Disulfiram: An Anticraving Substance?
Publication: American Journal of Psychiatry
To the Editor: We read with interest the Treatment in Psychiatry article by Bankole A. Johnson, D.Sc., M.D. (1), published in the June 2010 issue of the Journal. Hereby, we would like to briefly comment on the author's statements regarding disulfiram.
Disulfiram has been used for more than 50 years as an aversion therapeutic agent in the treatment of alcohol dependence (2). However, categorizing disulfiram as a “psychological pill” does not encompass the whole potential of the substance, since emerging evidence suggests that it also possesses anticraving properties (3). Besides its well-known mechanism of action (i.e., aldehyde dehydrogenase inhibition), disulfiram also inhibits dopamine beta-hydroxylase, leading to an increase of dopamine concentrations while decreasing concentrations of norepinephrine in the brain (4). Since dopaminergic transmission in the ventral striatal reward system is suggested to play a key role in the development of addictive disorders and craving (5, 6) and reduced activation of this system has been shown in alcohol dependence (7), cocaine dependence (8), and non-substance-related addictions such as pathological gambling (9), disulfiram could be hypothesized as a common treatment option for these disorders. In cocaine dependence, disulfiram has already shown preliminary efficacy in reducing craving and relapse rates (10). Furthermore, in a patient with alcohol dependence and comorbid pathological gambling, treatment with disulfiram led to a significant reduction in alcohol craving and urges to gamble as well as to maintenance of abstinence from both alcohol and gambling for more than 12 months (11). In alcohol dependence, most of the clinical trials conducted with disulfiram have possessed significant methodological shortcomings and have not measured changes in alcohol craving under treatment (2). Therefore, to evaluate the potential of disulfiram as an anticraving agent also in alcohol dependence, further randomized controlled trials would be needed.
Footnote
accepted for publication in October 2010.
References
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Barth KS, Malcolm RJ: Disulfiram: an old therapeutic with new applications. CNS Neurol Disord Drug Targets 2010; 9:5–12
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Frascella J, Potenza MN, Brown LL, Childress AR: Shared brain vulnerabilities open the way for nonsubstance addictions: Carving addiction at a new joint? Ann N Y Acad Sci 2010; 1187:294–315
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Asensio S, Romero MJ, Palau C, Sanchez A, Senabre I, Morales JL, Carcelen R, Romero FJ: Altered neural response of the appetitive emotional system in cocaine addiction: an fMRI study. Addict Biol 2010; 15:504–516
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Reuter J, Raedler T, Rose M, Hand I, Glascher J, Buchel C: Pathological gambling is linked to reduced activation of the mesolimbic reward system. Nat Neurosci 2005; 8:147–148
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Pani PP, Trogu E, Vacca R, Amato L, Vecchi S, Davoli M: Disulfiram for the treatment of cocaine dependence. Cochrane Database Syst Rev 2010:CD007024
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Mutschler J, Buhler M, Grosshans M, Diehl A, Mann K, Kiefer F: Disulfiram, an option for the treatment of pathological gambling?. Alcohol Alcohol 2010; 45:214–216
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Accepted: October 2010
Published online: 1 January 2011
Published in print: January 2011
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The authors report no financial relationships with commercial interests.
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