To the Editor: Changes in central cortical inhibitory pathways, especially associated with γ-aminobutyric acid (GABA) neurotransmission, have been widely implicated in the pathogenesis of major depressive disorder. Furthermore, a number of studies have supported the view that response to antidepressant interventions is accompanied by an increase in GABA-ergic neurotransmission. In accordance, there is evidence that antidepressant therapeutic brain stimulation techniques, such as vagus nerve stimulation and ECT may act via GABA-ergic pathways (1, 2). Transcranial magnetic stimulation is a noninvasive investigational tool that has been extensively used over recent years to assess human motor cortex excitability (3).

After approval by a local ethics committee and receipt of written informed consent, we tested the motor threshold, postexcitatory inhibition, and intracortical excitability to clarify the influence of vagus nerve stimulation and ECT on motor cortex excitability with transcranial magnetic stimulation in two female patients with unipolar major depressive disorder (40 and 65 years old); each received two different antidepressant stimulatory interventions. In the premenopausal patient, each of the three assessments was performed within the follicular phase of her menstrual cycle. Antidepressant medication (tranylcypromine, 40 mg/day, and venlafaxine, 150 mg/day) was kept constant at least 4 weeks before the first stimulation treatment and throughout the whole treatment. Response was defined as a 50% reduction in score on the 21-item Hamilton Depression Rating Scale.

Ms. A did not respond to 12 sessions of right unilateral ECT (her Hamilton depression scale score dropped only 1 point, from 27 to 26) and was then successfully treated with vagus nerve stimulation (her Hamilton depression scale score dropped from 26 to 12). Ms. B did not respond to 10 weeks of vagus nerve stimulation (her Hamilton depression scale score increased by 2 points, from 29 to 31) and was then successfully treated with 12 sessions of ECT (her Hamilton depression scale score dropped from 31 to 10). In both patients, measurements of motor cortical excitability were performed at baseline, after completion of the first unsuccessful intervention, and after the completion of the second (successful) intervention. Regardless of the type of intervention, all parameters remained unchanged after the first therapeutic trial. After the second therapeutic intervention (vagus nerve stimulation in Ms. A and ECT in Ms. B), both patients showed a treatment response and an increase in cortical silent-period duration and intracortical inhibition.

To our knowledge, this is the first report of an increase in motor cortical inhibition in depressed patients receiving vagus nerve stimulation and ECT. The data suggest that a common GABA-ergic pathway is activated in both vagus nerve stimulation and ECT responders. Furthermore, the data indicate that measurement of motor cortical excitability may be a useful tool for investigating and monitoring inhibitory brain effects of different antidepressant stimulation techniques. In the future, further studies with larger groups are needed.