UK CDAR Leads Research Investigating Progressive Therapies to Treat Opioid Addiction

Opioid addiction is a complex medical disorder that impacts the entire nation, but much of the problem is condensed to disparate regions of Kentucky. This is the third and final installment of a series of articles exploring the work of University of Kentucky researchers and UK HealthCare medical providers who are making progress toward solutions to the epidemic in our state and at large.

LEXINGTON, Ky. (July 26, 2016) — Even with the assistance of detoxification and rehabilitation programs, 80 percent of people attempting recovery from opioid addiction will relapse.

The firm grip of opioid addiction on a person’s life necessitates sustainable therapeutic approaches proven effective through scientific trials and evidence.

“We increasingly recognize that opiate addiction is a complex medical disorder with significant psychosocial influences as well,” said Dr. Michelle Lofwall, an addiction medicine specialist and psychiatrist at the University of Kentucky Center on Drug an Alcohol Research (CDAR). “This is similar to other chronic complex medical disorders that are not amenable to a quick treatment.”

As a complex disease, opioid addiction involves biological, psychological and behavioral components, all of which must receive attention through holistic medical care. According to experts at the CDAR, the first step in any opioid treatment program is loosening the grip of physical dependency. Opioid maintenance therapies are medications designed to help suppress withdrawal, reduce cravings and block the effects illicit opioids produce, such as euphoria or feeling high. Opioid maintenance therapies stabilize the pharmacological addiction while providing a window of opportunity to address other complex needs. 

“Pharmaceuticals give patients a fighting chance to address the other parts of their addiction,” said Dr. Sharon Walsh, an addiction specialist and director of the CDAR. “They have a fighting chance to work on the recovery and focus on the behavioral and social issues that they may have.”

However, initiating an opioid maintenance therapy, especially for those patients the early stages of a recovery program, raises numerous concerns for health care providers and patients. For one, prescribing an opioid maintenance therapy like buprenorphine, an FDA-approved drug to treat opioid addiction, demands the patient’s absolute cooperation and adherence to the provider’s dosage recommendations. Maintenance drugs, such as Suboxone and Subutex carry some street value, so diversion is a common concern for health care providers.

Patients are also exposed to social and safety risks when prescribed standard forms of prescription opioid maintenance therapies. Capable of causing overdose, particularly when combined with other substances like alcohol and benzodiazepines, maintenance drugs may pose risks to members of the patient’s household, especially children. Patients possessing these medications can become victims of theft. The stigmatization of opioid maintenance prescriptions in society further muddles the patient’s circumstances, as these therapies are considered taboo or even illegal in certain settings. Patients can experience uncomfortable encounters and stigmatization when filling their prescription at the pharmacy counter. Traveling with an opioid maintenance prescription is also stressful as patients worry about having it stolen or lost in baggage.

Research studies underway at the CDAR are transforming how opioid therapies are administered to patients to reduce risks and negative outcomes associated with the standard forms of opioid maintenance therapies. With a team of international authorities in the field of substance abuse treatment, the CDAR serves as a lead research site for projects investigating progressive and effective medication delivery systems. Lofwall and Walsh have collaborated with major pharmaceutical developers to test novel delivery systems for opioid therapies. The clinical trials conducted at CDAR have demonstrated the efficacy, safety and, in some cases, potential for superiority of new therapeutic delivery systems when compared to standard prescriptions in the form of sublingual tablets.

Walsh and Lofwall are leading two multi-site studies testing a subcutaneous sustained-release injectable buprenorphine therapy as a potential treatment for opioid dependent patients. These studies are evaluating the efficacy of monthly and weekly injectable buprenorphine known as CAM-2038 for opioid maintenance therapy and assessing efficacy of different doses. If approved by the FDA in the future, this therapeutic could represent a significant advantage over the daily sublingual formulations for patients new to treatment or for those already receiving treatment.

“These novel delivery systems may really mitigate a lot of the concerns and stigma about buprenorphine treatment because it is addressing the risks of abuse and diversion that are associated with the tablets and films,” Lofwall said.

In addition, product developer Braeburn Pharmaceuticals recruited Walsh and Lofwall to participate in a nationwide clinical trial testing the efficacy of an implantable opioid maintenance delivery system. Modeled after pregnancy contraceptives, Probuphine is an implantable therapeutic that slowly releases buprenorphine throughout a six-month period. The treatment involves a minor surgical implantation of four rods into the arm. The CDAR was selected to participate along with 21 sites conducting tests in patients who were considered clinically stable.

The results of the initial trial showed that Probuphine was as effective in controlling the symptoms of addiction and maintaining patient stability as the standard buprenorphine treatment. A secondary analysis of the data showed the new therapeutic delivery system was superior to the standard oral formulation in maintaining opioid abstinence during the six-month trial. The experimental group that received the implant was more likely to abstain from illicit opioids during a six-month period than the group receiving the oral formulation of buprenorphine. Of the Probuphine group, 86 percent were able to remain free of illicit opioid use for six months, compared with the 72 percent who were able to remain free from illicit use in the group receiving the standard therapy.

“This just streamlines the treatment from the physician to the patient,” Walsh said of the therapy. “The physician can be assured that the medicine has gone into the patient and that relieves any worries of misuse and diversion.”

Earlier this year, Walsh and Lofwall testified before a Food and Drug Administration (FDA) panel to present evidence in favor of the product’s efficacy and safety to treat addiction. Lofwall also presented the study at the American Society of Addiction Medicine annual conference. The product received FDA approval in May and the results were recently published in the Journal of the American Medical Association.

“This was exciting because it's not often you get to see a drug in development actually make it to the market and impact patients,” Lofwall said. “I think it's great that Kentucky, specifically UK and CDAR, were able to be a part of that.”

Opioid maintenance delivery systems investigated by the CDAR eliminate the myriad factors impeding successful and sustainable medical therapy for addiction. The innovative delivery systems obviate the possibility of diversion, theft, accessibility to others in the household and overdose. The products also relieve the health care provider of many uncertainties of their prescriptions. Dr. Jonathan Feddock, a radiation oncologist at UK Markey Cancer Center, volunteered as a collaborator with the CDAR and obtained licensure to train primary care providers throughout the nation on how to implant Probuphine in outpatient clinics.

“It’s going to ease concerns for physicians about patient safety, and it will ease concerns for patients about family safety,” Walsh said. “And it will make the delivery of treatment easier.”

Lofwall said experts at the CDAR and UK are upholding a decades-long tradition and duty to solve national substance abuse problems that in large part began at the Lexington Narcotics Farm, which was operated by the U.S. Public Health Service. CDAR faculty members are recognized internationally as authorities on opioid abuse liability, treatment and recovery. Other researchers at the CDAR and collaborators in the six health colleges at UK are conducting studies to understand the causes, consequences and intervening factors of opioid and heroin addiction. Lofwall said researchers at the CDAR are driven to find solutions to this epidemic because it hits so close to home.

“These are our patients and one of our No. 1 public health problems in the Commonwealth is opioid addiction,” Lofwall said. “And so it just makes sense that we are doing the best to help our population and the people that we treat here at UK.”

UK is the University for Kentucky. At UK, we are educating more students, treating more patients with complex illnesses and conducting more research and service than at any time in our 150-year history. To read more about the UK story and how you can support continued investment in your university and the Commonwealth, go to: uky.edu/uk4ky. #uk4ky #seeblue

MEDIA CONTACT: Elizabeth Adams, elizabethadams@uky.edu