Taking prescribed methadone as a treatment for pain at home carries a 46 percent greater risk for death than morphine SR (sustained release), an equally effective but more expensive pain reliever, according to a new study by Vanderbilt University Medical Center.
As a side effect, all opioid medications carry the risk of repressing respiration, but methadone is unusual in that its anti-pain effect is shorter than its respiration effect.
“This means that patients may sense the need for more medication even though there is still enough methadone in their bodies to cause respiratory problems, so they essentially inadvertently overdose themselves,” said the study’s first author Wayne Ray, Ph.D., M.S., professor of Health Policy.
There were approximately 4.4 million methadone prescriptions written in the U.S. in 2009 for treatment of pain, according to the researchers. This translates to 72 excess deaths per every 10,000 person-years of treatment — again, compared to morphine SR.
“That’s quite high by medical standards. And as far as we know, there’s no clinical benefit to using methadone as opposed to morphine SR, so for that reason these deaths are particularly concerning,” said Ray. “It’s a lot of increased risk for a drug that happens to be cheap, but confers no other benefits.”
Another problem is that methadone is a pro-arrhythmic drug that can trigger deadly ventricular arrhythmias (abnormally rapid heart rhythms).
Because of these concerns, in 2006, the Food and Drug Administration warned clinicians about methadone use. The Centers for Disease Control and Prevention scientists also recommended against using methadone as a first-line treatment for pain.
The researchers write that their findings “support recommendations that methadone should not be considered a drug of first choice for non-cancer pain.”
Using Tennessee Medicaid records for 1997 through 2009, the team tracked 6,014 patients who were given methadone and 32,742 who were given morphine SR. People entered and exited follow-up as they started and stopped filling these prescriptions. More than three-fourths of the total prescriptions were for back pain.
In all, there were 477 deaths during 28,699 person-years of follow-up.
The sole previous study comparing these two drugs produced a nearly opposite result: 44 percent decreased mortality with methadone.
“That study included a lot of very sick patients, such as patients with cancer, and this may have skewed their results. Our findings are much more consistent with the existing body of data,” Ray said.
To root out potential variables, people in the Vanderbilt study were excluded from follow-up while in the hospital and for 30 days following hospital discharge, and people with life-threatening illnesses or cancer were excluded outright, as were those over age 74 and those in nursing homes.
The authors found that methadone’s excess risk was present in the lower half of the dosing range.
“That’s what’s interesting,” Ray said, “because this is consistent with the potential of methadone to accumulate and for patients to inadvertently overdose themselves.
“Apparently the higher you go with the dose, the less difference there is between methadone and another opioid. That’s what’s particularly concerning in some ways: that a clinician might consider the low dose to be relatively free of overdose risk, but because of methadone’s particular pharmacologic properties that may be incorrect.”
The findings are published in the journal JAMA Internal Medicine.