To compare the anxiolytic efficacy and speed of onset of pregabalin (PGB) and venlafaxine-XR (VXR) in patients with GAD.

Adult outpatients with DSM-IV GAD and a HAM-A score >20 were randomized to 8-weeks of flexible-dose double-bind treatment with PGB 300-600mg/d (n=121), VXR 75-225mg/d (n=125), or placebo (PBO; n=128). Primary outcome: LOCF-endpoint change in HAM-A total score. Secondary outcomes included the Clinical Global Impression, Severity scale (CGI-S).

Study groups were similar at baseline, or PGB, VXR, and PBO, respectively, in terms of gender, mean age, and baseline HAM-A (27.6±0.4 vs. 27.4±0.4 vs. 26.8±0.4. Treatment with PGB was associated with significantly greater improvement than placebo at LOCF-endpoint, with onset of treatment effect beginning by day 4. HAM-A-total scores for PBO, PGB, and VXR at day 4 were: -3.4±0.5, -5.3±0.5 (P=.008), and -2.9±0.6 (P=.070), respectively; corresponding LOCF-endpoint HAM-A-total scores were: -11.7±0.9, -14.5±0.9 (P=.03), and -12.0±0.9 (P=.097). LOCF-endpoint CGI-S scores for PBO, PGB, and VXR were: -1.5±0.2, -2.0±0.2 (P=.02), and -1.7±0.2 (P=.36),

Severe AE rates were: PGB (9.1%), VXR (20.0%), and PBO (7.8%). Discontinuation due to AEs were: PGB (12.4%), VXR (17.6%), and PBO (5.5%).

Pregabalin was safe and effective, demonstrating significantly earlier onset of anxiolytic activity against GAD than venlafaxine-XR. Venlafaxine-XR did not demonstrate significant efficacy, possibly due to a relatively high placebo response.

Funded by Pfizer Inc