Efficacy and safety of pregabalin in the treatment of generalized anxiety disorder: a 6-week, multicenter, randomized, double-blind, placebo-controlled comparison of pregabalin and venlafaxine.

OBJECTIVE: Pregabalin has demonstrated robust, rapid efficacy in reducing symptoms of generalized anxiety disorder (GAD) in 4 placebo-controlled clinical trials. The current study compared the efficacy and safety of pregabalin and venlafaxine in patients diagnosed with moderate to severe GAD. METHOD: The study was conducted from December 21, 1999, to July 31, 2001. Outpatients (N = 421) in primary care or psychiatry settings meeting DSM-IV criteria for GAD were randomly assigned to 6 weeks of double-blind treatment with pregabalin 400 or 600 mg/day, venlafaxine 75 mg/day, or placebo. The primary analysis was change in Hamilton Rating Scale for Anxiety (HAM-A) total score from baseline to last-observation-carried-forward (LOCF) endpoint. Secondary analyses included the change in HAM-A psychic (emotional) and somatic (physical) factor scores, significant improvement at week 1, and week 1 improvement sustained at every visit through endpoint. RESULTS: Pregabalin at both dosages (400 mg/day, p = .008; 600 mg/day, p = .03) and venlafaxine (p = .03) produced significantly-greater improvement in HAM-A total score at LOCF endpoint than did placebo. Only the pregabalin 400-mg/day treatment group experienced significant improvement in all a priori primary and secondary efficacy measures. Pregabalin in both dosage treatment groups (400 mg/day, p < .01; 600 mg/day, p < .001) significantly improved HAM-A total score at week 1, with significant improvement through LOCF endpoint. Statistically significant improvement began at week 2 for venlafaxine. Discontinuation rates due to associated adverse events were greatest in the venlafaxine treatment group: venlafaxine, 20.4%; pregabalin 400 mg/day, 6.2%; pregabalin 600 mg/day, 13.6%; placebo, 9.9%. CONCLUSION: Pregabalin was safe, well tolerated, and rapidly efficacious across the physical-somatic as well as the emotional symptoms of GAD in the majority of patients studied in primary care and psychiatric settings.

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 neurotransmitters, presumably by binding to the alpha2-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 = 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, 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 alprazolam 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.

Fingolimod for the treatment of relapsing multiple sclerosis.

Fingolimod is the first oral agent approved in the USA for the treatment of relapsing forms of multiple sclerosis. Fingolimod is a sphingosine 1-phosphate receptor modulator that binds to sphingosine 1-phosphate receptors on lymphocytes, resulting in a downregulation of the receptor and a reversible sequestration of lymphocytes in lymphoid tissue. Effector memory T cells are not sequestered so that immune surveillance may be minimally affected. Two large-scale Phase III clinical trials have demonstrated the efficacy of fingolimod compared with placebo and intramuscular interferon ß-1a in relapsing-remitting multiple sclerosis. Due to its mechanism of action, fingolimod administration may be associated with first-dose bradycardia and macular edema. Therefore, patients should be observed for 6 h at the time of their first dose and undergo ophthalmologic evaluation prior to treatment initiation and at 3-4 months after initiation.