4 April 2003

Lancet article - strong science but serious ethical issues.

1-year retention and social function after buprenorphine-associated relapse prevention treatment for heroin dependence in Sweden: a randomised, placebo-controlled trial. Kakko J, Svanborg KD, Kreek MJ, Heilig M. (2003) Lancet 361:662-668

Dear Colleagues,

The Swedes have produced some of the most quoted data showing the life saving properties of methadone maintenance, partly because this treatment is so severely restricted in Sweden. Thus trial candidates who are randomized not to receive prescription treatment, or who are discharged from treatment, rarely receive agonist maintenance therapy which might be available in the normal course of medical practice in other ‘normal’ countries.

From work performed in the 1980s, Grönbladh and colleagues showed a very high mortality in those rejected from methadone treatment - almost 8% per year. In an even more rigorous and controlled study using sublingual buprenorphine, Kakko et al. have found what the accompanying Lancet editorial calls: "massive 20% mortality at one year in the placebo group versus 0% in the buprenorphine group [which] is immensely concerning". Indeed, a trial using placebo in heroin addiction treatment would be considered unethical in Australia.

This trial provides strong support for buprenorphine maintenance since at a fixed dose of 16mg daily it had a 12 month retention rate of 75% and no deaths, compared with placebo: 0% retention at 2 months and four out of twenty being dead from overdose by 12 months. All 'placebo' (actually '6 day reduction') cases had access to intensive levels of psychosocial supports, some of which were reported to have induced paradoxical cravings. I understand that one of the 5 buprenorphine drop-outs has also since died.

The mortality rate is even more worrying considering that these candidates were chosen from over 400 applicants based on less severe dependency and less poly drug/alcohol use. Thus none of the chosen candidates was suitable for the stringent Swedish criteria for methadone prescription (4 years hospital-documented multiple daily heroin use). All but one were injectors.
All of the placebo patients showed positive urine tests for opiates before dropping out of treatment. Thus none was an early abstinence success - despite this being the consented aim of the trial. About 75% of urine tests of the buprenorphine patients were negative for illicit substances tested for. Thus despite continued if less frequent drug use was still associated with good retention and reduced health problems measured in a variety of ways by these researchers.

Swedish drug policy is based on the belief that all drug addicts can and should stop using certain proscribed drugs immediately (abstinence orientated, or 'zero tolerance'). While this has been long abandoned in most other countries, Sweden continues despite their own research showing excess deaths, continued drug use and high rates of viral disease transmission when such policies are pursued. One fails to understand how in such a modern democracy such ill-founded policies are used.

Yet the world's two most persuasive studies are from their own country showing that if heroin addicts are left untreated (or "treated" in the compulsory manner used in Sweden) then the result is a high mortality of young Swedes from a totally preventable and treatable cause, drug overdose.

For related editorial commentary: Law FD, Nutt DJ. Maintenance buprenorphine for opioid users. Editorial. Lancet (2003) 361:634-5

comments by Andrew Byrne ..