title: Changes in CCK-4 induced panic after treatment with the GABA-reuptake inhibitor tiagabine are associated with an increase in 3alpha,5alpha-tetrahydrodeoxycorticosterone concentrations.
abstract: There is evidence that gamma-amino-butyric acid type A (GABA(A))-receptor modulating neuroactive steroids play a role in the pathophysiology of panic disorder. Antidepressant treatment has been suggested to stabilize the concentrations of neuroactive steroids. In this pilot study we investigated neuroactive steroid concentrations during GABAergic treatment, which might represent an alternative anxiolytic pharmacotherapeutic strategy. Neuroactive steroid concentrations were determined in 10 healthy subjects treated with tiagabine. To evaluate the anxiolytic effects of tiagabine a cholecystokinin-tetrapeptide (CCK-4) challenge was performed before and after treatment. Treatment with tiagabine led to a significant increase in 3alpha,5alpha-tetrahydrodeoxycorticosterone (3alpha,5alpha-THDOC) from 0.49 to 1.42 nmol/l (Z=-2.80, p=.005), which was significantly correlated with a decrease of panic symptoms in the CCK-4 challenge. Thus, it might be hypothesized that the anxiolytic effects of GABAergic treatment might in part be mediated by their influence on 3alpha,5alpha-THDOC concentrations.
authors.affiliation: Department of Psychiatry, Ludwig-Maximilian-University, Munich, Germany. zwanzger@ukmuenster.de
authors.forename: Peter
authors.initials: P
authors.lastname: Zwanzger
authors.forename: Daniela
authors.initials: D
authors.lastname: Eser
authors.forename: Elena
authors.initials: E
authors.lastname: Romeo
authors.forename: Flavia
authors.initials: F
authors.lastname: di Michele
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Baghai
authors.forename: Augusto
authors.initials: A
authors.lastname: Pasini
authors.forename: Frank
authors.initials: F
authors.lastname: Padberg
authors.forename: Rainer
authors.initials: R
authors.lastname: Rupprecht
mesh_terms: D000328:Adult; D003900:Desoxycorticosterone / Q000031:analogs & derivatives* / Q000097:blood; D005260:Female; D058805:GABA Uptake Inhibitors; D006801:Humans; D008297:Male; D014179:Neurotransmitter Uptake Inhibitors / Q000627:therapeutic use*; D009557:Nipecotic Acids / Q000627:therapeutic use*; D016584:Panic Disorder / Q000097:blood* / Q000139:chemically induced / Q000188:drug therapy; D010865:Pilot Projects; D013758:Tetragastrin; D000078308:Tiagabine
chemical_list: D058805:GABA Uptake Inhibitors; D014179:Neurotransmitter Uptake Inhibitors; D009557:Nipecotic Acids; D013758:Tetragastrin; D003900:Desoxycorticosterone; C009413:tetrahydrodeoxycorticosterone; D000078308:Tiagabine