Vigabatrin decreases cholecystokinin-tetrapeptide (CCK-4) induced panic inhealthy volunteers

Vigabatrin increases gamma aminobutyric acid (GABA) levels by irreversible inhibition of the GABA-catabolizing enzyme GABA-transaminase (GABA-T). Prec linical studies suggest anxiolytic effects in vigabatrin treated rats. Anxi olytic effects in patients with panic disorder (PD) could therefore be expe cted. To evaluate putative anxiolytic properties of vigabatrin in humans, C CK-4-induced panic symptoms were studied in healthy volunteers before and a fter vigabatrin treatment. After placebo-controlled administration of 50 mu g CCK-4, ten healthy volunteers received vigabatrin for seven days with a d aily dosage of 2 a. The treatment period was followed by a second CCK-4 cha llenge. Panic and anxiety were assessed using the Acute Panic Inventory (AP I) score and a DSM-IV derived panic-symptom-scale (PSS). ACTH and cortisol plasma levels were determined during the CCK-4 challenge. All subjects repo rted a marked reduction of CCK-4-induced panic symptoms and anxiety after s even days of vigabatrin treatment both in the API- and PSS-scores. Moreover , there was a significant attenuation of CCK-induced elevation of ACTH and cortisol levels following vigabatrin treatment. In conclusion, our data sho w that GABA-transaminase inhibitors exert anxiolytic effects in CCK-4-induc ed panic in healthy volunteers and suggest that GABA transaminase inhibitor s might be useful in ameliorating panic symptoms also in patients with PD. (C) 2001 American College of Neuropsychopharmacology. Published by Elsevier Science Inc.