Flupenthixol decanoate and relapse prevention in alcoholics: Results from a placebo-controlled study

Flupenthixol, with its broad receptor profile, interacts with a variety of dopamine and serotonin binding sites which are important in the neurobiolog y of alcohol dependence. Its pharmacology, together with encouraging result s from both animal studies and clinical trials with cocaine users, led us t o postulate that flupenthixol would significantly prevent relapse in detoxi fied alcohol-dependent individuals. We conducted a prospective, randomized, double-blind, placebo-controlled, multi-centre trial with two parallel gro ups and appropriate statistical evaluation. Subjects met criteria for moder ate to severe alcohol dependence (DSM-III-R), without any concomitant psych iatric disorder. After complete detoxification, 281 women and men received either 10 mg of flupenthixol decanoate or placebo as i.m injection every se cond week for 6 months on an out-patient basis, followed by 6 months of fol low-up. Efficacy was based on absolute abstinence, with relapse being defin ed as consumption of any alcohol after inclusion in the study. In contrast to the hypothesis, flupenthixol did not reduce, but was associated with mor e, relapses. Though well tolerated, relapse rates after 6 months of treatme nt were 85.2% (flupenthixol) versus 65.5% (placebo), a highly significant d ifference from the medication. Flupenthixol was also inferior to placebo wi th regard to other secondary criteria of efficacy (cumulative abstinence du ration, relapse rate after 12 months). These results indicate that a 10 mg dose of flupenthixol decanoate does not have a beneficial effect on abstine nce maintenance in alcohol-dependent individuals.