Crossover trial of pagoclone and placebo
in patients with DSM-IV panic disorder
by
Sandford JJ, Forshall S, Bell C, Argyropoulos S,
Rich A, D'Orlando KJ, Gammans RE, Nutt DJ.
Psychopharmacology Unit,
School of Medical Sciences,
University of Bristol, UK.
john.j.sandford@ukgateway.net
J Psychopharmacol. 2001 Sep;15(3):205-8

ABSTRACT

Pagoclone is a cyclopyrrolone that is believed to act as a partial agonist at the gamma-aminobutyric acid (GABA)-A/benzodiazepine (BDZ) receptor. In theory, 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 Panic 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 their first treatment period and the converse on their second. The primary measure was daily panic attack dairy. Fourteen patients completed the study, the mean number of panic attacks during screening was 5.8+/-0.8 (SEM), this 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 direct comparison of pagoclone with placebo or in any of the secondary measures (including Rickels withdrawal scale) or the adverse event profiles. The study provides preliminary evidence that pagoclone has anxiolytic properties in the absence of typical BDZ side-effects. This is consistent with its theoretical mode of action as a partial agonist at the GABA(A)/BDZ receptor.

Panic disorder
Benzodiazepines
Future anxiolytics
Making animals cry
Anxiety and depression
Subthreshold syndromes
Buspirone plus venlafaxine
Neuropepide Y and anxiety
Anxiolytics/antidepressants
Generalised Anxiety Disorder (GAD)
Neurobiology and genetics of anxiety

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