Von Korff醫師報告接受Johnson Johnson藥廠的資金，其他研究者的宣告請見原始文獻，McLellan博士宣告沒有相關財務關係。
Higher Doses of Opioids in Chronic Pain Patients Linked to Increased Overdose Risk
By Caroline Cassels
Medscape Medical News
January 20, 2010 — Individuals who receive higher-dose opioid therapy for chronic pain have almost a 9-fold increased risk for overdose compared with patients who receive the lowest doses of these medications, new research suggests. These findings have at least 1 leading expert calling for change to current pain management and opioid-prescribing practices.
Investigators at the Group Health Research Institute and the University of Washington found that among a cohort of adults who started use of opioid analgesics for a pain condition those receiving 100 mg/day of opioids had an 8.9-fold increase in overdose risk compared with patients receiving 1 to 20 mg/day of these medications. Further, patients receiving 50 to 99 mg/day had a 3.7-fold increase in overdose risk compared with patients in the lowest-dose group.
Annual overdose rate for the high-, medium-, and low-dose groups were 0.2%, 0.7%, and 1.8%, respectively.
"We observed increased risk for overdose in patients receiving medically prescribed opioids at higher doses. Most overdoses were medically serious, and 12% were fatal," the study authors, with lead investigator, Michael Von Korff, ScD, write.
The study is published in the January 19 issue of Annals of Internal Medicine.
Most Commonly Prescribed Class of Medications
Currently, opioids are the most commonly prescribed medication in the United States. According to investigators, long-term opioid therapy for chronic noncancer pain is becoming increasingly common, with more than 3% of adults now receiving such treatment. At the same time, they note that death rates from opioid analgesic poisoning have also increased.
Some research suggests that less than half of individuals who died of unintentional prescription drug overdose received opioids from a physician. However, they point out that the risk in patients receiving medically prescribed opioids has not been studied.
The researchers sought to estimate rates of opioid overdose and their association with an average prescribed daily opioid dose among patients receiving medically prescribed, long-term opioid therapy.
Using pharmacy record data from a large health maintenance organization, which provides prepaid care to more than 500,000 individuals in Washington, investigators identified a cohort of 9940 patients 18 years and older starting a new episode of opioid use.
Study subjects received at least 3 opioid prescriptions during a 3-month period from 1997 through 2005. Patients were being treated for conditions that included neck or back pain, headache, jaw pain, arthritis, and menstrual pain.
The study's primary outcomes included risk for nonfatal and fatal overdose as they relate to average daily opioid dose. Annual overdose rates were also calculated based on dose.
Back and Extremity Pain
The investigators report that 68% of individuals were receiving opioid therapy for back or extremity pain.
Approximately 60% of the cohort were women, with a mean age of 54 years. The mean daily dose of opioids prescribed was 13.3 mg, and at 46% hydrocodone was the most commonly prescribed opioid.
A total of 51 patients had 1 or more opioid-related overdoses. Of these patients, 40 experienced a fatal (6) or otherwise serious overdose and 11 had a nonserious overdose.
Potential limitations of the study include the fact that there were few overdoses and that they were assessed primarily through record review, introducing the possibility that some cases were missed.
In addition, the study authors note, it was not clear from the study whether dose-related differences in overdose rates were related to patient differences or to the direct or indirect effects of higher doses.
"Because of uncertainties regarding effectiveness and risks, long-term opioid therapy should be prescribed with awareness of risk and close patient monitoring, which may not be happening consistently at present. Further research on overdose risks of long-term opioid therapy and approaches to reduce associated risks is needed," the study authors write.
Need for More Responsible Prescribing
In an accompanying editorial, A. Thomas McClellan, PhD, White House Office of National Drug Control Policy, Washington, DC, said the study findings highlight the need for more responsible prescribing practices.
Dr. McLellan notes that the unadjusted data show that there were more overdoses among patients diagnosed as having depression or substance abuse or who were concurrently receiving sedative-prescribed hypnotics. All 3 of these factors, he points out, are well-known risks for adverse events from opioids.
"Therefore, these persons require substantial education and close oversight if opioids are prescribed," he writes.
In addition, he notes, the findings reinforce the importance of goal-directed therapy "such that continued or increased doses of opioid therapy should be contingent on clear improvements in function and quality of life. "Long-term therapy carries too many risks to justify use without improvements in health status."
The study also highlights the need for a prescription-drug monitoring program that makes it easy to track a patient's opioid prescriptions.
"The threat to patient safety is too great to allow current pain management and opioid-prescribing practices to remain as they are," Dr. McLellan writes.
Dr. Von Korff reports that he has grants pending from Johnson Johnson. The disclosures of the other investigators can be found in the original paper. Dr. McLellan has disclosed no relevant financial relationships.
