AN EVALUATION OF THE ANXIOLYTIC SC 48,274 IN GENERALIZED ANXIETY DISORDER (GAD)

1. The present study evaluated the safety and efficacy of two dosages of SC 48,274 (1 mg and 25 mg) as compared to placebo in subjects with Generalized Anxiety Disorder (GAD). 2. This was a randomized, double-blind, placebo-controlled, parallel-group study which was part of one of three large multicenter trials which evaluated a total of 5 doses of SC 48,274 (.25, 1, 5, 25, and 100 mg bid). Following a 7-day placebo baseline period, patients entered 4 weeks of double-blind treatment and a 7-day placebo follow-up period. 3. Efficacy was assessed weekly throughout the study with the Hamilton Anxiety Rating Scale (HAM-A), and Clinical Global Impression (CGI), and at treatment endpoint with the Covi Anxiety Scale, Raskin Depression Scale and Hamilton Depression Rating Scale (HAM-D). A diagnosis of GAD according to DSM-III-R criteria (with the exception that a GAD minimum duration of 3 months was allowed), a HAM-A score greater-than-or-equal-to 20 (anxious mood and tension items greater-than-or-equal-to 2), HAM-D less than HAM-A, Covi Anxiety Score greater-than-or-equal-to 8, Raskin Depression Scale less than the Covi Anxiety, and age of 18 to 65 years were necessary for inclusion in the study. 4. Patients received one of two dosages of SC 48,274, either 1 mg (n = 28), 25 mg (n = 9), or placebo (n = 28) bid, during the 4-week randomized portion of the trial. 5. Mean changes from baseline in HAM-A scores for the 1 mg, 25 mg, and placebo groups after 4 weeks treatment were -5.1, -4.2, and -1.9, respectively. Changes were significant for the 1 mg group vs. placebo (F = 8.93, p = 0.004), but not for the 25 mg group (F = 2.26, p = 0.138). 6. CGI severity of illness scores were also significant for the 1 mg group versus placebo at the end of treatment (X2 = 3.8, p = 0.05), but not for the 25mg group (X2 = 0.90, p = 0.343). Neither group showed significant CGI improvement scores by end of treatment. 7. The most frequent adverse events associated with the study drug (n = 37) were headache (n = 7), nausea (n = 3), palpitations (n = 4) and chest pains (n = 2). There was, however, no apparent pattern of adverse events distinguishing SC 48,274 from placebo.