Epidemic of Overdose Deaths Linked to Nonmedical Use of Prescription Opioids

Caroline Cassels

December 11, 2008

December 11, 2008 — Up to 93% of unintentional overdose deaths in West Virginia, 1 of the poorest US states, are due to nonmedical use of prescription pharmaceuticals, primarily opioid analgesics, new research shows.

A population-based, observational study by investigators at the Centers for Disease Control and Prevention (CDC), in Atlanta, Georgia, shows nearly two-thirds of all drug-overdose deaths involved prescription diversion, meaning those who died did not have prescriptions for the drugs that killed them.

"We had anticipated that drug diversion would be an important contributor to these [overdose] deaths. However, the finding that nearly two-thirds of the deaths involved prescription drug diversion was particularly noteworthy," principal investigator Aron J. Hall, DVM, told Medscape Psychiatry.

Furthermore, investigators found that "doctor shopping" was a major contributor to unintentional drug-overdose mortality. "Roughly 1 in 5 of those who died had evidence of doctor shopping, which was defined as an individual who had 5 or more health providers in the previous year writing prescriptions for controlled substances," he said.

The study is published in the December 10 issue of the Journal of the American Medical Association.

Dramatic Increase in Opioid Sales

Since 1997, when 2 expert panels in the United States introduced clinical guidelines for the management of chronic pain, which included expanded use of opioid pain medications, per capita retail sales of methadone, hydrocodone, and oxycodone have skyrocketed.

From 1997 to 2007, purchase of methadone, hydrocodone, and oxycodone in the United States increased 13-fold, 4-fold, and 9-fold, respectively.

The increase in sales of these agents paralleled a dramatic rise in emergency-department visits and unintentional drug-overdose deaths. Between 1999 and 2004, West Virginia experienced a 550% increase in such deaths — the highest in the United States.

Dr. Hall pointed out that drug overdose is a leading cause of unintentional injury in the United States, second only to motor-vehicle accidents.

According to study author Leonard J. Paulozzi, MD, from the National Center for Injury Prevention and Control, these findings highlight a need for better management of prescription opioid medications.

"I think it has been a good thing that people in chronic pain who need opioids are better able to get them. But we need to come up with good ways to manage the increased use of this powerful tool, so that we don't run into problems like this, which is basically an epidemic of prescription overdose," he told Medscape Psychiatry.

Greatest Increase in Drug Overdose in West Virginia

The investigators undertook the study based, in part, on a previous CDC report that highlighted specific states where overdose death rates were most pronounced and showed a strong association between overdose mortality in the more rural states.

"West Virginia in particular experienced the greatest increase in drug-overdose mortality between 1999 and 2004, so it seemed to be an important state to focus our attention on, with the recognition that it may have potential broader implications for the epidemic elsewhere," he said.

The study's objective was to evaluate the risk characteristics of individuals dying of unintentional pharmaceutical overdose in the state and identify the types of drugs involved and the role of drug abuse in the deaths.

Using data from medical-examiner, prescription drug–monitoring program, and opiate-treatment program records, the investigators identified all state residents who died of unintentional pharmaceutical overdoses in West Virginia in 2006.

A total of 295 individuals died of unintentional pharmaceutical overdose, a death rate of 16.2 per 100,000. Of these, 63.1% were had used pharmaceuticals that contributed to their death without documented prescriptions, and doctor shopping was a factor in 21.4% of deaths. Women were significantly more likely to have evidence of doctor shopping than men — 30.9% vs 16.7%.

Methadone Most Common Drug

The prevalence of diversion was most common among individuals aged 18 to 24 years. In addition, relative to all other age groups, the group aged 35 to 44 years had a significantly greater rate of doctor shopping than any other age group — 30.7% vs 18.2%. Of the total study population, 94.6% had at least 1 indicator of substance abuse.

Compared with deaths involving prescribed pharmaceuticals, those involving diversion were associated with a history of substance abuse, nonmedical route of pharmaceutical administration, and a contributory illicit drug.

In contrast, those with evidence of doctor shopping were significantly more likely to have had a previous overdose and significantly less likely to have used contributory alcohol compared with those who died of overdose but had no evidence of doctor shopping.

Multiple contributory substances were implicated in 79.3% of deaths, and opioid analgesics were the most prevalent class of drugs, contributing to 93.2% of deaths. Methadone was the most common drug identified and was involved in 40% of all deaths.

"Practicing physicians need to counsel patients not only on the risk of overdose when prescribing narcotic pain killers specifically, but about the risk of sharing their medications with others. They need to also need to reinforce to their patients the importance of maintaining control of their medication to prevent theft or intentional diversion," said Dr. Hall.

Lack of Awareness

While most clinicians are familiar with starting doses of opioids, the fact is there is not a great deal of exposure in medical school or residency programs to information about prescription drug dependence, said Dr. Paulozzi.

Therefore, he said, it is critical that physicians read and adhere to recently published practice guidelines for the management of chronic pain and refer patients as needed to pain-management specialists.

They also need to make use of state prescription drug-monitoring programs to determine whether their patients are getting scheduled drugs from other clinicians.

In an accompanying editorial, A. Thomas McLellan, PhD, from the Treatment Research Institute, and Barbara Turner, MD, from the University of Pennsylvania School of Medicine, both in Philadelphia, say the study will undoubtedly raise the question of whether access to opioid medications should be restricted.

However, they point out that opioids have demonstrated effectiveness in relieving pain and therefore physicians should consider strategies to reduce the likelihood of fatal overdose and intentional diversion.

These include consideration of an "opioid agreement with the patient, stipulating the frequency of obtaining medications, timely refills but no early replacements for lost prescriptions, safe storage, no sharing, single-source prescribing, monitoring through urine screens, and adherence to monitoring visits. The agreement should be presented as a way of simultaneously protecting the patient from adverse events and promoting a collaborative, responsible relationship," they write.

The authors report no relevant financial disclosures.

JAMA. 2008;300:2613-2620 Abstract, 2672-2673. Abstract

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