Efficacy and safety of lesopitron in outpatients with generalized anxiety disorder.
OBJECTIVE
To compare the relative efficacy and safety of lesopitron 4-80 mg/d versus lorazepam 2-4 mg/d and placebo in a subgroup of patients with anxiety history taken from a larger study of patients with a primary diagnosis of generalized anxiety disorder (GAD).


METHODS
Six-week, randomized, double-blind, parallel, placebo and lorazepam-controlled, Phase II, single-center, outpatient study.


METHODS
Outpatient clinic.


METHODS
One hundred sixty-one patients with GAD were randomized in the main study; 68 with a documented history of GAD or anxiety disorder not otherwise specified were included in the subgroup.


METHODS
After a one-week placebo lead-in, patients were randomized to receive placebo, lesopitron, or lorazepam twice daily for six weeks, followed by 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 baseline and end point for all three treatment groups was seen, with mean changes 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 (omnibus p = 0.044, uncorrected). Positive treatment effects were also observed in the subgroup population on several other measures and suggest that additional therapeutic trials may be warranted. Future trials could be stratified on the basis of referral status (symptomatic volunteer vs. clinical patient 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 outcome in GAD patients presenting with a history of previous episodes of GAD or anxiety disorder not otherwise specified compared with those who were experiencing their first episode of GAD and reported no anxiety history. Although the overall study analysis was equivocal, for the approximately 40% of patients with recurrent anxiety disorder, beneficial effects for both lesopitron and lorazepam are suggested.
Fresquet
A
A
Clinical Research, Laboratorios Dr. Esteve, S.A., Barcelona, Spain.
Sust
M
M
Lloret
A
A
Murphy
M F
MF
Carter
F J
FJ
Campbell
G M
GM
Marion-Landais
G
G
D000328:Adult; D000379:Agoraphobia / Q000188:drug therapy* / Q000523:psychology; D014151:Anti-Anxiety Agents / Q000009:adverse effects / Q000627:therapeutic use*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008140:Lorazepam / Q000009:adverse effects / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D010045:Outpatients; D010879:Piperazines / Q000009:adverse effects / Q000627:therapeutic use*; D011569:Psychiatric Status Rating Scales; D011743:Pyrimidines / Q000009:adverse effects / Q000627:therapeutic use*; D012008:Recurrence
D014151:Anti-Anxiety Agents; D010879:Piperazines; D011743:Pyrimidines; C075568:lesopitron; D008140:Lorazepam