In a study of opioid overdose survivors in Massachusetts, methadone and buprenorphine were found to reduce subsequent overdose deaths by 59% and 38%, respectively, compared with outcomes for survivors receiving no medication treatment after overdose. Patients treated with naltrexone after an overdose did not show any subsequent decline in overdose deaths, the study found.
For the study, published online June 19 in the Annals of Internal Medicine, researchers looked at state data sets covering 17,568 Massachusetts adults without cancer who survived an opioid overdose between 2012 and 2014. The study was funded by the National Institutes of Health and was conducted by Marc Larochelle, MD, of Boston Medical Center’s Grayken Center for Addiction and the Boston University School of Medicine, and colleagues.
Claims for methadone maintenance treatment or a record of treatment with the state system were used to identify receipt of methadone. The state's prescription drug monitoring program was used to identify dispensed buprenorphine. Injectable or oral naltrexone was identified via a pharmacy claim.
In general, all of the medications were underutilized, the researchers reported, despite the fact that they are considered the gold standard for treatment of opioid use disorder. In the year following the index overdose, 30% of the study participants received any medication: 8% received methadone, 13% received buprenorphine, 4% received naltrexone, and 5% received more than one of the medications.
Almost half of the patients who received methadone or buprenorphine after the index overdose had received the same treatment in the year before that overdose, compared with 19% who had received naltrexone. Overall, 41% of the patients received prescriptions for opioid analgesics, and 28% for benzodiazepines, in the year before the index overdose. In addition, 22% at some time had been through opioid detoxification before the index overdose.
The study, “Medication for opioid use disorder after nonfatal opioid overdose and association with mortality: A cohort study” is the first to look at the link between opioid use disorder medications and death after a nonfatal opioid overdose, the authors wrote. However, they said that the associations with methadone and buprenorphine and staying alive are consistent with findings from previous studies.
It is well known that methadone, and more recently buprenorphine, saves lives. Is this really a new finding? “There have been several observational studies that show reduced mortality for both methadone and buprenorphine,” conceded Larochelle in an interview with Addiction Professional. “But this is the first study that examined death rates as an outcome in a U.S.-based setting.” In addition, the researchers were able to look at the evidence around naltrexone, which did not show a reduction in deaths, Larochelle says.
Power in local study
The study has been “very powerful for our stakeholders here” in Massachusetts, says Larochelle. The study covers the time period when illicit fentanyl was infiltrating the opioid supply in Boston, resulting in many overdoses. And despite the fact that the evidence that the medication treatments work is clear, it’s always important to keep getting the message out, because “these treatments remain so very highly stigmatized,” he says.
“Some people who work in the field say, ‘I don’t need more evidence, I know these medications work,’” Larochelle says. “But not everyone knows the evidence.”
Although the numbers make it look as if methadone treatment was more effective than buprenorphine at reducing overdoses, the study was not designed to draw such a conclusion, Larochelle says. “We didn’t have the power statistically to say whether it’s better,” he says.
We asked whether it was possible to avoid conflating the treatment setting with the medication: Methadone can only be dispensed in highly regulated opioid treatment programs (OTPs), while buprenorphine and naltrexone can be dispensed in physician offices and pharmacies. “It’s impossible to disentangle the treatment settings,” says Larochelle. “It’s a reasonable question. Methadone is provided in highly structured OTPs, where most people go every day to receive their medication. For some patients, that structure does very well.”
Not returning for treatment
Why didn’t naltrexone, which in the study had worse results than no treatment, show a greater benefit? Just over 1,000 people received naltrexone, which was not a large number, Larochelle notes. But more significant is the fact that those who were on naltrexone did not stay on it very long, he says. The median duration of naltrexone treatment was only one month, compared with four months for methadone and five months for buprenorphine.
One of the problems with stopping naltrexone is that the protective factor is gone: Opioids are no longer blocked, and because the individual has lost tolerance, even lower doses than the patient was used to could result in an overdose. The study did not answer why people are not staying in treatment. “But what we know in general is that the more stable and longer-term the recovery is, the lower the chance of having a bad event like an overdose,” Larochelle says.
While some people are asking how long treatment needs to last in order to be effective, the weight of the evidence suggests that no matter how long it is, not being in treatment anymore increases risk, he says. “This is a chronic illness we don’t cure anyone from,” he says.
Ultimately, Larochelle would like to see more people accessing medications. Fewer than one-third of overdose survivors receive medication within a year, he says. He thinks the main reason is that the treatments aren’t accessible.
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