Box 1. Multiple somatic interventions reflect the complexity of major depression. Aside from pharmacological intervention, there are several devices currently used to treat patients with difficult to treat chronic or recurrent depression. These devices include electroconvulsive therapy (ECT), vagus nerve stimulation (VNS) and most recently, transcranial magnetic stimulation (TMS). Repeated administration of ECT is one of the most effective treatments of depression, particularly in suicidality situations when clinical intervention is immediately required. There is no conclusive regional specificity of ECT effects. The vagus nerve (cranial nerve 10) has afferent fibers that lead up toward the brain, including indirect input to the locus coeruleus, a major site of NE synthesis whose neurons make synaptic connections with the amygdala and orbito-frontal cortex. Vagus nerve stimulation appears to provide both acute symptom relief and continued benefits in patients with treatment resistance depression (George et al., 2000). Transcranial magnetic stimulation therapy is a relatively new approach for treating melancholia and overall behavioral despair. However, its antidepressant mechanisms of action are not well understood. As in ECT, there is no conclusive regional specificity of TMS effects although there is evidence that left prefrontal cortex application of rapid-rate TMS improves depression scores in melancholic patients (Chang, 2004). The reversible and adjustable nature of the above therapies is an appealing, if rather coarse, approach to treating depression. Large-scale clinical trials are now under way to test the possibility of using deep brain stimulation (e.g., in the sub-callosal cingulate gyrus) for the treatment of major depression. Deep brain stimulation is delivered via deeply implanted electrodes to alter abnormal chemical circuits underlying mood disorders.