ABECARNIL FOR THE TREATMENT OF GENERALIZED ANXIETY DISORDER - A PLACEBO-CONTROLLED COMPARISON OF 2 DOSAGE RANGES OF ABECARNIL AND BUSPIRONE

Background: The development of effective and well-tolerated anxiolytic agents is an area of critical clinical importance. Abecarnil, a beta carboline, is a partial benzodiazepine-receptor agonist that has demon strated promise as an anxiolytic agent. In this study, we examine the efficacy, safety, and discontinuation-related effects of abecarnil, bu spirone, and placebo in the acute and long-term treatment of patients who have generalized anxiety disorder. Method: This is a double-blind, placebo-controlled study of two dosages of abecarnil and buspirone. I n total, 464 patients were randomized. After a placebo run-in week, pa tients entered a 6-week double-blind treatment period, followed by an optional 18-week maintenance period for treatment responders; After ab rupt discontinuation of the acute or maintenance treatment, patients e ntered a 3-week placebo-substitution follow-up period. Treatment respo nse was assessed with the Hamilton Raring Scale for Anxiety and the Cl inical Global Impressions (CGI) Scale. Results: Compared with placebo, abecarnil showed significant anxiolytic activity early in the treatme nt period, particularly in the high-dosage group, though these differe nces did not maintain statistical significance at the end of the trial . Buspirone was associated with a slower onset of action and better sy mptom relief than placebo after 6 weeks of therapy. Withdrawal symptom s emerged in patients who abruptly discontinued abecarnil (particularl y at the higher dosage) only in those receiving a longer duration of t reatment. Conclusion: The results of this study need to be understood in the context of a high placebo-response rate, which hampers the abil ity to demonstrate significant drug-placebo differences. This study su ggests that abecarnil may be an effective anxiolytic agent; further at tention is warranted to assess its spectrum of clinical effectiveness.