Unexpectedly patients with panic disorder had signifi- cantly increased concentrations of the positive allosteric
nal antagonist for GABAA agonistic steroids, which might results in an increased GABA-ergic tone. Paroxetine treatment did not affect neuroactive steroid concentrati- ons which were highly stable for 24 weeks. In contrast, sodium lactate- and CCK-4 induced panic attacks of pati- ents were accompanied by pronounced decreases in the
mitant increase in the concentrations of the functional
drastically decreased GABA-ergic tone. No changes in neuroactive steroid concentrations could either be obser- ved following placebo in patients panic disorder or follo- wing placebo, lactate or CCK-4 in control subjects. The association between changes of plasma neuroactive steroid concentrations with panic attacks and the well documen- ted pharmacological properties of these compounds as GABAA receptor modulators suggest a causal relationship and may provide a lead for new drugs for the treatment of anxiety disorders such as panic disorder.
German J Psychiatry 2001; 4: S6 Impact of GABAergic treatment on CCK-4 induced anxiety
Zwanzger, D. Eser, T. Baghai, F. Padberg, C. Schuele,
-J. Möller and R. Rupprecht,
Department of Psychiatry, Ludwig-Maximilian University of Munich, Germany
Objectives: There is increasing evidence that dysregula- tion of the GABAergic system plays an important role in the pathophysiology of panic disorder. Selective en- hancement of GABAergic neurotransmission has been shown to improve anxiety in experimental animals and in
patients with panic disorder 1;2. To evaluate the impact of selective GABA enhancement on anxiety in humans we investigated anxiolytic effects of vigabatrin and tiagabine on cholecystokinin-tetrapeptide (CCK-4) induced panic 3. Methods: In study I ten healthy volunteers received vi- gabatrin 2 g daily for one week. In study II 15 healthy volunteers received tiagabine 15 mg daily for one week. A CCK-4 challenge was performed before and after treat- ment. Panic was assessed using the API- and PSS-score. Blood samples were taken for determination of ACTH and cortisol plasma levels. Results: Subjects reported a marked reduction of CCK-4 induced panic symptoms and anxiety after both vigabatrin and tiagabine administration. API and PSS–scores showed a significant reduction after one week of treat- ment. Moreover, we observed a marked and significant blunting of CCK-4 induced HPA stimulation after vi- gabatrin treatment, whereas HPA stimulation patterns after tiagabine treatment were not affected. Conclusion: Our data show a marked improvement of CCK-4-induced panic-symptoms following GABAergic treatment in healthy volunteers and suggest that GABAergic drugs might be useful in ameliorating panic symptoms also in patients with PD.
References: 1. Sherif F, Harro J, el-Hwuegi A, Oreland L. Anxiolytic- like effect of the GABA-transaminase inhibitor vigabatrin (gamma-vinyl GABA) on rat exploratory activity (1994). Pharmacol Biochem Behav. 49:801-805. 2. Zwanzger P, Baghai T, Boerner RJ, Möller H.-J., Rupp- recht R (2001). Anxiolytic Effects of Vigabatrin in Panic Disorder. J Clin Psychopharmacology (in press). 3. Bradwejn J, Koszycki D. The cholecystokinin hypothe- sis of anxiety and panic disorder (1994). Ann N Y Acad Sci. 713:273-82:273-282.