High-dose prescribing of opioids is associated with a significantly increased risk for unintentional opioid overdose death, new research suggests.

Investigators at the Department of Veterans Affairs, Ann Arbor, Michigan, found the risk for overdose death was directly related to the maximum prescribed daily dose of opioid medication.

"The present findings highlight the importance of implementing strategies for reducing opioid overdose among patients being treated for pain," the researchers, led by Amy S. B. Bohnert, PhD, write.

The study was published in the April 6 issue of the Journal of the American Medical Association.

Mortality Increase Troubling, Dramatic

According to investigators, the overdose mortality is "a pressing public health problem." They note that between 1999 and 2007 the rate of unintentional overdose in the United States increased by 124%, a phenomenon they attribute to increases in prescription opioid overdoses.

Some evidence suggests the risk for drug-related adverse events is higher in individuals prescribed opioids at doses equal to 50 mg or more per day of morphine.

The association of opioid-prescribing patterns may vary across patient groups, and recommendations for pain are usually specific to particular subgroups of patients with chronic noncancer pain, cancer-related pain, and substance use disorders, the investigators note.

However, they point out that potential subgroup differences in overdose risk related to opioid prescribing have not been examined.

"Achieving a better understanding of the factors contributing to prescription opioid overdose death is an essential step toward addressing this troubling and dramatic increase in overdose mortality," they write.

To examine the relationship between opioid dosing and scheduling (as needed, regular scheduling, or both) and death by unintentional prescription, the researchers used 2004 to 2008 data from two national Veterans Health Administration databases to gather information on patient encounters and prescription use and linked them to the National Death Index in patients with chronic pain, cancer, acute pain, and substance use disorders.

Higher Dose, Highest Risk

The study included data on all unintentional prescription opioid overdose decedents (n = 750) and a random sample of patients (n = 154,684) among individuals who used medical services in 2004 or 2005 and received opioid therapy for pain.

The researchers approximated the rate of overdose among individuals treated with opioids to be 0.04%. They found the adjusted hazard ratios associated with a maximum prescribed dose of 100 mg per day or more, compared with the dose category of 1 mg per day to less than 20 mg per day, were 4.54 (95% confidence interval [CI], 2.46 – 8.37) for those with substance use disorders, 7.18 (95% CI, 4.85 – 10.65) for chronic pain, 6.64 (95% CI, 3.31 – 13.31) for acute pain, and 11.00 (95% CI, 4.42 – 32.56) among those with cancer.

The investigators report that those who died of an opioid overdose were more likely to be middle-aged and white, more likely to have chronic or acute pain, substance use disorders, and other psychiatric diagnoses, and less likely to have cancer.

The investigators also found that the overdose rate was higher at higher maximum daily doses compared with lower maximum daily doses (≥100 mg per day vs 1 mg per day to <20 mg per day) across all diagnostic subgroups.

In addition, the investigators found that prescribing "as-needed" opioids only compared with having regularly scheduled opioids was associated with an increased risk for opioid overdose in cancer patients. Adjusted analyses revealed receiving both as-needed and regularly scheduled doses was not associated with overdose risk.

"The risk of opioid overdose should continue to be evaluated relative to the need to reduce pain and suffering and be considered along with other risk factors," the study authors write.

Need to Update Training

The same issue of JAMA also includes an analysis of national prescribing patterns by investigators at the National Institute of Drug Abuse (NIDA), which shows that more than half of all patients who received an opioid prescription in 2009 had filled another opioid prescription within the previous 30 days.

NIDA director Nora Volkow, MD, and colleagues report that approximately 56% of painkiller prescriptions were given to patients who had filled another prescription for pain from the same or different providers within the past month.

In addition, nearly 12% of opioids were prescribed to young people aged 10 to 29 years. Most of these were hydrocodone and oxycodone-containing products. Dentists wee the main prescribers for youth aged 10 to 19 years.

Nearly 46% of opioid prescriptions were given to patients between the ages of 40 and 59 years, and most of these were from primary care providers.

In an accompanying editorial, Dr. Volkow and Thomas McLellan, PhD, Center for Substance Abuse Solutions, University of Pennsylvania School of Medicine, Philadelphia, point out that opioid overdose is now the second leading cause of unintentional death in the United States, killing more people than heroin and cocaine combined.

"Some of the increased abuse of opioid analgesic likely reflects the misguided belief that because these medications are prescribed by physicians, they are safer than illicit drugs," Dr. Volkow and Dr. McLellan write.

They call for updated "clinical teaching and training practices for physicians, nurses, dentists, and pharmacists in the areas of pain management, opioid pharmacology, and abuse/addiction perhaps through interactive Web-based training.

"A more comprehensive and contemporary training curriculum for prescribers seems warranted," they write, adding "that guidelines recently adopted by the American Academy of Pain Medicine should be broadly adopted as a means to harmonize best practices among physicians and dentists regarding the initial prescription of opioids and the subsequent monitoring and management of patients with chronic noncancer pain."

None of the authors has disclosed any relevant financial relationships.

JAMA. 2011;305:1315-1321, 1346-1347, 1299-1300. Bohnert Abstract; Volkow Abstract; Editorial Abstract

Caroline Cassels • Medscape Medical News © 2011 WebMD, LLC