Abecarnil for the Treatment of Generalized Anxiety Disorder: A Placebo-Controlled Comparison of Two Dosage Ranges of Abecarnil and Buspirone

Background: The development of effective and well-tolerated anxiolytic agents is an area of criticalclinical importance. Abecarnil, a beta carboline, is a partial benzodiazepine-receptor agonist thathas demonstrated promise as an anxiolytic agent. In this study, we examine the efficacy, safety, anddiscontinuation-related effects of abecarnil, buspirone, and placebo in the acute and long-term treatmentof patients who have generalized anxiety disorder. Method: This is a double-blind, placebo-controlledstudy of two dosages of abecarnil and buspirone. In total, 464 patients were randomized. Aftera placebo run-in week, patients entered a 6-week double-blind treatment period, followed by an optional18-week maintenance period for treatment responders. After abrupt discontinuation of the acuteor maintenance treatment, patients entered a 3-week placebo-substitution follow-up period. Treatmentresponse was assessed with the Hamilton Rating Scale for Anxiety and the Clinical Global Impressions(CGI) Scale. Results: Compared with placebo, abecarnil showed significant anxiolytic activityearly in the treatment period, particularly in the high-dosage group, though these differences did notmaintain statistical significance at the end of the trial. Buspirone was associated with a slower onset ofaction and better symptom relief than placebo after 6 weeks of therapy. Withdrawal symptomsemerged in patients who abruptly discontinued abecarnil (particularly at the higher dosage) only inthose receiving a longer duration of treatment. Conclusion: The results of this study need to be understoodin the context of a high placebo-response rate, which hampers the ability to demonstrate significantdrug-placebo differences. This study suggests that abecarnil may be an effective anxiolytic agent;further attention is warranted to assess its spectrum of clinical effectiveness.