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Weighing Overdose Risk Among Veterans

April 7, 2015
Starting opioid naïve veterans on long-acting opioids increases adverse events, including overdose risk.

As a result of the injuries sustained during recent conflicts, pain is now the leading cause of short- and long-term disability among veterans.1 As more veterans with chronic pain are prescribed opioid medications, unintentional overdose is a growing risk, especially during the first weeks of treatment.

In a new study published in JAMA, researchers highlight a vulnerable patient group in the Veterans Administration (VA) that, once given long-acting opioids (LOA), had significantly more risk of unintentional overdose than those prescribed short-acting opioids (SAO).2

Who Was Studied

Using medical claims from the VA Healthcare System, researchers analyzed the outcomes of over 800,000 veterans who had chronic pain conditions, like headache, arthritis, arthropathies, neuropathies, and back pain. The majority of patients were given a monotherapy of a SAO (codeine, hydrocodone, and oxycodone). However, around 19,000 veterans received a LAO (morphine, methadone, fentanyl patches, etc.)

The researchers identified 319 unintentional overdose events. Veterans prescribed a LAO were twice as likely to suffer an overdose than those given a SAO. Approximately half of the 319 overdoses occurred in the first 60 days of treatment, so the crude risk of unintentional overdose was noticeably higher in the initial treatment phase. This was especially true within the first 2 weeks of opioid treatment, in which the risk of overdose was 5-fold higher with LAO.

While the majority of overdoses were related to SAO (282 of 319), the heightened risk was far greater for LAO, where the hazard ratio was 2.5 times higher than with a SAO. Even after the initial 60 day treatment period, patients on LAO had a 50% higher risk of overdose.

Higher Doses, Greater Risk?

The results also bolster an association between higher daily doses of opioids and higher overdose risk.3-5 Indeed, patients taking greater than 50 mg morphine equivalent daily (MED) had more than twice the risk of overdose than those taking 1 to 20 mg MED.

Although, past research has studied dosage level and overdose risk, opioid regimens can be more complex than measuring MEDs. Backgrounds and morbidities of the patients themselves could be relevant, especially if such data reveals drug abuse or polypharmacy.

Of those receiving LAOs, 83.2% were also being given a concomitant SAO, which helps to explain why they were more likely to receive higher daily doses, noted the authors. These patients were also more likely to have comorbid conditions, like back and neck pain, depression, anxiety, post-traumatic stress disorder, and substance use disorders, as well as receiving concomitant antidepressants and benzodiazepines, which could have increased their overdose risk.6

Red Flags

According to Jennifer P. Schneider, MD, PhD, a member of the Practical Pain Management editorial board, all of these factors would have increased those patients' overdose risk.

"What this tells me is that one cannot conclude that the cause of the increased overdose deaths in the sustained-release groups was that their opioid was long-acting rather than short-acting," said Dr. Schneider. "Rather, one has to question the thinking of the prescribing physicians as to why they chose to start this particular type of patient on an LAO rather than an SAO."

"And why did the LAO patients have morphine-equivalent daily doses 3 times as high as their SAO counterparts? The level of pain may have been a factor in the treatment decision. Also, if addiction or psychological issues were present, LAO could have lowered the overdose risk," she said.

Regardless, "starting an opioid-naïve patient on a high daily dose of opioids is not recommended," said Dr. Schneider, who is a nationally recognized expert in internal medicine, addiction medicine, and pain management.

Study Flaws

To Dr. Schneider, understanding all the relevant details of a patient's history are paramount to informed decisions on initiating an opioid treatment for chronic non-cancer pain. This highlights another limitation of the JAMA study, in that it used data from medical claims, which are known to have inaccuracies or incomplete information.

According to Dr. Schneider, knowing the details of the pain problem and past diagnostic studies and treatments aren't enough, though, as psychosocial factors can help doctors assess the patient's risk of opioid abuse and overdose.

"This is essential for risk assessment and should include the patient’s history of psychiatric problems, personal and family history of substance abuse and addiction, current cigarette, alcohol, and drug use or abuse, possible childhood trauma or other traumatic events, current relational and/or financial stressors, employment history and current job status, and patient’s current level of functioning. It is also important to obtain old relevant medical records."

Principal investigator Matthew Miller, MD, ScD, and Catherine W. Barber, MPA, received support for this research from an investigator initiated research grant from the Centers for Disease Control and Prevention. The authors reported no conflicts of interest.

Last updated on: April 28, 2015