Do Mortality Rates Differ by Type of Pharmacotherapy for Opioid Dependence?

The risk of death from overdose associated with induction, maintenance, or discontinuation of an opioid pharmacotherapy may depend on the opioid’s mechanism of action. For example, methadone (full agonist) treatment may pose the greatest risk during treatment induction, whereas oral naltrexone (an antagonist) may be riskiest immediately after treatment is discontinued because of diminished opioid tolerance.

In this study, Australian researchers analyzed coroner’s reports and various prescription data sources to estimate mortality rates possibly associated with these pharmacotherapies.

• From 2000 to 2003, 1 buprenorphine-*, 32 oral naltrexone-, and 282 methadone-related deaths occurred.
• The overall mortality rate associated with methadone was significantly lower than the rate associated with oral naltrexone (2.7 vs. 10.1 per 1000 treatment episodes).
• The mortality rate associated with methadone treatment was 3.0 per 100 person years during the first week of treatment versus 0.34 per 100 person years during the remainder of treatment.
• The mortality rate associated with oral naltrexone treatment was 1 per 100 person years during treatment versus 22.1 per 100 person years in the 2 weeks after treatment was discontinued. 

Comments:

Although the methods used permit only crude estimates and specific causes of death were not addressed, these findings heighten concerns about the possible increased risk of opioid overdose shortly after oral naltrexone treatment is discontinued. More rigorous studies are needed to refine the estimates presented here, to define risks and benefits of other (e.g., depot) preparations of naltrexone in treating opioid dependence, and to develop treatment protocols to further enhance the safety profiles of specific opioid pharmacotherapies.   

Marc N. Gourevitch, MD, MPH

Reference:

Gibson AE, Degenhardt LJ. Mortality related to pharmacotherapies for opioid dependence: a comparative analysis of coronial records. Drug Alcohol Rev. 2007;26(4):405–410.