REPLY

Helmut Niederhofer

Christian Doppler Klinik, 5020 Salzburg, Austria

(Received 11 April 2003; accepted 11 April 2003)

It was the purpose of our double-blind, placebo-controlled study to verify the efficacy of cyanamide in the treatment of adolescent alcohol abusers (Niederhofer et al., 2003Go). Cyanamide is registered for the treatment of alcohol misusers; we therefore thought it would be appropriate to ascertain its efficacy, and in particular its safety, in adolescents. Disulfiram has been reported to be effective in treating this type of patient, as suggested by Brewer (2003)Go, whereas Fuller and Roth (1979)Go found disulfiram to be of limited value only. Besson et al. (1998)Go pointed out that disulfiram may improve abstinence rates from 43 to 73% when combined with anti-craving medication (acamprosate). Severe side-effects, such as disulfiram hepatitis, were observed (Wright et al., 1988Go) in patients taking it as a deterrent medication. As far as we know, there are no systematic studies reporting the rates of adverse side-effects of these drugs, in particular disulfiram hepatitis, cyanamide-induced pancytopenia (for adults see e.g. Yerro et al., 2000Go) or histological changes of the liver in adolescents (for adults see e.g. Yokoyama et al., 1995Go). Moreover, the rate of pre-existing liver damage, related also to the duration of alcohol dependency, seems to be lower in adolescents than in adults. Finally, in the UK, alcoholism is more often combined with the intake of other illegal drugs than it is in other European countries. For this reason, the risk of liver damage seems to be of little importance in our population, and thus we decided to check cyanamide for its efficacy.

Feuerlein (1986)Go reported a higher relapse rate in adolescents than occurs in adults. This may lead to a higher probability that adolescents might continue or restart drinking while taking disulfiram or cyanamide. For this reason, we think that the use of substances such as disulfiram, which may cause severe adverse effects such as hepatitis, especially if combined with alcohol intake (Fraser, 1997Go), should be avoided. Cyanamide is reported to have fewer severe side-effects when combined with alcohol intake (Aragon et al., 1993Go), although its administration is not convenient as it has to be given three times daily, whereas disulfiram needs to be given only once a day.

Because there is a possibility of potential liver damage due to cyanamide in adolescents, the participants of our study were followed-up closely. This may have led to the significance of our results. Other studies, however, reported the superiority of deterrent medications to drugs such as naltrexone or acamprosate (Carroll et al., 1993Go) and because of this we did not compare cyanamide with these substances. We merely studied a drug which is more effective than naltrexone or acamprosate, for example, and also safer than disulfiram when combined with alcohol.

REFERENCES

Aragon, C. M., Spivak, K., Smith, B. R. and Amit, Z. (1993) Cyanamide and ethanol intake: how does it really work? Alcohol and Alcoholism 28, 413–421.[Abstract]

Besson, J., Aeby, F., Kasas, A., Lehert, P. and Potgieter, A. (1998) Combined efficacy of acamprosate and disulfiram in the treatment of alcoholism: a controlled study. Alcoholism: Clinical and Experimental Research 22, 573–579.[ISI][Medline]

Brewer, C. (2003) Cyanamide or Disulfiram in the treatment of adolescent alcohol misusers? Alcohol and Alcoholism 38, 442.[Free Full Text]

Carroll, K. M., Ziedonis, D. and O’Malley, R. (1993) Pharmacologic interventions for abusers of alcohol and not cocaine: a pilot study of disulfiram versus naltrexone. American Journal of Addiction 22, 77–79.

Feuerlein, W. (1986) Epidemiologie. In: Alkoholismus — Mißbrauch und Abhängigkeit. Thieme–Verlag, Stuttgart, pp. 15–16.

Fraser, A. G. (1997) Pharmacokinetic interactions between alcohol and other drugs. Clinical Pharmacokinetics 33, 79–90.[ISI][Medline]

Fuller, R. K. and Roth, H. P. (1979) Disulfiram for the treatment of alcoholism. Annals of Internal Medicine 90, 901–904.[ISI][Medline]

Niederhofer, H., Staffen, W. and Mair, A. (2003) Comparison of cyanamide and placebo in the treatment of alcohol dependence of adolescents. Alcohol and Alcoholism 38, 50–53.[Abstract/Free Full Text]

Wright, C., Vafir, J. A. and Lake, C. (1988) Disulfiram-induced fulminating hepatitis: guidelines for liver-panel monitoring. Journal of Clinical Psychiatry 49, 430–434.[ISI][Medline]

Yerro, C. P., Lopez, C. P., Bernardino, A. R., Martinez, R. M., delPorto-Gomez, E. and Carmona, A. A. (2000) Relapsing pancytopenia following exposure and re-exposure to cyanamide. European Journal of Haematology 65, 414–415.[CrossRef][ISI][Medline]

Yokoyama, A., Sato, S., Maruyama, K., Nakano, M., Takahashi, H., Okoyoma, K., Takagi, S., Takagi, T., Yokoyama, T. and Hayashida, M. (1995) Cyanamide-associated alcoholic liver disease: a sequential histological evaluation. Alcoholism: Clinical and Experimental Research 19, 1307–1311.[ISI][Medline]