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The Overdose Problem
For the most recent study of overdose risk, researchers examined the medical records of nearly 10,000 chronic-pain patients being treated within a Washington State health plan between 1997 and 2005. Published in the Annals of Internal Medicine in January, the study found that 51 patients had experienced overdose six of them fatal. The overall risk of overdose was small, but it was clearly associated with the dose of the medication originally prescribed: patients receiving the highest doses were nearly nine times more likely to overdose than patients on the lowest doses. "The overall risk among people who continued to use opioids was 0.25% per year [or two overdoses per 1,000 people]," says Michael Von Korff, a co-author of the study and senior investigator at the Group Health Research Institute in Seattle, adding that most people involved in the study were on low doses.
Some of the overdose cases involved known drug misuse or suicide attempts, while others were due to patient error, but the study could not identify exactly what went wrong in all of the cases. Was it the high-prescribed dose alone, or were there other risk factors like illness, escalation of pain or undiagnosed addiction? While Von Korff and Volkow agree that prescription dose is a major contributor to overdose risk, they say better studies are needed to determine the precise causes and consequences. "One would hope that for a treatment regimen that millions of people are using, we'd have large, long-term, well-designed randomized controlled trials, and we don't," says Von Korff.
Which Painkiller Is Right?
One opioid is associated with a significantly higher risk of overdose than other drugs: methadone, which is being used increasingly to treat chronic pain because it is cheaper and draws less scrutiny than other strong, long-acting opioids like Oxycontin.
According to a review presented in February at the American Academy of Pain Medicine's annual meeting, methadone accounted for 5% of opioid prescriptions in the U.S. between 1999 and 2009 but was involved in 30% of opioid overdose deaths, as reported in malpractice cases, medical literature and federal and state databases. Some of these deaths occurred in heroin users being treated with methadone for addiction, but the overwhelming number of cases were in people who were prescribed the drug for chronic pain.
Much of the blame may fall on the Food and Drug Administration (FDA) and physician ignorance. Until 2006, FDA guidelines, which have since been revised, suggested starting pain patients on 80 mg of methadone a day a dose that could kill people who haven't developed tolerance to this class of medications. The current recommendations call for 30 mg to start.
"I happen to think that methadone is an extraordinarily valuable drug," says longtime opioid researcher Gavril Pasternak, head of molecular pharmacology at Memorial Sloan-Kettering Cancer Center in New York City. "It works in many patients who don't respond to other agents, but it is more dangerous in the sense that it's more difficult to prescribe appropriately. We have to do better in terms of educating physicians."
That's true also for the use of over-the-counter painkillers like ibuprofen and naproxen, and other non-steroidal anti-inflammatory drugs (NSAIDs) like Celebrex (celecoxib). Guidelines written and published by the American Geriatrics Society warned against using these drugs chronically and at moderate-to-high doses in patients age 75 or older with persistent pain. Citing the many risks of long-term NSAID use, including fatal ulcers and gastrointestinal bleeding, increased risk of heart attack and stroke and dangerous interactions with other drugs commonly prescribed to the elderly, the American Geriatrics Society suggested that seniors try acetaminophen instead. If that doesn't ease pain, older patients are advised to use opioids like codeine or morphine, which don't have the same risks.
"We're not saying opioids are innocuous. They are dangerous drugs," says Dr. Bruce Ferrell, who chaired the panel that authored the guidelines. "We are saying that there is a substantial proportion of the population for which opioids might be a better choice than NSAIDs."
But while the risk of opioid addiction in the elderly is low, there are other cautions. A study published in January by Von Korff and colleagues linked high-dose opioid use to a doubling of the risk of broken bones in the elderly. "One-third of these were hip and pelvic fractures," Von Korff says. "These can really be debilitating." The authors speculate that the patients may have been prone to falls caused by dizziness or sedation, side effects of drug treatment that tend to occur early in a new drug regimen or when dosage changes.