Should the reins be tightened on the use of long-term opioid therapy for patients with chronic noncancer pain (CNCP)?
That question is at the heart of a controversy that has boiled over since July when 37 physicians in pain management, public health, psychiatry and other specialties issued a citizen petition calling on the FDA to require opioid label changes that would strike the word “moderate” from CNCP opioid treatment indications and limit the drug’s use solely to severe pain—and then only for a maximum of 90 days at no more than the equivalent of 100 mg of morphine daily.
The petition from Physicians for Responsible Opioid Prescribing (PROP) cited growing U.S. rates of opioid addiction and overdose deaths along with what it said was a lack of evidence for the safety and effectiveness of long-term opioid use for CNCP as the main reasons for the group’s action.
“Unfortunately,” the petition stated, “many clinicians are under the false impression that chronic opioid therapy (COT) is an evidence-based treatment for chronic noncancer pain and that dose-related toxicities can be avoided by slow upward titration. These misperceptions lead to overprescribing and high dose prescribing.”
Pharmacists and physicians opposed to PROP’s proposed label restrictions were quick to respond. Professionals for Rational Opioid Monitoring and Pharmacotherapy (PROMPT), a group of 26 physicians, sent a letter to the FDA expressing its own concerns about the safety of chronic opioid use, but suggesting an alternative approach emphasizing “clinician education, proactive risk stratification and appropriate therapeutic monitoring.”
Pain Medicine News talked with the principals of both PROP and PROMPT and found a depth of conviction on the issue from both sides.
PROP’s Kolodny: More Opioid Oversight Needed
Andrew Kolodny, MD, president of PROP and chairman of the Department of Psychiatry at Maimonides Medical Center in New York City, spoke about a decade of rising addiction and overdose death rates “fueled by overprescribing of opioids” mostly for “people with a diagnosis of chronic noncancer pain.”
“What caused this increase,” he said, “was a very effective marketing and education campaign to convince doctors that we were underutilizing opioids.” Physicians were “incorrectly” told, he said, that “we didn’t have to worry about getting patients addicted and that opioids were effective.
“This increase in prescribing,” he added, “has led to this public health crisis. We think it’s now time for the FDA to communicate clearly to the medical community that long-term use of opioids for chronic noncancer pain has not been proven safe and effective.”
According to Dr. Kolodny, “the best available evidence does not suggest that they’re safe and effective. In the United States, where we’re consuming a large portion of the world’s opioid supply, there’s absolutely no evidence that we’re doing any better a job of treating chronic pain than in countries where opioids are prescribed more cautiously.
“In fact,” he added, “the best available epidemiologic data that’s looked at this question comes from Denmark. What they found in a very large study [Pain2006;125:172-179] was that people who are on opioids long-term for chronic pain were doing very poorly compared with people who were having their pain treated with nonopioid analgesics. There are other studies from the United States that have replicated that.”
He added: “So I don’t believe a reduction in prescribing of opioids for chronic pain will worsen the problem of untreated chronic pain. In fact, because I don’t believe that opioids are effective for most people with chronic pain, I think it exacerbates the problem of untreated chronic pain and to some extent we’re undertreating pain by overprescribing opioids.”
PROMPT’s Dr. Fudin: A More Rational Solution Needed
Jeffrey Fudin, PharmD, FCCP Diplomate, American Academy of Pain Management, chairman of PROMPT and adjunct associate professor of pharmacy practice and pain management at Albany College of Pharmacy and Health Sciences, in New York, offered a number of objections to PROP’s proposals. First, he said, it was “absurd” of PROP to ignore the multiplicity of therapeutic options required to treat all of the “unique disorders” that cause CNCP. Moreover, he said, “a lot of patients [with chronic pain] can’t take [other] analgesics for one reason or other.”
Also, limiting opioid dosages to the equivalent of 100 mg of morphine per day disregards the variability in conversion calculations that can occur among different opioid products. He pointed to one study of accepted conversion charts that showed variations in calculations ranging “all the way from –50% to +245%.”
As for adverse events associated with chronic analgesic treatment, Dr. Fudin said many more are linked to nonsteroidal anti-inflammatory drugs than to opioids, including bleeding disorders, kidney dysfunction and death. He also said that most opioid deaths occur in patients on multiple sedating medications including alcohol and in those abusing multiple medications, not in patients being treated by knowledgeable pain management clinicians and who takes the medication as prescribed.
Moreover, he noted that the largest contributor to rising opioid mortality rates was methadone. A recent report by the Centers for Disease Control and Prevention, he said, found that although 2% of all opioid prescriptions are written for methadone, 33% of opioid-related deaths involve the synthetic opioid. “That’s huge,” Dr. Fudin said. “Methadone pharmacokinetics are very complex and a lot of prescribers don’t have experience and should not be prescribing it.”
A clear example of this, he noted, was seen in the state of Washington, where “the state’s decision to list methadone as a preferred painkiller to cut costs contributed to increasing numbers of overdoses among patients covered by Medicaid” (JAMA2012;8:749-750).
So what is the answer to the problems that PROP is addressing?
Dr. Fudin believes the FDA’s risk evaluation and mitigation strategy (REMS) program for extended-release opioids “is a step in the right direction,” but regulations “should go further and make education mandatory for all people who prescribe opioids.
“It doesn’t matter if [the opioids] are extended-release or not,” he continued. “[Prescribers] need to learn about risk stratification, and they need to be trained in how to do urine drug screens and how to interpret them. They also need to know that if the urine screen shows something unusual, they have to take the next step to order a qualitative confirmation or perhaps follow up with a [serum analysis], and they need to know how to evaluate those serums.”
If prescribers had that knowledge, he said, “outcomes would be much better.”
The PROP proposal is on the FDA docket, and the agency has until January 2013 to respond. Dr. Kolodny noted that even if the agency decided to require label changes, individual physicians would not be restricted from prescribing off-label for longer-term opioid therapy at higher doses for patients with CNCP. “The FDA doesn’t regulate the practice of medicine. It regulates drug companies,” he said.
Dr. Fudin said that although physicians would be able to prescribe off-label, the presence of label restrictions could dissuade many from doing so because of liability concerns, thus denying relief to patients needing more potent analgesics. Additionally, he said, many health insurers including Medicare and Medicaid likely would withhold payments for opioid prescriptions not adhering to label indications, a potential financial hardship for people unable to work because of painful disabilities.
He cited Florida’s experience with the so-called “Pill Mill” legislation. The new law, he said, is causing many doctors to fear prescribing opioids and pharmacies unwilling to fill prescriptions, leaving many elderly patients with chronic pain syndromes not only in pain but also going through withdrawal. “If Florida represents even a small percentage of what we can expect countrywide from the PROP petition, it will be a disaster.”
Dr. Kolodny said the assertion that medical insurers would withhold payments from physicians prescribing opioid therapy off-label was “just plain wrong,” adding that psychiatrists like himself “do a lot of prescribing for off-label indications” and encounter no payment problems with Medicare and Medicaid or other insurers. He also maintained that the reluctance of many legitimate retail pharmacies in Florida and other states to fill prescriptions for opioids like oxycodone was due not to state laws seeking to curb illicit “pill mills,” but to their fear of robberies and because “they just don’t want to be caught in the middle of all this.”
Attorney Doug Stoehr is a personal injury lawyer who takes claims for clients who have chronic pain as a result of an accident or injury caused by another. For more information on his Altoona, PA practice, please visit his website athttp://www.stoehrlaw.com