5 May 2013

Reply to Luty - BMJ letter - Maintenance not rocket science.

This letter was published in response to Luty's interesting item about the UK decision to ban methadone maintenance and insist that all treatment be abstinence directed (!). http://www.bmj.com/content/346/bmj.f1481

Dear Editor,
Luty is unduly pessimistic about long term abstinence after opioid maintenance treatment.1 About 4% of addicted people become abstinent each year, regardless of treatment.2 By 10 years, over a third are abstinent. The remainder are mostly on maintenance treatment, a small, efficient part of any health system, which often needs little more than an experienced GP and pharmacist. This saves lives and reduces many negative aspects of addiction.3

Those denied appropriate treatment have death rates up to seven times higher than those treated.4 This is especially important on prison release, where access to treatment should be the dual responsibility of the health and custodial systems.

Politically inspired rule changes by the NHS cannot alter what is sound medical practice. Opioid pharmacotherapy is fundamentally no different from treating other chronic conditions but is better researched than most. New and unstable patients need frequent reviews, whereas others can be seen less often to check dose levels, progress, ancillary services, and so on.

Another disadvantage in the UK is that buprenorphine, the only evidence based alternative to methadone, is sometimes not available because of its high cost.

Opioid maintenance is not rocket science, yet for decades the UK had the twin problems of inadequate dose levels and almost non-existent formal dose supervision.5 These factors so limited success that many now doubt the benefits of the treatment as used in the UK. Current and past leaders in the dependency field must take responsibility for those deficiencies, which are currently causing politicians to dismantle an essential intervention implemented in most Western countries, and now even in China.


1 May 2013

‘Something old and something new’: naloxone studies.

Effects of sublingually given naloxone in opioid-dependent human volunteers. Preston KL, Bigelow GE, Liebson IE. Drug Alcohol Dependence 1990 25:27-34

Dear Colleagues,

This old publication was sent to me after some discussions about the use of naloxone in combination with other opioids as an attempt to prevent or deter injecting. My own feeling has always been that the evidence favouring this attractive theory was weak and that its continued abuse in practice was predictable. I still recommend pure buprenorphine (Subutex) as a result.

In this small but well constructed study sublingual (SL) naloxone was found to precipitate a withdrawal reaction in two of six heroin users and in all three methadone subjects who were given graduated doses of naloxone (2-8mg) sublingually. The authors concluded that ‘naloxone doses up to 1–2mg can be administered sublingually to opioid abusers/addicts without precipitating withdrawal’. The conventional wisdom from many quarters is that naloxone is not absorbed sublingually in clinically significant amounts. This study, by prominent authors, showed quite the reverse over 20 years ago.

A new study from Finland (2013* see below) looks at urine levels of naloxone and buprenorphine to check compliance, showing that the concept of adding naloxone is still being worked on. The study of 40 subjects in three groups, new entrants, stable and ‘unstable’, suggests that measuring drug ratios on urine may help to check compliance. Those who were ‘unstable’ had slightly higher naloxone levels. Yet the most logical thing to do with unstable buprenorphine patients would be to consider methadone. This study also seems to confirm that most patients were using buprenorphine before they came into treatment and, like New Zealand 20 years earlier, pharmaceutical buprenorphine was the most popular illicit injected opioid in Finland.

Regarding the combination product with naloxone, even the most basic comparison test of therapeutic equivalence has still not been performed to my best knowledge. Thus evidence needed for its general use is still deficient in my view. In fact some observational and anecdotal reports indicate those changed to the combination drug needed significantly higher buprenorphine doses (over 50% in Bell’s Sydney pilot study#). Others reported that the need for such increases was short lived (other refs on request). These results need clarification and the work would be relatively simple.

Higher doses of buprenorphine mean (1) higher doses of naloxone, (2) higher costs for the health system and (3) bigger profits for manufacturers. Despite the great success of the marketing of the combination drug in some countries, abuse reports are now commonplace and history is repeating itself. A pure drug will always be more desirable to the dependent person. A combination or mixture with anything else, eg. water, juice, chalk, vitamin D, paracetamol or butterscotch, will probably reduce its abuse potential - but may also have other adverse effects. Whether naloxone has any specific benefits to outweigh its costs and potential side effects is still unknown. It is no surprise that neither the manufacturers nor the authorities in most countries endorse the use of the combination drug in pregnancy nor in initiating treatment - despite this advice being widely ignored in both Australia and America.

There is still no doubt that buprenorphine is an excellent opioid maintenance drug for patients unwilling or unable to take methadone, and also in whom methadone is unavailable or unsatisfactory for other reasons. The introduction of a second option has made our professional lives much easier, allowing a choice for some long-suffering patients where previously there was none (apart from detox, which is still always a choice for dependent patients).

* Urine naloxone concentration at different phases of buprenorphine maintenance treatment. Heikman P, Häkkinen M, Gergov M, Ojanperä I. Drug Test Anal. 2013 Mar 19. doi: 10.1002/dta.1464

# Bell J, Byron G, Gibson A, Morris A. A pilot study of buprenorphine-naloxone combination tablet (Suboxone®) in treatment of opioid dependence. Drug Alcohol Rev 2004 23;3:311-318

Notes by Andrew Byrne ..

Medical blog: http://methadone-research.blogspot.com.au/

Full comments on the Preston study: http://methadone-research.blogspot.com.au/2013/04/old-study-on-withdrawals-induced-by.html