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Deaths related to prescription opioid therapy are under intense scrutiny, prompting those in pain medicine—clinicians, patient advocates, and regulators—to understand the causes behind avoidable mortality in legitimately treated patients.   Studies reporting on statistics, causes, and adverse events involving opioid treatment are now available in a special supplement of Pain Medicine, a journal published by Wiley-Blackwell on behalf of the American Academy of Pain Medicine (AAPM).

Opioids are prescribed to treat moderate to severe pain and include opioid analgesic drugs such as hydrocodone, methadone, morphine, and oxycodone.  According to the Food and Drug Administration (FDA), 29 million Americans age 12 and older misused extended-release and long-acting opioids in 2002, climbing to more than 33 million in 2007.  The FDA also estimates that opioids were responsible for nearly 50,000 emergency room visits in 2006. 

“Preventing unnecessary deaths from opioid therapy should be a central focus for everyone working in the field of pain medicine,” said Lynn R. Webster, M.D., FACPM, FASAM, Medical Director and Founder of Lifetree Clinical Research and Pain Clinic in Salt Lake City, Utah, and officer for the AAPM.  “Our primary objective is to increase understanding of the major risk factors associated with opioid-related deaths and exploring methods that mitigate the adverse effects involved in treating patients with analgesics that are potentially lethal.” 

One study in the Pain Medicine supplement on opioid mortality reports on the findings of epidemiologists at the Utah Department of Health (UDOH) who examined medication-related harm starting in 2004.  The research team, led by Christina A. Porucznik, Ph.D., MSPH, assistant professor in the Division of Public Health at the University of Utah analyzed several data sources including vital statistics, medical examiner records, emergency department diagnoses, and the state prescription registry.  “Our analysis showed that prescription drug-related harm, including death, in Utah primarily involved opioids,” said Porucznik.  “Additional studies are needed to indentify risky prescribing patterns and individual-level risk factors which contribute to opioid-related injury or death.”   

In a related study, a panel of pain medicine experts, led by Webster, reviewed the medical literature and state and federal government sources to assess frequency, demographics and risk factors associated with overdose deaths caused by opioids. Analysis revealed a pattern of increasing opioid-related overdose deaths beginning in the early 2000s.  While methadone represented less than 5 percent of opioid prescriptions dispensed, one-third of U.S. opioid-related deaths were attributed to this drug.

Researchers determined that root causes of deaths from methadone included physician error due to knowledge deficits, patient non-adherence to prescribed medication regimen, and unanticipated medical or mental health comorbidities.  Furthermore, some insurance companies require that methadone be used as first-line therapy to control pain over other opioid therapy.  Forcing the use of methadone by health care providers who may not be aware of how to safely prescribe this drug may lead to greater mortality risk. 

Additional contributors to overall opioid-related deaths included the presence of sleep-disordered breathing and use of other drugs that depress the central nervous system such as alcohol, benzodiazepines, and antidepressants.  Approximately two-thirds of opioid-related deaths are caused by opioids other than methadone. “Patients with depression, anxiety, or other mental illness who also have chronic pain need structured care that minimizes risks associated with opioid therapy,” concluded Webster.  “It is very difficult to safely treat chronic pain in patients who have serious mental health issues.  We must strike a balance between treating pain and preventing harm.”