Pregabalin for Treatment of Generalized Anxiety Disorder

Abstract

Background: Pregabalin inhibits release of excess excitatory neurotransmitters, presumably by binding to the ␣ 2 -␦ subunit protein of widely distributed voltagedependent 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, activecomparator 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 = 91).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,PϽ.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 alprazolam group had significantly (PϽ.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 (PϽ.02) improved by the 300-and 600mg 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.