Patients on higher prescription opioid doses have a significantly elevated risk of unintentional overdose and consequent death compared to those on lower doses, researchers from the Department of Veterans Affais, Ann Arbor, Mich., revealed in JAMA (Journal of the American Medical Association). The authors added that “receiving both as-needed and regularly scheduled doses is not associated with overdose risk.”

The researchers explained that the incidence of death from overdose has risen dramatically in the USA over the last ten years – it has now become a serious public health concern.

The authors wrote:

“Between 1999 and 2007, the rate of unintentional overdose death in the United States increased by 124 percent, largely because of increases in prescription opioid overdoses. 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.”

Amy S. B. Bohnert, Ph.D., and team looked at the relationship between opioid prescribing patterns and death risk from overdose between the beginning of 2004 to the end of 2008 among groups of patients with cancer, acute pain, substance abuse disorders, and chronic pain. Details were gathered from a national sample of Veterans Health Administration patients.

The study included information on all unintended death from prescription opioid overdose (total 750) and a random sample of patients (154,684) among those people who utilized medical services during the 2004-2008 period and received opioids for pain.

Approximately 0.04% of patients receiving opioid therapy overdosed. Those who died from opioid overdose tended to be middle-aged and Caucasian, with chronic pain, substance use disorders and other psychiatric problems. Those with cancer were found to be less likely to overdose.

The higher the maximum daily dose was the higher the overdose rate was, the authors discovered – a 100 mg/day compared to a 1 mg/day to less than 20 mg/day. This trend existed in all patient subgroups, such as those with chronic pain, acute pain, cancer, and substance use disorders.

The researchers wrote:

Having as-needed opioids only compared with having regularly scheduled opioids was associated with an increase in risk of opioid overdose among patients with cancer. Receiving both as-needed and regularly scheduled doses was not associated with overdose risk after adjustment.

Opioids are commonly prescribed for the treatment of pain. They include such drugs as codeine, oxycodone, morphine, and methadone. Examples of brand names include Lomotil, Percocet, Vicodin, Demerol, Darvon, Percodan, Avinza, OxyContin, and Kadian.

There are several types of opioids, which are classified as endogenous, fully synthetic, semi-synthetic and natural. Codeine and morphine are derived from the opium poppy and are examples of natural opioids. Oxycodone and hydrocodone are examples of semi-synthetic opioids – they are made by chemically altering natural opioids. Methadone, a fully synthetic opioid, is synthesized from non-opioid substances in labs. Endorphins, which are produced by the body, are examples of endogenous opioids.

The authors wrote:

“The present findings highlight the importance of implementing strategies for reducing opioid overdose among patients being treated for pain. This study documents a relationship between opioid prescribing and opioid overdose in a large, national, prospective cohort of individuals receiving opioid therapy for a variety of medical conditions. 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.”

“Association Between Opioid Prescribing Patterns and Opioid Overdose-Related Deaths”
Amy S. B. Bohnert, PhD; Marcia Valenstein, MD; Matthew J. Bair, MD; Dara Ganoczy, MPH; John F. McCarthy, PhD; Mark A. Ilgen, PhD; Frederic C. Blow, PhD
JAMA. 2011;305(13):1315-1321. doi: 10.1001/jama.2011.370

Written by Christian Nordqvist