Pregabalin for treatment of generalized anxiety disorder - A 4-week, multicenter, double-blind, placebo-controlled trial of pregabalin and alprazolam

Background: Pregabalin inhibits release of excess excitatory neuro transmitters, presumably by binding to the alpha(2)-delta subunit protein of widely distributed voltage-dependent calcium channels in the brain and spinal cord. Objective: To assess the anxiolytic efficacy of pregabalin in patients with generalized anxiety disorder. Design: Double-blind, placebo-controlled, active-comparator trial. Patients were randomized to 4 weeks of treatment with pregabalin, 300 mg/d (n = 91), 450 mg/d (n = 90), or 600 mg/d (n = 89); alprazolam, 1.5 mg/d (n = 93); or placebo (n = 9 1). Setting: Psychiatry research and clinic settings Patients: Outpatients meeting the DSM-IV criteria for generalized anxiety disorder, with a baseline Hamilton Anxiety Rating Scale (HAM-A) total score of 20 or greater. Main Outcome Measures: Change from baseline to end point in total HAM-A score in the pregabalin and alprazolam groups compared with the placebo group. The end point response criterion was 50 % or greater reduction in the HAM-A total score. Results: Pregabalin and alprazolam produced a significantly greater reduction in mean SE HAM-A total score at last-observation-carried-forward end point compared with placebo (-8.4 +/- 0.8): pregabalin, 300 mg (-12.2 +/- 0.8, P < .001), 450 mg (-11.0 +/- 0.8, P = .02), and 600 mg (-11.8 +/- 0.8, P = .002), and alprazolam (-10.9 +/- 0.8, P = .02). By week 1 and at last-observation-carried-forward end point, the 3 pregabalin groups and the alprazolain group had significantly (P < .01) improved HAM-A psychic anxiety symptoms compared with the placebo group. Compared with the placebo group, HAM-A somatic anxiety symptoms were also significantly (P < .02) improved by the 300- and 600-mg pregabalin groups, but not by the 450-mg pregabalin (week 1, P = .06; week 4, P = .32) and the alprazolam. groups (week 1, P =.21; week 4, P =. 15). Of the 5 treatment groups, the 300-mg pregabalin group was the only medication group that differed statistically in global improvement at treatment end point not only from the placebo group but also from the alprazolam group. Conclusion: Pregabalin was significantly more efficacious than placebo for the treatment of psychic and somatic symptoms of generalized anxiety disorder and was well tolerated by most study patients.