Higher prescribed doses of opioids for chronic pain significantly increased the risk of overdose, data from a large retrospective study showed.

Patients prescribed opioid doses of 100 mg/d or more had almost nine times the overdose risk of patients prescribed daily doses of 1 to 20 mg.

Patients taking 50 to 99 mg/d had almost four times the risk of low-dose patients, investigators reported in the Jan. 19 issue of Annals of Internal Medicine.

“This study was the first to look at opioid overdose, nonfatal as well as fatal, among people who we know were getting opioids for chronic pain from a physician,” Michael Von Korff, ScD, of the Group Health Research Institute in Seattle, said in an interview.

Although prescribed opioids had a low overall risk of overdose, patients who receive higher doses require careful monitoring. The findings have considerable clinical relevance, given evidence that higher opioid doses do not lead to better pain control, he added.

• Explain to patients that higher prescribed doses of opioid drugs are associated with an increased risk of overdose.

Increasingly, patients with chronic noncancer pain receive long-term opioid therapy, prescribed by healthcare providers. Previous studies of opioid overdose had focused on drug diversion and abuse, said Von Korff. The overdose risk associated with medically prescribed opioids had not been examined.

To explore this risk, Von Korff and colleagues analyzed opioid prescription data from a large healthcare system. They identified patients who initiated opioid therapy for chronic noncancer pain from 1997 through 2005, who filled three or more prescriptions for opioids within the first 90 days of the pain episode, and who had no opioid prescriptions in the previous six months.

The analysis identified 9,940 patients for inclusion. Follow-up from the initial 90-day prescription period averaged 42 months.

The authors compared the average daily opioid dose over the prior 90 days with reported fatal and nonfatal overdoses. The analysis revealed 51 opioid-related overdoses, six of which were fatal.

Patients prescribed daily opioid doses of 1 to 20 mg had an annual overdose rate of 0.2%. Patients taking 50 to 99 mg/d had an annual overdose rate of 0.7%, roughly 3.7 times greater than patients taking lower doses (95% CI 1.5 to 9.5). Daily opioid doses of 100 mg or greater were associated with an annual overdose risk of 1.8%, an 8.9-fold increase compared with patients taking 1 to 20 mg/d (95% CI 4.0 to 19.7).

Patients who had not recently received opioids had less than one-third the overdose risk of patients who received the lowest daily doses of opioid drugs (HR 0.31).

“Observational studies suggest that many patients receiving opioids for chronic noncancer pain often continue to experience appreciable pain and activity limitations,” the authors wrote.

“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,” they added.

The findings make a case for user-friendly, real-time, prescription-drug monitoring programs that allow physicians to track all opioid prescriptions for a patient, A. Thomas McLellan, PhD, of the White House Office of National Drug Control Policy, wrote in an accompanying editorial. Promising systems have been designed, but none is satisfactory at this point.

“Frankly, we do not know how to increase clinical diligence without additional work, time, or money, although technology can facilitate some of these suggested practice changes,” McLellan wrote. “The threat to patient safety is too great to allow current pain management and opioid-prescribing practices to remain as they are.”