Opioids Not Created Equally: Conversion Can Be Lethal

In a unique and comprehensive literature review of poisoning deaths involving opioids from 1999—2009, the deaths involving methadone were found to be disproportionately high. Methadone represented less than five percent of all opioid prescriptions but is responsible for a third of the deaths.

After four years of investigation, the major underlying cause was found to be fundamental misunderstandings about the properties of the medicine—a “knowledge deficit,”—especially when converting patients from other opioids. The results of the literature review, root causes of the increase in poisoning deaths during this time period, and suggested solutions to this issue were presented today at the American Academy of Pain Medicine’s 26th Annual Meeting.

After a rapid increase of opioid-related deaths was reported in Utah, then president of the Utah Academy of Pain Medicine, Dr. Lynn Webster decided to find out why, and then find a solution. By reviewing state and federal sources as well as PubMed, he was able to assess demographics, prevalence, and other risk factors related to this significant increase in poisoning deaths involving opioids. Webster found that methadone deaths had more to do with misunderstandings about when to prescribe it, how to convert patients to it from other pain medicines, and how to inform patients about its risks.

“Opioids are important tools that pain physicians need in order to have a full range of treatment options for patients who are suffering,” said Dr. Webster. “As a scientist and practitioner dedicated to helping patients and the practice of pain medicine, I wanted to understand the increase in opioid-related deaths, and then bring the pain community together to find a solution.”

Webster reviewed published data and case reports and found trends in the information that led him to develop theories about the cause of this increase in opioid deaths. The first was the high-proportion of methadone-related deaths in comparison to other opioids. Although it represented about five percent of the opioid prescriptions in this time period, it was mentioned in one-third of the deaths.

The research also showed that one-third of the deaths occurred within five days after a dosage change—also suggesting that unfamiliarity with the medicine could lead to accidental deaths.

Webster then brought this information to a consensus conference sponsored by the LifeSource Foundation where an esteemed panel of colleagues representing the best in research, practice, epidemiology, and public health helped him determine root causes of the problem.

After reviewing and discussing the data, the panel identified the following as probable causes underlying the spike: physician error due to knowledge deficits, patient non-adherence to medication regimen, unanticipated medical and psychiatric co-morbidities (including substance abuse), and payer policies that mandate methadone as a first-line coverage.

“Not all pain medicines—even within a class—and not all patients—are created equally,” said Dr. Webster. “Methadone is a safe and effective opioid with pharmacokinetics and pharmacodynamics unlike other opioids, so knowledge about it and how it may affect a specific patient is paramount to a positive clinical outcome. Education about pain medicine is the best safeguard against the unintended deaths and side effects we’ve seen with methadone in the last decade.”

According to Webster, simple conversion from one opioid twice a day to another twice a day is not safe. Patient pharmacogenetics (a patient’s unique response to medicine based on his or her genetics), especially when converting between opioids, along with the properties of the medicine must be taken under advisement to determine appropriate therapy.

In addition he advises that switching a patient to methadone must be done slowly and over time: start with a low dose, and titrate from there in increments that make sense for the patient and the pain condition.

Additionally, Webster and the panel agreed that to solve the main underlying problem, which they define as a “knowledge deficit,” the US Food and Drug Administration, pharmaceutical manufacturers, and scientific experts should use the last decade’s worth of data on methadone, as well as his review of the increase from 2001—2005, to guide and determine Risk Evaluation and Mitigations Strategies now under consideration.

Source: American Academy of Pain Medicine