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Factors that Increase Risk of Overdose for Patients Starting Treatment with Medication for Opioid Use Disorder

April 1, 2023
Meg Brunner, MLIS
Brandt L, et al. Risk of experiencing an overdose event for patients undergoing treatment with medication for opioid use disorder. AJP In Advance 2023 (in press). Find it in the CTN Dissemination Library.
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What’s the Question?

Research has shown that treatment with medication for opioid use disorder (MOUD), like methadone, buprenorphine, or extended-release injectable naltrexone, can decrease both risk for overdose and death from other causes for people with opioid use disorder (OUD). 

However, though the risk of drug-related death is lowered when someone with OUD begins MOUD, the risk doesn’t disappear completely, and there seems to be an especially elevated risk of overdose during the initial “induction” phase to MOUD and the time immediately after stopping treatment.

Researchers in this study wanted to try to learn more about overdose risk during a course of treatment with MOUD – what might be contributing to that risk during induction or after stopping the medication, and how might providers be able to mitigate that risk?

How Was This Study Conducted?Image of pill bottle on shelf at store

To look more deeply into this issue, researchers examined data from three NIDA National Drug Abuse Treatment Clinical Trials Network (CTN) studies -- CTN-0027 (START), CTN-0030 (POATS), and CTN-0051 (X:BOT) – with a focus on adverse events, especially overdose events.

The overall risk of having an overdose event in the 24 weeks after randomization in the studies was compared for each study arm (one for methadone, one for naltrexone, and three for buprenorphine).

What Did Researchers Find Out?

Analysis found that by week 24, 39 participants (out of a total of 2,199) had experience one or more overdose event, with the highest rate of overdose events for those assigned to naltrexone (5.3% compared to 1.51% for methadone and 1.15% for buprenorphine).

However, 27.9% of patients assigned to naltrexone did not successfully start taking the medication, and their overdose rate was 8.9% compared with 3.9% among those who DID start on naltrexone.

Significantly higher rates of overdose were also observed for people who reported benzodiazepine use when they began the study, as well as for people who either never successfully started on their assigned study medication or who stopped taking their medication after initial induction.

What are the Implications for the Workforce?

This study showed that among patients with OUD seeking medication treatment, the risk of overdose events over the next 24 weeks is higher among those who fail to start their medication or who stop taking their medication, as well as those who report benzodiazepine use. The risk seems to be slightly higher for patients seeking treatment with naltrexone, but this may be because induction to naltrexone can be more challenging for patients (patients can’t use any opioids for 7-10 days prior to starting naltrexone). 

Providers caring for patients interested in starting any MOUD, especially if they also report benzodiazepine use, should be sure to provide education about overdose risk, the protective effects of MOUD, and the dangers of discontinuing medication. Patients struggling to start on their MOUD, or who use benzodiazepines in addition to opioids, may require additional support.

Find it in the CTN Dissemination Library.