Ritanserin, a central 5-HT2 antagonist, in heavy social drinkers: desire to drink, alcohol intake and related effects

Ritanserin, a 5-HT2 receptor antagonist, decreased alcohol intake in some, but not all, animal studies and in an open clinical study. We tested the short-term effects of ritanserin in 39 (35 male, four female) heavy social drinkers (consuming at least 28 drinks/week), aged 19-63 years, who were not seeking treatment. After an intake assessment, they received placebo for 7 days in a single-blind baseline. They were then randomly assigned to one of three double-blind treatments for 14 days: ritanserin 5 mg/day (n = 12), ritanserin 10 mg/day (n = 13) or placebo (n = 14). Subjects recorded daily outpatient alcohol intake. Feelings of intoxication and interest, desire, craving and liking for alcohol were rated retrospectively at each weekly study visit. Experimental drinking sessions were conducted after baseline (EDS1) and treatment (EDS2); in each session subjects were offered 18 mini-drinks (total = six standard) and rated their desire to drink, intoxication and mood (POMS). Outpatient results: ritanserin 5 mg/day decreased desire and craving for alcohol (vs. baseline, p < 0.05) but not alcohol intake. Liking of alcohol decreased from baseline with ritanserin 10 mg/day (p = 0.01) and placebo (p = 0.05). Changes in alcohol intake from baseline with ritanserin 10 mg/day (increase, p > 0.05) and placebo (decrease, p > 0.05) were different (p < 0.05). EDS results: in EDS2, desire ratings for the first three mini-drinks were lower after ritanserin 5 mg/day than after ritanserin 10 mg/day (p < 0.05), but the decreases were not statistically significant when EDS1 desire ratings were controlled for. Ritanserin 10 mg/day increased alcohol-induced feelings of intoxication and friendliness, compared with placebo (p < 0.05). Both ritanserin 5 mg/day and 10 mg/day enhanced alcohol-induced decreases in fatigue, compared with placebo (p < 0.05). These results indicate that ritanserin may have differential effects on alcohol intake, desire, craving and liking, intoxication and some of alcohol's effects on mood. However, they suggest that ritanserin has limited efficacy in reducing alcohol intake in heavy drinkers.