Dear John

The two studies published last fall, Tanum et al and Lee et al, were the first, and so far, the only studies that have compared extended-released naltrexone to buprenorphine-naloxone. The first was a 3-month study, and the second a 6-month study.

regards

Kristin

Depot naltrexone (DNTX) - injected or implanted - should not be thought of as superior (or inferior) to buprenorphine, methadone or other opiate maintenance but different, and it attracts two different broad classes of opiate addict/abuser/user (pick your term). Comparing the two treatments is a bit like comparing barrier contraception with hormonal or intrauterine contraception - their comparative effectiveness is important to family planners but much less important to people who just don't like the idea or the effects of taking pills or having bits of plastic wandering around their wombs.

DNTX should be considered as a possible first choice for young patients who have only a short history of opiate abuse and as a later possibility for patients who have done well on agonist maintenance and now want to liberate themselves from its bureaucratic restrictions and from their existential annoyance at being in thrall to opiates. Especially if opiates are their only - or main - drug problem. By the time they reach 30, there are many patients in this category.

DNTX is not attractive to people who still feel and function below par despite having been opiate-free for several months. Some of them know this from past experience; others discover it only after a few months on DNTX. They will probably function better on agonist maintenance, though they may try DNTX again if they feel a bit stronger, or can take more time off work. Good symptom relief during this difficult transition period is essential if patients are to have the best chance of staying on DNTX for long enough to learn new cognitive and behavioral habits and to make those habits so automatic that they will persist even after DNTX is discontinued. As with disulfiram in alcoholism, that process often needs around 18 months. Insomnia is common in the first month or two, very demoralising and a common cause of relapse and discontinuation of DNTX. Chemical sleep is usually better than no sleep.

However, many suitable patients will never experience the potential benefits of DNTX because with conventional detox/withdrawal programmes, rates of completion and transfer to DNTX are very poor. Rates of 50-60% on an intention-to-treat basis count as high. Our own National Addiction Centre in London reported a 27% completion rate. A month later, about a third of those had relapsed and 10% died in the following year from opiate-related causes, though DTNX was not easily available at that time.

Using antagonist-precipitated withdrawal with even modest levels of sedation and good non-sedative symptom control (clonidine, octreotide, ondansetron etc) gives completion and DNTX transfer rates of 100% with no mortality or, at worst, less mortality than surgery for food addiction or aesthetic vanity. Full anaesthesia is a luxury (and very safe in experienced hands, as cohorts of up to several thousand have shown) but not essential. The Asturian Technique, originally developed in Northern Spain, is a domiciliary 24-hr oral antagonist-precipitated withdrawal and oral NTX induction procedure, requiring no medical or nursing involvement, that costs the equivalent of only a few hundred dollars and permits almost 100% transfer to DNTX the next day.

Increasing DNTX uptake will not solve the appalling opiate overdose crisis in the US but could make a modest dent in the statistics. It will only do this if addicts are offered a stepped-care approach to withdrawal, so that those who are cursed - genetically and/or psychologically - with withdrawal symptoms at the severe end of the spectrum have the same chance of starting DNTX as the fortunate majority whose symptoms are less severe and dissipate more quickly. Enough of the 'no pain, no gain' Puritanical nonsense.

Within a year or two, with luck, some American opiate addicts may be able to benefit from the NTX implants developed in Australia and used there for over 15 years. They can provide complete opiate blockade for around 6 months and high protection against lethal respiratory depression for a further 3 months or more. NTX is an old and extremely non-toxic drug, safe even in patients with life-threatening liver disease. Promising new extended-release formulations of it deserve a fast track, as well as the sort of multi-centre academic studies that the the USA does so well (though the Norwegians have shown the way with much smaller resources).

Hi Colin.

Interesting viewpoint! I would like to read the article about the London study you are referring to. Was that oral NTX or some kind of depot formula (you indicated that DNTX was not easily available at the time, so I guess it's some time ago)? 27% completion rate seems discouraging. An on-going naturalistic Norwegian DNTX study hope to find better completion rate than that. They're using the one-month lasting intramuscular injection NTX (Vivitrol). In our welfare oriented system, we have the means to do the needed tapering of opioids in a safe environment (detox), though it may be more expensive as the full anaesthesia technique in the long run. Is that technique still in use somewhere?

We had a promising earlier RCT with the 6 month lasting NTX implants, but the provision of those discontinued, disappointingly.

Article Naltrexone implants after in-patient treatment for opioid de...

Best

John-Kåre

Dear John-Kåre. The London study is:

Strang J, McCambridge J, Best D, Beswick T, Bearn J, Rees S, Gossop M. 2003. Loss of tolerance and overdose mortality after inpatient opiate detoxification: follow up study. BMJ; 326, 959-60.

I would be interested in the medication and outcome of your Norwegian programme.

Thanks! The new study is undertaken by approx the same team as described in the article above (Tanum et al) and our hospital also joined in (Sørlandet Hospital / Southern Hospital Trust). The team just started recruiting. I'm sure they will update when they have some results, I can send you a note.

Best

John-KÅre