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 critical clinical importance. Abecarnil, a beta carboline, is a partial benzodiazepine-receptor agonist that has demonstrated promise as an anxiolytic agent. In this study, we examine the efficacy, safety, and discontinuation-related effects of abecarnil, buspirone, and placebo in the acute and long-term treatment of patients who have generalized anxiety disorder.


METHODS
This is a double-blind, placebo-controlled study of two dosages of abecarnil and buspirone. In total, 464 patients were randomized. After a placebo run-in week, patients entered a 6-week double-blind treatment period, followed by an optional 18-week maintenance period for treatment responders. After abrupt discontinuation of the acute or maintenance treatment, patients entered a 3-week placebo-substitution follow-up period. Treatment response was assessed with the Hamilton Rating Scale for Anxiety and the Clinical Global Impressions (CGI) Scale.


RESULTS
Compared with placebo, abecarnil showed significant anxiolytic activity early in the treatment period, particularly in the high-dosage group, though these differences did not maintain statistical significance at the end of the trial. Buspirone was associated with a slower onset of action and better symptom relief than placebo after 6 weeks of therapy. Withdrawal symptoms emerged in patients who abruptly discontinued abecarnil (particularly at the higher dosage) only in those receiving a longer duration of treatment.


CONCLUSIONS
The results of this study need to be understood in the context of a high placebo-response rate, which hampers the ability to demonstrate significant drug-placebo differences. This study suggests that abecarnil may be an effective anxiolytic agent; further attention is warranted to assess its spectrum of clinical effectiveness.
Pollack
M H
MH
Massachusetts General Hospital, Boston 02114, USA.
Worthington
J J
JJ
Manfro
G G
GG
Otto
M W
MW
Zucker
B G
BG
D000293:Adolescent; D000328:Adult; D014151:Anti-Anxiety Agents / Q000627:therapeutic use*; D001008:Anxiety Disorders / Q000175:diagnosis / Q000188:drug therapy* / Q000523:psychology; D002065:Buspirone / Q000627:therapeutic use; D002243:Carbolines / Q000627:therapeutic use*; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010919:Placebos; D011569:Psychiatric Status Rating Scales; D016896:Treatment Outcome
D014151:Anti-Anxiety Agents; D002243:Carbolines; D010919:Placebos; C062769:abecarnil; D002065:Buspirone