A recent double-blind, parallel group, placebo-controlled Phase 2 clinical trial aimed to evaluate the efficacy and safety of a combination treatment involving prazosin (an a1b blocker) and cyproheptadine (a 5HT2A blocker) in reducing alcohol consumption among individuals with severe Alcohol Use Disorder (AUD). The study, conducted in 32 addiction treatment centers in France, enrolled 154 participants who met DSM-5 criteria for severe AUD with a high-risk drinking level, defined as >60 g/d for men and >40 g/d for women. Participants were randomly assigned to one of three groups: a low-dose group (LDG) receiving 8 mg cyproheptadine and 5 mg prazosin extended-release (ER) daily, a high-dose group (HDG) receiving 12 mg cyproheptadine and 10 mg prazosin ER daily, or a placebo group (PG) receiving placebo of cyproheptadine and prazosin ER. The primary outcome measured was the change in total alcohol consumption (TAC) from baseline to month 3.

Researchers found a significant reduction in TAC in both the HD and LD treatment groups (Figure). Specifically, the HDG showed a clinically relevant reduction of alcohol consumption of 23.6 g/d (P = 0.016) and the LDG showed a reduction of 18.4 g/d (P = 0.048). Subgroup analysis of participants with very high-risk drinking levels (> 100 g/d for men, > 60 g/d for women) also showed significant reductions in TAC in the HDG compared to the PG (-29.8 g/d, P = 0.031). Importantly, both treatment groups demonstrated a favorable safety profile with both low and high combinatorial doses being well-tolerated. Overall, these results suggest that a combinatorial treatment of prazosin and cyproheptadine may be highly effective for reducing overall alcohol consumption for those with severe AUD.

Reference:

Aubin H et al. Addiction 2024; 1-13. Epub ahead of print. Abstract