6 May 2007

Research on buprenorphine and naltrexone now 30 years old.

Dear Colleagues,

The latest Swedish and American reports (Kakko 2007; Brigham 2007) mark 30 years since the first papers on buprenorphine for addiction treatment. With naltrexone also just 30 years old, it is instructive to draw a birthday parallel between these two opioid derivatives which have such very different characteristics. Each was proposed for addicion treatment in the 1970s when methadone was just becoming established as a useful modality for certain addicts at certain times in their lives (Resnick 1977; Jasinski 1978). Early work with buprenorphine showed favourable results while naltrexone trials had limited results involving poor compliance and high relapse rates (Tucker 2000). Randomised placebo controlled trials of naltrexone for relapse prevention showed no effect (San 1991, Lerner 1992).

The research on buprenorphine has become ever more focused on improvements to the original successful work. Several RCT’s, second daily dosing, higher doses, flexible dose, combination with naloxone, blood level measurement, community use with less supervision and other innovations have been tried and tested. These outcomes have taught us more about its successful use in clinical practice and the treatment of drug addiction has been improved dramatically as a result.

On the other hand, good research with naltrexone is quite limited. Both relapse prevention and rapid detoxification seemed to be associated with overdoses, suicides and other negative consequences (see Miotto 1997). Rather than giving up, staunch naltrexone enthusiasts continue to this day trying it in new and customised methods, mostly with small numbers and using protocols so varied that fair comparison is not possible (see Camarasa 2007 n=10). With poor results from oral naltrexone, some proponents have taken to using ‘home-made’ and largely untested implants. They are bound and compounded in a variety of ways which are meant to cause slow release from under the skin incision made for their insertion under anaesthetic. The largest implant currently is reportedly being used by the Chinese and is 7 grams (= 7000mg).

This constitutes an uncontrolled community trial and reports are conflicting and hard to interpret. Some units report “no deaths” publicly while acknowledging in meetings that dozens have occurred in patients who have been treated with naltrexone, but saying that ‘naltrexone did not cause any deaths’ (sic). The first reports of detoxification under sedation (using bromides) were reported in the British Medical Journal over 100 years ago (and deaths were reported then as well).

We should continue trying to match appropriately assessed patients with optimal treatment. It would seem that for many patients a brief history will reveal what works for that individual and what does not. For new patients needing opioid maintenance we should still consider methadone the drug of choice. Kakko reported an 80% success rate against half that for buprenorphine. Oral naltrexone should probably not be used for relapse prevention due to a lack of evidence. Implants are still experimental. Many regular addiction workers have met addicts who have dropped out after naltrexone implant treatment. Most of the 50 or so that I have met state that they would not have had the treatment if they had known all the facts at the time. Many have paid very large sums of their own money for these unapproved treatments (not FDA, TGA, PBS or manufacturer approved as rapid detox or implants). The first RCT on naltrexone implants will be eagerly awaited by the field. The same scrutiny and safeguard are necessary for naltrexone as for any other drug doctors prescribe.

Comments by Andrew Byrne .. (references below) http://www.redfernclinic.com/


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Brigham GS, Amass L, Winhusen T, Harrer JM, Pelt A. Using buprenorphine short-term taper to facilitate early treatment engagement. Journal of Substance Abuse Treatment 2007 32;4:349-356

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