Vigabatrin increases gamma aminobutyric acid (GABA) levels by irreversible inhibition of the GABA-catabolizing enzyme GABA-transaminase (GABA-T). Preclinical studies suggest anxiolytic effects in vigabatrin treated rats. Anxiolytic effects in patients with panic disorder (PD) could therefore be expected. To evaluate putative anxiolytic properties of vigabatrin in humans, CCK-4-induced panic symptoms were studied in healthy volunteers before and after vigabatrin treatment. After placebo-controlled administration of 50 g CCK-4, ten healthy volunteers received vigabatrin for seven days with a daily dosage of 2 g. The treatment period was followed by a second CCK-4 challenge. Panic and anxiety were assessed using the Acute Panic Inventory (API) score and a DSM-IV derived panicsymptom-scale (PSS). ACTH and cortisol plasma levels were determined during the CCK-4 challenge. All subjects reported a marked reduction of CCK-4-induced panic symptoms and anxiety after seven days of vigabatrin treatment both in the API-and PSS-scores. MoreoverThe new antiepileptic drug vigabatrin is a selective irreversible inhibitor of GABA-transaminase (GABA-T), the main degradative enzyme of GABA (Harden 1994). Vigabatrin increases CSF GABA levels by 2 to 3-fold when administered in anticonvulsant doses (Ben-Menachem 1989). Preclinical studies suggest that vigabatrin has anxiolytic properties in addition to its anticonvulsant effects. Sayin et al. (1992) compared the anxiolytic effects of diazepam and vigabatrin in rats and found a significant decrease of anxiety with both substances using the elevated plus maze test. Sherif and colleagues investigated the effects of GABA-transaminase inhibition on exploratory behaviour in socially isolated rats using both the elevated plus maze and the open field NO . 5 test (Sherif et al. 1994;Sherif and Oreland 1995). Despite these promising results in animal models it is still unclear whether vigabatrin exerts anxiolytic properties also in humans.CCK-4 has potent anxiogenic properties both in patients with panic disorder and in healthy volunteers (Bradwejn et al. 1990;Bradwejn et al. 1991a;Bradwejn et al. 1991b). Recent data suggest that CCK-4-induced panic is attenuated by antipanic treatment. A decrease of the anxiogenic effects of CCK-4 has been shown after treatment with benzodiazepines in healthy volunteers (de Montigny 1989). Moreover, antidepressants that are commonly used as antipanic treatment, e.g. imipramine (Bradwejn and Koszycki 1994a), fluvoxamine (van Megen etal. 1997) and citalopram (Shlik et al. 1997) reduced CCK-4-induced panic in patients with panic disorder.CCK-4-induced panic appears to be a suitable model to assess anxiolytic properties of psychopharmacological drugs in humans. To evaluate the putative anxiolytic properties of the selective GABA transaminase inhibitor vigabatrin, we therefore studied the effects of treatment with vigabatrin for seven days on CCK-4-induced panic symptoms in healthy male volunteers. METHODSTen male healthy volunteers (mean age ϭ 30.7 years, S...

Objectives: There is evidence that the antioxidant enzyme glyoxalase-1 (Glx-1) may play a role in anxiety-related behaviour. However, discordant findings between Glx-1 expression and anxiety-related behaviour have been observed in animal models. Because no data are available on the relation between Glx-1 mRNA expression and human anxiety so far, we investigated the expression of Glx-1 mRNA in peripheral red blood cells in relation to cholecystokinin-tetrapeptide (CCK-4) induced anxiety in healthy subjects. Methods: Twenty-three healthy subjects underwent challenge with CCK-4. Glx-1 mRNA expression was assessed by quantitative real-time polymerase chain reaction prior to CCK-4 injection. Baseline anxiety was assessed with the State-Trait-Anxiety-Inventory (STAI) and panic response was measured with the Panic Symptom Scale (PSS). Results: CCK-4 elicited a marked anxiety response accompanied by a significant increase in heart rate. Glx-1 mRNA expression correlated significantly with severity of CCK-4 induced anxiety. In contrast, Glx-1 activity did not correlate with state or trait anxiety. Conclusions: The positive correlation between Glx-1 mRNA expression and CCK-4 induced panic severity suggests that Glx-1 is involved into the acute anxiety response to CCK-4. Our preliminary findings support preclinical findings and point towards a role of Glx-1 for human anxiety.

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Introduction: The effectiveness of electroconvulsive therapy (ECT) in pharmacotherapy resistant major depression and schizophrenia has been shown for all age groups. Nevertheless, age specific side effects such as greater cognitive impairment and higher somatic risks due to medical comorbidities and concomitant medication may be limiting factors in geriatric patients. Methods: We retrospectively evaluated 4457 treatments in 380 patients. Clinical variables, treatment modalities, ictal and postictal neurophysiological parameters were analysed. For modelling the influence of age on these varibles of interest, linear regression models, if necessary logistic regression models, were performed (statistical software package R 2.8.1). Results: We found a considerable clinical improvement over all age groups. Higher severity of disease at admission came up with a better clinical response. In comparison of the whole patient sample versus the elderly over the age of 60, there were no significant differences in need and number of concomitant psychotropic, but in medical co-medication. Ictal and postictal EEG parameters were only in part predictive for clinical outcome, but age had a significant influence on most of them. Cardiovascular side effects and cognitive disturbances were more frequent in the elderly but were only transient, and in most cases there was no need for any specific treatment. Conclusions: The outcome results show excellent effectiveness and tolerability of ECT in all age groups. The very old are more prone to adverse events, but nonetheless tolerate ECT well and are likely to benefit.