Crossover trial of pagoclone and placebo in patients with DSM-IV panic disorder

Pagoclone is a cyclopyrrolone that is believed to act as a partial agonist at the gamma -aminobutyric acid (GABA)A/benzodiazepine (BDZ) receptor. In t heory, such partial agonists should be anxiolytic but lack the adverse side -effects of sedation, tolerance and withdrawal associated with full GABA-A/ BDZ agonists. The objective of the randomized double-blind crossover study was to assess whether pagoclone was an effective anti-panic agent and also to assess its side-effect profile. Patients recruited had a diagnosis of Pa nic Disorder (DSM-IV) with at least one panic attack per week. Following a 2-week screening period, patients entered a 6-week trial consisting of two 2-week treatment periods, each followed by a 1-week washout. Patients were randomly assigned to receive either pagoclone 0.1 mg t.d.s. or placebo on t heir first treatment period and the converse on their second. The primary m easure was daily panic attack dairy. Fourteen patients completed the study, the mean number of panic attacks during screening was 5.8 +/- 0.8 (SEM), t his fell to 3.6 +/- 0.5 during treatment with pagoclone (p = 0.05) and 4.3 +/- 0.8 with placebo (p = 0.14). There was no significant difference on dir ect comparison of pagoclone with placebo or in any of the secondary measure s (including Rickels withdrawal scale) or the adverse event profiles. The s tudy provides preliminary evidence that pagoclone has anxiolytic properties in the absence of typical BDZ side-effects. This is consistent with its th eoretical mode of action as a partial agonist at the GABA(A)/BDZ receptor.