Buprenorphine versus methadone maintenance therapy: a randomized double-blind trial with 405 opioid-dependent patients. Mattick RP, Ali R, White JM, O'Brien S, Wolk S, Danz C. Addiction 2003 98:441-452
Dear Colleagues,
This vital multicentre trial comparing 3 months maintenance treatment gives us invaluable information on the use of buprenorphine for heroin addicts. Unlike some other fixed dose studies, the patients in both groups here were treated in a clinical, 'naturalistic' manner with flexible doses supervised with true 'blinding' of medications (each started with active/dummy). Inductions and dosing practices were in broad accordance with established guidelines, such as those from the UK (Strang, 1999) and the various Australian clinical guidelines. In the second month of treatment daily doses of up to 150mg of methadone and 32mg of buprenorphine were used (means 57mg and 11mg respectively). Dose increases were in response to patient reports of cravings, illicit drug use and doses just 'not holding' them.
If the overall numbers randomized to each treatment are considered (205 and 200), the retention rates at 13 weeks can be calculated at 58.5% for methadone and 48% for buprenorphine. My amateur statistical estimation sees this as reaching significance. However, in their own calculations, these authors exclude the patients who did not receive an initial dose (significantly, 3 for methadone and 8 for buprenorphine, a drug with more clinical limitations on starting) making their retention rates 59.4% and 50.0% (p=0.06). While this may seem picky, the authors also spend some effort looking at this significance. Regarding (1) the mean length of stay, 59 vs. 67 days and (2) evidently by applying a survival analysis across the 13 weeks there was a significant difference between the groups (but not at 6 weeks). The authors speculate about a possible 'type I error' since there were some parallel questions with possible 'overlapping' factors.
The overall findings are that this study again confirms that in the normal clinical context buprenorphine is almost as good as methadone at retaining opioid-dependent patients in treatment. It also showed equal benefits regarding reduced illicit heroin use and equal side effect profile for those remaining in treatment. This profile is much more extensive that my own experience: up to two dozen significant side effects suffered by patients in both groups (eg. nausea 16-17%; vomiting 8%; 'flu symptoms 7-10%; headache 11-13%). In my own practice I have seen virtually no side effects with buprenorphine and only sweating, constipation and some sexual dysfunction as prominent problems in some methadone patients. I understand that these researchers spared no effort in regularly canvassing for reports of side effects, some of which just might have been from withdrawals or other causes, hence a possibility of over-reporting compared to other research.
The question seemingly posed originally by these researchers, "is buprenorphine better than methadone" is no longer a useful question to my mind. We now known from years of research that buprenorphine works well as an outpatient treatment for opioid addiction, in many ways comparable with methadone prescription. Now we need to implement the treatment in a logical fashion for those who may benefit from it. The drug is much more expensive than methadone. It has limited long term safety data, although that which exists is reassuring. Buprenorphine is not proven safe in pregnancy although there too, early studies indicate no problem in many pregnancies studied while the drug was continued.
Hence, like the second antibiotic introduced after penicillin, buprenorphine should be used initially for those unable or unwilling to take methadone. It may be that it will become a first line drug at some stage but in my book it is currently an excellent alternative in cases where there are problems with methadone. My own practice has 15% of our maintenance patients taking buprenorphine. The state of NSW has 1,600 out of 16,000 on the newer drug 2 years after its introduction under the same general conditions as for methadone maintenance (but fewer take-home provisions).
Comments by Andrew Byrne ..
