MUSC becomes first in state to offer special implant to treat opioid dependence

The Medical University of South Carolina became the first in the state Monday to administer Probuphine, a buprenorphine implant for the treatment of opioid dependence.

Angela Dempsey, an obstetrician and gynecologist, says the outpatient surgery went well. The procedure, similar to that of contraceptive implantation, was not that different from what she usually does, but having a male patient was a bit different, she says.

“Situations like this raise the question of how siloed medicine has become. This is a model for improving patient access and experience and not limiting the treatment options,” she says, adding that it took the coordinated effort of many MUSC specialties to make offering this a reality. “I don’t think there’s any dispute what a crisis this is. We really have to have quite an organized response to this.”

Dempsey worked in coordination with a team that includes pharmacists and addiction specialists at MUSC Health’s Institute of Psychiatry to be able to offer this treatment. Probuphine, implanted in the arm, is designed to provide a constant, low-level dose of buprenorphine for six months in patients who are already stable on low-to-moderate doses of other forms of buprenorphine.

That there’s a need for more treatment options such as this is obvious.

• Since 1999, the number of overdose deaths involving opioids, including prescription opioids and heroin, quadrupled. 
• From 2000 to 2015 more than half a million people died from drug overdoses, with 91 Americans dying every day from an opioid overdose. 
• In South Carolina, opioid-related deaths rose from 237 in 2013 to 516 in 2014, with more than 600 people dying from opioid and heroin overdoses in 2015, according to the S.C. Department of Health and Environmental Control. 

Instrumental in getting this new treatment approved at MUSC was psychiatrist Sarah Book, an addictions specialist and professor in MUSC’s Department of Psychiatry and Behavioral Sciences.  

Last May, the FDA approved the use of Probuphine for this purpose, but it hasn't been a treatment patients could get in the state, she says. 

“The FDA has a very tight control over the process. To begin, a patient has to be engaged in addictions treatment at a program like MUSC’s Center for Drug and Alcohol Programs that is familiar with treating opioid use disorder using buprenorphine as Medication Assisted Therapy. In addition, the program has to have a surgeon to actually do the implant at MUSC. As you can imagine, it’s not too often that one program is going to be able to offer both types of expertise.”

At MUSC, the Addiction Sciences Division, formerly known as the Center for Drug and Alcohol Programs, and OB/GYN clinics are located close geographically, so doctors considered working together. “We have the addiction expertise, and they have the surgical expertise and were interested in working with us. They see what a problem it is, too.”

Being able to offer this treatment also provides a valuable training opportunity for doctors who are doing their addiction fellowships at MUSC, which is known for its strong focus on addictions research and clinical treatments. “We’re training the next generation of providers to fight this.”

Because the medication is surgically implanted, it reduces the hassle factor her patients’ experience in remembering to take a medication, and it minimizes the risk of diversion and abuse, she says. “I’m excited about it because of the innovation and because it takes the habit of taking a pill out of the patient’s daily routine. I’m excited to be able to partner with Dr. Dempsey and OB-GYN. I think it will make life easier for my patients as well because there is a significant hassle factor associated with getting this medication every month for a number of reasons.”

How buprenorphine works

Buprenorphine and methadone, both opioids, activate the opioid (mu) receptors on nerve cells and are used to treat opioid dependency. Buprenorphine is a partial mu agonist, unlike methadone, which is a full agonist. Both are used to treat patients with opioid-use disorder.

Books says buprenorphine, as a partial agonist, is an important treatment option and does not activate mu receptors to the same extent as methadone.

About a decade ago, the FDA approved the use of buprenorphine for the office-based treatment for people with opioid-use disorders. This happened about the same time that OxyContin was being abused and becoming a public health nightmare, so Naloxone was laced into buprenorphine for safety reasons, she says. “That’s the drug that emergency personnel give people when they’ve overdosed on an opioid. It reverses the effect of a full mu agonist,” Book says. 

Heroin is an example of a full agonist, which activates the opioid receptors in the brain, releasing a full opioid effect. “When you take heroin, you take it until you become tolerant of the dose and then you have to increase the dose, on and on, up the chain. It has no ceiling. That’s a characteristic of a full mu agonist.” 

Methadone, oxycodone, fentanyl, heroin and hydrocodone are all examples of full mu agonists. 

“Some of the dangers with them is they also depress your breathing centers, and you forget to breath, and you die. With heroin, if you stop for a while because you go to prison, for example, and then get out and start using at the level you were, you can easily overdose. Also, the purity of heroin has changed, so people are overdosing from that,” she says, adding that she’s alarmed at its spread on college campuses.

“There are interactions with alcohol and other medications that can be dangerous when taken together. When taken together, they are greater than the sum.”

Buprenorphine is a partial mu agonist, so there is a ceiling effect to the way people respond, especially to the breathing part of it. “As long as they are just using buprenorphine, there’s not as much risk of an overdose that will cause them to stop breathing unless they are using it together with benzodiazepines and alcohol.”

That means she can prescribe it to her patients as a long-term treatment option along with psycho-social counseling. The advantage of this implant is reducing the need to get a controlled, monthly prescription. Whether this will help people wean off the medication still needs to be studied, she says.

The vast majority of evidence in the literature suggests that when patients stop opioid replacement, they are at a very high risk for relapse to opioid use. “We view it as a long-term treatment option. People do come off buprenorphine, but it’s generally after they have engaged in some significant lifestyle changes. They have learned new coping skills. They have changed the way they interact with their environment. That takes time,” she says.

“I hope it takes them a step further along their journey of recovery and that ultimately it helps the ones who want to come off this medication – maybe it will set them up for success in being able to come off of it.”

Stemming the tide of opioid deaths

Book says it took several months for MUSC Health providers, including the invaluable contributions of pharmacy coordinator Amy Hebbard, PharmD, to figure out the complicated logistics of offering the Probuphine implant, but it makes perfect sense for an academic medical center. 

“Collaboration is part of our culture. When opportunities for interdepartmental collaboration arise, we’re all interested in parting the curtain and seeing what’s on the other side,” she says, adding how nice it is to work with colleagues in the Department of Pharmacy Services and Dempsey in OB/GYN. “There’s a spirit of collegiality in an academic medical environment. We all want to get back to our roots and see what our colleagues are doing.”

Everyone is on board because the number of opioid deaths in the state has gone through the roof, and there needs to be a plan to stem the tide, she says. Also, medical professionals want to see more treatment options for patients.

“Most of our efforts in the state are directed at decreasing access to opioids. There’s not much effort that’s been expended on the treatment of opioid use disorder. That’s what makes this exciting personally for me. I feel like I’ve been in the trenches for a long time with people with opioid use disorder. There’s so much more to be done to treat the people who actually already have the problem. I think those people get shortchanged.”

MUSC researchers also hope to be part of the solution. The research branch of MUSC’s Addiction Sciences Division is home to five internationally recognized program project grants that focus specifically on addiction research. Kathleen Brady, M.D., Ph.D., vice president for research, says it’s a priority for MUSC. “MUSC researchers are actively addressing the state’s opioid epidemic.”

Brady says the total number of opioid prescriptions written in South Carolina was equal to the total number of adults in the state in 2015. “Pain management has been one of the most common reasons for the over-prescription of opioids.” Research underway at MUSC has shown alternative treatments for pain management include transcranial brain stimulation, psychotherapeutic therapies and stress resiliency. MUSC scientists are also exploring therapies for detoxification and opioid withdrawal, including for opioid-addicted, pregnant women. 

Book says this new treatment option adds another lifeline for patients.

Eligibility for the Probuphine implant requires patients to have been stable on an 8 milligram dose or less of buprenorphine for at least 90 days and also to be engaged in counseling. Book encourages people in need of help, even those who aren’t sure if they have a problem with opioids or who may be afraid to seek treatment to try out MUSC’s walk-in evaluation clinic on 67 President Street. No appointment is needed, and it’s open Monday through Friday mornings until 11:30 a.m. on the fourth floor of the North building at the Institute of Psychiatry. 

The implant, as with all drugs, does have possible side effects, including implant site reactions, headache and constipation. Compared to the benefits her patients get, it’s worth it, she says.

“Most people who come to treatment for opioid use disorder, they are in a situation where they are desperate. They already have lost so much. They can’t keep a job. People who they love can no longer trust them. They have a terrible relationship with themselves. They have a very low self-image. The cost associated with that vs. mild side effects, such as constipation, most people pick the drug. This drug is life-changing.”

She’s been a psychiatrist for 25 years and has seen it give patients their lives back. “People are able to go back to school, keep a job. They are able to build relationships back with their family and their friends. That takes time, but it happens.”

The implant helps to lessen some of the stigma that some patients may feel in having to have a prescription filled monthly or, if they’re seeking help at a federally-approved methadone treatment center, having the disruption in their daily lives of getting that medication.

“This will add another treatment option to the mix, which means more people can be helped. No one wants to end up with an opioid dependency, but any brain can get hijacked. I just want the public to know, addiction is treatable. MUSC has great evidenced-based treatments available.”