients included in the study survey, the median consumption was much lower, at only 45 MME. Only 5.9% of patients who had leftover opioids reported disposal of the medication.

The results indicate that there is room for standardization and reduced opioid prescribing among non-surgical medical services in the hospital setting.

medical illustration of person with headache

VanderPluym JH, Halker Singh RB, Urtecho M, Morrow AS, Nayfeh T, Torres Roldan VD, Farah MH, Hasan B, Saadi S, Shah S, Abd-Rabu R, Daraz L, Prokop LJ, Murad MH, Wang Z. JAMA. 2021 Jun 15;325(23):2357-2369.

A migraine is common and debilitating headache for which a number of therapeutic interventions are used to lessen or prevent the full onset of migraines. In this study, the researchers reviewed the available evidence for a number of medicinal and nonpharmacological therapies.

The systematic review and meta-analysis was led by investigators from the Kern Center's Knowledge Synthesis Program and Mayo Clinic's Evidence-based Practice Center.

They included 15 systematic reviews and 115 randomized clinical trials for which the main outcomes included pain freedom, pain relief, sustained pain freedom, sustained pain relief, and adverse events.

The authors noted, "there are several acute treatments for migraine, with varying strength of supporting evidence. Use of triptans, nonsteroidal anti-inflammatory drugs, acetaminophen, dihydroergotamine, calcitonin gene-related peptide antagonists, lasmiditan, and some nonpharmacologic treatments was associated with improved pain and function."

The nonpharmacological options that appeared to have significant pain reduction benefits were:

  • Remote electrical neuromodulation.
  • Transcranial magnetic stimulation.
  • External trigeminal nerve stimulation.
  • Noninvasive vagus nerve stimulation.

The evidence for many other interventions, including opioids, was limited.

Bruce BK, Allman ME, Rivera FA, Abril A, Gehin JM, Oliphant LM, Nordan LM, White LJ, Martinez D, Niazi SK. J Clin Rheumatol. 2021 Aug 1;27(5):187-193.

Mayo Clinic regularly hosts an intensive 2-day Fibromyalgia Treatment Program to support people who suffer from fibromyalgia. It is a cognitive behaviorally based multicomponent treatment program focused upon evidence-based education and strategies to decrease central sensitization, including management tools to decrease pain and fatigue, assist with sleep disturbance, and improve cognitive issues associated with fibromyalgia. It is a group-based program that consists of 16 hours of treatment time focused on pain management strategies, exercise, sleep assistance, relaxation strategies, pacing, moderation, behavioral activation, and family involvement.

The researchers collected information from 698 patients admitted to the program over a 2-year time period. In addition to collecting fibromyalgia impact, pain catastrophizing and depression information through validated surveys, the team also gathered demographic and self-reported opioid use.

Despite widespread agreement in multiple guidelines that do not recommend opioid therapy as helpful for patients with fibromyalgia, 27% of the patients reported taking prescription opioids at the time of entry into the program.

The investigators found that opioid use correlated with a number of factors, including:

  • Longer duration of symptoms — in excess of three years.
  • Higher degree of functional impairment.
  • Increased pain catastrophizing.

Their findings led the researchers to suggest that more education or outreach needs to occur among health care providers who treat patients with fibromyalgia. In order to assist in disseminating more helpful strategies, the authors included discussion of alternative approaches to the management of fibromyalgia that do not involve opioids are reviewed in an effort to improve care.

Dr. Cunningham at a podium, speaking to a Mayo Clinic audience
Julie Cunningham, Pharm.D., provides specialized expertise and leadership within the Opioid Stewardship Program.

Ramel CL, Habermann EB, Thiels CA, Dierkhising RA, Cunningham JL. Mayo Clin Proc Innov Qual Outcomes. 2020 Aug; 4(4): 357–361.

Based on previous Kern Center research, the researchers knew that more than 75% of elective surgery patients have unused opioids remaining after their pain has resolved. It has been well established that leftover opioids pose risks to families and community members. In an effort to reduce the potential for misuse, the study team included education materials and a drug deactivation system for 200 patients filling their opioid prescription at a Mayo Clinic pharmacy after undergoing one of several different surgeries.

Subsequently the team conducted a phone survey, reaching 149 patients. The investigators found that providing information about safe and effective disposal of excess opioids, along with a convenient drug deactivation packet led to an increase in disposal. Patients who used the disposal system reported high satisfaction with the process.

"Based on the results of our study, the Mayo Clinic Pharmacy and Therapeutics Committee endorsed distribution of a drug deactivation system with new opioid prescriptions through all Mayo Clinic Pharmacies," says Julie Cunningham, Pharm.D., Mayo Clinic's associate chief pharmacy officer for Practice and Research and senior author of this study.

"Alluma, the Mayo Clinic pharmacy benefit manager, enthusiastically supported the risk aversion effort and supplied the deactivation systems for all Mayo Clinic insured lives at no charge, with financial support from the Mayo Medical Plan," says Dr. Cunningham. "It’s extremely gratifying to see the translation of our research into the hands of patients."

Soares WE 3rd, Melnick ER, Nath B, D'Onofrio G, Paek H, Skains RM, Walter LA, Casey MF, Napoli A, Hoppe JA, Jeffery MM. Ann Emerg Med. 2021 Mar 19:S0196-0644(21)00226-2.

In this study, the team found that in the first 12 months of COVID-19, total visits for nonfatal opioid overdoses in adults increased more than 10% over 2019 and 2018. These data came from reviewing the records of 25 emergency departments at health care facilities in six U.S. states and in diverse rural, urban and suburban populations.

The COVID-19 pandemic has caused numerous disruptions around the world, including in employment, education, physical and psychological wellbeing. People with opioid use disorder are vulnerable to disruptions in access to addiction treatment and social support, both of which have been adversely impacted by the pandemic.

Identifying changes in emergency department use by people with different needs helps build an understanding of what resources and interventions need to be expanded or modified to serve community needs during the pandemic. In previous research, the team found that overall use of emergency department for other health concerns declined during COVID-19.

The Mayo Clinic Kern Center for the Science of Health Care Delivery is fully embedded in Mayo Clinic's medical Practice. Its scientists collaborate across the Practice to identify and solve challenges for patients, providers and the health care system at large.