UAMS Study Finds Raising Opioid Dosage Increases Risks, Ineffective for Pain

By Ben Boulden

Brad Martin, Pharm.D., Ph.D., and Corey Hayes, Pharm.D., Ph.D., authored the two studies published separately online this month in the scientific journals Pain and  Addiction. The studies were funded by the National Institute on Drug Abuse.

Martin is a professor in the UAMS College of Pharmacy’s Division of Pharmaceutical Evaluation and Policy. Hayes is an assistant professor in the Center of Health Services Research in the College of Medicine Department of Psychiatry.

The Pain article looked at how dose escalation influenced the intensity of pain in patients and the Addiction article examined whether the risk of adverse effects increases with the opioid dose.

“What we found in one paper was that the pain relief the provider and the patient are going for really isn’t there when they increase their doses,” Hayes said. “You don’t see the benefit, but you do see the risk. Our overall message is, when you’re thinking about increasing the dose, you need to realize the risk it brings, too.”

For both studies, Martin and Hayes drew from data from the same group of 18,358 patients. One subgroup of patients were “dose maintainers” who during the study period did not have their opioid doses significantly increased. A second group of “dose escalators” had their doses increased by 20 percent or more. The majority in the second subgroup had their doses increased by about 60 percent, often starting from a low dose.

“The first question we wanted to answer was whether we are seeing meaningful pain relief when clinicians decide to increase someone’s opioid dose,” Martin said. “The second question was whether there were risks associated with increasing someone’s dose.”

In answering the first question, they found dose escalators persistently had higher pain scores throughout the study.

“Opioid dose escalation among patients with chronic pain is not associated with improvements in pain scores,” the study stated.

In answering the second question, the research team compared the two groups on whether dose escalation also increased patients’ risk of adverse effects such as suicide attempts, fall accidents and substance use disorders.

“For people who escalated their dose, compared to people who just maintained their dose, the increase in risk for developing a substance use disorder was about 30% when we look at all substance use disorders,” Martin said. “Not surprisingly, it was highest for opioid use disorders, which increased about 50%. Use of other drugs and alcohol use disorders went up about 15-20%.”

For most of the other negative outcomes, opioid use also increased their risk, the study concluded.