The Opioid Dependence Big Picture

First Posted 1/16/2014

Below, internet colleague Paul Dessauer shares his extensive knowledge of opioids in comments about my naltrexone post. His comments were particularly interesting in that they provide evidence that at least someone is aware of the big picture about addiction to heroin and pain pills.

In my post about naltrexone, I described how some people favored the drug over buprenorphine because of its lack of opioid effects. Unlike buprenorphine, naltrexone is an antagonist that has no abuse potential.  But I wondered… at a time when so many young people are dying, shouldn’t the primary issue be whether naltrexone saves lives?  Sure, it is ‘safe’– but does it work?

Paul provided references to answer my question.  While everyone is focused on the fact that naltrexone can block opioid receptors, Paul’s data shows that when naltrexone is used in the real world, people die.  I’m excited that someone, somewhere, has the courage to investigate the one thing that is never addressed in discussions about addiction, whether related to residential treatment, counseling, or medication: Does it work?

Paul’s comments:

You wrote;

<<< If ‘success’ consists of moving to naltrexone—a medication that many real-world addicts reject– how long is naltrexone continued, and what happens when it is stopped? Do people go back to heroin again? If not, why not? The cycle of ‘use, treat, cease treatment, use, and repeat’ should be a black box warning on naltrexone >>>

The other “black box” issue is dropped tolerance overdose when someone exits naltrexone treatment and relapses to illicit opioid use.

You asked; <<< How many people will die in their quest—or their doctor’s quest—for ‘abstinent recovery’ with or without naltrexone? >>>

This study used Australian coronial records to compare mortality rates amongst patients in methadone treatment, buprenorphine treatment, and naltrexone treatment. The authors make it clear that they believe the mortality rates for naltrexone calculated here are significant underestimates, as coronial data does not record such deaths consistently, and they found the majority of known naltrexone-related deaths did not appear in this data.

<<< When expressed as deaths per number of treatment episodes, it was estimated that naltrexone had a mortality rate of 10.1 per 1000 treatment episodes. If the mean treatment retention in naltrexone treatment was estimated at 3 months (rather than two months, as assumed in the above estimate), the mortality rate for naltrexone treatment increased to 15.2 deaths per 1000 treatment episodes.

Naltrexone was associated with a mortality rate of 22.1 per 100 person years during the period of high risk (2 weeks post-treatment), and 1 per 100 person years during the period of low risk (during treatment)…. >>>

<<< …The estimated mortality rate was 0.02 per 1000 treatment episodes for buprenorphine and 2.7 per 1000 episodes for methadone.

The mortality rate for naltrexone was four times higher than for methadone when calculated as deaths per number of episodes of treatment, and substantially higher than for buprenorphine.

When considering deaths per periods of high and low risk, the mortality related to naltrexone was approximately seven times that of methadone during the period of high risk and three times the rate during the period of low risk. Naltrexone treatment was associated with a mortality rate of 22.1 per 100 person years during the period of high risk (two weeks following treatment cessation) and 1 per 100 person years during the period of low risk (during treatment). Buprenorphine mortality rates were not expressed in terms of periods of high and low risk due to the low number of deaths detected with this search method. >>>

<<< In comparing mortality rates associated with these pharmacotherapies, it is important to draw the reader’s attention to the rates of mortality for active heroin users. It has been estimated that mortality rates for heroin-dependent persons not in treatment are in the vicinity of 0.9 per 100 person years of risk, very similar to the mortality rate of a person in naltrexone treatment (during the period of low risk) calculated in this study. >>>

Actually, this is slightly less than the risk of naltrexone-associated death calculated in the study, which is believed to be an underestimate.

And the risk of naltrexone-related death calculated for the “high risk” period (the two weeks immediately following cessation of naltrexone) is more than TWENTY TWO TIMES higher than the risk of death estimated for someone using street heroin who is not in any form of treatment at all.

<<< While maintained in methadone or buprenorphine treatment after the initial induction stages, opioid-dependent people are at lower risk of dying. Clearly, an important aspect of methadone and buprenorphine treatment for opioid dependence is the improvement of treatment retention rates.

The mortality risks associated with oral naltrexone treatment, particularly following treatment cessation, warrant serious attention. This is especially the case considering that the majority of unselected opioid-dependent persons will return to opioid use soon after leaving naltrexone treatment. It is recommended that future trials of all treatments for opioid dependence include monitoring of post-treatment mortality risk >>>

Gibson, A. and Degenhardt, L. (2005) Mortality related to naltrexone in the treatment of opioid dependence: A comparative analysis, Sydney: National Drug and Alcohol Research Centre