Higher doses of prescribed opioids associated with increased overdose risk

Patients prescribed higher doses of opioids are at increased risk for overdose, according to a new study.

Researchers sought to determine the rate of opioid overdose in relation to an average prescribed daily opioid dose among patients receiving medically prescribed, long-term opioid therapy. The study population included 9,940 adults from a single HMO who had received at least three opioid prescriptions for chronic noncancer pain within 90 days between 1997 and 2005. Patients were followed for a mean of 42 months (range, <1 to 119 months). The primary study outcomes, nonfatal and fatal overdoses, were determined by diagnostic inpatient and outpatient care codes and confirmed by review of medical records. The study results appeared in the Jan. 19 Annals of Internal Medicine.

During follow-up, 51 patients had one or more opioid-related overdoses; six of these overdoses were fatal. The annual overdose rates were 0.2% in patients receiving 1 to 20 mg of opioids per day, 0.7% (a 3.7-fold increased risk) in those taking 50 to 99 mg/d, and 1.8% (an 8.9-fold increased risk) in those taking at least 100 mg/d. The authors found that patients receiving higher opioid doses were more likely to be men and current smokers and were more likely to have a history of depression or substance abuse treatment and higher Charlson comorbidity scores.

The authors acknowledged that their study was observational and could not determine whether difference in overdose risk reflected direct effects of differences in doses or patient characteristics. They concluded that because of uncertainties regarding effectiveness and the risk for overdose, long-term opioid therapy should be prescribed carefully and patients receiving these drugs should be closely monitored.

An accompanying editorial pointed out that prescriber practices could have played a role in the overdoses noted in the study and reiterated the authors' recommendation for monitoring through such measures as an opioid contract between patient and physician. The current study findings “show the need to assess the risk for opioid misuse, provide close oversight, dose judiciously, and continually reevaluate the benefit of these potentially risky drugs,” the editorialists wrote.