11 November 2003

Some opiate antagonist therapy 'escaped the usual process of therapeutic controls'.

Streel E, Verbanck P. Ultra-rapid opiate detoxification: from clinical application to basic science. Addiction Biology (2003) 8:141-146

Dear Colleagues,

This ‘Invited Review’ from Brussels describes the rise of opiate antagonist therapy over the past 20 years, much of which has ‘escaped the usual process of therapeutic controls’. We are told that most new treatments should start with animal studies - yet with antagonists the reverse has happened. These two Belgian authors quote some of their own recent work on addicted rats given anaesthetics and antagonists to quell the symptoms and signs of opiate withdrawal. Objective findings are hard enough to find (ever tried to detect pin-point pupils in a rat?) - but subjective withdrawal effects are necessarily even more elusive (where is the Pied Piper when you need him?). The authors quote a number of studies showing contradictory effects on withdrawals from anaesthetics, sedatives and antagonists. Some even concluded that animal modelling, at least with rats, was not applicable for rapid opiate detoxification (‘ROD‘).

The article contains two major misconceptions, starting with the first line that rapid detoxification ‘has become increasingly popular in both private and public addiction centres’ (no reference). The treatment has never been ‘popular’ in public treatment agencies I am aware of, nor is its use necessarily still increasing in the for-profit sector. Secondly, the authors seem to have been persuaded that naltrexone maintenance therapy leads to long-term abstinence in a substantial proportion of those who are prescribed it. The evidence I have read is otherwise, with reported compliance as low as 10% at 6 to 12 months. Promising outcomes were reported in only three of the many well conducted trials - and two of these three utilised enforced supervision in the prison or probation system (Chan 1996; Cornish 1997). The encouraging outcomes of Gerra (1995) were never replicated by other researchers. Excess deaths and self harm were reported in one trial (Miotto 1997). Australian studies have been equally disappointing (Foy 1998) although mortality was not specifically sought from official sources so final outcomes remain uncertain for those who were lost to the authors’ follow up.

Like certain other authors on the subject, Streel and Verbanck state that the process is probably best conceptualised as ‘rapid antagonist induction’ and not ‘rapid detoxification’. This almost sounds like a ‘mantra’ from some. In fact, the process is both of these, and the problem is not conceptualisation, but whether the overall treatment is actually both ‘safe and effective’ for addicted patients who receive it.

It is to the credit of Addiction Biology that, like Lancet, it is prepared to publish items at the ‘edge’ of medical practice, some of which would be rejected by more ‘purist‘ journals. Rapid detoxification under anaesthetic/sedation and naltrexone implants are still not evidence-based modalities and some of these reports may not fit all aspects of the ‘Farmington consensus’ introduced by NAC sister journal, Addiction.

The list of 43 references in this invited review is a who’s who of the field, including Loimer, Brewer, Resnick, Kleber, Strang, Seoane, Legarda, Currie, O’Neil and Hulse. The article emphasises the need to do animal studies and ‘basic science’ prior to introducing treatments into clinical practice. The authors thus regret the situation where the use of naltrexone implants and long acting depot preparations are not always first used in appropriate laboratory experiments. The article makes persuasive reading.

Comments by Andrew Byrne ..