Medications and Alcohol Craving

Alcohol Research & Health, Fall, 1999 by Robert M. Swift

Ondansetron. Through its action at the [5HT.sub.3] receptor, serotonin helps regulate the release of dopamine into the nucleus accumbens, thereby affecting the development of reinforcement. Researchers have shown [5HT.sub.3]-receptor antagonists to block dopamine release in animals and also to reduce alcohol consumption in rats Litten et al. 1996). In a placebo-controlled outpatient trial with 71 socially stable, mildly alcoholdependent men treated with the [5HT.sub.3] antagonist ondansetron (Zofran(r)), researchers found that a low dose, but not a high dose (0.25 versus 2.0 mg twice daily), of ondansetron moderately reduced alcohol consumption. A significant difference between treatment effects was observed only after excluding the heaviest drinkers (Sellers et al. 1994). In a human laboratory study, ondansetron reduced subjective measures of the desire to drink alcohol measured by VAS 1 hour after administration of the medication and also reduced some of the pleasurable effects of alcohol consumption (John son et al. 1993).

Acamprosate

The medication acamprosate helps restore the balance of excitatory and inhibitory neurotransmission in the nucleus accumbens (Litten et al. 1996). The drug has been found to reduce alcohol consumption in rats trained to drink alcohol (Litten et al. 1996). In randomized, placebo-controlled clinical trials with human alcoholics, acamprosate significantly increased the proportion of patients who remained continuously abstinent as well as the duration of abstinence. Effects on craving for alcohol, however, have been more variable.

A 12-month multicenter study conducted in France compared the effects of 1.2 and 2 grams of acamprosate daily with that of a placebo (Paille et al. 1995). While the higher acamprosate dose significantly increased the proportion of subjects who remained abstinent at 6 and 12 months, no effect on alcohol craving occurred at these time periods. However, the higher dose of acamprosate reduced craving at 3 months, when the intensity of craving was much higher (Paille et al. 1995).

Additional randomized, double-blind, placebo-controlled clinical studies confirm that acamprosate increases the rare and duration of abstinence in alcoholics who receive concurrent psychosocial therapy, but all studies have been negative with respect to craving, as measured with single-item VAS. In a study using 600 subjects, Lhuintre and colleagues (1990) found more marked reductions in craving among the most severe alcoholics (i.e., those with the highest initial craving scores) but with no difference between the drug and the placebo groups. In a study by Sass and colleagues (1996), abstinence rates improved in treated alcoholics during a 48-week period. However, self-reported craving by VAS showed wide variability over this period and did not correlate with drinking behavior (Sass et al. 1996).

Acamprosate has been approved in several European countries for the treatment of alcohol dependence (see Geerlings et al. 1997) and is currently undergoing clinical testing in the United States (Litten et al. 1996).