Depression, Depressionen

Editorial

Vagus Nerve Stimulation for Treatment-Resistant Depression

As criteria for the diagnosis of treatment-resistant depression (TRD) do vary, so do the estimated prevalence rates. hut it is indisputable that patients who do not respond. poorly respond, and no longer respond to available antidepressant therapies represent a substantial minority of those with major depressive disorder (MDD). These individuals bear the burden of inescapable misery. Current therapeutic approaches include multiple sequential trials of combinations of psychotropic drugs, psychotherapies, electroconvulsive therapy, and, rarely, psychosurgery. A successful intervention in this disorder is one of the most gratifying outcomes in medicine. The possibility of a new remedy for this condition is indeed a welcome one.

In this issue Rush and colleagues present prospective but open data on the efficacy in TRD of a novel therapeutic intervention for psychiatry, vagus nerve stimulation (VNS) as delivered by the NeuroCybernetic Prosthesis (NCP) System. Approved by the FDA in 1997 for management of medically refractory partial-onset seizures, the device has also been widely available in Europe and has been used in over 6000 patients to decrease seizure frequency, often as a last alternative to surgery.

Two major drivers in psychopharmacologic development, epilepsy and serendipity, combined to play a key role in the identification of this potential antidepressant intervention. The observation of mood improvement in patients treated for seizure disorders set the stage for a treatment trial of VNS in TRD. Thus, VNS recapitulates some elements of antidepressant treatment evolution. Electroconvulsive therapy, arguably the best available intervention for TRD, resulted from observations of mood improvement after seizures in epileptics, and the most prescribed class of mood stabilizers for bipolar and related disorders is, of course, anticonvulsants. As with antidepressants themselves, which evolved from agents first developed for other conditions, the initial biological effects of VNS are evident, but the ultimate mechanism alleviating symptoms is as yet undiscovered. Once again there appears to be a latency to response, suggesting that the treatment is initiating a process of adaptation leading to eventual benefit rather than targeting the specific pathophysiology of the disorder directly. Similar also to earlier interventions, however, is the hope and possibility that study of the treatment mechanism will shed light on new places to look for the blueprint of the biology of MDD. In fact, studies of VNS in animal models of depression are being planned (J. Weiss, personal communication, December 15, 1999).