Addiction Biology March 2004 edition.
Dear Colleagues,
This journal contains a bumper crop of research, practicalities and history lessons. The two lead items are invited reviews which initially seem rather esoteric, being about cellular changes in the bone marrow and brain cells of alcoholics. However, on closer reading, the first authors delineate the evolving evidence of very specific changes in red cells due to alcohol's first metabolite, acetaldehyde. The second item is on genetic alterations in neuronal cells following exposure to alcohol. While neither is even remotely practical presently, both are more than distant 'shots in the dark' at causation of the 'permanent' changes which occur in the alcohol dependent state.
There are three items on naltrexone, none a scientific trial, sorry to say. One is a useful report from London of a hepatitis B/C seroconversion case which seemed to run a benign course in spite of being concurrently on naltrexone, which was continued, albeit under close supervision and observation. It would seem that this report, plus the passage of time should reduce fears of naltrexone-related hepatitis. Such fears are largely based on a small number of cases of high-dose naltrexone-treated bulimia cases with elevated transaminases reported some years ago.
These would now seem to be of less immediate concern to opioid treatment at usual doses of 50mg daily orally. The positive results often reported by naltrexone 'enthusiasts' are not always borne out in independent studies. The group from Perth has largely upbeat things to report about their experience with naltrexone implants and maintenance of 'adequate' serum levels of the drug. But their methodology lacks a prospective scientific protocol. The evolving slow-release subcutaneous pellets appear not to have been standardised nor independently validated prior to their use in this private medical practice. It is also disappointing that the authors do not define their selection criteria for long-term naltrexone implant treatment in opioid dependency cases.
This edition of Addiction Biology also contains abstracts presented at the annual meeting of the (centenarian) Society for the Study of Addiction. They reveal the cornucopia of treatment possibilities under the remnants of the "British system" of controlled drug prescription. This belies the real world of tragically limited interventions available in the field through the National Health System for drug and alcohol dependent patients in England - and long waiting lists to see addiction specialists. Most glaring is the reportedly grossly inadequate doses and lack of supervision given to methadone maintenance patients in most centres and in general practice.
Abstracts report on buprenorphine uptake - which is increasing steadily in England (11% of all maintenance prescriptions in 2002 - up from 5% in 2001) but is still unavailable in some areas, partly due to the high cost. A report on buprenorphine in 11 pregnancies mirrors other small reports of good outcomes with shorter and milder neonatal withdrawals (cf. G. Fischer). Transfer from up to 70mg methadone to buprenorphine was satisfactorily accomplished in 28 hospitalised patients using lofexidine (Glasper, Bearn et al). Benzodiazepine use in opioid maintenance as well as in withdrawals is examined in two papers from London. Oxazepam (Serepax) is tested against diazepam for prevention of seizures in alcohol withdrawal, and found wanting, possibly due to its shorter action. Cannabis use is surveyed in a large number of multiple sclerosis patients, finding widespread use for symptom relief (one in five) and only minor side effects. A retrospective analysis of ADD diagnoses in addiction cases showed a high prevalence, suggesting the need for further evaluation of this factor in research into the aetiology of addiction. Dextromoramide (Palfium) is sometimes used for opioid maintenance when other drugs are unsuitable (Holland, Australia, UK). The need for an equivalence table is broached by Strang and colleagues, also pointing out the difficulties in such attempts. Using 13 cases (mean dose 233mg, range 40-800mg daily) who were forced to transfer due to the drug becoming unavailable for commercial reasons, Strang and colleagues found a ratio of 1:1.35 equivalence to 24 hour morphine. They also describe a single case taking 1800mg dextromoramide daily plus large amounts of temazepam. The patient transferred in hospital and stabilized on 900mg methadone daily, a very large dose by any means, being over ten times the mean daily dose in New South Wales and about 25 times the mean dose reportedly used in the UK! Yet even higher doses of methadone (up to 1200mg) have been reported. If one takes methadone to morphine (24 hour total) equivalence as 1:4, then this equates to a dextromoramide to morphine ratio of 1:2 by my reckoning.
Such large opioid doses were first described by Thomas de Quincey in his book Confessions of an English Opium-Eater (32 grains daily, as laudanum) (My review available here).
