16 July 2007

Failure of naltrexone implant reported from Russia.

Dear Colleagues,

Griffith Edwards, long time Addiction editor, once wrote that case reports were of limited value scientifically - and he was right. However, sometimes simple clinical observations can be the start of something big, such as lithium on the positive side (Melbourne) and thalidomide (Sydney) on the negative one.

In this month�s Addiction (July p1164) Krupitsky, Woody and colleagues report on a patient who overcame the artificial blockade from a naltrexone implant, a product which is apparently now registered for use in Russia [1 gram ~ �one month blockade�].

A drug dealer engaged the patient as a courier, knowing that he had had an implant. He assumed that the man could therefore not avail himself of the large quantities of drugs he was to smuggle into a local prison on a regular basis.

After receiving numerous payments in the form of heroin he attempted to �test� the blockade by injecting first 2, then 4, then 8 and then even more �bags� of the illicit heroin. We are told that on the final injection he overdosed and became cyanotic. Having survived, he continued using the by now very large quantities of heroin until it ran out 2 weeks later. Suffering severe withdrawal symptoms, he was then re-admitted for detoxification. It is a mystery that methadone treatment is still illegal in the Russian Federation, yet an unproven formulation of naltrexone is being used by �narcologists�.

Detoxification only rarely results in abstinence for life and it is tragic that relapsing addicts in Russia have little alternative but to return to street opioids.

Doctors who use naltrexone implants in addiction treatment are taking risks both for themselves and their patients. The benefits of naltrexone implants might outweigh their very real dangers, yet no comparative research has yet been published to support their use. Since most return to heroin use at some stage, those recommending naltrexone need to propose strategies to prevent overdoses. After detoxification, there is very low tolerance and thus heightened vulnerability to overdose.

Hulse and Tait, who are usually strong advocates of naltrexone and these days are strong advocates of naltrexone implants, draw attention to another serious problem with naltrexone implants. Because opioids are generally ineffective at normal doses, some patients will die from overdose of combinations of non-opioid drugs (or from spectacularly high doses of opioids as above) (Hulse GK, Tait RJ. Opioid overdose deaths can occur in patients with naltrexone implants. MJA 2007 187;1:54). However, their estimate in the same letter that the mortality of patients on naltrexone implants is only one in 600 patient-years seems a tad optimistic and should not be accepted until replicated by others in well-designed studies. We have to be mindful that naltrexone supporters in Australia and overseas have often �over sold� the benefits while also under-estimating the negatives of naltrexone. Remember 'I woke up cured of heroin addiction' in the Woman's Weekly a decade ago?

Comments by Andrew Byrne ..



Krupitsky EM, Burakov AM, Tsoy MV, Egorova VY, Slavina TY, Grinenko AY, Zvartau EE, Woody GE. Overcoming opioid blockade from depot naltrexone (Prodetoxon�). Addiction 2007 102:1164-5

Hulse GK, Tait RJ. Opioid overdose deaths can occur in patients with naltrexone implants. [response] MJA 2007 187;1:54

Gibson AE, Degenhardt LJ, Hall WD. Opioid overdose deaths can occur in patients with naltrexone implants. MJA 2007 186;3:152-153