Yale clinicians pilot new technique to reduce opioid risk in pain treatment

Clinician-researchers at Yale School of Medicine have developed a new method for helping patients on long-term painkillers reduce opioid use, and unwanted side effects like grogginess, without significant withdrawal symptoms.

By overlapping buprenorphine therapy — a well-established treatment for opioid use disorder — with opioid therapy, they found they could successfully phase out use of oxycodone and morphine, highly addictive drugs known as full-agonist opioids because they fully activate the brain’s opioid receptors. In time, patients shifted to buprenorphine, improving their quality of life. Buprenorphine, a partial agonist, is safer for long-term use.

The findings, which look at the impact of the new therapy on six patients over the age of 55, provided impetus for the researchers to modify an ongoing multi-site $12 million study funded by the Patient-Centered Outcomes Research Institute to include this new treatment method, and another by the National Institutes of Health that is enrolling patients in September. Becker is co-principal investigator of the former and principal investigator of the latter, and a core investigator at the Pain Research, Informatics, Multimorbidities & Education (PRIME) center, a center of innovation dedicated to women veterans’ health at Yale.

The report appears in the April 6 edition of the Annals of Internal Medicine.

“For patients, this is a potential game-changer,” said Dr. William C. Becker, associate professor in internal medicine at Yale School of Medicine. “For patients on long-term opioids, the fear of withdrawal symptoms is hugely daunting and often prevents them from making needed changes.”

Clinicians first tried the new method on a 62-year-old man who was taking prescribed oxycodone to treat chronic lower back pain from degenerative disk disease and who reported being “in a rut,” according to the report. Despite high doses of oxycodone, the patient’s back pain remained intense and the oxycodone was impairing his mental acuity. But any attempt to lower the dose resulted in insomnia.

Clinicians decided to try a new therapy — overlapping the oxycodone with buprenorphine for four to five days so they could transition him from one drug to the other. After one month, and a successful drug transition, the patient reported feeling “overall better, clearer.” His pain intensity was unchanged, but he reported he could work more productively. His positive response prompted the clinicians to adopt the method for other patients referred to their clinic.

Becker said this technique of overlapping existing opioid treatment with buprenorphine mimics a technique they use for heroin-addicted patients known as “micro-dosing.” By using micro-dosing, he said, “the transition period itself is much better tolerated by patients.”

And there are other positive outcomes. In the six case studies, none of patients experienced withdrawal symptoms from transitioning, and almost all saw a reduction in unwanted side effects from long-term opioid agonists, like sleepiness and grogginess. Some saw a reduction in pain as well. But even those who didn’t were able to transition to a lower dose of oxycodone after the micro-dosing.

“In any of those cases, we see it as a win,” Becker said.

The patients included a 67-year-old man and a 58-year-old woman on morphine; a 72-year-old man on oxycodone; a 73-year-old man on morphine and oxycodone; and a 68-year-old man on methadone.

Becker said switching patients from long-term use of opioids like morphine and oxycodone to buprenorphine for pain treatment is important for patient safety.

“Buprenorphine is markedly safer, and reduces the risk of overdoses,” he said.

While the U.S. Department of Health and Human Services (HHS) recommends providers prescribe buprenorphine to patients who are not responding to gradual dose reduction of full-agonist opioids, according to the Yale findings, HHS also currently recommends complete cessation of full-agonist opioids before buprenorphine therapy is initiated.

But the prospect of related withdrawal symptoms leaves many patients unwilling to even attempt this method, Becker said.

“Many patients 60 and older on opioids for back pain and other chronic pain issues have been taking them since they were in their 40s,” said Becker. “Now they are on super high doses, and if they even think about tapering, they panic. Buprenorphine offers them a way out.”

Dr. Ellen Edens, associate professor of psychiatry, contributed to this report. Becker and Edens co-direct the Opioid Reassessment Clinic at VA Connecticut Healthcare System in West Haven.