Efficacy and safety of lesopitron in outpatients with generalized anxiety disorder

OBJECTIVE: To compare the relative efficacy and safety of lesopitron 40-80 mg/d versus lorazepam 2-4 mg/d and placebo in a subgroup of patients with a nxiety history taken from a larger study of patients with a primary diagnos is of generalized anxiety disorder (GAD). DESIGN: Six-week, randomized, double-blind, parallel, placebo and lorazepam -controlled, Phase II, single-center, outpatient study. SETTING: Outpatient clinic. PATIENTS: One hundred sixty-one patients with GAD were randomized in the ma in study; 68 with a documented history of GAD or anxiety disorder not other wise specified were included in the subgroup. METHODS: After a one-week placebo lead-in, patients were randomized to rece ive placebo, lesopitron, or lorazepam twice daily for six weeks, followed b y a one-week taper period. Efficacy was assessed using the Hamilton Rating Scale for Anxiety (HAM-A) and the Clinical Global Impressions scale. Safety was assessed through physical examinations, monitoring of vital signs, 12- lead electrocardiograms, laboratory analyses, and adverse event monitoring. RESULTS: An overall mean improvement in the HAM-A total score between basel ine and end point for all three treatment groups was seen, with mean change s of 3.4 (95% CI 2.0 to 4.8), 6.1 (95% CI 4.1 to 8.1), and 6.1 (95% CI 4.6 to 7.6) for the placebo, lesopitron, and lorazepam groups, respectively (om nibus p = 0.044, uncorrected). Positive treatment effects were also observe d in the subgroup population on several other measures and suggest that add itional therapeutic trials may be warranted. Future trials could be stratif ied on the basis of referral status (symptomatic volunteer vs. clinical pat ient with preexisting illness) or previous exposure to anxiolytics, and use a fixed-dose rather than flexible-fixed-dose design. CONCLUSIONS: The subgroup analysis represents a comparison of treatment out come in GAD patients presenting with a history of previous episodes of GAD or anxiety disorder not otherwise specified compared with those who were ex periencing their first episode of GAD and reported no anxiety history. Alth ough the overall study analysis was equivocal, for the approximately 40% of patients with recurrent anxiety disorder, beneficial effects for both leso pitron and lorazepam are suggested.