New Trends in Prescription Drug Monitoring

McCarberg, Bill, MD
Adjunct Assistant Clinical Professor
University of California, San Diego
Founder, Chronic Pain Management
Program
Kaiser Permanente
President, Western Pain Society
San Diego, California
Also by this Author 

Physicians treating patients with chronic pain face numerous challenges. Pain assessment, therapy selection, patient compliance and drug abuse are all significant issues.

Dr Bill McCarberg, Adjunct Assistant Clinical Professor at the University of California, San Diego and Founder of the Chronic Pain Management Program at Kaiser Permanente San Diego reviews these issues and looks ahead to developments, which hold promise for more effective treatment.

Pain Assessment - No Objective Measure

“The most difficult issue,” explains Dr McCarberg, “is that we don’t know for sure when a patient has pain or not – we have to go on what they tell us. The testing we do rarely tells us the level of pain, the level of disability, or what treatment would be best for a patient. Unlike with other conditions, we have to make a clinical decision using subjective information.”

Opioid Compliance – Approaches to Screening and Monitoring

Dr McCarberg cautions that opioids, commonly prescribed for chronic pain, have “a very narrow risk/benefit ratio.” They can have significant psychological effects causing anxiety, dulling of cognition and a decline in quality of life. Some patients become dysfunctional and show addictive behavior, and there is a risk of these medicines being diverted into the community.

Compliance to a drug regimen is always a concern but in pain management it takes on considerable significance. “There is evidence that people are not adherent when taking medication for any condition.” says Dr McCarberg, “but when it's an opioid, it becomes a big issue.”  Given the risks, initial risk assessment and monitoring to verify compliance, and identify possible abuse or misuse, are critical.

Reviewing prescribing history and refill intervals will verify whether prescriptions are being filled but not whether medication is being taken as prescribed. Most state medical boards and professional organizations recommend performing a urine drug test during regular follow-up visits, with some recommending its use on all, not just selected, patients. “You can't tell which patients are getting in trouble by just a history or physical exam,” explains Dr McCarberg, “and that’s been shown even in well-regarded pain clinics with experts: random urine tests showed there was a significant number of people that either weren’t taking their medicine or had other substances in their urine.”

Opioid Risk Evaluation and Mitigation Strategies (REMS)

A concern for all physicians is thepending introduction of Opioid Risk Evaluation and Mitigation Strategies (REMS) mandated by the government.  These are still in development but it is expected they will require healthcare professionals prescribing a scheduled drug to demonstrate a minimum level of knowledge and competency1.

Dr McCarberg believes this will have “tremendous negative implications” with many doctors opting not to prescribe such drugs and using less potent, less effective medications. “If doctors opt out because they don’t want to demonstrate competency by taking an exam, patients are going to suffer.” This in turn is likely to lead to an increase in referrals from primary care physicians to pain specialists.

Advances in the Field - Diagnostics

It is expected that developments in genetic testing will provide a basis for more targeted therapy. A test is already available for the cytochrome P450 2D6 (CYP2D6)2, which indicates whether a patient can convert codeine into morphine, and hydrocodone into hydromorphone. A significant minority of patients don’t have this 2D6 enzyme in their liver, which Dr McCarberg explains, “means they can take all the codeine or all the Vicodin® in the world but it wouldn’t make any difference. They can’t make the conversion which makes the drug analgesic.”

Dr McCarberg looks forward to further advances in the field, which will allow physicians to select the most effective drug for any one patient based upon their genotype. “Patients will get a medication that’s highly specialized to their genetic profile. Rather than giving everyone the same dose, we’ll be able to dose individually, based on whether someone is a fast or slow metabolizer.”

Improvements in functional MRI, will enable physicians to locate pain fibers and identify causes of pain more precisely. “Being able to delineate the cause better would help us select the most appropriate therapy – whether it’s something that treats the brain or central nervous system or something that acts more on the periphery.”

Advances in the Field - Therapeutics

In discussing potential advances in therapeutics, Dr McCarberg highlights three promising areas of development:

Anti-nerve growth factor drugs.Two drugs are in late stage development, and could be “the next best non-steroidal anti-inflammatories,” provided they do not have significant side effects.

Substance P. “Everybody knows it is intimately involved in pain transmission and in the chronicity of pain. So, people are exploring how we can keep pain from going from acute to chronic and whether monitoring or inhibiting substance P appropriately would make a difference.” 

Glial cells.“In contrast to traditional thinking, recent information has shown that glial cells are extremely active metabolically and probably instrumental in the messaging within the nervous system.” There is an increasing level of research activity to investigate the effect of anti-glial cell medications and whether these can modulate pain messaging. It is hoped that advances in both diagnostics and treatment will address some of the challenges of pain management and help physicians provide more effective care for patients with chronic pain.

  1. http://www.fda.gov/Drugs/DrugSafety/InformationbyDrugClass/ucm163647.htm
  2. http://www.questdiagnostics.com/hcp/testmenu/jsp/showTestMenu.jsp?fn=10490.html&labCode=SJC