Gender-related differences in pharmacological relapse prevention with flupenthixol decanoate in detoxified alcoholics

A study recently finished by our research group elucidated the effectiveness of flupenthixol decanoate (FLX) in maintaining abstinence in detoxified alcoholics. Flupenthixol decanoate is an established antipsychotic drug, which is well known for its mild antidepressant and anxiolytic activity as well as for its minimal sedation at low doses. It blocks dopamine binding at a number of receptor subtypes, primarily at D-1, D-2, D-3 and with less affinity at D4-receptors. It also affects serotonin binding at 5-HT2A and 5-HT2C receptors. In a double-blind placebo-controlled multicenter trial, 77 women and 204 men suffering from moderate or severe DSM-II-R alcohol dependence were randomly assigned to either 10 mg FLX or placebo both injected every second week over a period of 24 weeks (treatment phase) succeeded by a medication-free 24-weeks follow-up period. In the overall analysis the number of patients relapsed after 24 weeks of treatment (=main criterion of efficacy) was significantly higher in the FLX treated group (85.2%) than under placebo (65.5%). However, when differentiating this result according to sex the analysis revealed a gender-related discrepancy: while male patients had an almost 4-fold higher risk to relapse under FLX than under placebo (OR=3.95) this risk was barely elevated for female patients (OR=1.51). A significantly negative outcome due to FLX treatment was restricted to male alcoholics solely. In conclusion, gender-related differences to pharmacological relapse prevention with FLX have probably contributed to a better treatment outcome in women than in men.