17 October 2000

Hulse et al. omit deaths in naltrexone report.

re: Hulse GK, Basso MR. Reassessing naltrexone maintenance as a treatment for illicit heroin users. Drug Alcohol Review 1999 18:263-269

Comment letter published D&A Review 2000 19;3:347

[Note: no reply published from original authors]
Dear Editor,

I support the authors' contention that naltrexone be judged using the same criteria as other treatments to enable fair comparisons of outcomes.

It is self-evident that stricter acceptance criteria will yield lower apparent 'success' rates, but that these will not alter actual patient outcomes. Clinical trials are rarely directly comparable so one of the tasks of clinicians is to determine the significance of each addition to the scientific literature. For dependency treatments this is not difficult since the aims of treatment are relatively straightforward and can be verified by simple means.

Hulse and Basso have reported detailed outcomes of a naltrexone treatment trial using two criteria for reporting six month follow-up details. Despite using tables and text to illuminate these outcomes, they place these results out of clinical context by omitting the two deaths which were previously reported from this cohort [Hulse G. Naltrexone - Defining a framework for use. Australian Professional Society on Alcohol and other Drugs (APSAD) Newsletter 'Summer' 1998, p4].

Mortality is the most fundamental end point in any treatment trial. To ignore, omit or mis-state deaths or other end points makes interpretation of data impossible and is inappropriate in balanced scientific writing.

A comparison of methadone and naltrexone in dependency management should be rigorous and impartial. After twenty years and over 500 peer-reviewed papers demonstrating the benefits of methadone, there has been only very limited research favouring naltrexone treatment in heroin addicts in the same time period. Few if any accredited addiction treatment services use naltrexone as a first line drug although it shows promise in certain selected groups and is effective in alcoholism.

The authors of all scientific research studies should be scrupulous in all reporting, lest they be seen as advocates for particular causes instead of maintaining the detachment which is essential in ethical research.

Yours faithfully,

Andrew Byrne ..

8 August 2000

Another effective anti-craving drug for some alcoholics.

Dear Colleagues, In a most interesting development, researchers in Texas have shown significant improvements in drinking behaviour in some alcoholic patients given modest doses of ondansetron (Zofran). This widely used anti-serotonin, anti-nausea drug was given in a 3 month randomised, double-blind, placebo-controlled trial. Compliance was over 90% as measured by history and urine riboflavin tracer. Side effect profile was low with the only significant problem being constipation in 5% of patients. One death occurred in a patient falling down a flight of stairs, unrelated to the treatment (but possibly related to the condition being treated). Patients reported 'drinks per day', 'drinks per drinking day', 'percentage of days abstinent', and 'total days abstinent'. In older onset alcoholics the results were equivocal (n=160). The younger onset group (<25 years, n=161) are believed to comprise those with a stronger genetic component to their alcoholism and appear to have more psychiatric co-morbidity such as antisocial personality traits. In these patients the reductions in alcohol consumed was substantial and significant [those on 4ug/kg twice daily had a dramatic (p<0.001) response compared to placebo. The 'effect sizes' of the benefit of the twice daily medication were up to 0.41 which was in the 'moderate' range. "Patients with early-onset alcoholism who received ondansetron (1, 4, and 16 µg/kg twice daily) compared with those who were administered placebo, had fewer drinks per day (1.89, 1.56, and 1.87 vs 3.30; P = .03, P = .01, and P = .02, respectively) and drinks per drinking day (4.75, 4.28, and 5.18 vs 6.90; P = .03, P = .004, and P = .03, respectively)."

Self reported drinking frequencies were corroborated using serum carbohydrate deficient transferrin (CDT). Taken along with blood alcohol concentrations at visits, this makes the study very scientifically rigorous.

JAMA also contains an enthusiastic editorial by Dr Henry Kranzler from Connecticut ('Medications for Alcohol Dependence. New Vistas'). He waxes about the significance and importance of these findings in the context of disulfiram, naltrexone and acamprosate treatment. In addition, he mentions that SSRI drugs have a positive effect in the older age onset alcoholics, linking the serotonergic basis for much surrounding cravings, reward pathways and other still ill-understood areas.

This may be a landmark paper. It allows us to match diagnosis with an effective treatment in a way not previously imaginable in alcohol dependency. The findings are consistent with a smaller study (Sellers, Sobell et al. Ontario, 1994) and animal experiments, according to the authors.

These new findings place an even greater burden on the medical profession to be equal to the 'therapeutic challenge'. Society stands to gain enormously if these research findings can be widely implemented. It is a great tragedy and a travesty that naltrexone uptake has been so slow when it is so very effective in alcoholism, doubling the rates of abstinence. Many physicians still seem to take the line that there is 'nothing you can do for an alcoholic' and 'they have to help themselves'. comments by Andrew Byrne ..

Johnson BA, Roache JD, Javors MA, DiClemente CC, Cloninger CR, et al. Ondansetron for Reduction of Drinking Among Biologically Predisposed Alcoholic Patients. A Randomized Controlled Trial. JAMA (2000) 284:963-971


Kranzler H. Medications for Alcohol Dependence. New Vistas. Editorial. JAMA (2000) 284