Anxiolytic effects of low-dose clomipramine in highly anxious healthy volunteers assessed by frontal midline theta activity.

1. The appearance of Fm theta, the distinct EEG theta rhythm in the frontal midline area during performance of a mental task, reflects relief from anxiety in humans. 2. In the present study, the anxiolytic effects of low-dose clomipramine were examined by monitoring the Fm theta amount, the STAI scores and the plasma 5-HIAA concentration in 24 male university students with (Fm theta group, n = 12) and without (non-Fm theta group, n = 12) Fm theta. 3. Subjects were given placebo, 10 mg and 30 mg clomipramine in a double-blind crossover design. Blood samples were obtained, STAI scores were determined, and EEGs were recorded before and during the performance of an arithmetic addition task. The test was repeated twice: before and 3 hrs after drug administration. 4. In the non-Fm theta group, 10 mg clomipramine decreased the 5-HIAA concentration and state anxiety scores but increased the Fm theta amount, while 30 mg clomipramine slightly increased only the Fm theta amount. However, there were no differences in these items before and after clomipramine administration in the Fm theta group. 5. These results suggest that low doses of clomipramine such as 10 mg may exert anxiolytic effects during the acute phase of treatment in highly anxious humans.